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Intro Lecture

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

CAL assessment are image-based MCQs covering histology, physiology, anatomy


Q's are on material covered THAT SESSION - prepare in advance
CALS
1. hypothalamus + pituitary
2. thyroid, parathyroid, adrenal, endocrine pancreas
3. testis, ovary + associated tissues
hospital visit WK8 (Vinnie's/Mater) - endo clinic
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hospital visit WK8 (Vinnie's/Mater) - endo clinic

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1. PC (10/9) - Endocrinology Overview


11 September 2014

18:31

exocrine - duct
eNDOcrine - NO Duct

main elements of endo system


endocrine glands
hormones
target tissues & cells
hormone receptors
2nd messengers

major endocrine glands

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

endocrine system vs. nervous system

integration of nervous & endo system

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integration of nervous & endo system

pos. feedback: the response reinforces the stimulus


e.g.

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neg. feedback: the response counteracts the stimulus


e.g.

Clinical Endocrinology

CAUSES

EXAMPLES

endocrine gland hyposecretion

genetic (rec/enz deficiency)


immunologic (autoimmune dz)
dietary (lack of iodine)
toxicity
other dz. e.g. cancer

ADH - diabetes insipidus


growth h. - pituitary dwarfism
thyroxine h. - cretinism, myxoedema
insulin - diabetes mellitus Type 1

endocrine gland hypersecretion

genetic (mutations)
tumours
immunologic

growth h. - giantism
parathyroid h. - cardiac arrhythmia, tetany

target cell hyposensitivity

hormone resistance

insulin resistance - diabetes mellitus Type 2

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target cell hyposensitivity

hormone resistance
genetic (rec/enz def.)
hormone antagonism
acquired

insulin resistance - diabetes mellitus Type 2

target cell hypersensitivity

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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2. PC (12/9) - Hypothalamus &


Post. Pituitary Glands
16 September 2014

23:27

hypothalamus & pituitary: the two most important endocrine glands in the body

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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)

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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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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

shiver runs up your spine which is posterior


opposite to posterior

oxytocin (lactation, parturition in labour,


cuddling)
ADH/vasopressin (water balance)
oxytocin & ADH

hydration & cuddling are SUPER good craic

preoptic medial - Pre Med


getting the ride - GRH is all about sex prep

Morgan Parra needs to be hydrated for matches, he also loves


cuddling (French)
circadian cycle by stimulating pineal gland to you need to get enough sleep to be in good form and
secrete melatonin
charismatic
stimulates peristalsis
you swallow your chewing gum before you open the door to a
class
satiety
when you're full you sort of exhale like a vent
hunger & thirst
late for college, miss breakfast, hungry
memory (episodic)
mamillary sounds like memory
dopamine (prolactin inhibiting factor) &
on Noah's ARK the animals needed reward-motivation
growth hx releasing hx (GHRH) release
(dopamine) & there was a lot of growth
analgesia
spicy Nando's peri peri chicken is hot and painful

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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

hypothalamic-pituitary-thyroid (HPT) axis - regulation of metabolism


HT releases thyrotopin-RH when thyroid hx levels are low
pituitary releases TSH
thryoid releases thyroxine (T4) & triiodothyronine (T3)
HPT - the HPAT income keeps me going just like metabolism keeps everything going

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pituitary gland embryology

ant. PG: oral ectoderm


post. PG: neural ectoderm

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3. TF (17/9) - Hypothalamic &


Pituitary Anatomy
16 September 2014

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

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pineal gland
located in the post. roof of 3rd ventricle
secretes melatonin - circadian rhythm modulation

position of the hypothalamus


3rd ventricle
ant. boundary: optic chiasm
post. boundary: mammillary bodies
sup. relation: thalamus
inf. relation: pituitary

hypophyseal portal system


portal system: capillary bed drains into another capillary bed via veins/venules
hypophyseal: system of blood vessels HT & ant. PG

fenestrated caps allow entry of factors into circulation


primary capillary plexus receives blood from sup. hypophyseal artery
portal veins carry blood to secondary plexus which supplies endocrine cells in the ant. lobe

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5 major cell types in ant. pituitary


corticotrophs (ACTH - adrenocorticotropic hx)
somatotrophs (GH)
lactotrophs (prolactin)
gonadotrophs (FSH & LH)
thyrotrophs (TSH)

post. pituitary stores ADH & oxytocin (not simultaneously) from the supraoptic & paraventricular hypothalamic
nuclei
these hormones are produced by magnocellular neurosecretory cells

examples of positive & negative feedback systems

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HT & PG related structures

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

internal carotid artery


supplies brain & eye

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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!"

FSH, LH & the hypothalamic-pituitary-gonadal axis


FSH acts on sertoli cells (testes) and granulosa cells (ovary)
LH acts on leydig cells (testes) and thecal cells (ovary)
both hx are necessary for normal fertility & repro
neg. feedback regulation by estrogen/testosterone/inhibin

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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5. PC (24/9) - Growth Hormone & Insulin


Like Growth Factor-I Axis
25 September 2014

00:11

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6. JL (1/10) - Thyroid Gland


Anatomy
26 September 2014

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

lymph drainage follows the arteries


STA - upper DCNs
ITA - lower DCNs
thyroid ima - pretracheal nodes
thyroid innervation is by branches of the sympathetic trunk
nerves do not influence endocrine secretion - hx release is regulated by the pituitary

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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

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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

development - derivations of pharyngeal aka branchial arches


inf. PT derives from dorsal aspect of pouch 3
sup. PT derives from dorsal aspect of pouch 4
upside down
WK 7: inf. & sup. PTs migrate b/w sternum (swapping position) & fuse
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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

A specialized organ of the immune system


It enlarges during childhood and atrophies in adolescence, over time degenerating into fatty tissue
Composed of 2 lateral lobes which may be united or separated
Max. weight approx. 40g at peak of development
Located in the ant. sup. mediastinum, situated partly in the neck & partly in the thorax

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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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the thymus also determines which T-cells to destroy in 2 ways


1. Positive Selection: the cell comes in contact with self-MHC expressed by thymic epithelial cells; those with
no interaction are eliminated
2. Negative Selection: the cell interacts w/ thymic dendritic cell whereby T cells with high affinity interaction
are eliminated through apoptosis to avoid autoimmunity and
those with intermediate affinity survive
central tolerance is the mechanism by which newly developing T-cells (and B-cells) are rendered non-reactive to
self
the thymus degenerates over time but residual T-lymphopoiesis continues throughout adult life.

Cells of the thymus


Thymus cells can be divided into
thymic stromal cells incl. cortical epithelial, medullary epithelial, dendritic
cells of hematopoeitic origin (derived from bone marrow) incl. T-cells
Hassall's corpuscles aka thymic corpuscles
found in the medulla
formed from eosinophilic type VI epithelial reticular cells
unknown function
v. visible in thymic histology

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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

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8. PC (8/10) - Thyroid
Physiology
08 October 2014

19:20

Thyroid Hormones

synthesized + secreted by thyroid gland follicular epithelial cells


the 2 active hormones are triiodothyronine (T3) & thyroxine (T4)
the 2 structures differ only by one atom
T3 is more active but T4 constitutes 90% of the hormonal output
target tissues can convert T4 to the more active T3
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target tissues can convert T4 to the more active T3


euthyroid = the state of having normal thyroid gland function
synthesis
the secretory cells are arranged in follicles
the lumen of the follicle contains colloid which is made up of newly synthesised thyroid hx attached to
thyroglobulin

thyroid hx synthesis is complex, w/ 3 unique features


1. iodine is essential - must be acquired in diet
2. synthesis is partially intracellular & partially extracellular
3. T4 is the major secretory product despite being less active than T3

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iodination at C3 & C5 positions of outer & inner rings of tyrosine produces T3/T4

Steps in thyroid hormone biosynthesis

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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

Regulation of thyroid hormone secretion

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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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exopthalmos = eye bulging


Thyroid hormones in circulation
most T3 + T4 circulate bound to plasma protein thyroxine-binding globulin (TBG) (higher affinity for T4)
some are bound to T4-binding prealbumin & albumin or transthyretin
a small amount (<1%) are free and therefore active
TBG's role is to act as a reservoir and release thyroid hx when required e.g.
in hepatic failure less TBG is produced, so free levels of thyroid hx transiently increases
in pregnancy high estrogen levels inhibits TBG breakdown in the liver so free levels of thyroid hx transiently
decreases
the change is transient b/c feedback systems restore normal levels
the T3 resin uptake test can measure levels of free thyroid hx

T4 activation in target tissues


enzyme 5' monodeiodinase converts T4 to T3 by removing one atom of iodine
target tissues also convert some T4 to reverse T3 (rT3) which is an inactive competitive inhibitor of T3
T3 & rT3 are usually produced in approx. equal amounts but this is altered depending on the tissue's thyroid hx
requirement
in starvation 5' monodeiodinase is inhibited in skeletal muscle to reduce O2 consumption but not in the brain so
T3 levels in the brain are protected even in caloric deprivation

Actions of thyroid hormones


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Actions of thyroid hormones


they act on virtually every organ system in the body

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

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thyroiditis is autoimmune destruction of the thyroid gland


it is the most common cause of hypothyroidism
antibodies either destroy the gland or block thyroid hx synthesis
a thyrotoxic crisis (thyroid storm) is a hypermetabolic state characterised by extreme hyperthyroidism
mortality rate is 10-50%

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

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9. PC (10/10) - Adrenal Gland


Physiology
13 October 2014

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

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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

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basically
SALT
SUGAR
SEX

structure of adrenocortical steroids


they are all chemical modifications of a basic steroid nucleus - a 21-carbon structure w/ 4 rings
mineralocorticoids: oxygen double-bond at C18
glucocorticoids: ketone group at C3 & hydroxyl groups a C11 + C21
androgens: oxygen double-bond at C17, lacking C20,21 side chain 19 carbons only (estrogen is only 18)

cholesterol: the precursor for all adrenocortical steroids


most is obtained via circulation but some is synthesised de novo in the adrenal cortex
adrenocortical cell membranes have lipoprotein receptors to facilitate endocytosis of cholesterol-lipoprotein
complexes
inside the cell cholesterol is esterified and stored in cytoplasmic vesicles
the enzymes catalysing the conversion of cholesterol to steroid hormones require cytochrome P-450, molecular
oxygen & NADPH
adrenodoxin reductase (flavoprotein) & adrenodoxin (iron-containing protein) are intermediates in the transfer of
hydrogen from NADPH to cytochrome P-450
the basis for the specialization of steroid synthesis of the 3 cortical zones is the presence or absence of particular
enzymes
e.g. zona glomerulosa can produce aldosterone b/c it has aldosterone synthase
the first step is always the conversion of cholesterol to pregnenolone, catalyzed by cholesterol desmolase, which is
stimulated by ACTH (adrenocorticotropic hormone)

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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

mineralcorticoid regulation (zona glomerulosa)


RAAS
angiotensin II stimulates the first and last steps of the aldosterone synthesis pathway
a decrease in ECF volume causes a decrease in renal perfusion pressure which increases renin secretion by
juxtaglomerular cells of the kidney
renin catalyses the conversion of angiotensinogen to angiotensin I (inactive)
angiotensin-converting enzyme catalyses the conversion of ATI to ATII which then acts in the adrenal cortex to
stimulate aldosterone secretion
aldosterone stimulates Na+ reabsorption in the kidney to restore ECF volume

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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
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aldosterone acts in the renal tubule to increase K+ secretion, restoring normal K+ levels

glucocorticoid & androgen regulation (zona fasciculata & reticularis)

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

e.g. Cortisol Awakening Response


the peak of ACTH secretion is just before waking so that there is a cortisol boost to help us out in the morning
shifting the circadian rhythm (e.g. changing time zone) alters the pattern
the suprachiasmatic nucleus in the hypothalamus regulates the circadian rhythm
the pattern is also influenced by light

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Actions of adrenocortical steroids


mineralocorticoids
aldosterone increases Na+ reabsorption and K+ and H+ secretion in the distal tubule of the nephron
these changes increase ECF volume & blood pressure
problem: the affinity of renal cell mineralocorticoid receptors for cortisol is the same as for aldosterone
solution: renal cell enzyme 11-hydroxysteroid dehydrogenase converts cortisol to cortisone (low receptor affinity)

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
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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

2. Addison's Disease: hypocortisolism / primary aldosterone deficiency


causes
symptoms
autoimmune destruction of adrenal cortex hypoglycemia
ACTH XS
hyperpigmentation

Page 56

treatment
steroid replacement

Page 57

3. Conn's Syndrome: Aldosterone XS


causes
aldosterone secreting tumours
adrenal hyperplasia

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)

catecholamines are stored in cellular vesicles (chromaffin granules)


main trigger for secretion is the SNS (splanchnic nerve)

Page 59

adrenaline & noradrenaline act via plasma membrane adrenoceptors (GPCRs)


multiple receptor subtypes, differential ligand binding affinities and different tissue distribution allow for tissue
specificity and multiplicity of action

NE = norepinephrine = noradrenaline
E = epinephrine = adrenaline
Bloody Yanks!

-adrenergic receptors preferentially bind noradrenaline


1 receptors found mainly in vascular smooth muscle, heart, and liver
effects: vasoconstriction, intestinal relaxation and pupillary dilation
2 receptors found in platelets, vascular smooth muscle, nerve termini, and pancreatic islets
effects: platelet aggregation and vasoconstriction

-adrenergic receptors preferentially bind adrenaline


1 receptors found mainly in the heart
effects: smooth muscle contraction
2 receptors found mainly in the lungs (and other sites)
effects: smooth muscle relaxation

Page 60

Pheochromocytoma is a tumour of chromaffin cells, causing:


severe hypertension
hyperglycaemia
metabolic rate
arrhythmias
anxiety

Page 61

10. PC (15/10) - Endocrine


Pancreas & Glucose
Homeostasis
15 October 2014

18:16

the pancreas is 98% exocrine and 2% endocrine


the functional cells of the endocrine portion are arranged in clusters called the islets of Langerhans

Page 62

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

Structure & synthesis


insulin is a peptide hormone consisting of 2 straight chains
A chain (21 amino acids)
B chain (30 amino acids)
chains are linked by 2 disulfide bridges
a third disulfide bridge is located w/in the A chain
a gene on Chr. 11 directs synthesis of preproinsulin which contains 4 peptides: signal peptide, C-peptide and A+B
chains
the signal peptide is cleaved to from proinsulin
then the C-peptide is cleaved to form insulin
Page 63

then the C-peptide is cleaved to form insulin

proinsulin cleaved to insulin

Regulation of insulin secretion

the most important regulatory factor is blood glucose concentration


insulin's role is to transport glucose from blood to body cells
so more blood glucose triggers more insulin secretion
Page 64

so more blood glucose triggers more insulin secretion

1. transport of glucose into cell by facilitated diffusion via GLUT 2 transporter


2. phosphorylation: glucose is phosphorylated to glucose-6-phosphate by glucokinase
3. oxidation: glucose-6-phosphate is oxidized, producing ATP
4. ATP-sensitive K+ channels close due to increased intracellular ATP
5. depolarization of the cell membrane due to increased intracellular K+
6. voltage-gated Ca2+ channels open by depolarization
7. Ca2+ enters the cell
8. insulin secretion by exocytosis is stimulated by increased intracellular Ca2+
oral glucose is a more powerful stimulant than intravenous glucose b/c oral glucose also stimulates the secretion of
glucose-dependent insulinotropic peptide (GIP) which has an independent stimulatory effect on insulin
sulfonylurea drugs block K+ channels (step 4), mimicking the effect of glucose, can be used to treat DM2

insulin increases blood glucose entry into cells by directing GLUT 4 transporters to the cell membrane

Page 65

Mechanism of action of insulin


1. insulin binds to the subunits of the tetrameric insulin receptor on target cells
2. the receptor conformational change activates tyrosine kinase in the subunits, and they autophosphorylate
3. activated tyrosine kinase phosphorylates several other proteins involved in the physiologic actions of insulin
4. the insulin-receptor complex is endocytosed and degraded, also down-regulating its receptor

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

solid line indicates stimulation


dashed line indicates inhibition

Pathophysiology of insulin: diabetes mellitus


Type 1: autoimmune destruction of islet cells reduces insulin secretion
Type 2: down-regulation of insulin receptors in target tissues & insulin resistance blocks action of insulin

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

Page 67

Structure & synthesis


single straight chain polypeptide (29 amino acids)
initially synthesised as preproglucagon before cleavage

Regulation of secretion

the major stimulus, as with insulin, is blood glucose levels


both SNS & PSNS nerves stimulate glucagon secretion

Actions

Page 68

Glucose Homeostasis
exceptionally important b/c the brain virtually uses only glucose for its energy

Key pathways in glucose metabolism


glycogenesis: making glycogen from glucose for storage (after feeding - "postprandial")
glycogenolysis: breaking down glycogen to provide glucose (between meals/asleep/sudden exercise)
gluconeogenesis: making new glucose from non-carb sources
glycolysis: breaking down glucose for energy

Glycogen is just a big polymer of glucose w/ a protein core called glycogenin

Page 69

2 important antagonistic enzymes in glycogen metabolism


glycogen phosphorylase (GP) - degrades glycogen
glycogen synthase (GS) - synthesis glycogen

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

Page 70

euglycemia is a balancing act b/w opposing hormonal & biochemical actions

The Incretin Effect


incretins are a group of cheeky gastrointestinal hormones that stimulate insulin secretion by cells immediately after
eating (postprandial) in anticipation of elevated blood glucose levels
this gets the insulin mobilised early and avoids requiring a sudden burst of it
this is why oral glucose is a more potent insulin-stimulant than intravenous glucose
scouts who forewarn the islet cells about an approaching meal

e.g. Glucagon Like Peptides (GLP-1)


synthesised in the ileum & colon
enhance insulin release (insulinotropic) and suppress glucagon release
inhibits gastric emptying
acts as a satiety factor
Page 71

acts as a satiety factor


enhances hepatic & skeletal muscle insulin sensitivity

incretin action is impaired in DM2


targeted in DM2 therapeutics

Page 72

11. PC (22/10) - Calcium &


Phosphorus Homeostasis
22 October 2014

16:21

Why do we need calcium & phosphate inorganic ions?


1. calcium phosphate salts in bone provide structural integrity to the skeleton
2.

Ca2+ ions in many biochemical processes


neuromuscular excitability
blood coagulation
hormonal secretion
enzymatic regulation
cell signalling

3. PO43- in cellular processes e.g. signal transduction


4.

PO43- ions in structural roles


DNA/RNA
membrane phospholipids
ATP & creatine phosphate
complex carbs

Page 73

hypocalcemia = low plasma Ca2+


membrane Na+ permeability
nerves & muscles become over-excitable
tetany (involuntary muscle spasm)
Trousseau's sign of latent tetany is an early indicator of hypocalcemia

hypercalcemia = high plasma Ca2+


neuromuscular sensitivity
cardiac arrhythmia
groans (constipation)
moans (fatigue, lethargy)
bones (bone pain)
stones (kidney stones)
calcium in the body
99% in the skeleton (hydroxyapatite)
1% extraskeletal (rapidly exchangeable w/ ECF/plasma)
0.9% intracellular
0.1% extracellular
50% bound
50% free ionised
phosphorus in the body
total body phosphorus = 0.6kg
80% in skeleton
15% in soft tissue (muscles)
5% in plasma

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

bone composition & structure

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+

bone remodelling: ongoing process of resorption & formation


rates are usually in equilibrium
relative activity of blasts vs. clasts determines if there is net bone gain/loss
these cells are targets for endocrine & paracrine regulators of Ca2+ homeostasis
Page 75

these cells are targets for endocrine & paracrine regulators of Ca2+ homeostasis

blasts are in charge (the BOSS)


they produce 2 important mediators of clast development
1. RANKL (receptor activator of NFK ligand)
member of TNF cytokine superfamily
binds to RANK receptor on macrophages and promotes differentiation into clasts and their survival (antiapoptotic
meaning preventing apoptosis)
bone resorption, bone mass
2. OPG (osteoprotegerin)
soluble inhibitor/decoy receptor for RANK
bone resporption, bone mass

2 methods of Ca2+ release from bone


Page 76

2 methods of Ca2+ release from bone


1.

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-

3 principal hormones regulate Ca2+ and PO43- levels


parathyroid hormone
calcitonin
calcitriol (1,25-dihydroxy Vit D3)
they regulate levels in
bone (osteocytic osteolysis & osteoclastic resorption)
kidney (reabsorption)
intestine (absorption)

Parathyroid Hormone (PTH)


synthesised and secreted by calcium-sensing chief/principal cells of parathyroid glands
actions mediated by PTH receptor
Type 1: kidney + bone
Type 2: CNS, pancreas, testes + placenta
increases blood Ca2+ levels
PTH related peptide protein (PTHrP) has actions similar to PTH
minor role in Ca2+ homeostasis
secreted by many tumours (hence hypercalcemia in malignancy)

Page 77

Calcium Sensing Receptor (CaSR)


GPCR found on chief cells & other calcium sensitive cells
detects [Ca2+] and stimulates/inhibits PTH secretion accordingly via second messenger system

PTH: Physiological role


overall action: prevent/reverse hypocalcemia by increasing free plasma Ca2+ levels
Ca2+
PO43-

acts directly on bone


Ca2+ release
acts directly on kidney (distal tubule) Ca2+ reabsorption & PO43- reabsorption
acts indirectly on intestines
stimulates calcitriol synthesis which increases Ca 2+ absorption

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
Page 79

Vit D3 hydroxylated in liver to yield 25(OH)D3 aka calcidiol


2nd hydroxylation rxn in kidney yields 1,25(OH)2D3, catalysed by 1 hydroxylase
1 hydorxylase activity is regulated by:
feedback inhibition (1,25(OH)2D3)
PTH
hypophosphatemia
prolactin

Vit D in the Intestines


promotes intestinal Ca2+ and PO43- absorption
calcium
absorbed via vesicular & transcellular transport
net absorption: 200g/day
major site: duodenum
facilitated/active transport into enterocytes is via specific Vit D-dependent Ca2+ transporter (TRPV5/6)
Ca2+ is bound by high affinity binding protein calbindin 9k
binds 2 Ca2+ ions, lowers free intracellular Ca2+
maintains favourable Ca2+ gradient across apical memb. thus promoting absorption
some Ca2+ is stored in cell organelles but most is pumped out by Ca2+ pump and Na+/Ca2+ exchanger
phosphate
absorbed via transcellular transport
Na+ / PO43- co-transporter (NPT2)
less Vit D dependent than Ca2+
downregulated by PTH

Page 80

Vit D action on Bones


osteoblasts have Vit D receptors, osteoclasts do not (remember, blasts are the boss)
stimulates osteoclastegenesis leading to increased ca release from bone
stimulates osteocytic osteolysis
inhibits osteoblast collagen synthesis
bone formation requires Vit D
deficiency leads to XS osteoid (immature bone)
rickets = disease of bone deformation

Page 81

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

asymptomatic (elevated calcium on routine labs)


history kidney stones
unexpected fracture/osteopenia/osteoporosis

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

12. PC (24/10) - Type 1


Diabetes
24 October 2014

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

Page 84

Type 1 Diabetes Mellitus


aka insulin-dependent
accounts for 5-10% of cases
usually early onset but can develop in adults
caused by autoimmune destruction of insulin-producing pancreatic islet cells
only tx is lifelong insulin replacement therapy

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)

Page 85

Acute metabolic complications


hyperglycemia
ketoacidosis
iatrogenic hypoglycemia
long-term vascular complications
Fundamental defects
insulin deficiency
reduced entry of glucose into peripheral tissues
hyperglycemia
increased hepatic glucose production and release into circulation, exacerbating the situation of extracellular
glucose XS and intracellular glucose def. - "starvation in the midst of plenty"
disturbances in carb, protein & lipid metabolism
permanent catabolic state

Page 86

ketogenesis & ketoacidosis


complete insulin def. causes unrestrained lipolysis in adipose tissue ( fatty acid levels)
increased oxidation of FAs in the liver generates XS acetyl CoA, some of which is diverted from TCA cycle into
ketone body production
acetoacetate
-hydroxbutyrate
ketonuria = ketone bodies in urine
glycosuria = glucose in urine
grossly elevated ketone body levels causes plasma to become hyperosmolar

diabetic ketoacidosis (DKA)


the burning of fatty acids and production of acidic ketone bodies due to a shortage of insulin
predominantly seen in T1DM but sometimes in T2DM
15% of all diabetes hospital admissions
pear-like odour on breath
respiratory compensation of metabolic acidosis involves hyperventilation to excrete more acidic CO2 (Kussmaul
respiration)

Page 87

Page 88

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

Page 90

Page 91

13. PC (29/10) - Type 2


Diabetes
02 November 2014

00:58

relative insulin deficiency w/ peripheral insulin resistance


genetic susceptibility (polygenic)
lifestyle risk factors - physical inactivity, obesity

characterised by disorders of carb, lipid & protein metabolism


hyperglycemia
HONK/HHS (hyperosmolar non-ketosis or hypersomolar hyperglycemic state)
ketonemia/ketonuria (ketone bodies in the blood/piss)
glucosuria aka glycosuria
dyslipidemia
classic symptoms (the big 3)
polydipsia (thirsty)
polyphagia (hungry)
polyuria (need a piss)

Page 92

Diagnosis of DM

Page 93

glucotoxicity is the damage by glucose of body cells


it can cause DM either by damaging cells (type 1) or contributing to insulin resistance by affecting the insulin
receptors of peripheral cells type 2)

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%

android vs. gynoid fat distribution


a for android, a for apple, a for active

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

natural course of T2DM

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)

Page 96

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

Page 97

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"

Page 98

14. SK (5/11) - Development of Gonads


06 November 2014

15:57

Page 99

15. SK (7/11) - Anatomy of the


Schlong
06 November 2014

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

Page 101

3 longitudinal cylinders of erectile tissue


central corpus spongiosum
lateral corpora cavernosa x 2

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
Page 102

midline septum creates left + right compartments

muscles of the scrotum


walls contain a smooth dartos muscle & fascia - it takes big balls to be good at darts
the cremaster muscle suspends testes - nuff said

supply of scrotum (different to its contents)


BS: ext. + int. pudendal arteries, ext. pudendal veins
NS: ant. + post. scrotal nerves
LS: sf inguinal lymph nodes

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

Page 103

septae divide each testis into 250-300 lobules


each lobule contains 1-4 sperm-producing seminiferous tubules
seminiferous tubules from each lobule converge to form tubulus rectus that conveys sperm to posterior rete testis
sperm travels from rete testis to efferent ductules to epididymis
Sertoli cells produce Sperm
Leydig cells produce testosterone - testosterone overload will make you give someone a dig

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

Page 104

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
Page 105

begins at deep inguinal ring


through inguinal canal
through sf inguinal ring
terminates in scrotum

3 fascial layers of cord from 3 layers of abdominal wall


internal spermatic fascia from transverse fascia
cremasteric fascia from internal oblique fascia
external spermatic fascia from external oblique fascia
it makes sense just think about it

Disorders of the balls

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
Page 106

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
Page 107

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!

Vas deferens supply


BS: branch of either vesical artery, drainage into vein of ductus deferens
NS: inf. hypogastric nerve plexus

Page 108

Seminal vesicle (gland)


2 x elongated ducts b/w base of bladder & rectum
covered superiorly by pelvic peritoneum (infraperitoneal)
produces much of the seminal fluid
supply: inf. vesical + middle rectal vessels

Bulbourethral gland aka Cowper's


2 x pea-sized exocrine glands
homologous to Bartholin's glands in bitches
located posterolateral to membranous urethra
Page 109

located posterolateral to membranous urethra


2.5cm long duct opens into spongy urethra at base of schlong
during sexual arousal each gland produces pre-ejaculate (clear viscous secretion) for:
lubrication of urethra for sperm passage
neutralising residual piss
flushing away foreign matter

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

traversed by prostatic urethra and by both ejaculatory ducts


these 3 structures and fibrous septae divide prostate into:
medial lobe
lateral lobes x2, separated in midline by sulcus
anterior lobe
posterior lobe

Page 110

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

Page 111

Page 112

16. SK (12/11) - Anatomy of


the Clunge
06 November 2014

15:58

the shape of the external os changes after parturition

Page 113

Page 114

Page 115

VULVA (EXTERNAL GENITALIA)


aka the pudendum

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

distensible muscular tube


7-9 cm long
passes thru pelvic floor aka pelvic diaphragm
extends posteriorly and superiorly from the vestibule of the vulva to the cervix
the fornix is where the superior part of the vagina overlaps w/ the cervix
there is a posterior, anterior & lateral fornix, b/c the fornix is your PAL

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functions of the vagina


1. riding
2. childbirth
3. periods
relations
anterior: bladder, urethra
posterior: rectum, anus
laterally: ureter, uterine artery

Page 118

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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fertilisation occurs at the ampulla of the uterine tube


the zygote is moved to the uterus via the uterine tube by cilia where it implants on the wall
then the little fucker grows into a human being - weird

Page 120

the rectouterine pouch is larger than the vesicouterine

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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anteverted means lying over the bladder


anteflexed means bent forward

Page 122

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
Page 124

contraceptive pills contain estrogen/progesterone to mimic the secretory (luteal) phase to stop
ovulation

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17. SK (14/11) - Male Reproductive Physiology


06 November 2014

15:59

Page 126

18. SK (19/11) - Female


Reproductive Physiology
06 November 2014

15:59

Placental Hormones

1. Human Chorionic Gonadotropin (HGC)


synthesized by syncytiotrophoblasts
peak WK 10-12
used in pregnancy test
effects:
persistence of corpus luteum (and progesterone secretion)
prevents menstruation
development of decidual cells (part of the decidua which is the mucous memb. of the uterus after
fertilization has occurred)
production of testosterone on the fetal testes

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

4. Placental Lactogen (Human Chorionic Somatomammotropin)


secreted from WK 5 onwards
effects:
breast development
decreased insulin sensitivity / glucose utilization in the mother so that more glucose is available for the
fetus
release of fatty acids in the mother
promotion of fetal growth

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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)

induced by hormonal cascade


CRH (fetal hypothalamus)
ACTH (fetal pituitary)
cortisol (fetal adrenal cortex)
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cortisol (fetal adrenal cortex)


estrogen (placenta)
prostaglandins
oxytocin (maternal pituitary)
labour

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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Page 131

19. SK (26/11) - Pregnancy


06 November 2014

15:59

fertilisation occurs in ampulla of uterine tube


200 (capacitated) of 300million sperm reach fertilisation site
1. migrate through corona radiata (follicular cells)
2. penetrate zona pellucida (glycoprotein layer) using acrosome enzymes
3. move through perivetilline space
4. fuse to oocyte plasma membrane
after penetration ZP becomes impermeable to other sperms
second meiotic division of oocyte completes after fertilisation (transformation from secondary
oocyte to ovum)
still in s. oocyte form @ ovulation
post-fertilisation
first few cleavages very slow (1 per day)
maternal proteins distributed in cytoplasms in polarised manner @ first cleavage - accidental
separation produces identical twins
Page 132

day 4: 8 cells = morula (compact ball)


tight jns stabilise structure
gap jns enable passage of small mols + ions b/w cells

day 6/7: blastocyst


blastocoel = cavity in blastocyst
inner cell mass will become embryo
trophoblast will become extraembryonic tissues
day 8/9: implantation
blastocyst attaches to endometrium on ICM side
inner cell mass becomes epiblast (endometrium side) + hypoblast (blastocoel side)
trophoblast becomes synctiotrophoblast (invades EM, forms part of placenta) +
cytotrophoblast (surrounds BC)
you throw the placenta in the sink after birth
cavity on EB side - amniotic cavity
blastocoel becomes yolk sac

endometrium side: epiblast, synctiotrophoblast, amniotic cavity


blastocoel side: hypoblast, cytotrophoblast, yolk sac
embryonic disc = epiblast + hypoblast
basic field for embryo formation
epiblast gives rise to endoderm, mesoderm, ectoderm & primordial germ cells
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epiblast gives rise to endoderm, mesoderm, ectoderm & primordial germ cells
amniotic = dorsal
yolk sac = ventral (yolks go in your tummy)

chorion = wall of trophoblast-derived cells


continuous to placenta tissue
later forms sac outside amnion + yolk sac
twins
monozygotic: common placenta (separate/common amnions depending on time of split)
dizygotic: separate placentae

The Fetal Membranes


amnion: surrounds the fetus, increases in size during pregnancy, mechanical protection
chorion: smooth & villous parts

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diagnostics
Page 135

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

ethics of pre-implantation diagnostics (PID) in IVF


pro: only healthy embryos are transferred to the uterus, fewer abortions
contra: "design your own baby" - eugenics

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

Page 136

Page 137

CAL 1 (9/9) - Pituitary Gland


11 September 2014

18:35

pituitary gland (hypophysis) is located on the sella turcica ("Turkish saddle")

it is divided into the


anterior lobe (adenohypophysis) (90%)
posterior lobe (neurohypophysis) (10%)
intermediate lobe (indistinct in humans, distinct in other animals)
The two parts differ in function & histology
AH synthesizes & secretes hx
NH secretes hx that are synthesized by the hypothalamus

H&E Staining: adeno dark pink, neuro pale pink

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Page 139

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)

Page 140

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

Page 142

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)

Page 143

CAL 2 (14/10) - Thyroid,


Parathyroid, Pancreas & Adrenal
Glands
13 October 2014

21:51

Thyroid

follicular cells produce thyroid hormone


parafollicular cells (C-cells) produce calcitonin - transports calcium to bone
follicular epithelium is simple, non-stratified
follicles are separated by septae
vascularised CT surround follicles and contains parafollicular cells

Page 144

Parathyroid

Page 145

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

Page 146

acinar cells (exo)


the exocrine portion is divided into lobules which contain acini
exocrine acini contain many zymogen granules
acini produce and secrete pancreatic fluid which contains enzymes required for digestion in the duodenum
an acinus consists of 5-10 cells w/ peripheral nuclei
secretory cells surround an intercalated (intralobular) duct
centroacinar cells have no granules, they mark the beginning of a duct, they also secrete bicarbonate
ducts can be intra/interlobular and epithelium is cuboidal/columnar

Page 147

islet cells (endo)


these cell clusters produce and secrete hormones
granules are not as prominent as in acini
small round nuclei
paler appearance
cell types are difficult to distinguish by appearance
cell type
alpha
beta
delta
PP (gamma)
epsilon

%
20
70
5
5
<1

secretion
glucagon
insulin, amylin
somatostatin
pancreatic polypeptide
ghrelin

Adrenal
2 distinct parts - cortex & medulla

Page 148

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

Page 149

Page 150

CAL 3 (11/11) - Male &


Female Reproductive Tissues
10 November 2014

02:16

Male Reproductive Tissues


1. Testis
2. Penis
3. Vas deferens
4. Epididymis
5. Prostate
Female Reproductive Tissues
1. Ovary
2. Uterus
3. Placenta
4. Uterine Tube

MALE TISSUES
TESTIS

seminiferous tubules make up the majority of the parenchyma


Sertoli cells aka sustentacular cells are w/in seminiferous tubules - sperm-producing
Leydig cells are in the interstitium b/w tubules - testosterone-producing

Page 151

the fibrous capsule consists of:


tunica vaginalis (outer, thinner)
tunica albuginea (inner, thicker)

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

Page 152

PENIS

Page 153

erectile tissue consists of:


corpus cavernosum x 2
corpus spongiosum x 1 - there's only one spongebob squarepants
spongiosum contains the urethra - there is 1 of each
the corpora are separated by the tunica albuginea

penile arteries of the corpus cavernosum engorge w/ blood to produce an erection

Page 154

VAS DEFERENS

Page 155

epithelium: pseudostratified columnar (all cells make contact w/ basement membrane)


veins are relatively thick-walled so could be mistaken for arteries
muscle layers (from out to in)
skeletal striated
smooth longitudinal (round nuclei)
smooth circular (spindley nuclei)
smooth longitudinal

Page 156

EPIDIDYMIS

there is no spermatogenesis - only sperm maturation


the epididymis microscopic structure is simpler than the testis
epithelium is pseudostratified, tall, non-columnar
stereocilia are like a more precise, structured version of normal cilia

PROSTATE

Page 157

the prostate is surrounded by a fibrous capsule


mainly made up of prostate glands
they are separated from each other by septae of CT
vast majority of nuclei do not have nucleoli
indications for prostate ca.
no septae b/w glands
nucleoli in many nuclei
prostate glands surrounding nerves
corpora amylacea aka amyloids are accumulations of dense amounts of calcified materials
with age, prostate secretions become more calcified (concretions)

Page 158

FEMALE TISSUES
OVARY

Page 159

development of oocytes (ova)


primordial follicle = oocyte w/ squamous epithelium
primary follicle = oocyte w/ columnar/cuboidal epithelium
secondary follicle = oocyte w/ zona pellucida, surrounded by granulosa cells
Graafian follicle = oocyte w/ separating granulosa cells & large antrum

Page 160

an atretic follicle degenerates before reaching maturity

UTERUS
has the thickest collection of smooth muscle in the female body
consists of >90% smooth muscle & vessels
inner endometrial lining

Page 161

endometrial glands secrete uterine fluid (histotrophe) on which the foetus depends for its few days

PLACENTA
consists of:
amnion
chorion
umbilical cord

Page 162

the chorion is made up of villi

the deciduum is the mucous memb. layer lining the uterus

cytotrophoblasts & syncytiotrophoblasts

Page 163

umbilical cord aka placental cord

UTERINE (FALLOPIAN) TUBE

Page 164

intraperitoneal
fertilisation occurs at the ampulla of the uterine tube
fimbriae have cilia for transporting the ovum from the ovary towards the ampulla

Page 165

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