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Endocrine Biology
Endocrine Biology
Endocrine Biology
08 August 2014
16:19
module overview
structure + function of endocrine system + repro organs
specialised functions of endo glands & tissues incl. mechanisms of feedback regulation
hormone structure & mechanism of action
presentation & investigations w/ a witness pt. encounter
anatomical landmarks of major endo organs
biochemical markers in pts. to evaluate endo disorders
ASSESSMENT
30% continuous
5% biochemistry practical - notebook write up (prepare in advance)
5% CAL 2 (WK4)
10% CAL 3 (WK8)
10% CAL 4 (WK12)
70% exit exam
MCQ - best of 5, neg. marking
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18:31
exocrine - duct
eNDOcrine - NO Duct
the placenta is not generally considered to be an endo gland but does secrete hormones
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the placenta is not generally considered to be an endo gland but does secrete hormones
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Page 5
Clinical Endocrinology
CAUSES
EXAMPLES
genetic (mutations)
tumours
immunologic
growth h. - giantism
parathyroid h. - cardiac arrhythmia, tetany
hormone resistance
Page 6
hormone resistance
genetic (rec/enz def.)
hormone antagonism
acquired
genetic
hormone agonism
allergies
Graves Dz - sensitivity to TSH causes hyperthyroidism
summary
hormones are signalling mols carried in the bloodstream
endo and nerv systems work together to main homeostasis
endo system is slower but longer lasting
hypothalamus & pituitary glands are key in regulating peripheral endo glands
h. secretion is regulated by neg. feedback, humoral factors & neural inputs
h. action is influenced by secretion rate, metabolism & target cell factors e.g. rec. number + binding affinity
endo disorders can arise from hypo/hypersecretion & hypo/hypersensitivity
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23:27
hypothalamus & pituitary: the two most important endocrine glands in the body
Page 8
3 types of hormone
hypothalamus functions
homeostasis
thirst, hunger, sexual urges
hormone production (ADH & oxytocin) - both secreted by post. pituitary (neurohypophysis)
regulation of ant. pituitary (adenohypophysis) gland secretion
key difference
ant. pituitary synthesises and secretes its own hormones
post. pituitary secretes hormones synthesised by the hypothalamus
but, the hypothalamus still secretes regulatory hormones to stimulate/inhibit ant. pituitary secretion
the hypothalamus integrates signals from CNS, PNS & Endo System
co-ordinated response
visceral ANS (neural output)
neuroendocrine function (endocrine output)
Page 9
sidenote
The four ventricles of the brain are two laterals, 3rd & 4th
function is to allow flow of cerebrospinal fluid and to protect the brain
hypothalamic nuclei
nuclei have different functions
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Page 11
hypothalamic
nucleus
posterior
anterior
medial preoptic
supraoptic
paraventricular
suprachiasmatic
dorsomedial
ventromedial
lateral
mamillary
arcuate
periventricular
function
memory
temperature (shivering)
temperature
increases basic metabolic rate by
inhibiting thyrotropin releasing hx (TRH)
which
reduces TSH production which
reduces thyroid (esp. T3/T4 form) action
reduces energy expenditure & heat
production
releases gonadotrophic releasing hx (GnRH)
which
stimulates release of luteinizing hx (LH) &
follicle-stimulating hx (FSH) from ant. PG
blood pressure
thermoregulation
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hypothalamic-pituitary axes
hypophyseal portal circulation facilitates hypothalamic hormonal regulation (stimulation/inhibition) of ant. PG hx production
axes are complex sets of direct influences & feedback b/w the hypothalamus, pituitary & particular endocrine glands
hypothalamic-pituitary-adrenal (HPA) axis - reaction to stress e.g. physical activity, waking up, illness
1. HT produces corticotropin-RH & ADH
2. APG corticotroph cells secrete adrenocorticotropic hx (ACTH)
3. adrenal cortex releases a wave of steroid hx which modulate the body's reaction to stress
mineralocorticoids e.g. aldosterone
glucocorticoids e.g. cortisol
HPA - similar to GPA which is bloody stressful
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hypothalamic-pituitary-gonadal axis
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23:27
learning objectives
location & relations of HT & PG
development & divisions of PG
hypothalamic control of PG
clinical anatomy
some of this lecture is omitted as it has been covered in PC's other lectures
brain divisions
diencephalon ("interbrain")
consists
epithalamus
thalamus
hypothalamus
subthalamus
it is a region of the embryonic neural tube that gives rise to post. forebrain structures:
thalamus
hypothalamus
post. pituitary gland
pineal gland
Page 16
pineal gland
located in the post. roof of 3rd ventricle
secretes melatonin - circadian rhythm modulation
Page 17
post. pituitary stores ADH & oxytocin (not simultaneously) from the supraoptic & paraventricular hypothalamic
nuclei
these hormones are produced by magnocellular neurosecretory cells
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optic chiasm
intersection of the optic nerves
vision may be affected by pituitary lesion
mammillary bodies
pair of small round bodies that look like boobs (hence the name)
hypothalamic nuclei for memory
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cranial nerves
III, IV, V, VI pass by PG
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4. PC (19/9) - Anterior
Pituitary Gland
16 September 2014
23:28
location of adenohypophyis
sits in sella turcica (depression of sphenoid bone)
connected to hypothalamus by stalk/infundibulum
dense capillary plexus @ top of stalk
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the hypothalamic regulation of the ant. pituitary via the hypophyseal portal system is endocrine NOT neural
cells in ant. PG
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cells in ant. PG
chromophils - stain readily by chromium salts
acidophils (somatotrophs, mammotrophs)
basophils (corticotrophs, gonadotrophs, thyrotrophs)
cell type
somatotroph
lactotroph
thyrotroph
gonadotroph
corticotroph
hormone
GH
prolactin
TSH
FSH, LH
ACTH
histology
red, large cells in clusters
red, large solitary cells
blue, large, pale, irregular polyhedral shape,
dark blue, small round
pale blue, spherical
diurnal variation (fluctuations occurring throughout the day) of ACTH & cortisol
hypothalamic-pituitary-adrenal axis:
paraventricular nucleus of hypothalamus secretes corticotropin-releasing hx (CRH)
CRH stimulates adrenocorticotrophic hx (ACTH) release by ant. pituitary
ACTH stimulates cortisol synthesis in the zona fasiculata in the adrenal cortex
cortisol is a response to response and it mobilises glucose (by gluconeogenesis or glycogenolysis) for energy
the suprachiasmatic nucleus modulates circadian rhythm - influenced by levels of light
cortisol levels peak in the morning (kick up the arse) and trough in the middle of the night
prolactin
only major ant. pituitary hx that is not trophic (stimulating another endocrine gland)
triggered by estrogen & progesterone e.g. during pregnancy
inhibited by dopamine
physiological role: mammogenesis (glandular breast development) & lactogenesis (milk production)
prolactin levels remain high for months after parturition (childbirth) long after estrogen/progesterone levels have
dropped
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lactation amenorrhea is the temporary postnatal infertility when a woman is not menstruating and fully breastfeeding
amenorrhea = no menstruation - "No periods? Amen to that!"
in females
LH is essential for ovulation as it stimulates androgen production in thecal cells which is a substrate for estrogen
synthesis in granulosa cells
LH surge converts the follicle into the corpus luteum
FSH stimulates follicle growth/stimulation, upregulates estrogen synth. & induces inhibin synth. for neg. feedback
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FSH stimulates follicle growth/stimulation, upregulates estrogen synth. & induces inhibin synth. for neg. feedback
in males
LH stimulates leydig cells to produce testosterone which acts on sertoli cells to promote spermatogenesis
sertoli cells also induce inhibin synth.
sertoli cells produces androgen-binding protein & anti-mullerian hx
Growth Hormone & Insulin Like Growth Factor-1 (IGF-I) (covered in Lecture 5)
GH secretion influenced by multiple factors
GHRH
somatostatin
feedback regulation by GH and IGF-I (insulin like growth factor-I)
exercise, sleep, fasting, plasma glucose
growth disorders assoc. w/ GH
hyposecretion - pituitary dwarfism
hypersecretion - acromegaly, gigantism, hypersomatotropism (Robert Wadlow)
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00:11
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16:39
the thyroid is a butterfly-shaped endocrine gland located in the anterior neck, spanning b/w vertebrae C5-T1
it is wrapped around the cricoid cartilage and superior tracheal rings
sternohyoid & sternothyroid muscles border the gland anteriorly
It is situated in the visceral compartment of the neck along w/ the trachea, oesophagus & pharynx
it is divided into right & left lobes which are connected by an isthmus
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thyroid development
in embryogenesis the thyroid descends from the floor of the primitive pharynx down the neck via the thyroglossal duct
in 50% of individuals the duct fuses and regresses in adulthood
in the other 50%, the distal portion of the duct remains as an extra piece of thyroid tissue called a pyramidal lobe, w/o
clinical consequences
if other portions of the duct persist as thyroglossal duct cysts they may present w/ a mass in the midline of the neck and
require surgical excision
vascular supply
the thyroid is a highly vascularised tissue b/c it needs to secrete hormones directly into the bloodstream
blood supply is by two main arteries, both of which are paired left & right
sup. thyroid artery: first branch of ECA, supplies superior + anterior portions of the gland
inf. thyroid artery: arises from thyrocervical trunk which is a branch of the subclavian artery, inf. thyroid art. supplies the
postero-inferior thyroid
in 10% of people there is a 3rd artery called the thyroid ima artery which arises from the brachiocephalic trunk of the aortic
arch, supplying the ant. surface & isthmus
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venous drainage is by the superior, middle + inferior thyroid veins which from a venous plexus
sup. + mid. veins drain into int. jugular veins
inf. vein drains into the brachiocephalic vein
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clinical consideration
the L&R recurrent laryngeal nerves arising from their respective vagus nerves pass posterior to the thyroid gland to
innervate the larynx
care must be taken in thyroid surgery not to ligate these nerves
Page 30
7. JL (3/10) - Parathyroid
Glands & Thymus
26 September 2014
16:40
PARATHYROID GLANDS
small endocrine glands in the neck
produce parathyroid hormone which regulates calcium levels in the body
humans usually have 4 PT glands
located on posterior surface of thyroid
each gland weighs 50mg
yellow/brown colour w/ an ovoid shape
not normally palpable
variation: sometimes there may be 6 or 8 PT glands
rarely, they are located in the thyroid, chest or thymus
WK 7: inf. & sup. PTs migrate b/w sternum (swapping position) & fuse
PT cells
chief (principal) cells - synthesis & release of parathyroid hormone which transports calcium from bone
oxyphil cells - unknown function
parathyroid hormone (PTH)
increases the conc. of calcium in blood
has the opposite effect of calcitonin (which is secreted by the parafollicular or C-cells of the thyroid)
half-life is approx. 4 mins
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arterial supply
sup. PT: inf. thyroid arteries (arising from subclavian art.)
inf. PT: asc. branch of inf. thyroid artery or thyroid ima artery
venous drainage
sup, middle & inf. thyroid veins
sup. & mid. drain into jugular vein
inf. drains into brachiocephalic vein
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Lymphatic vessels drain into deep cervical & paratracheal lymph nodes
clinical: hyperparathyroidism/hypoparathyroidism characterised by alterations in blood calcium levels and bone
metabolism
THYMUS
Page 34
Relations
anterior: sternum, origins of sternohyoid & sternothyroid muscles
posterior: heart & pericardium
superior: lower border of thyroid gland
inferior: heart & pericardium
lower border is in line w/CC4
Immune function
T-lymphocytes mature from hematopoietic pregenitor cells in the thymus
developing T-cells are called thymocytes
these lymphocytes are key in the adaptive immune response as they attack specific foreign antigens
the thymus also determines which T-cells to destroy in 2 ways
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neurovascular
arteries: derived from int. thoracic, sup. thyroid & inf. thyroid
veins: drain into the L brachiocephalic & thyroid veins
nerves: exceedingly minute, derived from vagi & SNS, branches from descendens hypoglossi & phrenic reach
the investing capsule but do not penetrate into the parenchyma
Page 37
8. PC (8/10) - Thyroid
Physiology
08 October 2014
19:20
Thyroid Hormones
Page 39
iodination at C3 & C5 positions of outer & inner rings of tyrosine produces T3/T4
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1. Thyroglobulin is synthesized in the RER & Golgi and extruded from the follicular cells into the lumen
2. I- (iodide) is actively transported into the follicular cells
3. I- is oxidized to I2 aka iodine
4. Iodine is organified into MIT & DIT (mono & diiodotyrosine) i.e. combined w/ parts of thyroglobulin
5. DIT + DIT = T4, DIT + MIT = T3, the T4 rxn is 10x faster, hence more T4 is produced
6. TG (now containing T3, T4 and leftover MIT & DIT) is endocytosed from the lumen into the follicular cells
7. Lysosomal proteases hydrolyze peptide bonds to release T3, T4, MIT & DIT from TG, and T3 + T4 are delivered
via capillaries to systemic circulation
8. reverse of steps 3+4: DIT + MIT are deiodinated back to I- and tyrosine, which are recycled for the next cycle
TPO (thyroid peroxidase) is the enzyme in steps 3,4,5, uses H 2O2 as the oxidant
PTU = propylthiouracil (inhibitor of TPO) - used as tx in hyperthyroidism
high I- levels inhibit step 4 (Wolff-Chaikoff effect) - Wolf of Wall St. & Michael Cheika inhibit students from going
to colleges like MIT or DIT by encouraging them to become stockbrokers / rugby players
Page 41
hypothalamic-pituitary-thyroid axis
1. the hypothalamus secretes thyrotropin-releasing hx (TRH)
2. TRH stimulates thyrotrophs in the ant. pituitary to release thyroid-stimulating hx (TSH)
3. TSH stimulates thyroid release of thyroid hx by:
stimulating each step on the biosynthetic effect
trophic effect whereby the thyroid gland is enlarged
thyroid-stimulating immunoglobins bind to the TSH receptors on thyroid cells and elicit the same response as
TSH
Graves disease, a common form of hyperthyroidism, is caused by increased levels of these immunoglobins
a sign of Graves dz is low TSH due to negative feedback of high thyroid hx levels
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Mechanism of action
T3 binds to a nuclear receptor in the target cell
the T3-receptor complex stimulates DNA transcription
translation & protein synthesis follow
the new proteins carry out the multiple thyroid hx functions w/ specific proteins for each
1. Basal Metabolic Rate
T3 induces synthesis & activity of Na+-K+ ATPase which is involved in O2 consumption and resulting body heat
production & BMR
T3 may have a direct role on thermogenesis by synthesising mitochondrial uncoupling protein 3
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2. Metabolism
T3 induces synthesis of key metabolic enzymes
it increases both protein synthesis & degradation but the overall effect is catabolic (breaking down)
3. Cardiovascular & Respiratory
O2 consumption demands cardiac output
T3 upregulates cardiac -1 receptors which mediate the effects of the SNS to increase heart rate & contractility
4. Growth
T3 stimulates bone formation by promoting ossification & fusion of bone plates and bone maturation
5. Central Nervous System
in the perinatal period, T3 is essential for CNS normal maturation - nerve & dendrite cell growth, myelin
formation
hypothyroidism in the perinatal period causes irreversible mental retardation (cretinism) - newborn screening is
mandated
Pathophysiology
disturbances of thyroid hx levels are the most common endocrine abnormalities
Page 45
Goiter
enlarged thyroid gland
can be seen in hyperthyroidism/euthyroidism/hypothyroidism
TSH & TSH-like compounds such as thyroid-stimulating IGs (TSIGs) have a positive trophic effect on the thyroid
anything that increases the levels of these can lead to goiter e.g.
Graves disease (high TSIGs)
TSH-secreting tumour
iodide deficiency - transient T3 synthesis stimulates TSH secretion by neg. feedback
autoimmune thyroiditis - T3 levels stimulate TSH secretion - the gland enlarges even though it is not
effectively synthesising thyroid hormone!
exogenous T4 ingestion (factitious hyperthyroidism) decreases TSH by neg. feedback and so does not cause
goiter
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goiter
Page 47
21:50
The adrenal (suprarenal) glands are located in the retroperitoneal cavity above each kidney
Each gland is divided into an inner medulla and outer cortex
They receive a large blood supply
Page 48
ADRENAL CORTEX
composes 80% of tissue
mesodermal origin
secretes adrenocortical steroid hormones
the cortex is divided into 3 zones - GFR, like glomerular filtration rate
zona glomerulosa (10-15%)
zona fasciculata (75%)
zona reticularis (10-15%)
zone
glomerulosa
fasciculata
reticularis
secretion
mineralocorticoids e.g. aldosterone
glucocorticoids e.g. cortisol
androgens
Page 49
basically
SALT
SUGAR
SEX
Page 50
REGULATION
ACTH is essential for all adrenocortical steroid biosynthesis
zona glomerulosa pathway depends on ACTH for step 1 but is otherwise controlled by the renin-angiotensinaldosterone system (RAAS) and serum K+ levels
zona fasciculata & reticularis pathways are completely controlled by the hypothalamic-pituitary-adrenal axis
Page 51
serum K+ levels
high potassium levels depolarize adrenal cells which opens voltage-sensitive Ca2+ channels
the higher intracellular Ca2+ stimulates aldosterone secretion
aldosterone acts in the renal tubule to increase K+ secretion, restoring normal K+ levels
Page 52
aldosterone acts in the renal tubule to increase K+ secretion, restoring normal K+ levels
hypothalamic-pituitary-adrenal axis
hypothalamus secretes corticotropin-releasing hormone (CRH)
CRH acts on corticotrophs in the ant. pituitary to stimulate the release of ACTH
the ACTH is secreted in a pulsatile & diurnal pattern meaning the cycle repeats daily
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glucocorticoids
essential for life
main one is cortisol
adrenal androgens
DHEA and androstenedione are converted to testosterone
in males the role is minor b/c most testosterone is synthesised de novo in the testes
Page 54
in males the role is minor b/c most testosterone is synthesised de novo in the testes
in females adrenal androgens are v. important and are responsible for pubes, armpit hair & libido
adrenogenital syndrome = adrenal androgen synthesis, can lead to masculization of women
Pathophysiology
1. Cushings Syndrome: hypercortisolism
causes
cortisol secreting adrenal
tumour
pituitary ACTH XS (Cushings Dz)
prolonged glucocorticoid
therapy
ectopic tumours secreting
ACTH
Page 55
symptoms
hyperglycemia/glucosuria
insulin resistance (DM2)
obesity
treatment
drugs which block steroid hx biosynthesis
e.g. ketoconazole or metyrapone
if drugs are ineffective, bilateral adrenalectomy w/
hormone replacement therapy may be required
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treatment
steroid replacement
Page 57
symptoms
electrolyte imbalance
sodium reabsorption (hypernatremia)
potassium excretion (hypokalemia)
H+ excretion
HCO3 plasma calcium level
water retention
ADRENAL MEDULLA
composes 20% of the tissue
neuroectodermal origin
chromaffin cells secrete catecholamines adrenaline & noradrenaline
Page 58
treatment
surgery
spirinolactone (aldosterone
receptor antagonist)
Page 59
NE = norepinephrine = noradrenaline
E = epinephrine = adrenaline
Bloody Yanks!
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18:16
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innervation of islets
SNS: splanchnic nerve
-adrenergic: insulin, glucagon
-adrenergic: insulin
PSNS: vagus nerve
insulin, glucagon
communication b/w islet cells is by 3 ways
1. gap junctions - rapid cell-to-cell communication
2. blood supply - -cells get 'first pass' and venous blood from them can carry insulin to other islet cells
3. intraislet neural communication
the two major endocrine secretions are insulin & glucagon, whose coordinated functions are to regulate glucose,
fatty acid and amino acid metabolism
INSULIN
insulin increases blood glucose entry into cells by directing GLUT 4 transporters to the cell membrane
Page 65
Insulin is called the "hormone of abundance". It ensures that excess nutrients are stored away for a rainy day as:
glycogen in the liver
fat in adipose tissue
protein in muscle
Page 66
GLUCAGON
"when glucose is gone"
synthesised + secreted by islet cells
in most respects (regulation of secretion, actions, effects on blood levels) it is the mirror image of insulin
raises blood glucose levels
the hormone of 'starvation' rather than 'abundance'
promotes mobilization & utilization of metabolic fuels rather than storage
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Regulation of secretion
Actions
Page 68
Glucose Homeostasis
exceptionally important b/c the brain virtually uses only glucose for its energy
Page 69
regulation of GP + GS
allosteric regulation (local factors)
glucose-6-phosphate stimulates GS, inhibits GP
AMP stimulates GS
AMP inhibits GP
hormonal regulation (systemic factors)
phosphorylation inactivates GS
phosphorylation activates GP
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16:21
Page 73
Ca2+ and PO43- levels are inversely related so that [Ca2+] x [ PO43-] is constant
if [Ca2+] x [ PO43-] > 40mg/dl, there is potential for spontaneous precipitation
bone cells
osteoclasts chew up bone (resorption)
osteoblasts build up bone (formation) - requires Ca2+, PO43- & Vit D
osteocytes are mature osteoblasts that maintain bone
Page 74
organic collagen matrix on which hydroxyapatite (inorganic crystalline form of calcium) is precipitated
mineralised calcium phosphate = reservoir for Ca2+ storage
non-mineralised calcium phosphate = rapidly accessible pool of Ca2+
these cells are targets for endocrine & paracrine regulators of Ca2+ homeostasis
osteocytic osteolysis
fast (minutes)
no bone resorption, no loss in bone mass
activation of PTH-dependent Ca2+ pumps in osteocytic-osteoblastic memb.
2.
osteoclastic resorption
slow (weeks/months)
bone remodelling
destruction of organic collagen matrix, loss of bone mass
also releases PO43-
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Page 78
Vitamin D (cholecalciferol)
derived from 2 sources
1. Food (ingested in diet)
2. Sun (produced by keratinocytes)
not a "true" vitamin b/c it can be synthesised de novo
it is a "true" hormone b/c it has an endocrine mode of action
circulates complexed to vit D binding protein (<0.5% free form)
key role in Ca2+ homeostasis by promoting intestinal absorption and renal reabsorption
Vit D synthesis
7-dehydrocholesterol converted to Vit D3 in keratinocytes
Vit D3 hydroxylated in liver to yield 25(OH)D3 aka calcidiol
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Calcitonin
produced in thyroid C-cells aka parafollicular cells
minor role in decreasing blood Ca2+ levels
inhibits osteoclastic activity
inhibits Ca2+ reabsorption in kidney
inhibits Ca2+ absorption in intestine
major stimulus to secretion = plasma Ca2+ levels
Clinical disorders
Page 82
Clinical disorders
classification
cause
hyperparathyroidism
primary: hyperfunctioning PT Gland
secondary: result of hypocalcemia
tertiary: progression of 2y into autonomously
hyperfunctioning state (rare)
85% due to single PT adenoma
15% due to hyperplasia
clinical
presentation
diagnosis
hypercalcemia
PTH
low or normal PO4324 hour calcium/creatinine ratio
renal ultrasound
bone density
alkaline phosphatase
Page 83
hypoparathyroidism
primary - hypofunctioning PT gland
true: Ca2+ w/ PTH
pseudo: Ca2+ w/ PTH (PTH
resistance)
trauma during thyroidectomy
idiopathic
congenital deficiency (Di George
Synd.)
fatigue
psychological disturbance e.g. mood
swing
wheezing + dyspnoea
tetany
hypocalcemia
PTH
high or normal PO43alkaline phosphatase
13:43
Diabetes mellitus is a group of metabolic diseases in which there are high blood sugar levels over a prolonged
period.
High blood sugar produces the symptoms of frequent urination and increased thirst and hunger.
Acute complications include diabetic ketoacidosis and non-ketotic hyperosmolar coma.
Long-term complications include heart disease, stroke, kidney failure, peripheral vascular disease and eye damage.
Type 1 DM results from the body's failure to produce enough insulin, cause unknown.
formerly "insulin-dependent DM" (IDDM) or "juvenile diabetes"
Type 2 DM begins with insulin resistance where cells fail to respond to insulin properly. As it progresses a lack of
insulin may also develop
formerly "non insulin-dependent DM" (NIDDM) or "adult-onset diabetes"
this is the one you get from eating 2 many sweets
Gestational diabetes occurs when pregnant women w/o previous history of DM develop high blood glucose
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Etiology
generally unknown cause but genes & environmental triggers play a role
genetics
linkage to human leukocyte antigen (HLA) loci on Chr. 6q
DR3 & DR4 loci increase risk
DR2 locus decreases risk
environmental triggers
childhood viral infections e.g. mumps, rubella, coxsackie
cow's milk - controversial
Symptoms
polydypsia ( thirst)
polyuria ( urine volume)
polyphagia ( appetite)
weight loss
blurred vision
hyperglycemia (high blood glucose)
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iatrogenic hypoglycemia
over-administration of insulin
possibly combined w/ other factors e.g. reduced food intake, increased exercise
potentially fatal
seen in 80% of T1DM pts.
Page 89
long-term complications
microvascular
retinopathy
nephropathy
neuropathy
macrovascular
arteriosclerosis (MI, stroke)
risk of complications reduced by good glycaemic control
insulin therapy
oral administration useless b/c insulin is degraded by the GIT
usually administered subcutaneously/intravenously/intramuscularly
T1/2 of insulin in blood is 10 mins
the main aim is to avoid large fluctuation in insulin + glucose levels
no regimen can totally replace endogenous insulin action
best therapy for T1DM is a mixture of short + medium term lasting insulin injected before meals
the rate of absorption is altered by altering particle size
insulin glargine is v. long acting and reduces risk of night-time hyperglycemia
insulin pumps are an excellent method of glucose monitoring
insulin pens are convenient, accurate, more comfortable for pt. and associated w/ greater compliance and less
anxiety
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00:58
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Diagnosis of DM
Page 93
Epidemiology: BAD NEWS, especially for the Yanks - all those bloody Coca-Colas and Big Macs
biggest risk factor is obesity and obesity is on the rise
Page 94
Nauru, an island country in Micronesia in the South Pacific is the world's fattest nation - average weight 100kg
>90% of the 10,000 population are overweight/obese, 40% have T2DM
the Pima Indians in the States have the highest worldwide T2DM prevalence: 50%
adipose tissue is a metabollically active tissue and not just a storage of fat reserves
visceral fat is more metabolically active than subcutaneous
high circulating fatty acids are toxic to other tissues esp. the liver
Page 95
COMPLICATIONS
1. Retinopathy (eyes)
damage to retinal microvasculature
poor glycaemic control is a major risk factor
non-proliferative (early stage): increased vascular permeability, macular oedema
proliferative (advanced stage): retinal hypoxia & ischaemia stimulate angiogenesis
leading cause of blindness in working age adults
2. Nephropathy (kidneys)
high blood sugar damages renal microvasculature
more common in T1 than T2DM
pathological changes
glomerular BM thickens
mesangial cells expand
ECM accumulates/fibroses
progressive decline in glomerular filtration rate
leading cause of end-stage renal dz. (kidneys stop filtering blood)
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3. Neuropathy (nerves)
abnormalities of microvasculature supplying peripheral nerves
BM thickening
endothelial hyperplasia
leading cause of non-traumatic lower extremity amputation
4. Diabetic Foot
peripheral vascular dz. can cause ischemia & necrosis
neuropathy can cause loss of sensation and also a failure to notice injuries so that they are allowed to develop,
including:
ulceration
infection
neuropathic osteoarthropathy
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5.Macrovascular
ischaemic heart dz. (coronary heart dz.)
cerebrovascular dz. (stroke)
atherosclerosis (plaque formation in vessel wall)
6. HSS/HONK
HSS = hyperosmolar hyperglycemic state
HONK = hyperosmolar non-ketosis
"HONK IF YOU HAVE DIABETES"
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15:57
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15:58
the male reproductive system is made up of internal & external organs, collectively termed genitalia
duct system
epididymis
ductus deferens aka vas deferens
ejaculatory duct
urethra
accessory glands
seminal vesicles
bulbourethral glands
prostate
Page 100
EXTERNAL GENITALIA
penis
scrotum
testes
epididymis
spermatic cord
Penis
2 main functions
Riding: Undergoes erection during erotic stimulation, becoming engorged w/ blood. Following emission (mixing
of semen components in the prostatic urethra) ejaculation can occur, whereby semen exits the urethra thru the
external urethral orifice. Finally the penis undergoes remission and returns to a flaccid state
Pissing: The urethra carries urine from the bladder to the external urethral orifice where it is expulsed from the
body
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the corpus spongiosum (body) expands to form the bulb posteriorly and the glans anteriorly
penis is attached at the root (bulb + crura) to the perineal membrane of the perineum
Scrotum
a cutaneous sac forming an expansion of the perineum
embryologically derived from the genital folds
contains the testes, epididymis & the initial part of the spermatic cord
midline septum creates left + right compartments
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Testes
singular: testis or testicle
two ovoid, glandular organs located w/in scrotum
upper + lower poles
attached to spermatic cord
produce sperm
each testis is partially surrounded by two tunics
outer tunica vaginalis (peritoneal)
inner tunica albuginea (fibrous connective tissue)
my balls are surrounded by Albanian vagina 24/7
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Testis supply
arterial: testicular arteries (branch of abdominal aorta)
venous: pampniform plexus drains into testicular veins - sometimes you need to pamper your balls
vessels descend thru inguinal canal
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Epididymis
lies posterolaterally to testis
function: storage & maturation of sperm
duct w/ head, body, tail
tail leads to ductus deferens aka vas deferens
Spermatic cord
connective tissue sheath containing structures running to + from testes
vas deferens
testicular artery
cremaster muscle
nerves, veins, lymphatics
course
begins at deep inguinal ring
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1. Testicular Hydrocoele
defective absorption of fluid secreted b/w 2 layers of tunica vaginalis
congenital excess fluid in persistent processus vaginalis
results in painless enlargement
may lead to chronic infection of epididymis & testes if not surgically removed or fluid aspirated
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may lead to chronic infection of epididymis & testes if not surgically removed or fluid aspirated
Howard Long has Testicular Hydrocoele - him and his enormous blue balls
2. Testicular Cancer
most common ca. in young men (15-34)
1 in 280 Irish men will develop it
metastasises through preaortic nodes
tx: removal of tumour followed by radio + chemo, frequent follow up exam
3. Testicular Torsion
twisted spermatic cord cutting off blood supply to testicle
acute testicular pain
most common cause is congenital malformation of processus vaginalis
testicle is usually preserved w/ prompt diagnosis + tx (90% success w/ manual rotation w/in 6 hours, salvage rate
reduced thereafter)
INTERNAL GENITALIA
vas deferens
seminal vesicle
bulbourethral (Cowper's) gland
prostate gland
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prostate gland
Vas deferens
a continuation of the duct of epididymis
course
begins in tail of epididymis
ascends in spermatic cord
passes through both rings of inguinal canal
crosses ext. iliac vessels
enters pelvis
passes along pelvis lat. wall
crosses ureter near superolateral angle of urinary bladder
descends medial to ureter & seminal gland
enlarges to form ampulla @ fundus of bladder
narrows to join duct of seminal vesicle to form ejaculatory duct
passes through prostate gland to open into urethra
SPUNK!
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Prostate gland
walnut-sized fibromuscular organ b/w neck of bladder & UG diaphragm in blokes
fibrous capsule
base, apex, 3 surfaces: ant., post. + inferolateral
passive role: control of rate of urine flow from bladder to urethra via its muscle fibres that surround the urethra
active role: production of white glandular secretion in sexual arousal which makes up 1/3 of seminal fluid
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prostatic ducts open into sinuses of the prostatic urethra to drain its glandular secretion which constitutes part of
seminal fluid
Prostate supply
BS: Inferior vesical + middle rectal arteries
prostatic venous plexus
NS: Autonomic - pelvic splanchnic + inferior hypogastric nerves
Prostate Cancer
the prostate enters a maturation phase in adolescence and begins benign hypertrophy after 25 years
> 1100 Irish men develop prostate ca. annually
accounts for 11% of Irish cancers & 500 annual deaths
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15:58
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Functions
1. sensory tissue during riding
2. assist in micturition, directing the piss flow
3. protection of the repro tract from infection
Structures
Mons pubis: A fat pad at the anterior of the vulva, which is covered in pubic hair.
Labia majora: 2 hair-bearing external folds that fuse posteriorly and extend anteriorly to the mons
pubis.
Labia minora: 2 hairless folds of skin that lie w/in the labia majora. They fuse anteriorly to form the
prepuce (hood) of the clitoris and extend posteriorly either side of the vaginal opening. They fuse
again posterior to the vestibule, creating a fold of skin called the fourchette.
Vestibule: The area between and surrounding the labia where the external vaginal orifice (vaginal
opening) and urethra open.
Clitoris: Under the prepuce, formed of erectile corpora cavernosa tissue, becomes engorged with
blood during sexual stimulation.
Bartholins Glands aka greater vestibular nerves: Located either side of the vaginal orifice, secrete
lubricating mucus from small ducts during sexual arousal. - Bart Bass gets bitches aroused
Supply
BS: pudendal arteries, internal branch contributing mostly.
VD: pudendal veins, w/ the smaller labial veins as tributaries.
LD: sf inguinal lymph nodes.
NS: sensory
ant. portion - iliolingual & genital branch of genitofemoral
post. portion - pudendal & post. cutaneous n. of thigh
PSNS: cavernous nerves derived from the uterovaginal plexus
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STIs
Herpes simplex: most commonly caused by the Herpes simplex Type II virus. Symptoms include
localised itching and burning, with formation of painful red vesicles ~3 days after infection. These
may ulcerate and last up to 2 weeks, sometimes with recurrent attacks.
Genital warts: benign growths of epithelium caused by HPV (Human papilloma virus). Infection can
spread to the vagina and cervix, and is readily transmitted via sexual activity. Certain strains of HPV
may predispose affected individuals to dysplastic changes in the cervix, vagina and/or anus which
can potentially lead to carcinoma.
VAGINA
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Supply
BS: uterine & vaginal aa., both branches of int. iliac
VD: vaginal venous plexus, drains into int. iliac via uterine
LD: iliac & sf inguinal LNs
NS: uterovaginal nerve plexus in the base of the broad ligament supplies SNS + PSNS
sup. vagina: inferior fibres from UV n. plexus
inf. vagina: deep perineal nerve (branch of pudendal n.)
UTERUS
aka womb
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layers of uterus
endometrium: inner layer, shed in menstruation when fertilisation occurs
myometrium: smooth muscle layer
perimetrium: serosa
parametrium: broad ligament
ectopic pregnancy: implantation occurs outside the uterus
e.g. uterine tube, abdominal cavity, cervix, ovary
the embryo cannot survive
if untreated the mother can die from bleeding
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Ligaments (6)
Broad ligament
Round ligament of uterus
Ovarian ligament
Suspensory ligament of ovary
Uterosacral ligament
Cardinal ligament
OVARIES
female gonad, equivalent to testis in males
site of maturation of egg
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ovulation is the expulsion of a mature oocyte from the ovary into the abdominal cavity
it is collected by the infundibulum (distal end) of the fallopian tube which has fimbriae
D1: menstruation
D1-5: endometrium sheds (unless fertilisation occurs) - period
D5: follicle & thecal cells proliferate & secrete estrogen causing uterus endometrial lining to
proliferate
D14: FSH + LH rise - causes ovulation, meiosis 1 completion
D14-28: follicle becomes corpus luteum & secretes progesterone + estrogen. endometrium secretory
phase = prep for implantation. no implantation - CL degenerates after 3 days
GnRH stimulates LH + FSH which stimulate testosterone production by interstitial Leydig cells
Activin stimulates LH + FSH, inhibin has opposite function
contraceptive pills contain estrogen/progesterone to mimic the secretory (luteal) phase to stop
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contraceptive pills contain estrogen/progesterone to mimic the secretory (luteal) phase to stop
ovulation
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15:59
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15:59
Placental Hormones
2. Estrogen
synthesized by syncytiotrophoblasts from androgenic steroid compounds
peak: end of pregnancy
effects:
enlargement of breasts, uterus & external genitalia
increased elasticity of pubic symphysis to allow relaxation of pelvic ligaments
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3. Progesterone
between WK 7 & 12, luteolysis leads to abortion
after WK 12, placental production of progesterone is sufficient
effects:
converts the endometrium to its secretory stage to prepare for implantation
inhibits maternal immune response so that it accepts the pregnancy
development of decidual cells
reduced uterine contractility
inhibits lactation during pregnancy - post-natal drop in progesterone levels triggers lactation
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5. Relaxin
synthesized by placenta & corpus luteum
effects:
decreased uterine muscular contractility
relaxation of pelvic ligaments (facilitating birth)
Parturition
expulsion of fetus, placenta & fetal membranes
labour: sequence of uterine contractions (dilatation of cervix)
Stages of Labour
dilatation of cervix
expulsion (delivery of baby)
placental separation (expulsion of placenta & fetal membranes)
labour takes longer for a first-time mother (primigravidas) than for a multigravidas
Breast Development
begins in puberty (estrogen)
final differentiation of the duct system is in pregnancy due to estrogen, GH, prolactin, adrenal
glucocorticoids, insulin
breasts grow in pregnancy due to increase in stroma & adipose tissue
progesterone stimulates development of the lobule-alveolar system
Lactation
prolactin is secreted by lactotrophs of ant. pituitary
hypothalamic regulator: dopamine
prolactin promotes secretion of milk
suckling causes 10-20x increase in prolactin secretion & triggers oxytocin secretion
secretion just prior to parturition: colostrum (contains antibodies, higher in protein & lower in fat than milk)
milk secretion is supported by GH, cortisol, PTH, insulin
milk ejection Is induced by contraction of myoepithelial cells in the alveoli due to the effects of oxytocin
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15:59
epiblast gives rise to endoderm, mesoderm, ectoderm & primordial germ cells
amniotic = dorsal
yolk sac = ventral (yolks go in your tummy)
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diagnostics
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diagnostics
chorionic villus sampling (WK 7)
biopsy of chorionic villi
guided by ultrasonography
slightly increased risk of miscarriage
amniocentesis (WK 12)
sampling of amniotic fluid by insertion of a needle through abdominal wall & uterus
guided by ultrasonography
Menopause
cessation of ovary function (oocyte development & release, estrogen secretion)
age 44-55
defined as 12 months w/o periods
low AMH level, high FSH level
transition is called perimenopause
sym: hot flushes, night sweats, vaginal dryness, incontinences, osteoporosis, CV dz, mood
change, insomnia, fatigue
therapy: hormone replacement, plant estrogen, herbal drugs
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18:35
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1. adenohypophyis
derived from oral ectoderm (Rathke's pouch) - "AARGHH feel my rath" he shouted from his mouth
pars distalis
pars intermedia
pars tuberalis
(DIT)
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cells in ant. PG
chromophils - stain readily by chromium salts
acidophils - stain red
somatotrophs - somatotropin aka growth hx
mammotrophs - prolactin
basophils - stain blue (hx that stimulate sex, adrenal & thyroid glands) - baseball is played on Saturdays
corticotrophs - ACTH
gonadotrophs - FSH, LH & hCG (human chorionic gonadotrophin)
thyrotrophs - TSH
chromophobes - don't stain by chromium
melanotrophs - melanocyte-stimulating hx
amphophils - epithelial cells
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2. neurohypophysis
derived from neural ectoderm (diencephalon) - N with N (di for the 2 N's)
connected to hypothalamus by median eminence via the infundibulum stalk
pars nervosa
infundibulum stalk
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cells in post. PG
pituicytes - stain dark purple in H&E
assist in storage & release of NH hx
glial cells similar to astrocytes in CNS
pituicytomas believed to be caused by pituicyte neoplasm
herring bodies
ADH & oxytocin storage (not simultaneous)
contains ADP & a neurophysin (binding protein)
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21:51
Thyroid
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Parathyroid
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chief (principal) cells - synthesis & release of parathyroid hormone which transports calcium from bone. They
appear purple when loaded w/ PT hx and pale when empty
oxyphil cells - unknown function. They appear red w/ a larger cytoplasm & similar nuclei to chief cells
adipocytes (fat cells) - large, white
Pancreas
similar histologically to parotid gland, distinguishable by presence of Islets of Langerhans
divided into lobules
the organ has exocrine & endocrine elements
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%
20
70
5
5
<1
secretion
glucagon
insulin, amylin
somatostatin
pancreatic polypeptide
ghrelin
Adrenal
2 distinct parts - cortex & medulla
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cortex
divided into 3 zones - GFR, like glomerular filtration rate
zona glomerulosa
zona fasciculata
zona reticularis
zone
glomerulosa
fasciculata
reticularis
secretion
mineralocorticoids e.g. aldosterone
glucocorticoids e.g. cortisol
androgens
basically
SALT
SUGAR
SEX
medulla
chromaffin cells are neuroendocrine cells that secrete catecholamines - adrenaline (80%) & noradrenaline
(20%)
the medulla often has large central veins
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02:16
MALE TISSUES
TESTIS
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the rete testis located in the mediastinum of the testes is an anastomosing network of delicated tubules that
carries sperm from the seminiferous tubules to the efferent ducts
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PENIS
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VAS DEFERENS
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EPIDIDYMIS
PROSTATE
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FEMALE TISSUES
OVARY
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UTERUS
has the thickest collection of smooth muscle in the female body
consists of >90% smooth muscle & vessels
inner endometrial lining
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endometrial glands secrete uterine fluid (histotrophe) on which the foetus depends for its few days
PLACENTA
consists of:
amnion
chorion
umbilical cord
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intraperitoneal
fertilisation occurs at the ampulla of the uterine tube
fimbriae have cilia for transporting the ovum from the ovary towards the ampulla
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