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Table Of Contents:

What’s included: Ready-to-study anatomy, physiology and pathology notes of the endocrine system
presented in succinct, intuitive and richly illustrated downloadable PDF documents. Once downloaded,
you may choose to either print and bind them, or make annotations digitally on your iPad or tablet PC.

File List:

• Overview of The Endocrine System

• The Hypothalamo-Pituitary Axis
• Thyroid Function
• Insulin, Glucagon & Regulation of Metabolism
• Fluid & Electrolyte Balance
• Calcium & Phosphate Metabolism
• Physiological Response to Stress
• Reproductive Endocrinology
• ADH Disorders
• Adrenal Cortex Dysfunction
• Adrenal Medulla Dysfunction
• Calcium & Phosphate Imbalance Disorders
• Diabetes
• Diabetic Emergencies
• Gonadal Dysfunction
• Growth Dysfunction
• MENS Multiple Endocrine Neoplasia Syndrome
• Pituitary Dysfunction
• Thyroid Dysfunction
• Free bonus: ‘Endocrinology’ chapter of Toronto Notes for reference and further detailed reading.

 System: Endocrinology

Endocrinology:
- Endocrinology: The scientific study of Hormones (Chemical Messengers) and the endocrine organs.
- Endocrine system maintains Homeostasis in coordination with the nervous system.

Families of Chemical Messengers:

- Amino Acid Derivatives:
o Catecholamines (Eg. Adrenaline, Nor-Adrenaline & Dopamine) (Derived from Tyrosine)
o Histamine (Derived from Histidine)
o All Thyroid Hormones (Derived from Tyrosine)
- Proteins:
o All Pituitary Hormones
- Steroids:
o Sex Hormones (Derived from Cholesterol)
- Fatty-Acid Derivatives:
o Prostaglandins
o Thromboxanes
o etc.
- Purines
- Gases:
o Eg. Nitric Oxide.
- Acetylcholine

What is a Hormone?
Long distance chemical signals secreted by endocrine glands into the extracellular fluids
Travel in blood or lymph throughout the body.
ARE BIOLOGICALLY SPECIFIC: Interact with specific receptors of specific cells of specific target organs.
Either AMINO ACID BASED OR STEROIDS (cholesterol based) Mostly amino acid based.
o Only gonadal & adrenocortical hormones are steroids
Travel in blood or lymph throughout the body.

Synthesis of Chemical Messengers:

- Steroidogenesis:
o All steroid hormones are derived from Cholesterol.
o There are 5 Families of Steroids, each with their main physiological member:
Progestagens (Progesterone)
Androgens (Testosterone)
Mineralocorticoids (Aldosterone)
Glucocorticoids (Cortisol)
Oestrogens (Oestrogen)
- Protein/Peptide Synthesis & Processing:
o Synthesis of polypeptide hormones can be more complex than Transcription & Translation.
o Some Protein Hormones are initially synthesised as longer Pre-Prohormones.
o These Pre-Prohormones are then cleaved, leaving Prohormones.
o These Prohormones are then cleaved again, leaving active Hormones.

[Link]
R a P C a M
- Biological Specificity: Certain Chemical Messengers will only fit into certain receptors.
- Affinity: The degree to which a chemical is attracted towards a receptor.
- Efficacy: The degree of effectiveness of the binding of the messenger to the receptor.
- A Chemical Messengers with High Affinity & High Efficacy.
- A a Chemical Messengers with High Affinity but Low Efficacy.
NB: There are no Endogenous Receptor-Antagonists, Only Exogenous (Drugs)
- Hormone Binding Proteins: Proteins that inactivate hormones by binding to them, limiting Bioactivity.
- Epitope: An Immunologically active binding site on a protein to which an antibody can
attach.

Endocrine (diffuse) Glands:

- Endocrine Glands are Ductless and secrete by Exocytosis into the Extracellular Fluid Diffuses into Blood.

Classical Endocrine Glands:

Pineal gland
Hypothalamus
Pituitary gland
Thyroid gland
o Parathyroid glands (dorsal aspect of thyroid gland)
Thymus
Adrenal glands
Pancreas (has exocrine in parts)(endocrine part secretes insulin)
Gonads: Testes/Ovaries (also exocrine)

Long or Short Range?

Endocrine: Some signals are broadcasted thro gho t the entire bod ia bloodstream Hormones
(produced by endocrine cells) [TV]
Autocrine: Signals that affect only cells of the same cell type as the emitting cell. [doctor conference]
Paracrine: Signals (aka local mediators) that act on cells in the vicinity of the emitting cell but on different
cell types than the emitting cell. [Lecture]

[Link]
2 Main Receptor Types: (Intracellular & Membrane-bound Receptors)
Intracellular Receptors:
o Lipid-soluble hormones (steroid/thyroid hormones) & even gasses (nitric oxide-blood vessel
dilation)
Steroid hormones bind to receptor proteins in the cytosol or the nucleus that regulate
gene expression.

Plasma-Membrane-Bound-Receptors:
o Most signal molec les can t cross the plasma membrane of the target cell
o Most intracellular signalling proteins act as molecular switches activated by either
phosphorylation OR GTP-Binding (swapping a GDP for a GTP)
o 3 Types:
Ion-Channel-Linked Receptors
Resulting signal is a flow of ions across the membrane produces an electric
current.
Enzyme-Linked Receptors
o When activated act as enzymes or are associated with enzymes inside the
cell.
G-Protein-Linked Receptors (more common)
o Binds to a class of membrane-bound GTP-Binding-protein (G-Protein)
becomes activated and released to migrate across the membrane, initiating a
cascade of other effects.
o Some G-Proteins directly regulate ion channels in the plasma membrane.
o Other G-Proteins activate membrane-bound enzymes. Eg. adenylyl-cyclase
increases the [second messenger (cyclic-AMP)] activates an intracellular
signalling protein (eg. A protein kinase) OR turns on genes via activated
P K a A PKA .

Tissue Responsiveness:
- Receptor Downregulation:
o Where a decreased receptor density in the membrane decreases the responsiveness of that cell to
that receptor s stim li
o This is achieved by Internalising the receptor-ligand complex, dissociating the ligand, and recycling
the receptor back to the surface.

- Receptor Desensitisation:
o Where a change in receptor structure decreases the responsi eness of that cell to that receptor s
stimuli.
o Why? To prevent multiple, rapid stimulations.

[Link]
Regulation of Hormone Release:
- 3 Mechanisms:
o 1. Humoral:
Where the concentration of a solute in the blood (Eg. High Glucose/Low Calcium) is
detected by a specific gland, stimulating hormone release (Eg. Insulin/Parathyroid
Hormone)
o 2. Neural:
Where the Nervous System Directly stimulates hormone release.
Eg. Sympathetic NS Activated Stimulates Adrenal Medulla Secretes Catecholamines.
o 3. Hormonal:
Where one hormone stimulates the release of another hormone from a different cell.
Eg. The Hypothalamus secretes hormones Stimulate Ant. Pituitary Secretes
Hormones.
Eg. The Ant. Pituitary secretes Hormones Stimulate other organs to secrete hormones.

FEEDBACK:
Negative:
o Most common
o Maintains levels around a stable intrinsic/preset level.
o Involved in homeostatic control.
Positive:
o Uncommon
o Unstable mechanism
o Stopped by removal of initial stimulus.

Levels of Feedback Loops:

- Feedback ma occ r at man different le els ithin a single H pothalamo-Pituitary-Target a is
o Ultra-Short Loop:
Autocrine Feedback - The secreted hormone feeds back to the same tissue that secreted it.
Eg. A Hypothalamic Hormone feeds back to the Hypothalamus.
o Short Loop:
The secreted hormone feeds back to the tissue that stimulated its secretion.
Eg. The Hormone secreted by the Target Organ feeds back to the Pituitary.
Or. The Hormone secreted by the Pituitary feeds back to the Hypothalamus.
o Long Loop:
The hormone secreted by the target organ feeds directly back to the Hypothalamus.

[Link]
Endocrine Disorders:
- Level-Of-Function Disorders:
o Hypofunction Disorders:
Where the gland produces less than it should.
Common Causes:
Loss of reserve
Hypo-secretion
Agenesis failure to develop embryonicaly
Atrophy Wasting away due to injury/disease/lack of use.
Active Destruction
Tumour
o Hyperfunction Disorders:
Where the gland produces more than it should.
Common Causes:
Hyper-secretion
Loss of suppression
H perplasia Proliferation
Neoplastic Change (Tumour)
Hyperstimulation
Ectopic Sites of Secretion (Some far-off tumours secreting hormone)

- Hierarchical Classification of Hypothalamo-Pituitary Axis Disorders:

o NB: Endocrine disorders of the Hypothalamo-Pituitary Axis are often classified in a Hierarchical
Fashion depending on the origin of the disorder:
o Primary:
Disorder of the Target Gland
(eg. Primary Hypothyroidism the Thyroid Gland itself is under-responsive to TSH
stimulation)
o Secondary:
Disorder of the Pituitary Gland
(eg. Secondary Hypothyroidism the Pituitary Gland is under-producing TSH)
o Tertiary:
Disorder of the Hypothalamus
(eg. Tertiary Hypothyroidism the Hypothalamus is under-producing TRH)

Testing for an Endocrine Disorder:

- Basal Hormone Testing:
o A single snapshot measurement of the concentrations of specific hormones.
Eg. High [Thyroid-Stimulating Hormone] Therefore Primary Hypothyroidism.
o Problem Some secretions are Pulsatile meaning random meas rements don t acc ratel
diagnose a disorder of that gland. The Solution: Dynamic Hormone Testing.
- Dynamic Hormone Testing:
o Using exogenous chemicals/hormones to Stimulate/Suppress activity of a target gland. This tests
the responsiveness of a target gland to feedback stimuli.
Suppression Tests:
When Hyperfunction is suspected, an inhibitor is administered and then the
hormone concentration is re-measured to see if it has decreased. If not,
Hyperfunction is confirmed.
Stimulation Tests:
When Hypofunction is suspected, a stimulator is administered and then the
hormone concentration is re-measured to see if it has increased. If not,
Hypofunction is confirmed.

[Link]
Typical Endocrine Symptoms:
- Diabetes (1 & 2):
o Weight Change
o Polyuria, Nocturia & Thirst
o Visual Disturbances
o Infections & Immunosuppression
o Constant Hunger
o Nausia + Vomiting
o Fatigue
o DKA (Diabetic Ketoacidosis) = Emergency Presentation
- Hyperthyroidism:
o Weight Loss
o Fatigue
o Suppressed TSH
o Elevated T4
- Hypothyroidism:
o Weight gain
o Pretibial Myxoedema
o Periorbital Oedema
o Bradycardia
o Bradypnoea
- PolyCystic Ovarian Syndrome:
o Weight Gain
o Hirtism
o Infertility
- Cushings Syndrome:
o Caused by Excess Corticosteroids
o Moon Facies (Fat, white, round faces)
o Muscle Wasting + Weakness
o Weight Gain (Truncal Obesity)
o Stretch Marks due to Weight Gain
- Pituitary Adenoma:
o Peripheral Vision Loss
o Compression symptoms or Secretory Symptoms
o Secretory eg. Prolactin Galactorhoea + Gynacomastia
eg. GH Gigantism (Pre-Purbety) Acromegaly (Post Puberty)
eg. ACTH: C shing s S ndrome
- Acromegaly:
o Soft-Tissue Swelling
o Arthritis
o Hyperhydrosis
o Headache + Visual Field Defect
- Addisons:
o Autoimmune
o Weight Loss
o Fatigue
o Hypotension
o Hyponatraemia
o Hyperkalaemia
o Hyperpigmentation
- Anorexia:
o Weight Loss
o Fatigue
o BMI
o FSH LH D e to no o lation
o GH
o Hypokalaemia (often due to vomiting) Arrhythmias

[Link]
 Week 2
Endocrinology Notes
The Hypothalamo-Pituitary Axis

General Location of the Hypothalamus & Pituitary Gland

Embryology of the Pituitary Gland:
- Q: Why is the Ant. Pituitary Endocrine, & the Post. Pituitary Neuronal?
- A: Because they have different embryonic origins.
o Anterior Pituitary:
§ Arises from an upward out-pouching of the Oral-Ectoderm from the roof of the oral cavity
called Rathke’s Pouch. This pouch pinches off from the oral cavity and is later separated by
the sphenoid bone.
§ Consists of Epithelial/Glandular Tissue, & therefore Manufactures & Secretes Hormones.
o Posterior Pituitary:
§ Originates from a downward out-pouching of Neuro-Ectoderm from the brain in the floor of
the 3rd ventricle.
§ Consists of Neural Tissue, & therefore Secretes Neurohormones.

1. 2.

3.

[Link]
The Hypothalamus & Pituitary Glands:
- Hypothalamus:
o Links the nervous system to the endocrine system via the pituitary gland.
o Controls body temperature, hunger, thirst, fatigue, anger, and circadian cycles.
o Secretes neurohormones (hypothalamic-releasing hormones) Stimulate/Inhibit Pituitary Gland.
Abbreviation Full Name Stimulated/Inhibited Hormone
GRH Growth-Hormone Releasing Hormone Stimulates Release of Growth Hormone
SS Somatostatin Inhibits Release of Growth Hormone & TSH
TRH Thyrotropin Releasing Hormone Stimulates Release of TSH & Prolactin
PRF Prolactin Releasing Hormone Stimulates Release of Prolactin
GnRH Gonadotropin Releasing Hormone Stimulates Release of Gonadotropins; FSH & LH
CRH Corticotropin Releasing Hormone Stimulates Release of ACTH
- Pituitary Gland:
o Has 2 Major Lobes:
Posterior Pituitary: (Neurohypophysis)
Nervous Tissue
Supraoptic & Paraventricular Nuclei in the hypothalamus synthesize Oxytocin &
ADH Transport them to their axon terminals in the Posterior Pituitary.
o Hormones released as needed via exocytosis in [Link]
ADH
Oxytocin
Normal Histology Just like normal brain tissue. (Neural Origin)
o NB: NO neurones, but plenty of axons.
o Many supporting cells (Astrocytes, oligodendrocytes)
o Plus Blood Vessels ( ei he a e ie ei b P al Ve el Ie. Blood
comes only from the hypothalamus carries the hypothalamic
hormones.)
Anterior Pituitary: (Adenohypophysis)
Glandular Tissue (adeno = gland)
Releasing-Hormones from Ventral Hypothalamus that stimulate Ant. Pituitary:
o CRF
o TRF
o GRH FSH/LH
o GHRH
o Prolactin Releasing Factor (PRF)
Normal Histology Glandular structure:
o Clusters of acini surrounded by blood vessels
o Acini - mosaics of different cells:
(acidophils red, basophils dark blue, chromophobes - colourless)
NB: Pituitary Tumours may be from any of the 3 cells
o PLENTY f bl d e el ei he a e ie ei b P al Ve el Ie.
Blood comes only from the hypothalamus carries the hypothalamic
hormones.)

[Link]
 o Blood Supply:
Arterial blood enters via Hypophyseal Branches of the Internal Carotid Arteries.
(BUT SHASHI SAYS NO ARTERIES...PORTAL SYSTEM)
o Venous Drainage:
Venous blood leaves via venules which drain into the Dural Sinuses.

- Pituitary Hormones & their Target Tissues/Organs

o NB: All these hormones are PROTEIN-based hormones.

[Link]
Secretory Setup of the Hypothalamus & Pituitary Gland:
- Anterior Pituitary:
o Neurons of the Ventral Hypothalamus terminate in the Primary Capillary Plexus within the
Infundibulum (Stalk).
o These Neurons secrete Releasing-Hormones into the Primary Cap. Plexus, which flow to the
Secondary Capillary Plexus, stimulating Endocrine Cells of the Ant. Pituitary to synthesize/secrete
hormones.
- Posterior Pituitary:
o Neurons of the Supraoptic & Paraventricular Nuclei synthesize Oxytocin & ADH in the
hypothalamus, then transport them as granules to their axon terminals which terminate in the
Posterior Pituitary.
o When one of the hormones is needed, it is released from the axon via exocytosis into the
bloodstream via the Inferior Hypophyseal Circulation.
- NB: Remember that the Ant. & Post. Pituitary don’t act entirely independently (there is some flow of
hormones from the Post. Pituitary à Ant. Pituitary via the ‘Short Portal Vein’)

[Link]
The Hypothalamus: A ‘Relay-Station’ for Higher Brain Centres:
- The Hypothalamus receives information from multiple higher brain centres, integrates it, decides on a
response, and orders the pituitary to secrete specific hormones to elicit the response.
- Inputs:
o RAS (Reticular Activating System/Substance) – Regulates drowsiness by releasing Serotonin.
o Thalamus – Plays a role in Pain Perception
o Neocortex & Limbic System – Emotional Centre
o Optical System – Vision
- Outputs:
o Anterior Pituitary
o Posterior Pituitary
o Brain-Stem (Autonomic NS)

Feedback Control:
- Negative:
o Where the Biological Response causes a Decreased Hormone Release.
o Maintains levels around a stable intrinsic/preset level.
- Positive:
o Uncommon (Lactation & Parturition)
o Where the Biological Response causes an Increased Hormone Release
o Are therefore Unstable mechanisms
o Stopped by removal of initial stimulus.

[Link]
Levels of Feedback Loops:
- Feedback may occur at many different levels within a single ‘Hypothalamo-Pituitary-Target’ axis.
o Ultra-Short Loop:
§ The secreted hormone feeds back to the same tissue that secreted it.
• Eg. A Hypothalamic Hormone feeds back to the Hypothalamus.

o Short Loop:
§ The secreted hormone feeds back to the tissue that stimulated its secretion.
• Eg. The Hormone secreted by the Target Organ feeds back to the Pituitary.
• Or. The Hormone secreted by the Pituitary feeds back to the Hypothalamus.

o Long Loop:
§ The hormone secreted by the target organ feeds directly back to the Hypothalamus.

[Link]
 Endocrine Regulation of Growth

Phases of Growth:
- NB: These Differ in their Rates of Growth and Regulators/Contributors:

Major Regulators/Contributors
Phase of Growth Nutrition Hormonal Genetics
Foetal Yes - #1 Insulin (Acts as a growth factor No
(In Utero) in this phase)
IGF-I
Infantile Yes - #1 GH & IGF is present, but in low Yes – (Only after a few months
(Birth 2yrs) amounts – NOT Imperative. after birth)
Pre-Pubertal -Ve influence only if - IGF Levels Increase Yes - #1
(Childhood) malnourished - GF Receptors Increase
NB: Growth Velocity progressively declines during this phase (Transition from Infant Child)
NB: Body Proportions start to change.
Pubertal -Ve influence only if Sex Hormones:
(Early Teens) malnourished - GH Release
- Epiphyseal Closure
GH Causes IGF Release
GH + IGF Bone Elongation
Post-Pubertal NB: Growth Velocity peaks & then stays same for yrs.
(Late Teens) - (The last 3 years mainly concern the Trunk)

Major Hormones involved with Growth:

- Growth Hormone, AKA: Somatotropin
- Insulin-like Growth Factors (Somatomedins) (IGF-I & IGF-II)
- Somatostatin (Inhibits secretion of GH from Ant. Pit.)
- Thyroid Hormone
- Cortisol – (Not Direct – has a ‘permissive’ role. Ie. Other growth hormones are more effective if it’s present
- Sex Hormones (Oestrogen/Testosterone)

The Growth Hormone Axis:

[Link]
Hypothalamic Hormones of Growth:
- (+) GRF (Growth-Hormone Releasing Factor)/GRH (Growth-Hormone Releasing Hormone):
o Produced Mainly in: Hypothalamus (But also in GIT, Pancreas & Placenta)
o Exerts Effects on: Somatotropes (Anterior Pituitary) Growth Hormone Release.

- (-) Somatostatin:
o What is it?:
Produced almost everywhere: (Hypothalamus, Gut, Pancreas, CNS)
Inhibits Somatotropes Growth Hormone.
o Actions of Somatostatin:
Inhibits some Hypothalamic-Releasing Hormones:
GH (Grow Hormone)
TSH (Thyroid Stimulating Hormone)
PRL (Prolactin)
ACTH (Adreno-Cortico Tropic Hormone)

Anterior Pituitary Hormone of Growth:

- Growth Hormone:
o Produced by: Anterior Pituitary After mths old
o Regulation of Release:
Stimulation Inhibition
GRH - (Growth-Hormone Releasing Hormone) Somatostatin
o Actions:
Growth-Promoter from Early Childhood Onwards
Longitudinal Bone Growth & Remodelling
Skeletal Muscle Growth
Liver Growth
Stimulates IGF-Binding Protein Synthesis (Important carrier for IGF)
Stimulates IGF Synthesis
Metabolic Effects:
Stimulates:
o Lipolysis
o Ketogenesis
o Gluconeogenesis
o Protein Synthesis
o Lactation
Inhibits Insulin Action.
Boosts Immune Function.

Defects in Endocrine Control of Growth:

- Hyper:
o Too Much Growth Hormone &/or Growth Factors (Rare):
Eg. Childhood Gigantism
Eg. Adults - Acromegaly
o Non-GH Causes:
Eg. Precocious Puberty
- Hypo:
o Defective Growth Hormone Axis:
GH-Deficiency:
Primary GH Deficiency:
o Hypothalamic Defect
o And/Or Pituitary Defect
Secondary Pituitary Deficiency:
o Eg. Tumour & other Destructive Diseases.
o Eg. Psychosocial Deprivation (Ie. Kids in abusive/non-supportive
environments GH-Deficiency exhibit slowed growth)

[Link]
 Liver
Insulin-Like Growth Factors (IGF’s):
- Both IGF-I & IGF-II are Structurally Similar to Proinsulin (The Insulin Precursor)
- IGF-I - Chromosome 12
- IGF-II - Chromosome 11
- Circulates bound to IGFBP (Insulin-like Growth Factor Binding Protein)
- Bind to Specific Receptors
- Stimulate Cell Division together with other Growth Factors.
- Foetal Life:
o Act in Paracrine Fashion
o IGF made by all foetal tissues (However, mainly by liver after birth)
o Absence of IGF-I in Foetal Life à Intra Uterine Growth Retardation

Long Bone Growth

[Link]
 Thyroid Function

Anatomy of Thyroid Gland:

- A Bilobar Gland (2 Lobes L&R) connected in the middle by the I h of the Thyroid.
- Location:
o Immediately below the Larynx on each side of, and anterior to, the Trachea.
- Rich Blood Supply:
o Required for Building Blocks of Hormones.
o Required for Quick Release of Hormones.
o Flow - Regulated by the Sympathetic NS.

- C ed f M f Follicles
o Each contains a pool of Thyroid “Colloid” of stored Thyroid Hormones bound to Thyroglobulin.
Allows for a 2-3mth reserve of thyroid hormones.
o Each pool is lined by a layer of P i ci al F llicle Cell that secrete Thyroid Hormones (T3 & T4).
o There are also patches of Pa af llic la Cell that secrete Calcitonin.

Physiology of the Thyroid Gland:

o Iodine Balance:
NB: Iodine is essential for Thyroid Hormone Production.
Iodine is Actively taken up by Thyroid Gland via I di e T a i g .
TSH Th id I dine U ake
o Main Hormones:
T4 Thyroxine (93%) (Iodinated Tyrosine 4x Iodines) (Less Biologically Active)
T3 Triiodothyronine (7%) (Iodinated Tyrosine 3x Iodines) (Most Biologically Active)
Calcitonin (Polypeptide)
Secreted By The Parafollicular Cells of the Thyroid Gland
F c Plasma-Ca+ levels B O e cla Ac i i Osteoblast Activity)
Stimulated By: E acell la Ca+] (NB: Opposite of PTH)
o Effects of TSH on the Thyroid:

[Link]
 Thyroid Follicle Hyperplasia
I dine U ake f m he Bl d Iodine Trapping)
Th id H m ne S n he i
Relea e f T3 & T4
o Synthesis of Thyroid Hormone:
I dide U ake I dine T a ing
2. Iodide Activation via Oxidation
3. Secretion of Active/Oxidised Iodine into Colloid
4. Synthesis of Thyroglobulin from Tyrosines & Secretion into Colloid
5. Iodines stick to Thyroglobulin in Colloid DIT or MIT (Di/Mono-Iodo Tyrosine)
o Release of Thyroid Hormone:
Colloid is Endocytosed and Enzymatically Cleaved into T3 & T4.
Vesicles of T3 & T4 release contents into Cytosol
T3 & T4 Diffuse out of Follicle Cell & Into Bloodstream
Thyroxine-Binding Proteins (incl. Albumin)in Blood transport T3 & T4 to the rest of the body.
o Metabolic Effects of Thyroid Hormone:
NB: Because Thyroid Hormones act by Gene Activation, they are said to have a Long
La e Pe i d , during which they seem to have no discernible effect.
Skeletal - B ne T n e Re i n
Muscular - S eed f C n ac i n S eed f Rela a i n
Sympathetic NS - Ca ech lamine Sen i i i f Hea M cle Fa L m h c e
CVS - HR CO
GI - G M ili Sec e i n A e i e
Carbohydrate Metabolism - He a ic Gl c ne gene i He a ic Gl c l i
Lipid Metabolism - Li l i FFA in Pla ma
Metabolic Changes:
Ca b h d a e Fa P ein Me ab li m
Mi ch nd ial Ac i i N mbe
Na K-ATPase Activity
O2 Consumption
FFA in Plasma
Bodily Changes:
B d Tem Sweating
Me ab li m Ba al Me ab lic Ra e

[Link]
Thyroid Embryology:
- Forms from Pharyngeal Pouches (@4-5wks)
- Forms from the Endoderm germ layer.
- Once formed, it migrates downwards & becomes Bi-lobed.
o NB: Sometimes things go wrong during this migration, leaving a person’s thyroid gland between the
back of the tongue & where it normally sits. (See dotted red line on pic below)

Major Thyroid Hormones Produced (And Proportions):
- T3 – Triiodothyronine (7%) (Iodinated Derivative of Tyrosine – 3x Iodines) (Most Biologically Active)
- T4 – Thyroxine (93%) (Iodinated Derivative of Tyrosine – 4x Iodines) (Less Biologically Active)
NB: Because these hormones are stored in the ‘Colloid’, there is ≈2-3mths of ‘backup’ Reserve.
- Calcitonin (Polypeptide)


Iodine Balance:
- NB: Iodine is an essential component of the 2 major Thyroid Hormones & Is a Dietary Requirement.
- Of the Iodine ingested;
o 20% is Selectively Removed from blood by Thyroid Gland & used in Thyroid Hormone Synthesis.
o 80% is Excreted by the Kidneys
- NB: This process of Active Iodine Uptake by the Thyroid Gland is called “Iodine Trapping”.
- NB: The Rate of Iodine Uptake (Trapping) depends on TSH Concentration.

How TSH Stimulates Thyroid Hormone Synthesis/Secretion:
- Binding of TSH to Follicle Cell à Activates AdenylylCyclase à ↑cAMP à Activates pKa (Protein Kinase A)
à Phosphorylates Various Enzymes in Follicle Cell à Changes Activity of:
1. ↑Cleavage of Thyroglobulin in Lysosomes (Ie. ↑Release of T3 & T4)
2. ↑Activity of Iodine Pump (The Rate Limiting Step) à ↑Iodine Available for Synthesis
3. ↑Iodination of Tyrosine à ↑Synthesis of DIT’s & MIT’s à ↑Thyroid Hormone Synthesis
4. ↑Size & Secretory Activity of Follicle Cells
5. ↑# of Follicle Cells

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Synthesis of Thyroid Hormone: (Stimulated by TSH)
1. Active Uptake of Iodide by the Principal/Follicle Cells (Iodide “Trapping”):
a. Active Iodide uptake against massive Electrochemical Gradient.
b. NB: This is the Rate-Limiting Step of TH Synthesis.
2. Iodide Oxidation (by Peroxidase):
a. Oxidation of Iodide Ions (I-) à Iodine Molecules (I2).
3. Secretion of Active Iodine into Lumen of Colloid:
4. Synthesis of Thyroglobulin by Rough-ER+Golgi & Secretion into Lumen of Colloid:
a. Tyrosines – the basis of Thyroglobulin (A large poly-peptide of ≈70 Tyrosines)
5. Iodines stick to the Tyrosines on the Thyroglobulin in Colloid à DIT or MIT (Di/Mono-Iodo Tyrosine)

Hormone Release Mechanism:
6. Some of the Thyroglobulin Colloid is Endocytosed + Combined with Lysosome:
a. Lysosomal Enzymes cleave the T3 & T4 from the Thyroglobulin.
b. NB: In the process, many of the unpaired DIT’s/MIT’s are also released. These are De-Iodinised by
Deiodinase. Both the freed Iodines & Tyrosines are recycled.
7. Vesicle of Cleaved T3 & T4 Breaks Down, Releasing Hormones into Cytosol
8. Hormones in Cytosol Diffuse through Basement Membrane à Combine with Binding Proteins in the Blood
Stream (Thyroxine-Binding Protein/Albumin)

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Regulation of Thyroid Hormone Production/Release:
1. Hypothalamus Secretes “Thyrotropin-Releasing Hormone” (TRH) into portal circulation of Pituitary.
2. TRH Stimulates Anterior Pituitary to Secrete “Thyroid Stimulating Hormone” (TSH).
3. TSH Stimulates Thyroid Gland to Secrete:
a. *Primarily Thyroxine (T4) (The relatively inactive Thyroid Hormone à converted to T3)
b. And Some Triiodothyronine (T3) (The most active Thyroid Hormone)
4. T3 & T4 Circulate in the Bloodstream Eliciting their effects + Provide [Link] to Ant. Pituitary

Transport of Thyroid Hormones (Binding Proteins):
- NB: 75-100µg of Thyroid Hormone is secreted per day
- Thyroid hormone must be bound to carrier proteins when in bloodstream to avoid filtration by kidneys.
- Common Thyroid-Hormone Carrier Proteins:
o 70% - “Thyroxine-Binding Globulin” (TBG)
o 30% - Albumin
o NB: The minute %age of unbound Thyroid Hormones are those eliciting their effects.
§ Ie. TH must be unbound to be able to enter cells & bind to Intracellular Receptors.

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Mechanism of Action of Thyroid Hormone:
1. Thyroxine (T4) reaches target cell
2. Binding Protein releases Thyroxine (T4)
3. Thyroxine (T4) diffuses into cytosol à Converts to T3
4. T3 (The most active form) enters Nucleus à Binds to Nuclear Receptor on DNA à Alters Gene Transcription.
5. Activating Different Genes à leads to Change in Cell’s Protein/Enzyme profile à Change in Activity.

- Cellular Changes:
o ↑Carbohydrate/Fat Metabolism
o ↑Glucose Uptake
o ↑Protein Synthesis + Catabolism
o ↑Mitochondrial Activity & Number
o ↑Na/K-ATPase Activity
- Bodily Changes:
o ↑O2 Consumption à ↑Cardiac Output, HR & Respiration
o ↑Food Intake (↑Glucose Absorption from GIT)
o ↑Secretion of Digestive Juices
o ↑GIT Motility
o ↑Insulin Secretion
o ↑[FFA] in Plasma
o ↑Body Temp à Sweating
o ↑Metabolism (Basal Metabolic Rate)
o ↑Vitamin Requirements due to ↑Quantities of Enzymes (Of which vitamins are a vital component)

- NB: Because Thyroid Hormones act by Gene Activation, they are said to have a Long ‘Latent Period’, during
which they seem to have no discernible effect.
o Thyroxine: 2-3 Days
o Triiodothyronine: 6-12 Hours

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