SUGER Flashcards
(577 cards)
1
Q
Define Genotype
A
complete genetic composition of an individual
2
Q
In humans, is the sex of the embryo determined by the sperm or egg?
A
The spermatozoa - can contribute an X or Y. The egg is always X.
3
Q
Why does the presence of the Y chromosome lead to the development of the male gonads?
A
Presence of the SRY gene
(Sex
determine Region of the Y chromosome)
4
Q
Which protein does the SRY gene on the Y chromosome produce?
A
Testis determining factor: under its influence male development takes place.
5
Q
What is the importance of testis determining factor?
A
Under its influence male development takes place.
6
Q
If there is an absence of the SRY gene as no Y chromosome what is formed?
A
female gonads (ovaries)
7
Q
What is lyonisation?
A
When two X chromosomes are present (in a female), only one is functional,
the non-functional X chromosome condenses to form a nuclear mass called
the sex chromatin or BARR BODY
8
Q
From which site do both male and female gonads derive embryologically?
A
Urogenital ridge
9
Q
When are embryos no longer indifferent?
A
They are indifferent until the end of the 6th week.
10
Q
Describe the migration of primordial germ cells.
A
Originate in the epiblast and migrate through the primitive streak. They migrate along the dorsal mesentery of the hindgut to reach and invade the genital ridge by the 6th week.
11
Q
Up until when are the primordial gonads undifferentiated?
A
6th week
12
Q
What is the indifferent stage?
A
When the Wolffian and Müllerian ducts are both present. It is impossible to tell the sex of the embryo.
- undifferentiated reproductive tract double duct system
13
Q
When do the testes begin to develop?
A
7th week - SRY gene expressed at this time in the urogenital ridge cells and triggers development
14
Q
Name the two tracts that most of the reproductive tracts develop from
A
- Wolffian ducts
- Mullerian ducts
15
Q
In males which genital duct system persists and which one regresses?
A
• In the male, the Wolffian ducts persist and the Mullerian ducts REGRESS
16
Q
Why does the Müllerian duct degenerate in males?
A
Sertoli cells of the testes produce a protein hormone - Mullerian-inhibiting factor (MIF)
- The SRY gene induces the expression of MIF which in turn results in
the degeneration of the Mullerian duct
17
Q
What does testosterone stimulate?
A
Differentiation of the Wolffian duct into the epididymis, vas defrens, ejaculatory ducts and seminal vesicles
18
Q
Which cells secrete testosterone in embryological development?
A
interstitial cells of Leydig
19
Q
When do Leydig cells start producing testosterone?
A
8 weeks
20
Q
In females which genital duct system persists and which one regresses?
A
Mullerian ducts persist and the Wolffian ducts
REGRESS
21
Q
Why does the Müllerian duct degenerate in Males?
A
Due to the inhibiting substance being released from Sertoli cells. Sertoli cells release MIF.
22
Q
In females why does the Mullerian system persist and why does the Wolfian duct regress?
A
Absence of SRY gene, no testosterone and MIF secreted
- absence of the MIF Mullerian system stays and develops into fallopian tubes and uterus
- absence of testosterone Wolffian duct degenerates
23
Q
What does the Müllerian duct form in females?
A
The uterine tubes, uterus, cervix, fallopian tubes and proximal 1/3 of the vagina.
24
Q
Until what week are male and female primitive gonads identical?
A
6th week
25
what can germ cells develop into?
Sperm and Ova, gamete production
26
Where do germ cells originate from?
• Originate from the yolk sac of the hindgut
27
What is the first stage of gametogenesis?
the proliferation of the primordial (undifferentiated)
| germ cells by MITOSIS
28
When does mitosis occur in embryonic testes to generate primary spermatocytes?
- some at birth
| - mostly begins during male puberty and continues through life
29
When does mitosis of germ cells occur in the ovary?
- primarily during fetal development resulting in the generation of primary oocytes
30
What is the second stage of gametogenesis?
meiosis
31
What is the importance of meiosis in gametogenesis?
It prevents polyploidy and increases genetic variability and so diversity through crossing over and independent assortment
32
Spermatogenesis: what does meiosis 1 produce?
2 secondary spermatocytes.
33
What are the start and end products of meiosis in oogenesis?
Start primary oocyte.
Middle: secondary oocyte.
End: 1x ovum.
34
When is the first polar body produced in oogenesis?
after the first meiotic division - has no function
35
Spermatogenesis: what does meiosis 2 produce?
4 spermatids.
36
Describe the timing of the second meiotic division in males
- In males, this occurs continuously AFTER puberty with the
| production of spermatids and ultimately mature sperm cells
37
Describe the timing of the second meiotic division in females
- In females the second meiotic division does not occur until
AFTER FERTILISATION of a secondary oocyte by a sperm -
this results in the production of a zygote (contains 46
chromosomes - 23 from the oocyte (maternal) & 23 from the
sperm (paternal)) & the second polar body which also has no
function
38
where does meiosis occur in males?
seminiferous tubules
39
Where does meiosis occur in females?
ovaries
40
Describe oogenesis.
Oogonia undergo around 30 mitotic divisions in utero. The oogonia develop into primary oocytes and begin a meiotic division by replicating their DNA. They do not complete meiosis 1 in the foetus = meiotic arrest. At puberty, there is renewed activity in the ovaries and those oocytes destined for ovulation complete meiosis 1. Meiosis 2 occurs if the secondary oocyte is fertilised; this will produce one ovum.
41
How long does spermatogenesis take?
Approximately 60 days.
42
Why does each primary oocyte yield only one secondary oocyte?
Because only one ovum can be yielded per primary oocyte. The secondary oocyte divides into one ovum and a second polar body.
43
Where are Detrusor muscles found, innervation and inhibited or stimulated during filling and micturition
- Found on the walls of the bladder, smooth muscle
- Parasympathetic innervation (causes contraction)
- micturition stimulated
- filling inhibited
44
Describe internal urethral sphincter muscle type, innervation and inhibited or stimulated during filling and micturition
Smooth muscle
Sympathetic (contraction)
Filling - stimulated
micturition - inhibited
45
Describe external urethral sphincter muscle type, innervation and inhibited or stimulated during filling and micturition
Skeletal muscle
Somatic motor (causes contractions)
Filling - stimulated
micturition - inhibited
46
What is the role of the external striated urethral sphincter?
contraction of the external striated urethral sphincter can contract and prevent urination even if the detrusor muscles and contracting strongly
47
Describe bladder filling
- Parasympathetic input to the detrusor muscle is minimal, relaxed
- when the detrusor muscle is relaxed the internal urethral is passively closed
- strong sympathetic input to the internal urethral sphincter
- strong sympathetic input to external urethral sphincter via somatic motor
- means during the filling phase the detrusor muscles are relaxed and the internal and external sphincters are closed
48
Describe the bladder reflex arc
1. Bladder fills with urine, and the bladder walls stretch
2. Sensory nerves (afferent) detect the stretch and transmit to the spinal
cord
3. Interneurones within the cord relay the signal to the parasympathetic
efferents (PELVIC NERVE)
4. The pelvic nerve acts to contract the detrusor muscle and thus
stimulate micturition
49
Describe what occurs during micturition
- As the bladder fills pressure increases
- stimulates stretch receptors in the bladder wall.
- afferent neurons from receptors enter the spinal cord and stimulate the parasympathetic neurons (pelvic splanchnic nerve S2-S4)
- Causes the detrusor muscles to contract
- Change in shape of detrusor muscle pulls open internal urethral sphincter
- afferent input at the same time inhibits the sympathetic neurons (Hypogastric nerve T1-L2) to the internal urethral sphincter, further contributes to opening
- afferent also inhibit somatic motor neurons pudendal nerve S2-S4 to the external urethral sphincter, relaxation
- Opening of both sphincters and contraction of detrusor muscles able to produce urination
50
Which nerve provides parasympathetic supply to the muscles of the bladder?
• ParaSympathetic - Pelvic Splanchnic nerve (S2-S4)
51
Which nerve provides sympathetic supply to the muscles of the bladder?
• SympathetiC - HypogastriC (T1-L2)
52
Which nerve provides somatic motor supply to the muscles of the bladder?
• Somatic Motor - Pudendal (S2-S4)
53
What is the role of the hypogastric nerve (T12-L2) in muscle control of the bladder?
- sympathetic
- HYPOGASTRIC NERVE (T12-L2) - causes the relaxation of the detrusor
muscle - promoting urine retention
54
What is the role of the pelvic splanchnic nerve (S2-S4) in muscle control of the bladder?
- parasympathetic
- increased signals from this nerve causes
contraction of the detrusor muscles - thereby stimulating micturition
55
What is the role of the pudendal nerve (S2-S4) in muscle control of the bladder?
- somatic motor control
- innervates the external urethral sphincter made of skeletal muscle
- - it can cause it to constrict (storage phase) or relax (micturition)
56
Are there sensory (afferent) nerves from the bladder that report to the brain?
Yes
located in the bladder wall they signal the need to urinate when the
bladder becomes full
57
What is the function of the Urinary tract?
- To collect urine
- Store it under safe LOW-PRESSURE conditions
- Store it until it is socially acceptable to release urine
58
Define bladder compliance
Bladder to hold urine at low pressure via receptive relaxation - detrusor (T12-L2)
59
Define bladder voiding
- Voluntary complete emptying
60
Name three consequences of bladder dysfunction
• Consequences of bladder dysfunction:
- Incontinence
- Infection & bladder stones
- Upper urinary tract injury - due to high pressure etc.
61
Describe the voiding reflex
- intense bladder-afferent firing to pelvic nerve
- triggers spinobulbospinal reflex
- afferent signals passed to PAG (relay centre) via A-delta fibres
- PAG stimulates the pontine micturition centra
- PMC acts as an on/off switch
- PMC causes parasympathetic outflow to the bladder
- inhibits sympathetic and pudendal outflow
62
What is the periaqueductal grey?
A visceral and somatic control centre for the lower urinary tract.
63
What fibre input does the periaqueductal grey receive?
A delta fibres.
64
What is urinary incontinence?
The involuntary release of urine.
65
Name 2 types of incontinence.
1. Stress incontinence.
| 2. Urge incontinence.
66
What can stress incontinence be due to?
Sneezing, coughing, exercise.
67
What can cause urge incontinence (desire to urinate)?
Any irritation to the bladder or urethra e.g. a bacterial infection.
68
Where does meiosis occur in the male testes?
Seminiferous tubules
69
Give two ways that the scrotum is cooled for spermatogenesis?
Air circulating around the scrotum and by a heat exchange mechanism in the blood vessels supplying the testes - the pampiniform plexus
70
If we look at a magnified cross-section of the testes what would we see as we go closer to the centre of the seminiferous tubules?
- central fluid-filled lumen contains the mature spermatozoa and around the diameter, there are spermatogonia and spermatocytes, gets mature as we reach the centre
71
What are the undifferentiated germ cells called in spermatogenesis?
Spermatogonia
72
When do spermatogonia begin to divide via mitosis
At puberty
73
What two cells do spermatogonia divide into?
Type A and Type B spermatogonium
74
Which type of spermatogonia remains outside the blood testicle barrier?
Type A spermatogonia
75
What is the role of Type A spermatogonia?
Constantly undergo mitosis to produce more daughter cells until death
76
What do spermatogonia differentiate into via mitosis?
Type A spermatogonia and Type B spermatogonia
77
What is the role of type B spermatogonia and what do they produce?
differentiate into primary spermatocytes and move through the blood testes barrier towards the lumen of the seminiferous tubules - new tight junctions form behind these Sertoli cells
78
What is produced after meiosis 1 of primary spermatocyte?
2 secondary spermatocytes
79
What is produced after meiosis 2 of secondary spermatocytes?
4 spermatids
80
Describe spermiogenesis
transformation of spermatids into spermatozoa
- sprouts tail and discards cytoplasm to become lighter
- the cytoplasm of the Sertoli cells around the
sperm retracts and the sperm are released into the lumen to be bathed in luminal
fluid
81
Describe the hypothalamic-pituitary-gonadal axis of the male reproduction system
- Hypothalamus secretes GnRH (gonadotrophin-releasing hormone)
- GnRH travels to the anterior pituitary hypothalami-hypophyseal
portal vessels and triggers the release of both LH & FSH
- • FSH primarily acts on the Sertoli cells to stimulate the secretion of paracrine
agents required to initiate SPERMATOGENESIS
- LH acts primarily on the Leydig cells to stimulate TESTOSTERONE secretion:
- testosterone diffuses from interstitial spaces to the seminiferous tubules.
- testosterone then enters the Sertoli cells
- where it
is able to facilitate SPERMATOGENESIS
82
Describe the negative feedback mechanism in the hypothalamic-pituitary-gonadal axis
- Testosterone INHIBITS LH secretion in two
ways:
1. Acts on the hypothalamus to decrease
the amplitude of GnRH bust resulting in a
decrease in the secretion of GnRH
2. Acts directly on the anterior pituitary
gland to decrease LH response to
GnRH
- Sertoli cells (stimulated by FSH) release a
protein hormone called INHIBIN which acts on
the anterior pituitary to inhibit the release of
FSH
83
What changes does the sperm make with regards to its structure?
- It discards excess cytoplasm.
- Grows flagellum.
- Lots of mitochondria.
- Acrosomes at its head.
84
What is the role of the acrosomes
a protein-filled vesicle
| containing enzymes to penetrate the egg
85
what is the role of the flagellum
Most of the tail is flagellum - a group of
contractile filaments that produce
a whiplike movement capable of propelling
the sperm at a velocity
86
how long do the spermatozoa spend in the testes?
40 to 60 days
87
Describe the efferent ductules in the male reproductive tract
- 12 small ciliated ducts collecting sperm from the rete testes and transporting to the epidydimis
88
Describe the epididymis
6m long coiled duct adhering to the posterior of testis
| - site of sperm maturation and storage for 40-60 days
89
Describe the vas defrens
- muscular tube - 45 cm long
- from the scrotum through the inguinal canal to the posterior surface of the bladder
- widens into the terminal ampulla
90
describe the ejaculatory duct
- 2cm duct formed from ductus deferens and seminal vesicles passing through prostate to empty into the urethra.
91
What proportion of ejaculate is spermatozoa?
10%
| 90% prostatic and seminal secretions
92
Name three ducts that produce secretions that contribute to the production of ejaculate
bulbourethral
prostate gland
Seminal vesicle
93
How does the father decide the sex of the baby
Either X or Y sperm that fertilises the egg
94
What is the function of GnRH?
It acts on the anterior pituitary gland stimulating it to release FSH and LH.
95
Describe endocrine glands?
are ductless and release hormones directly into the blood
96
Where is the thyroid gland located?
anterior neck between C5 and T1 on top of the trachea
97
describe the structure of the thyroid gland
Have two lobes joined by a narrow isthmus
98
Which neck muscles does the thyroid lie behind?
Sternohyoid & sternothyroid
99
Name the two arteries which supply the thyroid
superior and inferior thyroid arteries
100
Which artery is the superior thyroid artery a branch of?
external carotid artery
101
Which artery is the inferior thyroid artery a branch of?
the thyrocervical trunk which in turn is a branch of the subclavian artery
102
Describe the nervous innervation of the thyroid gland
Branches from the sympathetic trunk
103
Does sympathetic innervation control hormone release?
No, the pituitary gland controls hormone release
104
Embryology: Where and when do the thyroid glands first appear?
Appear at 3-4 weeks
| appear as an epithelial proliferation at the base of the pharynx under the tongue and migrates down towards larynx
105
Embryology: when do the thyroid glands first start secreting thyroxine?
at 18-20 weeks
106
Name the two functional units of the thyroid glands and their functions?
Follicular cells - produce hormones T3 and T4
| C cells - produce calcitonin for Ca2+ homeostasis
107
What does the thyroid hormone affect?
Increased metabolism, increased sympathetic action, heat production, essential for growth and development too.
108
What is the common name for T4?
Thyroxine.
109
What is the full name of T3?
Triiodothyronine.
110
How many iodine molecules does triiodothyronine contain?
3.
111
Which molecule is active T3 or T4?
T3
112
More T4 is produced than T3 in the thyroid. What process produces T3 elsewhere?
As T3 is more active it can be produced peripherally from the conversion of T4.
113
Briefly describe oogenesis
- Oogonia stop dividing around 7th month of gestation
- during foetal life all of the oogonia differentiate into primary oocytes
- Meiosis 1 begins in utero before 12 weeks
- meiosis is arrested at metaphase 1 until puberty
- resumption after puberty only eggs destined for ovulation will complete meiosis 1
- first polar body produced
- meiosis 2 where the secondary oocyte becomes an ovum
- meiosis 2 is arrested at metaphase 2 until fertilisation
114
How many secondary oocytes does each primary oocyte yield?
1 secondary oocyte and 1 non-functional polar body.
115
What are the start and end products of mitosis in oogenesis?
Start: oogonia.
End: primary oocyte.
116
What are the start and end products of meiosis in oogenesis?
Start: primary oocyte.
Middle: secondary oocyte.
End: 1x ovum.
117
Describe the hormonal changes that occur at puberty.
1. Increased amplitude of GnRH and GHRH.
2. Increased levels of FSH, LH and sex steroids.
3. Increased levels of growth hormone.
118
What factors can influence puberty?
1. Nutrition (body mass).
2. Leptin, insulin (hormones).
3. Genetics.
4. Exercise.
5. Socio-cultural.
119
What are the 2 phases of the menstrual cycle?
1. The follicular phase.
2. The luteal phase.
The phases are approximately equal in length and are separated by ovulation.
120
Describe the follicular phase very briefly
- During which mature/Graafian follicle & secondary oocyte develop
121
Describe the luteal phase very briefly
- Beginning after ovulation and lasting until the death of the corpus
luteum
122
What do follicles begin as?
primordial follicles
123
What does a primordial follicle consist of?
- One primary oocyte
| - thin layer of granulosa cells
124
What do granulosa cells secrete?
* Oestrogen
* Small amounts of progesterone just before ovulation
* Peptide hormone inhibin
125
What does the primordial follicle develop into?
primary follicle
126
What happens during the development of the primary follicle?
- oocyte increases in size
- oocyte becomes separated from the granulosa cells by the zona pellucida
- cytoplasmic processes and gap junctions allow for oocyte communication
127
What is the role of the zona pellucida?
- The zona pellucida contains glycoproteins that play an important role in the
binding of a sperm cell to the surface of the egg after OVULATION
128
What does the primary follicle develop into?
Preantral follicle
129
Describes what occurs during the development of the early antral follicle?
- primary oocyte reaches full size
| - Fluid-filled space called the antrum begins to form due to fluid secreted by granulosa
130
What does the preantral follicle develop into?
early antral follicle
131
Describes what occurs during the development of the preantral follicle?
- mitosis of granulosa cells, increase in size
- connective tissue surrounding the granulosa cells differentiate into theca cells
- theca cells function together with granulosa cells to synthesise oestrogen
132
Approx how many early antral or preantral follicles begin to develop into larger antral follicles at the start of the menstrual cycle?
10-25
133
At what point in the cycle is the dominant follicle chosen and how?
- One week into the cycle further selection
| - only one of the larger antral follicles - the dominant follicle begin to develop
134
What happens to the non-dominant follicles?
- Atresia - enlarge then degeneration - apoptosis
135
What happens to the dominant follicle as ovulation approaches?
- primary oocyte emerges from its meiotic arrest ( due to LH surge)
- completes first meiotic division to become a secondary oocyte
136
Describe what occurs during ovulation?
- the mature follicle becomes so large it balloons out onto the surface of the ovary
- thin walls of the follicle rupture
- secondary oocyte surrounded by zona pellucida and granulosa cells carried out of the ovary by the antral fluid at Day 14
137
What happens to the Graafian follicle after the discharge of egg and antral fluid?
- Rapid transformation
| - Granulosa cells enlarge and a gland-like structure called corpus luteum forms
138
What does the corpus luteum secrete?
Oestrogen
large amounts of progesterone
- inhibin
139
What happens to the corpus luteum when the discharged egg is not fertilised?
Corpus luteum fully developed at 10 days
- rapid apoptosis that triggers menstruation
- degenerates into the corpus albucans.
140
Where and when is oestrogen synthesised and released before ovulation?
Follicular phase
| - granulosa cells
141
Where and when is oestrogen synthesised and released after ovulation?
luteal phase
| - corpus luteum
142
Where and when is progesterone synthesised and released before ovulation?
released in small amounts by granulosa and theca cells
143
What is the major source of progesterone after ovulation?
Corpus luteum
144
Name five factors released that affect the ovary
GnRH, FSH, LH, Oestrogen &
| Progesterone
145
What is FSH required for in follicular development?
development of the follicle beyond preantral & early antral
| - granulosa cells multiply and produce oestrogen
146
Menstrual cycle: why do LH and FSH levels decrease after ovulation?
They are inhibited by the high progesterone and oestrogen concentrations.
147
Menstrual cycle: why do FSH levels increase at the end of the cycle?
The fall in progesterone and oestrogen concentration means FSH is no longer inhibited and so its plasma concentration begins to rise
148
Which cells does FSH act on in the follicle?
Granulosa cells
149
What is the affect of oestrogen on the granulosa cells?
Paracrine/autocrine agent
- along with FSH and growth factors stimulates proliferation of granulosa cells
- further oestrogen production
150
What is the function of theca cells?
They produce androgens (oestrogen precursors) which diffuse into granulosa cells to form oestrogen.
151
Describe the hypothalamo-pituitary-ovarian-axis?
GnRh from hypothalamus acts on the anterior pituitary to release LH and FSH. LH acts on theca cells stimulating androgen release. Androgen diffuses from theca to granulosa. FSH acts on granulosa cells stimulating the conversion of androgen into oestrogen (aromatase enzyme). Inhibin is also released from granulosa cells. Inhibin and oestrogen have a negative feedback affect on the hypothalamus and anterior pituitary.
152
Menstrual cycle: what is the effect of decreasing FSH levels in the follicular phase?
Decreasing FSH levels cause the non-dominant, immature follicles to degenerate.
153
Why does the development of the dominant follicle decrease FSH?
Dominant follicle starts to produce more Oestrogen
| - negative feedback on the secretion of gonadotrophins for both anterior pituitary and hypothalamus
154
Why does the FSH level decrease more than the LH levels?
Granulosa cells also secrete inhibin
| - inhibits mainly the secretion of FSH
155
Menstrual cycle: what is the effect of oestrogen at high levels on the gonadotropins?
At high levels oestrogen exerts positive feedback on gonadotropin secretion, this stimulates the LH surge.
156
Menstrual cycle: what is the effect of the LH surge?
Stimulates ovulation.
| - stimulates the remaining granulosa and theca cells of the follicle to turn into the corpus luteum
157
What does LH act on in follicles?
Theca cells
158
What is the effect of LH on theca cells?
Proliferation
- synthesise androgens
- diffuse to granulosa cells and converted to oestrogen by aromatase
159
What are two things are needed for the secretion of oestrogen by granulosa cells?
both granulosa and theca cells
| - both pituitary gonad gonadotrophins
160
Which cells bear similarities to Leydig cells in males and why?
theca cells
- synthesise mainly androgens
- stimulated by LH
161
Which cells bear similarities with Sertoli cells in females and why?
Granulosa cells
- controls the microenvironment in which the germ cell matures and develops
- Stimulated by FSH and oestrogen
162
When is the concentration of inhibin the highest?
luteal phase
| - increases during the late follicular phase
163
What is the effect of large amounts of oestrogen on the anterior pituitary and hypothalamus?
- anterior pituitary to INCREASE the SENSITIVITY of LH-releasing
cells to GnRH (from the hypothalamus) - a POSITIVE FEEDBACK MECHANISM
• The net result is that the rapidly rising oestrogen leads to the LH surge
164
Which gonadotrophin is needed to maintain the function of the corpus luteum?
- Low LH concentration
165
What causes the corpus luteum to degenerate into corpus Albicans?
Absence of an increase in gonadotrophins
166
When the corpus luteum degenerates what happens to the concentration of Progesterone, oestrogen, LH and FSH?
- progesterone and oestrogen decreases
| - increased FSH and LH due to removed negative feedback
167
What phase starts from Day 1 of the menstrual cycle?
Menstrual phase
168
What stimulates the menstrual phase?
withdrawal of progesterone- degeneration of corpus luteum
169
What can be seen histologically in the menstrual phase?
stromal haemorrhage
- granulocytes in stroma
- stromal and glandular fragmentation
170
how long does the menstrual phase last?
3-5 days
171
What is the next phase after the menstrual phase and when does it occur?
From day 5 for around 10 days
- proliferative phase
- between the cessation of menstruation and start of ovulation
172
What happens in the proliferative phase?
- menstrual flow decreases and endometrium begins to thicken under the influence of oestrogen
- oestrogen causes growth of endometrium and myometrium
- oestrogen also indices the synthesis of progesterone receptors in endometrial cells
173
Describe the histological appearance of the proliferative phase
```
• Straight gland —oestrogen stimulation—>
mitotic activity —> tortuous glands
• No luminal secretions
• Stromal cells; spindled, compact, show
mitotic activity
```
174
which follicle phase corresponds to the menstrual and proliferative phases?
Follicular phase
175
Which phase comes after the proliferative phase and when?
Secretory phase
| - between ovulation and the onset of the next menstruation
176
Under the influence of which factors does the secretory phase occur?
progestrone and oestrogen
177
What occurs in the secretory phase?
endometrium begins to secrete glycoproteins and glycogen from glandular epithelium
- progesterone acts upon the endometrium to convert it into active secreting tissue to make it a hospitable environment for implantation and nourishment for the embryo
- Progesterone also inhibits myometrial contractions by opposing oestrogen important for fertilised egg to safely implant in uterus
178
Describe the histological appearance of the secretory phase
```
• Early: sub-nuclear vacuoles
• Mid:
- Vacuoles above & below
nucleus
- Intraluminal secretions
(pink)
- Rounded glands
- Stromal oedema
• Late:
- Spiral arteries in stroma
- Elongated, saw-soother glands with increased luminal secretions
```
179
which follicle phase corresponds to the secretory phase?
Luteal phase
180
What are the effects of progesterone and oestrogen on the secretion of mucus in the cervix?
Oestrogen alone causes the mucus to be clear and watery at the time of ovulation to allow sperm to move through the cervix easily
- significant amounts of progesterone after ovulation cause the mucus to become thick and sticky forming a plug which prevents bacteria entering the uterus - protects the embryo
181
summarise the menstrual cycle
- Days 1-5 - oestrogen and progesterone are low because of the corpus luteum regression, endometrium lining sloughs, and more secretion of FHS and LH therefore several growing follicles are stimulated to mature (menstrual phase)
- day 7 a single follicle becomes dominant
- 7-12 / Oestrogen increases because of dominant follicle therefore endometrium proliferates
- 7-12/ LH and FSH decrease due to oestrogen and inhibin negative feedback, therefore atresia of non-dominant follicles
- 12-13 LH surge induced by plasma oestrogen, therefore, oocyte induced to complete first meiotic division and follicle stimulated to release digestive enzymes
- day 14/ ovulation
- day 15-25/ corpus luteum forms under the action of low but adequate LH, it secretes oestrogen and progesterone therefore secretory endometrium forms and secretion of FSH and LH is inhibited no new follicles develop
- day 25-28/ corpus luteum degenerates if no implantation therefore oestrogen and progesterone concentrations decrease therefore endometrium begins to slough and a new cycle begins
182
Menstrual cycle: what causes oestrogen levels to rise in the follicular phase?
Oestrogen is released from granulosa cells and also from the developing and dominant follicle.
183
Menstrual cycle: what is the effect of oestrogen at low levels on the gonadotropins?
At low levels oestrogen inhibits gonadotropin release.
184
Menstrual cycle: what is the effect of decreasing FSH levels in the follicular phase?
Decreasing FSH levels cause the non-dominant, immature follicles to degenerate.
185
Menstrual cycle: what is the effect of oestrogen at high levels on the gonadotropins?
At high levels oestrogen exerts a positive feedback on gonadotropin secretion, this stimulates the LH surge.
186
Menstrual cycle: why do progesterone and oestrogen levels increase following ovulation?
The ruptured follicle has transformed into a corpus luteum which releases large amounts of progesterone and oestrogen.
187
Menstrual cycle: why do LH and FSH levels decrease after ovulation?
They are inhibited by the high progesterone and oestrogen concentrations.
188
Menstrual cycle: what is the importance of the low LH concentration in the luteal phase?
Low but adequate LH acts to maintain the corpus luteum.
189
Menstrual cycle: what causes oestrogen and progesterone concentrations to fall towards the end of the luteal phase?
The corpus luteum degenerates into the corpus albicans if fertilisation does not occur. Therefore progesterone and oestrogen are no longer released.
190
Menstrual cycle: why do FSH levels increase at the end of the cycle?
The fall in progesterone and oestrogen concentration means FSH is no longer inhibited and so its plasma concentration begins to rise.
191
Menstrual cycle: why does the corpus luteum not degenerate if fertilisation occurs?
When the blastocyst implants the invading trophoblast cells release human chorionic gonadotropin (hCG). This acts to maintain the corpus luteum throughout pregnancy.
192
In order for pregnancy to occur when must the introduction of sperm occur?
Between 24-48 hours of fertilisation as the egg only stay viable for this time
Sperm can remain capable for fertilisation till 4-6 days
193
Describe how the egg is transported to the fallopian tube
- ovulation extruded onto the surface of ovaries
- smooth muscle of the fimbria at the end of the fallopian tube causes the fimbria to pass over the ovary while the cilia beat inwards
- the ciliary movement sweeps the egg into the fallopian tube
- once inside the fallopian tube the cilia are slow and it takes around 4 days for the egg to be beaten into the uterus.
194
Describe sperm transport into the fallopian tube
- Ejaculation results in the deposition of semen into the vagina during
intercourse
- Fluid pressure of the ejaculate helps the sperm travel out of the vagina into the cervix
- passage through cervical mucus is dependant on the release of oestrogen causing mucus to be watery to enable sperm to easily travel through it
- Sperm travels through into the uterus and fallopian tube using its flagella for propulsion
195
Why is sperm mortality extremely high during the trip from the vagina to the fallopian tube?
- Vaginal environment is acidic to protect against yeast and bacterial infections
- The length and energy requirements for the trip is very large for the sperm
- reason why ejaculate contains so many sperm to increase the chance of fertilisation
196
Once the sperm has reached the fallopian tube can they fertilise the egg straight away?
No, they must mature and reside in the fallopian tube for several hours to be acted upon by secretions of the tract
197
Describe what occurs during capacitation
The final stage of sperm maturation occurs in the female genitalia. Before this spermatozoa would be unable to fertilise an oocyte.
198
What does capacitation cause?
- The previous wavelike beats of the sperms tail to be replaced by a more
whip like action that will propel the sperm forward in stronger surges
- The sperms plasma membrane to become altered so that it will be
capable of fusing with the surface membrane of the egg
199
Where does fertilisation occur?
- Ampulla of the fallopian tube
200
What in particular does the sperm bind to during fertilisation?
- Zona pellucida
201
What is the role of the zona pellucida during fertilisation?
- glycoproteins present act as receptors for sperm surface proteins
- Triggers the acrosome reaction
202
What is the acrosome reaction?
Many sperm move through granulosa cells to bind with the zona pellucida. This binding triggers acrosomal enzymes from the sperm's head to digest through the zona pellucida. The sperm advances through; the first sperm to penetrate the entire zona pellucida and to reach the egg's plasma membrane will fuse. now called a zygote
203
What is the function of block to polyspermy?
It is a mechanism to prevent the entry of additional sperm fusing with the egg.
204
Describe the mechanism of the block to polyspermy.
Cortical reaction initiated by
1. The egg releases contents of secretory vesicles by exocytosis.
2. Enzymes from the vesicles enter the zona pellucida and inactivate sperm binding sites and harden the zona pellucida
205
When does meiosis 2 occur?
4-7 hours after gamete fusion when the zygote is still in the fallopian tube
206
How long does the zygote remain in the fallopian tube?
3-4 days
207
Why does the zygote stay in the fallopian tube for 3-4 days?
• The main reason for this is that oestrogen maintains the contraction of the
smooth muscle near where the fallopian tube enters the uterus (essentially
holding the zygote in the fallopian tube - as plasma progesterone levels
increase, this smooth muscle relaxes and allows the zygote to pass
through the fallopian tube
208
What is cleavage?
24 hours after fertilisation mitotic divisions, no cell growth, increase totipotent cell numbers
209
What is compaction phase in development ?
Day 4 - cells flatten and maximise intracellular contacts, tight junctions, essential in being able to differentiate quickly
210
What occurs during cavitation and differentiation?
Day 5 - Fluid-filled cavity expands to form BLASTOCYST
- BLASTOCYST is defined as having greater than
80 cells - these cells have lost their
totipotentiality and have begun to differentiate
- Blastocyst consists of an outer layer of cells
known as the trophoblast, an inner cell mass & a
central fluid-filled cavity
211
What occurs to the blastocyst during expansion?
day 5-6
- Cavity expands further and the diameter of the blastocyst increases and the
zona pellucida THINS
212
what occurs during hatching?
Day 6+
- Blastocyst expansion & enzymes result in the hatching of the embryo from the
zona pellucida
necessary for implantation
213
Describe implantation.
The blastocyst implants into the endometrium on day 6. The trophoblast cells overlying the ICM invade the endometrium. Nutrient rich endometrial cells provide the metabolic fuel for early embryo growth until the placenta takes over.
214
What is secreted to prevent antigenic rejection of the embryo?
interleukin-2
215
describe the development of the placenta
the 8-cell morula arrives in the uterus and develops into the blastocyst.
- the outer cell layer - trophoblasts cell mass invades the endometrium which degenerates and the trophoblasts are in contact with the stroma
216
What day is implantation usually complete by?
11 days post ovulation
217
What can the trophoblast differentiate into during implantation?
Cytotrophoblast
• Syncitiotrophoblast (erodes endometrial blood vessels - using proteolytic
enzymes)
218
What is the role of the cytotrophoblast?
Forms solid masses covered by syncytiotrophoblast - primary chorionic villi. These masses become filled with stroma, forming secondary chorionic villi. Capillaries appear in the stroma – tertiary chorionic villi.
219
What is the role of the syncytiotrophoblast?
Uptake of oxygen and nutrients from the maternal blood.
Release of CO2 and waste products into the maternal blood. The exchange surface is gradually increased during maturation due to the branching of the villi.
220
What is the Chorion?
The embryonic portion of the placenta supplied by the outermost layer of trophoblast cells
221
What are the chorionic villi?
finger-like projections of the trophoblast cells extend from the chorion to the endometrium
- contain a rich network of capillaries that are part of embryos circulation
- endometrium around villi is altered by enzymes from invading villi so each villi is surrounded by a pool of maternal blood
222
through which vessels does the maternal blood enter the placental sinuses?
UTERINE
ARTERY; the blood flows through the sinuses and then exits via the UTERINE
VEINS
223
Which vessels transport blood from the foetus into the capillaries of the chorionic villi?
Umbilical arteries and out of capillaries back into the foetus via the umbilical vein - all umbilical vessels contained with the umbilical cord
224
What is the decidua basalis?
A part of the endometrium invaded by trophoblast
225
What is the decidua capsularis?
A part of the endometrium overlying the blastocyst
226
What is the decidua parietalis?
Endometrium lining the rest of the uterine cavity.
227
What invades the decidua basalis?
Syncytiotrophoblast.
228
Why is it important that the chorionic villi branch in maturation?
Branching increases the surface area for the exchange of nutrients.
229
What does the placenta provide for the developing foetus
- Nutrition
- Gas exchange
- Waste removal
- Endocrine & immune support
230
what are the three main functions of the placenta?
- Placental metabolism (synthesises glycogen, cholesterol and fatty acids) to provide nutrients and energy
- transport, transports - Gases & nutrition; O2 & CO2 - to & from baby, CO
- Water
- Glucose (facilitated diffusion via hexose transporters)
- Vitamins
- Amino acids - by active transport
- Hormones, mainly steroid NOT PROTEIN
- Electrolytes
- Maternal antibodies IgG and NOT IgM
- Waste products; urea, uric acid & bilirubin (conjugated is poorly
transported but unconjugated from foetus crosses placenta easily)
- Drugs and their metabolites - can result in fetal drug addiction
- Infectious agents
231
Name the placental barriers to transport materials from mother to foetus
- Maternal endothelial cells
- Maternal connective tissue
- Endometrial epithelial cells
- Chorionic epithelial cells
- Fetal connective tissue
- Fetal endothelial cells
232
Describe how the amniotic cavity forms
forms between the inner cell mass and the
| chorion whilst the placenta develops
233
throughout pregnancy which hormone plasma concentration continuously increase?
Oestrogen and progesterone
234
What is the function of oestrogen during pregnancy?
- stimulates the growth of uterine muscle mass for the contractile force during delivery
- regulates progesterone levels
- prepares breast for feeding
- induces the synthesis of oxytocin receptors which is a powerful stimulator of uterine muscle contraction
- increases throughout pregnancy
235
What is the role of progesterone during pregnancy?
- Inhibits uterine contractility so foetus not expelled prematurely
- increases throughout pregnancy
- increases the thickness to uterine lining to prevent miscarriage
236
For the first two months of pregnancy which structure supplies almost all progesterone and oestrogen?
Corpus Luteum
237
Menstrual cycle: why does the corpus luteum not degenerate if fertilisation occurs?
When the blastocyst implants the invading trophoblast cells release human chorionic gonadotropin (hCG). This acts to maintain the corpus luteum throughout pregnancy.
238
Which hormone is used to test for pregnancy?
Human Chorionic Gonadotrophin (hCG)
| gets into the maternal circulation
239
hCG stimulates oestrogen and progesterone levels to increase rapidly in pregnancy. What are their functions?
- Oestrogen: prepares the uterus and regulates progesterone levels.
- Progesterone: inhibits uterine contractility so the foetus is not delivered prematurely.
240
What is the role of hCG?
prevents the degeneration of corpus luteum
| - strong stimulation to corpus luteum to secrete oestrogen and progesterone
241
Why don't pregnant women have additional menstrual cycles?
- hCG stimulates oestrogen and progesterone to increase rapidly in pregnancy
- negative feedback on maternal gonadotropin secretions
- inhibits further LH and FSH release
242
What happens as the hCG levels decrease?
The placenta begins to secrete large amounts of oestrogen and progesterone
243
When does the corpus luteum regress in pregnancy?
3 months
244
The sharp increase in oestrogen and progesterone levels during the last 6 months of pregnancy is due to what?
secretion by the trophoblast cells of the placenta as the corpus luteum regresses after 3 months.
245
Name three areas Where does the placenta receive androgens from?
- Maternal ovaries
- Maternal adrenal medulla
- FOETAL adrenal medulla
246
Why does the placenta need a supply of androgens for the synthesis of oestrogen?
The placenta has the enzymes to synthesise progesterone, but not those required for the formation of androgens which are precursors of oestrogen,
- placenta converts the androgens to oestrogen via the enzyme aromatase
247
When does the concentration of prolactin increase and why?
Increases at the end of pregnancy when oestrogen and progesterone decrease
248
Where is prolactin produced?
Anterior pituitary gland
249
What is the role of prolactin?
- Has roles in milk production and the prevention of ovulation
- After birth, oestrogen & progesterone levels drop DRAMATICALLY - this
allows prolactin to stimulate the production of milk
- Release is also controlled by suckling
250
Describe the concentration of relaxin in early pregnancy
High in early pregnancy
251
Where is relaxin produced
Ovary and placenta
252
What is the role of relaxin?
- Helps to limit uterine activity, soften the cervix and involved in cervical
ripening
253
Describe the concentration of oxytocin through pregnancy
- Secreted throughout pregnancy, but increases at the end
254
Which gland produces oxytocin?
Posterior pituitary gland
255
What is the role of oxytocin?
- Stimulates uterine contractions during pregnancy & labour
- Triggers caring reproductive behaviours
- Drug used to induce labour
256
Name 2 prostaglandins released in labour.
1. PGE2. - 10 times more powerful
| 2. PGF2-alpha (main one).
257
What produces prostaglandins?
Produced by uterine tissues
258
What is the role of prostaglandins?
initiate labour
259
Describe what occurs to the cardiac output during pregnancy?
Increases
260
What happens to the systemic blood pressure during pregnancy?
Reduced
261
What happens to the total peripheral resistance during pregnancy?
reduced
262
what happens to the uterine blood flow during pregnancy?
Increased
263
What happens to the blood volume during pregnancy?
Increased
264
What happens to the plasma and blood cells mass during pregnancy?
increased
265
What respiratory changes occur during pregnancy?
Increased alveolar respiration
266
What are the adaptations to the skin in pregnancy?
Linea nigra and striae gravidarum/stretch marks may appear on the skin, usually the abdomen. There is also a darkening of the areola.
267
Why do women gain weight during pregnancy?
increased protein and lipid synthesis
268
Define parturition.
Giving birth.
269
What are the 3 layers of the uterus?
1. Perimetrium (inner).
2. Myometrium.
3. Endometrium.
270
Which hormone maintains the smooth muscle being disconnected during pregnancy?
Progesterone
271
What affect does oestrogen have on the smooth muscle cells in the last weeks of pregnancy
smooth muscle develop gap junctions between cells allow for coordinated contractions
272
Describe cervical ripening.
Softening of the cervix that begins prior to labor. It is necessary for cervical dilation. It occurs under the influence of relaxin and placental hormones (placental prostaglandins) and oestrogen.
273
What are the 2 main stages of labour?
1. Latent: little cervical dilation.
| 2. Active: cervix dilates and opens.
274
What hormones are needed for the initiation of labour?
Prostaglandins and oxytocin.
275
Prostaglandins: What is the function of PGF2 alpha?
It enhances oxytocin activation.
276
What are the sub-divisions of the active stage of labour?
1st - cervix dilation begins.
2nd - cervix is fully dilated and birth begins.
3rd - birth and expulsion of the placenta.
277
How do oral contraceptives work?
Work prior to implantation and as oestrogen and progesterone can inhibit anterior pituitary gonadotropin release, therefore, preventing ovulation
278
Define menopause.
Cessation of menstruation.
279
What physiological changes happen in menopause?
- There is depletion of the primordial follicles.
- Oestrogen levels decrease as less follicular production; - FSH and LH, therefore, increase as they're not inhibited by negative feedback.
- decline in inhibin so further increase in FSH
- increase in FSH results in a rapid increase of oestrogen in existing follicles
- shorter menstrual cycles
- fewer follicles, increase in FSH no longer stimulates increased oestrogen
- decrease in oestrogen and lack of ova results in menopause
280
What happens to oestrogen levels at menopause?
They fall.
281
What happens to LH and FSH levels at menopause?
They increase as they're no longer inhibited by negative feedback.
282
What are the short-term symptoms of menopause?
Hot flushes, night sweats, palpitations, irritability, lethargy, decreased libido, vaginal dryness, vaginal pH change, dry skin and hair, brittle nails.
283
What are the long-term symptoms of menopause?
Osteoporosis and increased risk of cardiovascular disease.
284
Name 4 treatments that can help with the symptoms of menopause.
1. HRT.
2. Sedatives.
3. Calcium supplements.
4. Vitamin D supplements.
285
What hormones are given in HRT?
Oestrogen and progesterone.
286
What is the secretory phase?
When the corpus luteum releases progesterone and the endometrium generates blood vessels and proteins etc needed for the implantation of a fertilised embryo.
287
What is the proliferative phase?
When the endometrium grows rapidly under the influence of oestrogen.
288
What are the mechanisms to ensure block to polyspermy?
Enzymes are released that harden the zona pellucida and inactivate sperm binding sites.
289
What hormone does the hypothalamus release that stimulates release of the gonadotropins?
GnRH - gonadotropin releasing hormone.
290
What cells does FSH act on in males?
Sertoli cells.
291
What cells does FSH act on in females?
Granulosa cells.
292
What cells does LH act on in males?
Leydig cells.
293
What cells does LH act on in females?
Theca cells.
294
What is the function of sertoli cells?
They release MIF, inhibin and activins (regulate FSH secretion), and androgen binding protein (increases testosterone concentration).
295
What is the function of granulosa cells?
They convert androgens into oestrogen using aromatase enzyme.
296
What is the function of leydig cells?
they produce testosterone.
297
What enzyme converts androgens into oestrogen?
Aromatase
298
What is the predominant hormone responsible for the proliferative phase?
oestrogen
299
What is the predominant hormone responsible for the secretory phase?
progesterone
300
Where do primordial germ cells originate from in the embryo?
The epiblast.
301
What is the mesovarium?
Mesentery attaching the ovary to the posterior broad ligament.
302
Where in the embryo do embryonic stem cells come from?
The inner cell mass.
303
What are the 3 histological layers of the uterus?
1. Endometrium - mucosal lining, pseudostratified columnar.
2. Myometrium - smooth muscle wall.
3. Perimetrium.
304
What is the function of the smooth muscle in the myometrium?
It helps the uterus to expand and acts to protect the foetus. It also provides a mechanism for foetal expulsion.
305
What are the characteristics of the endometrium in the proliferative phase?
Straight glands, no secretions. Stromal and epithelial mitoses.
306
What are the characteristics of the endometrium in the early secretory phase?
Coiling of glands and subnuclear vacuoles.
307
What are the two types of hormone?
1. Made at response e.g. steroids.
| 2. Stored and released at response e.g. pituitary hormones (peptides).
308
Where are the receptors for steroid hormones located?
Steroid receptors are intracellular - steroids pass through plasma membranes bound to proteins. hydrophobic molecules which are lipohillic
309
Where are the receptors for peptide hormones located?
On cell membranes.
310
Briefly describe the mechanism of prolactin.
Hypothalamus -> dopamine -> anterior pituitary -> prolactin -> mammary glands -> milk production -> positive feedback on dopamine.
311
What hormone from the hypothalamus stimulates the anterior pituitary to release prolactin?
Dopamine.
312
What hormones are involved in pregnancy?
1. Human chorionic gonadotropin.
2. Oestrogen.
3. Progesterone.
4. Prolactin.
5. Prostaglandins.
6. Oxytocin.
7. Relaxin.
313
Why does blood pressure decrease in pregnancy?
There is mass vasodilation which reduces the TPR and so BP decreases. (BP=TPRxCO).
314
What are the cardiovascular maternal adaptations?
1. Cardiac output increases.
2. Blood pressure decreases.
3. Uterine blood flow increases.
315
Why does uterine blood flow increase in pregnancy?
To ensure enough nutrients are delivered to the foetus.
316
What ligament attaches the uterus to the pelvic wall?
The broad ligament.
317
What does the broad ligament divide the pelvic cavity into?
1. The uterorectal pouch.
| 2. The uterovesical pouch.
318
What does the vagina develop from?
Upper 1/3 - mullerian duct. Lower 2/3 - urogenital sinus.
319
What causes the mullerian duct to degenerate in the male?
Sertoli cells release MIF.
320
What forms the blood testes barrier?
Tight junctions between sertoli cells.
321
What is the function of the blood testes barrier?
It prevents the movement of cytotoxic agents from the blood into the lumen of the seminiferous tubules. This ensures proper conditions for germ cell development.
322
What does semen contain?
Sperm, fructose, fibrinogen, clotting enzymes, fibrinolysin.
323
What layer of the trilaminar disc are the kidneys derived from?
Intermediate mesoderm
324
Is the kidney a retroperitoneal organ or intraperitoneal?
Retroperitoneal
325
Which kidney is lower than the other and why?
Right lower due to the liver superior.
326
What are the three distinct structures from outside to in of the kidney?
Cortex
Medulla - 20 upside-down pyramids
Pelvis - urine collecting lined by transitional epithelium
327
What is present in the renal cortex?
Renal corpuscles (glomerulus and bowman's capsule)
- PCT and DCT
- Medullary rays - a collection loop of Henle and collecting ducts going to the medulla
328
What gives the cortex a striated appearance?
Medullary rays
329
What is present in the renal medulla?
- No renal corpuscles
- just tubes and blood vessels
- Loop of Henle
- Collecting ducts
- blood vessels
330
What is the role of the renal pelvis
- Space where urine drains into continuous with the collecting ducts proximally and the ureters distally
331
What is the epithelial lining of the renal pelvis?
Urothelium - same as urinary bladder
332
At what vertebral level does the renal artery come from the abdominal aorta
L1
333
Which artery does the renal artery branch from
abdominal aorta
334
what is the glomerular tuft supported by?
Smooth muscle - mesangial cells
335
in order to distinguish the mesangial cells from the capillaries, the tissue can be stained with...?
PAS stains glycoproteins in the glomerulus basement
membrane - highlighting capillaries and allowing you
to see the mesangial cells in-between
336
What are the three main functions of the mesangial cells?
- Structural support for the capillary
- contraction tightens the capillaries and reduced the GFR - tubuloglomerular feedback
- Phagocytosis of Glomerular filtration membrane breakdown products.
337
Where can the granular cells be found in the nephron?
Expanded endothelium cells on the afferent arteriole to form the granular cells
338
What is the role of the granular cells in the juxtaglomerular apparatus?
Secrete renin in response to low BP
339
Where can the macula densa cells be found in the nephron?
Expansion of cells in the distal convoluted tubule at the juxtaglomerular apparatus
340
What is the role of the macula densa cells?
- detect sodium levels
341
Briefly describe the mechanism of the macula densa cells?
if filtration is slow then more sodium will be absorbed and the macula densa cells will send a signal to reduce the afferent arteriole resistance and increase the glomerular filtration
342
Name three cell types that are found at the juxtaglomerular apparatus?
- Granular cells
- macula densa cells
- Lacis cells
343
Describe the histological appearance of the PCT
- Cuboidal epithelium
- microvilli fuzzy brush border
- lots of mitochondria
344
What is the role of the PCT?
Bulk reabsorption of Na+, Cl-, K+, HCO3-, amino acids, glucose, proteins and water
345
Are there more lysosomes in the PCT or the DCT?
PCT
346
What is the epithelial lining of the thin and thick segment in the loop of Henle?
thin: Simple squamous
thick: cuboidal
347
What are the blood vessels called that supply the loop of Henle?
RIch vasa recta
348
What occurs at the thin segment of the loop of Henle?
Only water flows out into the high osmolarity interstitium. therby concentrating the urine
349
Why does water flow out of the thin descending limb of the Loop of Henle?
high osmolarity interstitium outside the thin limb.
350
What occurs at the thick ascending limb?
The ions the body wants back are actively pumped by the ascending limb leaving water and waste
351
Why is the loop of Henle most prone to ischaemia?
the vasa recta are far from the glomerulus, afferent arteriole has already lost some oxygen
352
describe the histological appearance of the DCT
No microvilli, no fuzzy brush border
- much shorter than the PCT meaning if you look at the cortex you will see more PCT
- cells are cuboidal and contain abundant mitochondria
353
What is the role of the DCT?
- Regulating the acid-base balance
- acts to acidify the urine by adding the H+ ions
- exchanges urinary Na+ for body K+
- mediated by aldosterone which can lead to hypernatraemia and hypokalemia
354
Describe the physiological role of the collecting ducts
- made of two cell types
- principal cells ( respond to aldosterone exchanging Na+ for K+)
- principal cells respond to ADH, water reabsorption through the insertion of aquaporin -2 membrane channel for water reabsorption
- intercalated cells responsible for exchanging acid both ways
- alpha intercalated cells secrete acid
- beta intercalated cells secrete bicarbonate
355
Describe the histological appearance of the collecting ducts?
cuboidal epithelium, more plump epithelium than the loop of Henle with round central nuclei
356
Describe the histological appearance of the collecting duct?
Lined by urothelium
357
Why is urothelium a good covering of the renal pelvis and the bladder?
- Can stretch in three dimensions
| - waterproofing
358
What is the role of the renal pelvis?
To transmit filtrate from nephron to the ureters
359
Describe the structure of the urothelium
Surface layer of umbrella cells
- several tight junctions between umbrella cells for waterproofing
- basal layer consists of cuboidal cells
- there are the surface layer, intermediate layer and the basal layer
360
Describe the structure of the ureters
- Spiral muscular tube
- inner : longitudinal
- Outer : circular
- No serosa
- Loose adventitia
361
What helps move the urine along the ureter?
peristalsis
362
What is the epithelial lining of the bladder?
transitional epithelium
363
Name the layers of the bladder inside to out
* Lamina propria
* Muscularis mucosa
* Submucosa
* Muscularis propria
* Subserosa & serosa
364
What prevents reflux of urine from the bladder back into the ureters?
the oblique passage of the ureters into the bladder produces a functional valve
365
How long is the urethra in females?
4-5cm
366
How long is the urethra in males?
20cm
367
What is the epithelial lining of the urethra in females?
Proximally: transitional epithelium
| Distally : Squamous epithelium
368
Name the three divisions of the male urethra?
Prostatic urethra
membranous urethra
penile urethra
369
What is the epithelial lining of the male urethra
1. Prostatic urethra
2. Membranous urethra (transitional epithelium)
3. Penile urethra (pseudostratified epithelium proximally & stratified
squamous epithelium distally)
370
Name the three main functions of the kidney?
1. Endocrine function (secreting hormones)
2. Maintain balance of salt,water & pH
3. Excrete waste products
371
How much of the total cardiac output does each kidney receive?
20% - to filter and excrete the metabolic waste products
372
What is the total urine flow rate in the kidneys?
1ml/min
373
Name the divisions of the renal artery
1. Renal artery
2. Segmental artery
3. Interlobar artery
4. Arcuate artery
5. Interlobular artery
6. Afferent arteriole
7. (Nephron) - Glomerular
capillary
8. Efferent arteriole
9. (Nephron) - Peritubular
capillary
10. vein
374
How many capillary beds are there in the nephron?
2- Gloemrulus and the peritubular area
| connected by the efferent arteriole
375
as blood flows through the glomerulus how much plasma filters into Bowman's space?
20%
376
Name the 3 things to make up the Glomerular Filtration barrier.
1. Fenestrated capillary endothelium.
2. Double-layer basement membrane.
3. Foot processes of podocytes.
377
which part of the nephron is supplied by the peritubular capillaries
PCT and DCT
378
What is tubuloglomerular feedback?
Macula densa cells of the DCT detect NaCl levels and use this as an indicator of GFR.
NaCl levels increase as GFR increases.
379
Define glomerular filtration
The passage of fluid from Bowman space to form the filtrate
380
Describe the flow of glomerular filtrate through the nephron starting at the glomerular capsule and ending at the urethra
1. Glomerular capsule
2. Proximal convoluted tubule
3. Nephron loop
4. Distal convoluted tubule
5. Collecting duct
6. Papillary duct
7. Minor calyx
8. Major calyx
9. Renal pelvis
10. Ureter
11. Urinary bladder
12. Urethra
381
Name 5 factors that determine a molecule crossing the filtration barrier.
1. Pressure.
2. Size of the molecule.
3. Charge of the molecule (negative molecules are repelled).
4. Rate of blood flow.
5. Binding to plasma proteins.
382
Why does is albumin repelled at the glomerular basement membrane
basement membrane has a fixed negative charge, can not easily pass into the tubule
383
Should the filtered fluid be protein-free or should it have proteins?
should be protein-free, the only protein that is found is uromodulin (Tamm Horsfall protein) produced by the thick ascending limb
384
What is GFR?
The volume of fluid filtered from the glomeruli into Bowman's space per unit of time (minutes)
385
What effect does vasoconstriction of the afferent arteriole have on GFR?
GFR will decrease as the HPgc decreases.
386
What effect does vasodilation of the afferent arteriole have on GFR?
GFR will increase as the HPgc increases.
387
What effect does vasoconstriction of the efferent arteriole have on GFR?
GFR will increase. Efferent arteriolar constriction tends to push blood back to the glomerulus and so increases the HPgc.
388
What effect does vasodilation of the efferent arteriole have on GFR?
GFR will decrease as the HPgc decreases.
389
Name 2 ways in which GFR is regulated.
1. Autoregulation.
| 2. Tubuloglomerular feedback.
390
What is tubuloglomerular feedback?
Macula densa cells of the DCT detect NaCl levels and use this as an indicator of GFR.
NaCl levels increase as GFR increases.
391
What would happen if Nacl levels reaching the macula densa cells were very high?
The macula densa cells would signal to the afferent arterioles to vasoconstrict therefore reducing GFR.
392
How could you measure GFR?
Look at the excretion of a marker substance.
393
What substance can be used clinically to estimate GFR?
Creatinine.
394
What equation can be used to calculate GFR?
GFR = (Um x urine flow rate) / Pm.
- Um = concentration of marker substance (m) in urine.
- Pm = concentration of marker substance (m) in plasma
395
Give an example of the process of autoregulation in regulating GFR.
Pressure in afferent arteriole increases -> stretches the vessel walls -> contraction of smooth muscle -> arteriolar constriction.
396
Regulating GFR: Why does autoregulation cause arteriolar constriction when the pressure in afferent arterioles increases?
It acts to prevent an increase in systemic pressure reaching the capillaries and so allows GFR to be maintained.
397
What would happen if Nacl levels reaching the macula densa cells were very low?
The macula densa cells release prostaglandins to act on granular cells which then release renin. Renin release activates RAAS leading to increased GFR.
398
What equation could be used to calculate the net glomerular filtration pressure?
HPgc - HPbs - πgc
HPgc - glomerular capillary hydrostatic pressure, favours filtration
πgc - osmotic/oncotic pressure of glomerular capillary - opposes filtration
399
Name the GFR equation
GFR = KF (PGC - PBS - πGC)
400
What is the oncotic pressure in Bowman's space and why?
0 because no proteins in the filtrate can pass through the capillaries
401
in a 70kg person, what is the average GFR?
In a 70kg person the average GFR = 125ml/min
402
Name three things that determine the GFR
- Net filtration pressure
- Permeability of the corpuscular
membranes
- Surface area available for filtration
403
List 3 qualities necessary of a marker substance.
1. Freely filtered.
2. Not metabolised.
3. Not reabsorbed or secreted.
404
if a disease causes you to lose nephrons what happens to the GFR?
GFR falls, hence GFR is a good measure of kidney function
405
What is creatinine?
It is a muscle metabolite with constant production
serum concentration varies with muscle mass
- freely filtered by the glomerulus
406
What is the filtration fraction equation and what does it show?
- Filtration fraction = GFR/ renal plasma flow
| - proportion of renal blood flow that gets filtered
407
What is the usual value of the filtration fraction?
20%
408
Define renal clearance.
The volume of plasma from which a substance is completely removed by the kidney per unit time.
409
If substance X is freely filtered at the glomerulus and is neither absorbed nor secreted what will the Clearance of substance X be?
Substance X is freely filtered at the glomerulus and is neither reabsorbed nor
secrete in the tubule thus all the X that is filtered will end up in the urine - no more
(since it's not secreted) no less (since it's not reabsorbed)
• Thus, all the plasma that is filtered is cleared of X
• So the clearance of substance X is 125ml/min (equal to the GFR)
410
What is the equation for clearance?
Clearance = urine concentration x urine volume/ plasma concentration
411
Urea has a clearance value of 65ml/min and normal GFR is 125ml/min, What does this mean?
- freely filtered
| - clearance is less than GFR (125ml/min) so some urea must have been reabsorbed
412
If glucose has a clearance of 0ml/min what does this show?
glucose is completely reabsorbed
413
Give an example of the process of autoregulation in regulating GFR.
Pressure in afferent arteriole increases -> stretches the vessel walls -> contraction of smooth muscle -> arteriolar constriction.
414
Why do we need autoregulation of capillary pressure, GFR and renal blood flow?
This mechanism prevents an increase in systematic arterial pressure from reaching
and damaging the capillaries
415
Which part of the tubules is responsible for bulk absorption and which tubule is responsible for fine-tuning?
- The proximal convoluted tubule is responsible for BULK ABSORPTION (leaky)
• The distal convoluted tubule is responsible for FINE TUNING (impermeable)
416
Summarise what occurs at the proximal tubule?
- Proximal tubule: bulk reabsorption: Na, Cl, glucose, amino acids, HCO3
(bicarbonate) & secretion of organic ions
417
Summarise what occurs at the loop of Henle?
```
more Na reabsorption, urinary dilution & generation of
medullary hypertonicity (where medulla is very concentrated meaning water
wants to flow into it)
```
418
Summarise what occurs at the distal tubule?
Fine regulation of Na,K,Ca, Pi & the separation of Na from H20 -
essentially where the separation of salt (Na) from water occurs
419
Summarise what happens at the collecting duct?
similar to the distal tubule, also acid secretion and regulated
H20 reabsorption thereby concentrating the urine
420
Describe how bulk reabsorption takes place at the PCT?
- The primary active transport of Na+ via a basolateral NaKATPase pump
out of the proximal tubule cells and into the interstitial fluid
- Intracellular Na+ low compared to lumen
- Na+ moves downhill out of the lumen into the tubular epithelial cells
- As Na+ moves in other substances also follow such as glucose and phosphate
- said to be co-transported
- Thus, in the proximal tubule, Na+ reabsorption drives the reabsorption
of the co-transported substances and the secretion of H+
- water follows the ions and flows into the cell via osmosis.
421
Describe how bicarbonate is reabsorbed at the PCT?
- Na+ HCO3- transporter actively pumps Na+ and 3HCO3- from the tubular cells into the peritubular capillary
- Na+/K+ ATPase works on the basolateral surface
- inside the cell the CO2 and H20 can react to form H2CO3 and then dissociated to form H+ and HCO3-, the HCO3- can then be pumped out of the cell into the capillary
- H+ ions can then be counter transported via the entering Na+
- H+ reacts with HCO3- to form H2CO3
- Converted to CO2 and H20 under the action of carbonic anhydrase
- The CO2 & H2O can then diffuse into the tubular cells and the process
then repeated
- Overall resulting in the reabsorption of HCO3-
422
What is amino acid transport in the PCT similar to?
absorption of glucose and phosphate
423
Why might glucose start to appear in the urine (glucosuria)?
transport maximum has been exceeded. the binding sites on the membrane transport proteins become saturated
424
What is the effect of efferent arteriolar constriction on peritubular capillary hydrostatic pressure?
Reduces
425
What is the function of the loop of Henle?
- More Na reabsorption, urinary dilution & generation of medullary
hyperosmoticity (where medulla is very concentrated meaning water
wants to flow into it)
426
Which limb of the loop of Henle is water permeable and which is impermeable?
* The descending limb is water PERMEABLE
| * The ascending limb is water IMPERMEABLE
427
Where does solute reabsorption occur in the loop of Henle?
Thick ascending limb
428
Which two ions are reabsorbed at the ascending limb?
Na+ & Cl-
429
Which specific pump transports sodium, potassium and chloride from the ascending limb to the medullary interstitial fluid
NKCC2 pump
430
Why does the medulla become very hyperosmotic?
Solutes are reabsorbed without water as the thick ascending limb is impermeable to water/
431
What channels do loop diuretics target?
NKCC2
432
What channels do loop diuretics close?
NKCC2 - reduced Na+ and K+ secretion.
433
Why do diuretics work e.g. furosemide?
- NKCC2 pump closed
- less sodium, potassium and chloride ions pumped out of ascending limb
- reduced hyperosmolarity of medullary interstitium
- meaning less water will diffuse out into the blood
- more water loss in the urine
434
Describe how the vasa recta supplying the loops of Henle minimise excess loss of solutes?
- As the vasa recta flows down deeper into the medulla there is indeed diffusion of sodium and chloride into the vessel and water out of the vessel
- however the vasa recta is a hairpin structure and when it loops back up the the process is reversed
- so the hair pin loops of the vasa recta is the solution
435
Name an osmotically active compound
Urea
436
Urea is freely filtered in the glomerulus. What proportion of urea is reabsorbed in the proximal tubule?
50% of the filtered urea is
reabsorbed in the proximal tubule, and the remaining 50% enters the loop of
Henle
437
What happens to the urea that has accumulated in the medullary interstitium?
Secreted back into the tubular lumen by facilitated diffusion
438
What is the function of the DCT?
- fine-tuning
- Fine regulation of Na, K, Ca, Pi & the separation of Na from H20 - essentially
where the separation of salt (Na) from water occurs
- Continues the active dilution of urine by reabsorption of Na+ in water-
IMPERMEABLE setting
439
What is the sodium chloride cotransporter called on the plasma membrane in the DCT?
NCC cotransporter which helps reabsorb Na+/Cl-
440
What channels do Thiazides target?
NCC
441
What does the drug thiazide do in the DCT?
- inhibits NCC cotransporter
| - resulting in less Na+ & Cl- reabsorption
442
What is the function of the collecting duct?
- Similar to the distal tubule
| - also acid secretion and regulated H20 reabsorption to concentrate urine
443
Is the collecting duct impermeable or permeable to water?
impermeable surrounded by hypertonic medullary interstitium which is derived from loop of henle
444
What are the epithelial sodium channels called on the principal cells in the collecting ducts?
ENaC sodium channels
445
How does aldosterone drive Na+ reabsorption and K+ secretion?
- Aldosterone increases the transcription of ENaC and NaKATPase.
• This increases apical Na+ influx
• This charge movement facilitates K+ efflux
• Thus aldosterone drives both Na+ reabsorption & K+ secretion
446
How does vasopressin (ADH) work?
- Acts on principal cells
- binds to V2R receptor
- results in the insertion of vesicles containing aquaporin 2 into the apical membrane
- increases water permeability and thus reabsorption to make the urine more concentrated
447
What is the role of the intercalated cells in the collecting ducts?
Secretes acid into the collecting duct
448
What is the equation for plasma osmolality?
2(Na + K) + glucose + urea
449
How is tonicity regulated?
controlling H2O movement
450
Briefly describe ADH action.
1. Osmoreceptors in the hypothalamus detect an increase in plasma osmolality.
2. The posterior pituitary is signalled to release ADH.
3. ADH acts on the collecting ducts and increases insertion of aquaporin 2 channels, permeability to H2O increases, more H2O is retained.
451
Where is ADH produced?
hypothalamus and secreted by posterior pituitary
452
Is ADH a vasoconstrictor or a vasodilator?
Vasoconstrictor.
453
What is the effect on ADH secretion if osmolarity increases?
ADH secretion will increase.
454
Describe what occurs when there is decreased plasma volume due to diarrhoea or haemorrhage?
- Increase in aldosterone release via the renin-angiotensin
- increases vasopressin (ADH) release
- due to a decrease in atrial and arterial pressures detected by baroreceptors
- baroreceptors transmit fewer impulses to the hypothalamus resulting in ADH secretion from PP
- Increased plasma ADH
- binds to V2R receptor
- vesicles containing aquaporin 2 moves to the apical surface
- increases water permeability
- decreased water secretion
455
How can ADH (vasopressin ) help maintain the hyperosmolarity of the medulla?
- Increases urea permeability of the collecting duct as urea moves through aquaporin-2
456
Where does most sodium reabsorption occur in the nephron?
PCT - bulk transport
457
What effect does low sodium have on plasma volume and consequently cardiovascular pressure?
Low total-body sodium = low plasma volume = decrease in cardiovascular
pressure
458
How can GFR be controlled to alter Na+ reabsorption
- When Na+ is low this elicits a decrease in GFR which in turn results in a
reduced net glomerular filtration pressure
- occurs due to a decreased arterial pressure in the kidneys
- the decreased arterial pressure in the kidneys is due to the decrease in cardiovascular pressure resulting in vasoconstriction of the afferent arteriole
- vasoconstriction of the afferent arteriole results in the reduction in GFR
- Conversely - increase in GFR usually caused by neuroendocrine inputs when the sodium levels are high which increases plasma volume,
- increased GFR results in increased renal loss of Na+ returning the extracellular volume back to normal
459
What is the purpose of the renin-angiotensin-aldosterone system?
• For the long-term regulation of Na+ excretion, the control of Na+ reabsorption is
MORE IMPORTANT than the control of GFR
460
List the 3 main triggers for the release of Renin by the juxtaglomerular cells.
1. Sympathetic stimulation.
2. Low BP detected by afferent arteriole. - low blood volume due to the lack of Na+
3. Low Na+ detected by macula densa cells.
461
What is the role of renin when it enters the blood?
Angiotensinogen produced by the liver is cleaved into a smaller polypeptide called angiotensin 1
462
Describe the RAAS?
1) Renin released in response to sympathetic stimulation, Low BP detected by Macula densa and low sodium
2) renin enters the bloodstream and cleaves angiotensinogen from liver into angiotensin 1
3) angiotensin 1 undergoes further cleavage under the enzyme ACE which is produced in the lungs to form the active agent angiotensin 2
4) angiotensin 2 stimualtes zona glomerulosa in adrenal cortex of the adrenal glands to secrete the steroid hormone aldosterone
5) aldosterone is a vasoconstrictor especially at the efferent arteriole which increases GFR
6) increased sodium reabsorption in PCT
7) salt and water retention and vasoconstriction which both increase blood pressure
463
What is the role of aldosterone in the RAAS?
act on principal cells of the collecting duct
- Stimulates the transcription of Epithelial Sodium Channels (ENaC’s) thereby
resulting in increased Na+ reabsorption and also H2O reabsorption
- Acts more slowly than vasopressin since it induces changes in gene
expression and protein synthesis
-ENac enables more reabsorption of Na+ but as Na+ comes into the
principal cells, potassium is exchanged for the sodium - so if you reabsorb
more Na+ then you will leak out more K+
464
Where is aldosterone secreted from?
Steroid hormone that is secreted and produced by the zona glomerulosa cells
in the adrenal cortex of the supradrenal/adrenal glands
465
Where is Atrial natriuretic peptide secreted and synthesised
Cardiac atria
466
What is the role of ANP?
to INHIBIT Na+ REABSORPTION by
blocking the ENaC’s in the collecting ducts
- It also acts as a RENAL VASODILATOR resulting in afferent arteriole dilation which
INCREASES GFR which further contributes to increased Na+ excretion
- inhibits aldosterone secretion leads to Na+ excretion
467
Why does the secretion of ANP increase when there is excess Na+?
Excess Na+ leads to more H2O in the vessels
| - meaning the blood volume increases meaning the atria become stretched which in turn stimulates ANP secretion
468
Where in the nephron is the most potassium reabsorbed?
PCT
469
Where can K+ be secreted in the nephron?
collecting ducts
470
What happens to K+ secretions when a high K+ diet is ingested?
enhanced basolateral uptake of K+ via the NaKATPase resulting in enhanced K+ secretion
471
How does aldosterone affect potassium secretion?
- aldosterone enhances potassium secretions
- since more potassium has to be exchanged for sodium
• The cells of the zona glomerulosa in the adrenal cortex of the adrenal
glands, which secrete aldosterone, are sensitive to K+ concentration of
the extracellular fluid
• Thus an increased intake of K+ will lead to an increased extracellular K+
the concentration which in turn directly stimulates the adrenal cortex to
produce aldosterone
• The increased plasma aldosterone increases K+ secretion and thereby
eliminates the excess potassium from the body
472
What does the parathyroid control?
Serum Ca2+. (Hyperparathyroidism -> hypercalcemia).
473
What can hyperparathyroidism lead to?
Hypercalcemia
474
What hormone does the parathyroid secrete and what is its function?
PTH - it increases the absorption of Ca2+ in the kidneys thereby decreasing the urinary Ca2+ excretion and is secreted when Ca2+ levels fall.
475
What cells in the parathyroid detect Ca2+ levels?
Chief cells.
476
What is the normal pH of the blood?
7.35-7.45
477
What is the anion gap?
The difference between measured cations and anions: [Na+] + [K+] - [Cl-] - [HCO3-]
478
Name 3 urinary buffers.
1. Ammonium.
2. alkaline Phosphate (commonest urinary buffer).
3. Bicarbonate.
479
Describe how the alkaline phosphate (HPO4-) buffer works?
- in the proximal tubule
- when all the filtered HCO3- has combined with secreted H+ the additional H+ secreted due to Na+ absorption exchanged for H+
- combines with non-bicarbonate buffer, mainly HPO4 2-
- combines and excreted in the urine
- increases in HCO3- concentration of the plasma and hence alkalinizes it
480
describe how the ammonium urinary buffer works?
- in the proximal tubule
- tubular cells take up glutamine from the filtrate and peritubular plasma
- metabolism into NH3 and bicarbonate
- the NH3 reacts with H+ in the cell
- NH4+ is then actively secreted via sodium/NH4+ counter transporter into the lumen and excreted while HCO3- moves into the peritubular capillaries
- increases HCO3- in the plasma
- alkalizing the blood plasma
481
How does respiratory acidosis effect the ammonium buffer?
The uptake and synthesis of ammonia is increased.
482
Is renal compensation to an acid/base disturbance fast or slow?
Slow. Respiratory compensation is fast.
| can take days
483
What is the renal compensation mechanism for respiratory acidosis?
Increased ammonia production. H+ secretion increases in the form of NH4+ and HCO3- reabsorption increases.
484
What is the renal compensation mechanism for respiratory alkalosis?
H+ secretion decreases and HCO3- reabsorption decreases.
| - more HCO3- excretion
485
What is the respiratory compensation mechanism for metabolic acidosis?
Chemoreceptors are stimulated in the lungs enhancing respiration. PaCO2 decreases.
486
What is the respiratory compensation mechanism for metabolic alkalosis?
Chemoreceptors are inhibited reducing respiration. PaCO2 increase.
487
What does erythropoietin (EPO) do?
Stimulates bone marrow, promotes RBC maturation.
488
which organ secretes erythropoietin?
kidneys
489
What can cause an increase in erythropoietin secretion?
anaemia, cardiopulmonary disorders and altitude
490
What can cause a decrease in erythropoietin secretion
- polycythaemia
| - renal failure
491
What is the role of the Kidneys in Vitamin D activation?
Converts 25-OH D into 1,25-diOH D. (Enzyme: 1-hydroxylase)
492
Describe the process of vitamin D activation.
- >Dietary vit D
- > plasma vit D
- > liver
- > 25-OH cholecalciferol (conversion occurs in the liver with the enzyme 25-hydroxylase)
- > kidneys
- > 1,25-diOH cholecalciferol (conversion occurs in the kidney with the enzyme 1-hydroxylase)
- > plasma 1,25-diOH cholecalciferol
493
What is the effect of a high serum Vit D concentration?
decreased parathyroid PTH secretion
- inhibits bone resorption
- increased calcium and phosphate reabsorption in the kidney
- increased calcium and phosphate in the intestine
494
Where are the adrenal glands located?
located above the kidneys
495
are the adrenal glands retroperitoneal or intraperitoneal?
reteroperitoneal
496
Describe the arterial blood supply to the adrenal glands
```
• Superior adrenal artery - from
inferior phrenic
• Middle adrenal artery - from
abdominal aorta
• Inferior adrenal artery - from
renal artery
```
497
Describe the venous drainage of the adrenal glands?
- Right adrenal veins drain directly into the IVC since it lies more on the right side
- left adrenal vein drain into the left renal vein
498
What is the nervous supply of the adrenal glands?
The splanchnic nerves
499
describe the two sections of the adrenal glands?
Cortex and medulla
500
Where is aldosterone synthesised?
In the adrenal cortex by glomerulosa cells. in the zona glomerulosa
501
What does the adrenal cortex produce?
steroid hormones
502
What are the 3 layers of the adrenal cortex?
1. Zona glomerulosa.
2. Zona fasciculata.
3. Zona reticularis.
503
What does the zona glomerulosa secrete?
mineralocorticoids i.e. aldosterone
504
What does the zona fasciculata secrete?
- glucocorticoids
i.e. cortisol & small amounts of
androgens
505
what does the zona reticularis secrete?
- androgens (sex
| hormones) & small amounts of cortisol
506
What does the adrenal medulla produce?
Adrenaline and noradrenaline (catecholamines).
507
What is the precursor molecules for corticosteroids?
cholesterol as they are steroid hormones
508
What is the role of mineralocorticoids?
- Regulate body electrolytes
| - most predominant is aldosterone
509
What is the role of glucocorticoids?
cortisol is a glucocorticoid and has important effects on the metabolism of glucose and other organic nutrients
- synthesised in zona fasciculata predominantly and the zona reticualta
510
What is the role of cortisol?
Glucocorticoid, facilitates response to stress and regulation of immune system /brake function
- helps maintain blood pressure
- control of metabolism of organic nutrients
511
Why is there increased cortisol released in response to stress?
Stress poses a threat to homeostasis. Cortisol acts to maintain BP, provide extra energy sources and to shut down non-immune functions so homeostasis can be maintained.
512
Describe the mechanism of ACTH?
- stress detected by the hypothalamus
- stimulates the secretion of CRH from the hypothalamus
- carried to the anterior pituitary
- release of ACTH
- travels to the adrenal cortex through circulation
- to the adrenal cortex where it stimulates cortisol (glucocorticoid) release
- negative feedback on the hypothalamus and the anterior pituitary
513
What do steroid hormones bind to so they can be transported through the blood?
CBG - corticosteroid-binding globulin
| some to albumin
514
Why do steroid hormones bind to CBG proteins?
They are H2O insoluble and so need to bind to CBG for transport through the blood.
515
What regulates cortisol synthesis?
ACTH - produced by the anterior pituitary
516
Give two ways in which cortisol is essential in fetal and neonatal life?
• Responsible for the proper differentiation of numerous tissues
& glands including parts of the brain, adrenal medulla,
intestines & lungs
• Cortisol is ESSENTIAL for the production of SURFACTANT
517
What are the physiological functions of cortisol not in response to stress?
1. Permissive action on smooth muscle cells that surround blood vessels; this helps to maintain BP.
2. Maintains concentrations of enzymes involved in metabolic homeostasis.
3. Anti-inflammatory and anti-immune functions: dampens the immune response.
518
What are the physiological functions of cortisol in response to stress?
1. Mobilises energy sources: increases protein catabolism, lipolysis and gluconeogenesis. This help to maintain blood glucose levels.
2. Enhanced vascular reactivity; maintains vasoconstriction with noradrenaline.
3. Suppresses inflammatory and immune responses.
4. Inhibition of non-essential functions e.g. growth and reproduction.
519
Why is infertility a consequence of stress?
When someone is stressed, their cortisol levels increase, the extra cortisol acts to shut down non-essential functions such as reproduction and so can result in infertility.
520
Give an example of a sex hormone secreted by the zona reticualta in the adrenal cortex?
DHEA - very weak androgen
521
Which hormone controls the secretion of DHEA and other androgens and from where?
- ACTH
| - anterior pituitary gland
522
What regulates the secretion of adrenaline and noradrenaline?
Autonomic innervation, mainly sympathetic.
523
Where is adrenaline synthesised?
Adrenal medulla
524
Which receptors have a high affinity for noradrenaline?
alpha receptors
525
Which receptors have a high affinity for adrenaline?
beta receptors
526
Briefly describe thyroid hormone synthesis.
Follicular cells take up circulating iodide through sodium cotransport, Na+ pumped back out via Na/K-ATPase.
- Iodide diffuses to colloid which contains thyroglobulin.
- Iodide is oxidised to iodine. Iodine attaches to tyrosine residues within thyroglobulin.
- Tyrosine either binds 1 or 2 iodine molecules forming MIT or DIT.
- Thyroid peroxidase stimulates MIT and DIT binding forming T3 and T4. Proteolysis of thyroglobulin releases T3 and T4 into the ECF and then into the blood.
527
What enzyme stimulates T3 and T4 formation in the thyroid?
thyroid peroxidase
528
What 2 molecules can combine to form T3?
MIT+DIT
529
What 2 molecules can combine to form T4?
DIT+DIT
530
Describe the control of thyroid function
- The hypothalamus releases TRH
- Plasma TRH increases
- anterior pituitary is stimulated to release TSH
- increased plasma TSH
- increased thyroid secretions thyroxine T4 & T3
- increase in plasma thyroid hormone
- > T4 and T3 have a negative feedback effect on the hypothalamus and pituitary.
- T4 converted to T3 in peripheries
531
What would be the effect on TSH if you had an under-active thyroid?
TSH would be high as there would be little negative feedback as fewer T4 and T3 are being produced.
532
What would a low TSH tell you about the action of the thyroid?
Low TSH = overactive thyroid.
| Lots of T4 and T3 being produced and so there is more negative feedback on the pituitary and less TSH.
533
What hormone from the hypothalamus stimulates the anterior pituitary to release TSH?
TRH - hypothalamus
534
Why might thyroid glands hypertrophy? (goitre)
- If the thyroid is exposed to greater TSH concentrations than normal
- TSH also causes increases protein synthesis in follicle cells
- increased DNA replication
- Increased cell division
- increased RER for PS
535
What happens when TSH acts on the thyroid?
T1 and T2 molecules are cleaved from their thyroglobulin backbone and join to create T3 or T4.
536
What process needs to occur before T3 and T4 can be released into the bloodstream?
Proteolysis.
537
What does the thyroid hormone affect?
Increased metabolism, increased sympathetic action ( up-regulates beta-adrenergic receptors), heat production, essential for growth and development too.
538
Why can a tumour of the pituitary gland affect vision?
The optic chiasm lies just above the pituitary gland and is likely to be affected if there's a tumour.
539
briefly describe how the pituitary gland forms embryologically?
- form from different tissues joining together
- protrusion of ectoderm from the mouth called Rathke's pouch grows upwards to form the anterior pituitary
- the posterior pituitary is neuronal in origin and is an extension of the hypothalamus
540
How does the anterior pituitary gland receive its blood supply?
Via a portal venous circulation from the hypothalamus.
541
What hormones from the hypothalamus stimulate the anterior pituitary to release GH?
GHRH (+ve affect) and SMS (-ve affect).
542
What hormone from the hypothalamus stimulates the anterior pituitary to release LH and FSH?
GnRH.
543
What hormone from the hypothalamus stimulates the anterior pituitary to release ACTH?
CRH.
544
What hormone from the hypothalamus stimulates the anterior pituitary to release TSH?
TRH.
545
What hormone from the hypothalamus inhibits the anterior pituitary to release prolactin?
Dopamine.
546
Where does the anterior pituitary gland originate from?
It is epithelial in origin. Derived from the primitive gut tube endoderm
547
Are there any neuronal connections between the hypothalamus and the anterior pituitary gland?
No
548
Does the anterior pituitary gland have an arterial blood supply?
No - through a portal venous circulation from the hypothalamus.
549
What is the advantage of the hypothalamo-hypophyseal portal veins?
to allow hormones of the hypothalamus to directly alter the activity of the anterior pituitary cells bypasses the circulation
- key for regulation
550
The hypothalamic hormones that regulate
anterior pituitary gland function are collectively
termed what?
hypophysiotropic hormones or
hypothalamic releasing or inhibiting hormones:
- one exception being dopamine
551
Name 6 hormones produced by the anterior pituitary gland.
1. FSH - produced in lactotrophs
2. LH - produced in lactotrophs
3. GH- produced in somatotrophs
4. ACTH - produced in corticotrophs
5. TSH - produced in thyrotrophs
6. Prolactin - produced in lactotrophs
mneumonic - FLATPIG
552
What is the role of ACTH?
• Stimulates the adrenal cortex to secrete CORTISOL
553
What is the role of TSH?
Stimulates thyroid to secrete T3 & T4 resulting in an increase in
metabolism
554
What is the role of prolactin?
• Stimulates the breasts to produce milk & helps with breast development
555
What is the role of GnRH?
```
lutenizing hormone (LH) & follicle
stimulating hormone (FSH) -> target gonads to increase oestrogen, progesterone &
testosterone
```
556
What is the role of GHRH?
```
growth hormone (GH) -> stimulates
growth & protein synthesis
```
557
What is the of somatostatin?
SMS - inhibits growth hormone (GH) -> inhibits growth & protein
synthesis
558
What is the role of CRH being secreted by the hypothalamus ?
```
adrenocorticotrophic hormone (ACTH) ->
increases cortisol production in the adrenal cortex from zona fasiculata
```
559
What is the role of dopamine?
-> inhibits prolactin -> inhibits growth & milk production
560
Why can a tumour of the pituitary gland affect vision?
The optic chiasm lies just above the pituitary gland and is likely to be affected if there's a tumour.
561
What can pituitary tumours cause?
1. Pressure on local structures e.g. optic chiasm. Can result in bitemporal hemianopia.
2. Pressure on normal pituitary function; hypopituitary.
3. Functioning tumour can result in Cushing's disease, gigantism and prolactinoma.
562
What is the posterior pituitary gland?
- an extension of the hypothalamus
| - stores and releases two peptide hormones
563
Name 2 hormones produced by the posterior pituitary gland.
1. ADH.
| 2. Oxytocin.
564
Name the 2 hypothalamic nuclei whose axons extend into the posterior pituitary gland via the pituitary stalk.
1. Paraventricular nuclei.
| 2. Supraoptic nuclei.
565
What hypothalamic nucleus contains cells responsible for ADH?
Supraoptic nucleus.
566
What hypothalamic nucleus contains cells responsible for oxytocin?
Paraventricular nucleus.
567
Describe the role of vasopressin/ADH?
- decrease water reabsorption, water retention
| - acts on smooth muscle around blood vessels to cause vasoconstriction to increase BP
568
Name a few things which can cause ADH secretion
- Decreased blood volume
- Trauma
- Stress
- Increased blood CO2
- Decreased blood O2
- Increased osmotic pressure of blood
569
What is the function of oxytocin?
It is important in the onset of labour, uterine contraction. It produces milk in response to suckling and is thought to be involved in caring behaviours.
570
What is the difference between the exocrine pancreas and the endocrine pancreas?
Endocrine - ductless and release hormones directly into the blood
Exocrine - secrete products into ducts and then secretions
571
Which parts of the pancreas are retroperitoneal and intraperitoneal?
the uncinate, head, neck and body are retroperitoneal and the tail is intraperitoneal.
572
what proportion of pancreas cells are the islet of Langerhans cells?
1-2%
| 99-98% acini for exocrine functions
573
What are the 4 cells to make up the islets of langerhans?
1. Beta cells: insulin. (70%)
2. Alpha cells: glucagon. (20%)
3. Delta cells: somatostatin. (8%)
4. Pancreatic polypeptide secreting cells. (2%)
574
What is the importance of the alpha and beta cells being located next to each other in the islets of langerhans?
This enables them to 'cross talk' - insulin and glucagon show reciprocal action.
575
What is the function of insulin?
1. Suppresses hepatic glucose output: decreases glycogenolysis and gluconeogenesis.
2. Increases glucose uptake into fat and muscle cells.
3. Suppresses lipolysis and muscle breakdown.
576
What is the function of glucagon?
1. Stimulates hepatic glucose output: increases glycogenolysis and gluconeogenesis.
2. Reduces peripheral glucose uptake.
3. Stimulates the release of gluconeogenic precursors.
4. Stimulates lipolysis and muscle breakdown.
577
What substance can tell you if high insulin levels are due to endogenous insulin production and why?
The presence of C peptide.
- proinsulin is joined by C peptide
- when insulin produced proinsulin cleaved and high level of C peptide in blood
- not found in synthetic insulin
