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YR2 BCS Study Points SEM 1 > Block 7 - Endocrinology > Flashcards

Block 7 - Endocrinology Flashcards

1
Q

What are the 8 Hormones released from the Anterior Pituitary?

A

Anterior Pituitary Hormones:

  1. Human Growth Hormone (hGH) / Somatotropin
  2. Thyroid-Stimulating Hormone (TSH) / Thyrotropin
  3. Follicle-Stimulating Hormone (FSH)
  4. Luteinizing Hormone (LH)
  5. Prolactin (PRL)
  6. Adrenocorticotropic Hormone (ACTH) / Corticotropin
  7. Melanocyte- Stimulating Hormone (MSH)
  8. Endorphins (Neuropeptide)
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2
Q

What is the target tissue and principal role of each of the anterior pituitary hormones?

A
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3
Q

What is the target tissue and principal role of the two hormones of the posterior pituitary?

A
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4
Q

Mechanism of Action of ADH?

A

Antidiuretic hormone stimulates water reabsorbtion by stimulating insertion of “water channels” or aquaporins into the membranes of kidney tubules.

  1. The primary function of AVP in the body is to regulate extracellular fluid volume by regulating renal handling of water, although it is also a vasoconstrictor and pressor agent (hence, the name “vasopressin”). AVP acts on renal collecting ducts via V2 receptors to increase water permeability (cAMP-dependent mechanism), which leads to decreased urine formation (hence, the antidiuretic action of “antidiuretic hormone”). This increases blood volume, cardiac output and arterial pressure.
  2. A secondary function of AVP is vasoconstriction. AVP binds to V1 receptors on vascular smooth muscle to cause vasoconstriction through the IP<u>3</u> signal transduction pathway and Rho-kinase pathway, which increases arterial pressure; however, the normal physiological concentrations of AVP are below its vasoactive range. Studies have shown, nevertheless, that in severe hypovolemic shock, when AVP release is very high, AVP does contribute to the compensatory increase in systemic vascular resistance.
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5
Q

Discuss the regulation of anterior pituitary hormone secretion by the hypothalamus and by feedback inhibition.

  • How many hormones secreted by the hypothalamus are secretory and how many are inhibitory?
  • Which hormones of the anterior pituitary are controlled via a Negative Feedback Loop?
  • What is the hypothalamus bounded by? What can pass through?
  • Where do the glucose-sensitive neurons reside?
A

Regulation of Anterior Pituitary Hormones:

Hypothalamus Hormones: Neurosecretory cells in the hypothalamus secrete five releasing hormones (which stimulate secretion) and two inhibiting hormones (which suppress secretion)

Hormone Negative Feedback Loops: Secretory activity of thyrotrophs, gonadotrophs, and corticotrophs decreases when blood levels of their target gland hormones rise.

  • Hypothalamus is bounded by specialised regions that lack effective blood brain barrier
  • Endothelium at these sites is fenestrated to allow free passage of large proteins and other molecules
  • Steroids and glucocorticoids are sensed by specialised neurons
  • Glucose sensitive neurons in arcuate and ventromedial areas
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6
Q

Anterior Pituitary Hormones - Human Growth Hormone (hGH) / Somatotropin

  • Secreted by?
  • Hypothalamic Releasing Hormone?
    • 9 Things that stimulate GHRH?
  • Hypothalamic Inhibiting Hormone?
    • 8 Thing that stimulate GHIH?
A

Human Growth Hormone (hGH) / Somatotropin

  • Secreted By → Somatotrophs
  • Hypothalamic Releasing Hormone (Stimulates Secretion) → Growth Hormone Releasing Hormone (GHRH) / Somatocrinin
  • Stimulates GHRH:
    1. Hypoglycaemia
    2. Decreased fatty acids
    3. Increased amino acids
    4. NREM sleep (stages 3 and 4)
    5. Increased SNS activity (stress and exercise)
    6. Glucagon
    7. Estrogens
    8. Cortisol
    9. Insulin
  • Hypothalamic Inhibiting Hormone (Suppresses Secretion) → Growth Hormone Inhibiting hormone (GHIH) / Somatostatin
  • Stimulates GHIH:
    1. Hyperglycaemia
    2. Increased fatty acids
    3. Decreased amino acids
    4. REM sleep
    5. Emotional deprivation
    6. Obesity
    7. Low thyroid hormones
    8. Low human growth hormone
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7
Q

Anterior Pituitary Hormones - Thyroid-Stimulating Hormone (TSH) / Thyrotropin

  • Secreted by?
  • Hypothalamic Releasing Hormone?
    • What inhibits TRH?
  • Hypothalamic Inhibiting Hormone?
A

Thyroid-Stimulating Hormone (TSH) / Thyrotropin

  • Secreted by → Thyrotrophs
  • Hypothalamic Releasing Hormone (Stimulates Secretion) → Thyrotropin-Releasing Hormone (TRH)
  • Inhibits TRH:
    1. High levels of T3 and T4 via negative feedback
  • Hypothalamic Inhibiting Hormone (Suppresses Secretion) → Growth Hormone–Inhibiting Hormone (GHIH)
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8
Q

Anterior Pituitary Hormones - Follicle-Stimulating Hormone (FSH)

  • Secreted by?
  • Hypothalamic Releasing Hormone?
    • What inhibits GnRH & FSH?
  • Hypothalamic Inhibiting Hormone?
A

Follicle-Stimulating Hormone (FSH)

  • Secreted by → Gonadotrophs
  • Hypothalamic Releasing Hormone → Gonadotropin-Releasing Hormone (GnRH)
  • Inhibits GnRH and FSH:
    • Estrogens in females and testosterone in males via negative feedback
  • Hypothalamic Inhibiting Hormone → Nil
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9
Q

Anterior Pituitary Hormones - Luteinizing Hormone (LH)

  • Secreted by?
  • Hypothalamic Releasing Hormone?
    • What inhibits GnRH & LH?
  • Hypothalamic Inhibiting Hormone?
A

Anterior Pituitary Hormones - Luteinizing Hormone (LH)

  • Secreted by → Gonadotrophs
  • Hypothalamic Releasing Hormone → Gonadotropin-Releasing Hormone (GnRH)
  • Inhibits GnRH and LH → Estrogens in females and testosterone in males via negative feedback
  • Hypothalamic Inhibiting Hormone → Nil
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10
Q

Anterior Pituitary Hormones - Prolactin (PRL)

  • Secreted by?
  • Hypothalamic Releasing Hormone?
    • What stimulates PRH?
  • Hypothalamic Inhibiting Hormone?
    • What Inhibits PIH?
A

Anterior Pituitary Hormones - Prolactin (PRL)

  • Secreted by → Lactotrophs
  • Hypothalamic Releasing Hormone → Prolactin-Releasing Hormone (PRH). Thought to exist, but exact nature is uncertain.
    • What stimulates PRH? → Pregnancy
  • Hypothalamic Inhibiting Hormone → Prolactin-Inhibiting Hormone (PIH), which is dopamine.
    • What Inhibits PIH? → The sucking action of a nursing infant (allows milk)
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11
Q

Anterior Pituitary Hormones - Adrenocorticotropic Hormone (ACTH) / Corticotropin

  • Secreted by?
  • Hypothalamic Releasing Hormone?
    • What stimulates CRH and ACTH? (2)
    • What inhibits CRH and ACTH? (1)
  • Hypothalamic Inhibiting Hormone?
A

Anterior Pituitary Hormones - Adrenocorticotropic Hormone (ACTH) / Corticotropin

  • Secreted by → Corticotrophs
  • Hypothalamic Releasing Hormone → Corticotropin-Releasing Hormone (CRH)
  • Stimulates CRH and ACTH
    1. Stress- related stimuli (eg. low blood glucose or physical trauma)
    2. Interleukin-1
  • Inhibits CRH and ACTH → Glucocorticoids via negative feedback.
  • Hypothalamic Inhibiting Hormone → Nil
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12
Q

Anterior Pituitary Hormones - Melanocyte- Stimulating Hormone (MSH)

  • Secreted by?
  • Hypothalamic Releasing Hormone?
  • Hypothalamic Inhibiting Hormone?
A

Anterior Pituitary Hormones - Melanocyte- Stimulating Hormone (MSH)

  • Secreted by → Corticotrophs
  • Hypothalamic Releasing Hormone → Corticotropin-Releasing Hormone (CRH)
  • Hypothalamic Inhibiting Hormone → Dopamine
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13
Q

Posterior Pituitary Hormones (2)

  • Synthesized by?
  • Control of Secretion?
    • What stimulates OT? (2)
    • What stimulates ADH? (5)
      • What inhibits ADH? (3)
A

Oxytocin (OT)

  • Synthesized By: Hypothalamus Neurosecretory Cells
  • Stimulates OT: Uterine distension and stimulation of nipples

Antidiuretic Hormone (ADH) / Vasopressin

  • Synthesized By: Hypothalamus Neurosecretory Cells
  • Stimulates ADH:
    1. Elevated blood osmotic pressure
    2. Dehydration
    3. Loss of blood volume
    4. Pain
    5. Stress
  • Inhibits ADH:
    1. Low blood osmotic pressure
    2. High blood volume
    3. Alcohol
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14
Q

Review the anatomy and histology of the pituitary gland.

  • Shape?
  • Location?
  • What is the Sella Turcica?
  • Attachments?
  • Portions?
A

Anatomy of Pituitary Gland:

  • Shape: Pea-shaped structure that measures 1–1.5 cm in diameter
  • Location: Lies in the hypophyseal fossa of the Sella turcica of the sphenoid bone
  • Sella Turcica: A deep depression within the middle cranial fossa which lies the pituitary
  • Attachments: Attaches to the hypothalamus via the infundibulum (a stalk)
  • Portions: Anterior pituitary and posterior pituitary (different function and blood supplies)
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15
Q

Anterior Pituitary

  • Alternative name?
  • Embryological Origin?
  • 2 Parts?
  • Histology?
  • Blood Supply?
A

Anterior Pituitary (Adenohypophysis or Pars Anterior):

  • Origin: Invagination of oral ectoderm (forms Rathke’s pouch)
  • Parts: Consists of the pars distalis (larger portion) and the pars tuberalis (forms a sheath around the infundibulum).
  • Histology: Composed of epithelial tissue
  • Blood Supply (Hypophyseal Portal System): Blood flows from capillaries in the hypothalamus into portal veins that carry blood to capillaries of the anterior pituitary
    1. Superior hypophyseal arteries (branches of the internal carotid arteries) bring blood into the hypothalamus.
    2. At the junction of the median eminence of the hypothalamus and the infundibulum, these arteries divide into a capillary network called the primary plexus of the hypophyseal portal system.
    3. From the primary plexus, blood drains into the hypophyseal portal veins that pass down the outside of the infundibulum.
    4. In the anterior pituitary, the hypophyseal portal veins divide again and form another capillary network called the secondary plexus of the hypophyseal portal system.
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16
Q

What is the Mechanism of Hormone Transport of the Anterior Pituitary?

A

Mechanism of Hormone Transport:

  1. Above the optic chiasm are clusters of specialised neurons called neurosecretory cells which synthesise the hypothalamic releasing and inhibiting hormones in their cell bodies and package the hormones inside vesicles, which reach the axon terminals by axonal transport.
  2. Nerve impulses stimulate the vesicles to undergo exocytosis.
  3. The hormones then diffuse into the primary plexus of the hypophyseal portal system.
  4. Quickly, the hypothalamic hormones flow with the blood through the portal veins and into the secondary plexus. This direct route permits hypothalamic hormones to act immediately on anterior pituitary cells, before the hormones are diluted or destroyed in the general circulation.
  5. Hormones secreted by anterior pituitary cells pass into the secondary plexus capillaries, which drain into the anterior hypophyseal veins and out into the general circulation.
  6. Anterior pituitary hormones then travel to target tissues throughout the body.
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17
Q

Blood supply of the pituitary gland?

A
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18
Q

Posterior Pituitary

  • Alternative name?
  • Embryological Origin?
  • 2 Parts?
  • Histology?
  • Blood Supply?
A

Posterior Pituitary (Neurohypophysis):

  • Origin: Developed as extension of the hypothalamus so is neural tissue
  • Parts: Consists of the pars nervosa (larger bulbar portion) and the infundibulum
  • Histology: Composed of neural tissue
  • Blood Supply:
    1. Inferior hypophyseal arteries (branch from the internal carotid arteries) drain into a single plexus (plexus of the infundibular process) before draining out to the body.
    2. From this plexus, hormones pass into the posterior hypophyseal veins for distribution to target cells in other tissues.
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19
Q

What is the Mechanism of Hormone Transport of the Posterior Pituitary gland?

A

Mechanism of Hormone Transport (Hypothalamohypophyseal Tract): Axons of hypothalamic neurosecretory cells extend from hypothalamic nuclei to the posterior pituitary

  1. Neurosecretory cells (paraventricular and the supraoptic nuclei) of the hypothalamus synthesise hormones.
  2. Hormones are packaged into secretory vesicles, which move by fast axonal transport to the axon terminals in the posterior pituitary, where they are stored until nerve impulses trigger exocytosis and release of the hormone.
  3. The capillary plexus of the infundibular process receives the secreted hormones.
  4. Hormones pass into the posterior hypophyseal veins for distribution to target cells in other tissues.
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20
Q

What is the Pars Intermedia?

A

NB: Evolutionary thought was that there were three lobes to the anterior pituitary (third called intermediate lobe or pars intermedia). However in humans it is only a few cells thick and is considered part of anterior lobe. It atrophies during human fetal development and ceases to exist as a separate lobe in adults. It secretes melanocyte– stimulating hormone (MSH) also produced in the anterior lobe.

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21
Q

Outline the pathology and clinical signs of endocrine disorders that affect the pituitary gland, causing both hypo- and hyper-function

  • List of things that can go wrong?
A
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22
Q

What is a Pituitary Adenoma? What is the Endocrine effect?

A

Pituitary Adenoma

Benign neoplasm/tumour of anterior pituitary cells

• May be functional (hormone-producing) or nonfunctional (silent)

  • Young adults to middle age
  • Sella turcica > ectopic sites
  • 25% of intracranial neoplasms
  • 30% of 50-60 year olds have clinically

undetected tumours

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23
Q

Pituitary Adenoma (Hyperpituitarism) - Prolactinoma

  • Treatment?
  • Clinical Signs?
A

Prolactinoma:

  • Most common.
  • Treatment is dopamine agonists (bromocriptine or cabergoline) to suppress prolactin production (shrinks tumor) or surgery for larger lesions.
  • Clinical Signs:
    • Presents as galactorrhea and amenorrhea (females)
    • Libido and headache (males)
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24
Q

Pituitary Adenoma (Hyperpituitarism) - GH Cell Adenoma

  • Diagnosis?
  • Treatment?
  • Clinical Signs?
A

GH Cell Adenoma:

  • Secondary diabetes mellitus is often present (GH induces liver gluconeogenesis).
  • Diagnosed by elevated GH and insulin growth factor- I (IGF-1) levels along with lack of GH suppression by oral glucose.
  • Treatment is octreotide (somatostatin analog that suppresses GH release), GH receptor antagonists, or surgery.
  • Clinical Signs:
    • Presents as gigantism in children (increased linear bone growth as epiphyses are not fused) and acromegaly in adults (enlarged bones of hands, feet, and jaw, growth of visceral organs leading to dysfunction an enlarged tongue)
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25
Q

Pituitary Adenomas

  • FSH, LH, TSH Adenoma?
  • Invasive Adenoma?
  • Giant Adenoma?
A
  • FSH, LH and TSH Adenoma: Rare
  • Invasive Adenoma: Extra-Sella, no capsulation and local invasion. Adenomatous tissue can enter blood vessels and embolise, but not grow as metastases. Invasive growth can occur along dura, optic nerve or into sphenoid or cavernous sinus.
  • Giant Adenoma: Extra-Sella, capsulated and compressive
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26
Q

What stain is used for the Histochemical classification of pituitary adenomas?

A

Histochemical classification uses orange-G-PAS stain

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27
Q

Pituitary Adenomas

  • What are the Macroscopic Features?
  • What are the Microscopic Features?
A

Pituitary Adenomas

  • Macroscopic Features:
    • Soft and solid, occasionally cystic.
    • Size ranges from microadenoma to giant adenoma.
    • Grey to red due to high degree of vascularity.
  • Microscopic Patterns:
    • Diffuse, sinusoidal or papillary.
    • Dystrophic calcification and endocrine amyloid (Congo red and polaroscopy).
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28
Q

5 Nonfunctional Clinical Signs of Pituitary Adenoma?

(Mass effects?)

A

Nonfunctional Clinical Signs of Pituitary Adenoma

  1. Bitemporal hemianopia occurs due to compression of the optic chiasm
  2. Hypopituitarism occurs due to compression of normal pituitary tissue
  3. Hydrocephalus occurs due to upward expansion into hypothalamus and third ventricle or backward expansion to compress aqueduct
  4. CN III, IV and VI palsy due to lateral expansion into cavernous sinus
  5. Headache due to raised ICP
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29
Q

What is a Craniopharyngioma?

  • Embrological derivative?
  • Macroscopic features?
  • 5 Clinical Signs?
A

Craniopharyngioma

  • Solid and cystic suprasellar tumour
  • Derived from Rathke’s Pouch
  • Resembles ameloblastoma (a tooth tumour which occurs in the jaw)
  • Usually suprasellar, can be intrasellar
  • 75% show calcification
  • Solid and cystic areas
  • Cyst contains ‘motor oil fluid’ which is straw to brown cholesterol-rich fluid
  • Clinical Signs
    1. Extremely infiltrative
    2. Visual field defects
    3. Diabetes insipidus
    4. Hydrocephalus
    5. Pituitary dwarfism in children (Lorraine-Levi Syndrome)
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30
Q

What is Hypopituitarism?

  • When do symptoms arise?
  • Causes - adults vs. children?
  • Clinical Signs?
    • Pituitary adenoma
    • Sheehan syndrome
    • Empty sella syndrome
A

Hypopituitarism

  • Insufficient production of hormones by the anterior pituitary gland
  • Symptoms arise when> 75% of the pituitary parenchyma is lost
  • Caused by pituitary adenomas (adults) or craniopharyngioma (children) due to mass effect or pituitary apoplexy (bleeding into an adenoma causing hemorrhagic infarction)
  • Can be caused by Sheehan syndrome → pregnancy-related infarction of the pituitary gland (gland doubles in size during pregnancy, but blood supply does not increase significantly, blood loss during parturition precipitates infarction).
  • Can be caused by Empty Sella syndrome (congenital defect of the Sella). Herniation of the arachnoid and CSF into the Sella compresses and destroys the pituitary gland.
  • Clinical Signs
    • Pituitary Adenoma: Present with features based on the type of hormone produced & May see features based on loss of other hormone production
    • Sheehan Syndrome-Pregnancy-Related Infarction: Presents as poor lactation, loss of pubic hair, and fatigue
    • Empty Sella Syndrome: Pituitary gland is absent on imaging, Empty Sella turcica
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31
Q

What is a Pituitary Carcinoma?

A

Pituitary Carcinoma

  • Extremely rare
  • Term is only used when definite metastases occur which survive and grow
  • Cannot predict benignancy, invasiveness or malignancy on histopathological features (they all look benign)!
  • Metastasis is the only criterion for diagnosis
  • May lead to signs of infiltration
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32
Q

What is Acute Pituitary Insufficiency? Clinical Signs? (3)

A

Acute Pituitary Insufficiency

  • Portal venous system collapses due to low perfusion causing central pituitary necrosis
  • Due to trauma, surgery or shock states such as Sheehan syndrome
  • Central zone necrosis in portal venous circulation area
  • Clinical Signs - Acute Pituitary Failure:
    1. Pallor
    2. Lethargy
    3. Coma culminating in death approximately 2 weeks later
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33
Q

Chronic Pituitary Insufficiency

  • What is Simmond’s Disease?
  • Microscopy?
  • Clinical Signs?
A

Chronic Pituitary Insufficiency

  • Simmond’s Disease:
    • Usually <10% of functional parenchyma left
    • Occurs in survivors of Sheehan syndrome, healed TB, sarcoidosis, meningitis, tumours and lymphocytic hypophysitis (autoimmune)
  • Microscopy: Scarring, calcification, ossification and specific aetiology
  • Clinical Signs - Hypopituitarism:
    1. Cannot produce breast milk
    2. Amenorrhoeic
    3. Pale and loss of body hair
    4. Myxedema
    5. Addison’s Disease
    6. Viscera abnormally small due to loss of growth hormone
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34
Q

What are 4 Posterior Pituitary Gland Pathologies?

A

Posterior Pituitary Gland Pathology:

  1. Central Diabetes Insipidus
  2. Nephrogenic Diabetes Insipidus
  3. Syndrome of Inappropriate ADH (SIADH) Secretion
  4. Neurohypophysal Tumours
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35
Q

Posterior Pituitary Gland Pathology: Central Diabetes Insipidus

  • Cause?
  • How to test?
  • Treatment?
A

Posterior Pituitary Gland Pathology: Central Diabetes Insipidus

  • ADH deficiency
  • Due to hypothalamic or posterior pituitary pathology such as tumour, trauma, infection, or inflammation
  • Water deprivation test fails to increase urine osmolality (useful for diagnosis)
  • Treatment is desmopressin (ADH analog)
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36
Q

Posterior Pituitary Gland Pathology: Nephrogenic Diabetes Insipidus

  • Cause?
  • Clinical features?
A

Posterior Pituitary Gland Pathology: Nephrogenic Diabetes Insipidus

  • Impaired renal response to ADH
  • Due to inherited mutations or drugs (lithium and demeclocycline)
  • Clinical features are similar to central diabetes insipidus, but there is no response to desmopressin
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37
Q

Posterior Pituitary Gland Pathology: Syndrome of Inappropriate ADH (SIADH) Secretion

  • Mechanism?
  • Causes?
  • Treatment?
A

Syndrome of Inappropriate ADH (SIADH) Secretion

  • Excessive ADH secretion
  • Most often due to ectopic production (small cell carcinoma of the lung)
  • Other causes include CNS trauma, pulmonary infection, and drugs (cyclophosphamide)
  • Treatment is free water restriction or demeclocycline
  • Clinical Signs - Retention of Free Water:
    • Hyponatremia and low serum osmolality
    • Mental status changes and seizures as hyponatremia leads to neuronal swelling and cerebral edema
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38
Q

Posterior Pituitary Gland Pathology: Neurohypophysal Tumours

A

Posterior Pituitary Gland Pathology: Neurohypophysal Tumours

  • RARE tumours
  • Metastases (COMMONEST!)
  • Astrocytoma/Pituicytoma
  • Seminoma (midline location)
  • Dermoid Epidermoid Cysts
  • Lymphoma
  • Ganglioglioma/Gangliocytoma
  • Granular Cell Tumour
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39
Q

Pharmacology of Pituitary Disorders: GH Deficiency

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects? (5)
A

GH Deficiency

  • Treatment: Synthetic human growth hormone (somatropin)
  • Mechanism: Increases amount of growth hormone (somatropin) in body. Promotes growth of skeletal, muscular and other tissues, stimulates protein anabolism and influences fat and mineral metabolism.
  • Examples: Genotropin, Scitropin, Norditropin NordiFlex and Humatrope
  • Indications: Used for the treatment of short stature in children due to GH deficiency, Turner’s syndrome, chronic renal insufficiency, Prader-Willi syndrome as well as treatment of GH deficiency in adults.
  • Side Effects:
    1. Peripheral oedema
    2. Paresthesia (common)
    3. Hyperglycaemia
    4. Benign intracranial hypertension
    5. Systemic allergic reaction (rare)
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40
Q

Pharmacology of Pituitary Disorders: GH Excess

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects? (5)
A

GH Excess

  • Treatment: Long acting somatostatin analogues
  • Mechanism: Inhibits the release of GH from the anterior pituitary
  • Examples: Octreotide (Sandostatin) and Lanreotide (Somatuline)
  • Indications: Acromegaly and relief from the symptoms associated with tumours
  • Side Effects:
    1. Abdominal pain
    2. Nausea, vomiting
    3. Hair loss (common)
    4. Pancreatitis
    5. Hypothyroidism (rare)
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41
Q

Pharmacology of Pituitary Disorders: ADH Deficiency

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects? (5)
A

ADH Deficiency

  • Treatment: Vasopressin agonists or synthetic vasopressin
  • Mechanism: Increase amount of ADH in body
  • Examples: Argipressin (synthetic ADH), Desmopressin (specific vasopressin V2 receptor agonist), Terlipressin (inactive prodrug of vasopressin) and Ornipressin (vasopressin analogue)
  • Indications: Central diabetes insipidus (Argipressin and Desmopressin), bleeding oesophageal varices and hepatorenal syndrome (Terlipressin) and to reduce blood loss during some surgical procedures (Ornipressin)
  • Side Effects: Different based on drug. Headache, abdominal cramps, nausea, diarrhoea, pallor, hyponatraemia, allergic reactions, angina, MI, arrhythmias, thrombosis, gangrene and rhabdomyolysis.
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42
Q

Pharmacology of Pituitary Disorders: ADH Excess

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects?
A

ADH Excess

  • Treatment: Vasopressin antagonist
  • Mechanism: Blocks the effects of excess ADH in the body
  • Examples: Demeclocycline (selective ADH antagonist at renal tubules) and Tolvaptan (selective vasopressin V2-receptor antagonist)
  • Indications: Treatment of SIADH resistant to fluid restriction (Demeclocycline) and for the treatment of euvolaemic or hypervolaemic hyponatraemia (Tolvaptan).
  • Side Effects: Different based on drug. Reversible nephrogenic diabetes insipidus.
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43
Q

Pharmacology of Pituitary Disorders: TSH Deficiency

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects?
A

TSH Deficiency

  • Treatment: Thyroid hormone
  • Mechanism: Thyroid hormone replacement
  • Examples: Levothyroxine (thyroxine, T4)
  • Indications: Hypothyroidism and myxoedema
  • Side Effects: Tachycardia, heat intolerance, tremors and arrhythmias
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44
Q

Pharmacology of Pituitary Disorders: TSH Excess

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects?
A

TSH Excess

  • Treatment: Antithyroid hormone
  • Mechanism: Block thyroid hormone synthesis. Propylthiouracil also inhibits peripheral conversion of T4 to T3.
  • Examples: Carbimazole and propylthiouracil
  • Indications: Graves’ disease, preparation for thyroid surgery, or radioactive iodine treatment and thyroid storm
  • Side Effects: Itching, rash, mild leukopenia, nausea, vomiting, gastric discomfort, headache and arthralgia
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45
Q

Pharmacology of Pituitary Disorders: Oxytocin Deficiency

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
A

Oxytocin Deficiency

  • Treatment: Oxytocin
  • Mechanism: Stimulates labour, uterine contractions, milk let-down and controls uterine hemorrhage
  • Indications: Parturition and lactation
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46
Q

Pharmacology of Pituitary Disorders: Prolactin Excess

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
A

Prolactin Excess

  • Treatment: Dopamine receptor agonists
  • Mechanism: Stimulate dopamine D2 receptors and inhibit prolactin secretion
  • Examples: Bromocriptine or cabergoline
  • Indications: Prolactinoma
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47
Q

Adrenal Glands

  • Embryological derivative?
  • Zones of the Cortex?
    • Hormones? Regulation?
  • Cells of the medulla?
  • Most common tumor of the adrenal medulla in adults?
  • Most common tumor of the adrenal medulla in children?
A
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48
Q

Adrenal Gland Pathology: Hypercortisolism (Cushing Syndrome)

  • Causes?
  • Diagnosis?
  • Tx?
A

Cushing Syndrome

  • Increased cortisol
  • Due to exogenous corticosteroids
  • Due to primary adrenal adenoma, hyperplasia or carcinoma
  • Due to ACTH secreting pituitary adenoma (Cushing disease) or paraneoplastic ACTH secretion
  • Cushing disease main cause!
  • Diagnosis is made by increased 24-hour urine cortisol levels
  • High-dose dexamethasone (cortisol analog) suppresses ACTH production by a pituitary adenoma (cortisol levels decrease), but fails to suppress ectopic ACTH production by a small cell lung carcinoma (cortisol levels remain high)
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49
Q

Adrenal Gland Pathology: Hypercortisolism (Cushing Syndrome)

  • 12 Clinical Signs?
A

Cushings Syndrome

  1. Hypertension
  2. Weight gain (due to high glucose and fat storage)
  3. Moon facies
  4. Muscle weakness (cortisol breaks down muscle producing AAs for gluconeogenesis)
  5. Abdominal striae (due to impaired synthesis of collagen with thinning of skin)
  6. Truncal obesity
  7. Buffalo hump
  8. Skin changes (thinning, striae)
  9. Osteoporosis
  10. Hyperglycaemia (insulin resistance)
  11. Amenorrhea
  12. Immunosuppression
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50
Q

Adrenal Gland Pathology: Hypocortisolism (Primary Adrenal Insufficiency)

  • Acute?
  • Chronic?
  • Waterhouse-Friderichsen Syndrome?
A

Hypocortisolism (Primary Adrenal Insufficiency)

  • Deficiency of aldosterone and cortisol production due to loss of gland function
  • Acute: Sudden onset (i.e. due to massive hemorrhage) which may present with shock
  • Chronic: Addison disease. Due to whole adrenal cortex atrophy or destruction by disease (autoimmune destruction most common in the Western world whilst TB most common in the developing world).
  • Waterhouse-Friderichsen Syndrome: Acute due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitidis), DIC or endotoxic shock
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51
Q

What is Addison’s Disease?

A
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52
Q

What is Waterhouse-Friderichsen syndrome?

A
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53
Q

Adrenal Gland Pathology: Hypocortisolism (Primary Adrenal Insufficiency)

  • Clinical Signs? (10)
A

Adrenal Gland Pathology: Hypocortisolism (Primary Adrenal Insufficiency)

  1. Hypotension
  2. Hyponatremia (increased salt craving)
  3. Hypovolemia
  4. Hyperkalemia
  5. Weakness
  6. Hyperpigmentation of skin and mucosa (due to increased MSH, a byproduct of ACTH production from POMC)
  7. Metabolic acidosis (low pH and HCO3-)
  8. Vomiting
  9. Diarrhea
  10. NB: Primary Pigments the Skin/Mucosa!
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54
Q
A
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55
Q
A
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56
Q

Adrenal Gland Pathology: Hyperaldosteronism

  • Primary vs. Secondary?
  • Clinical Signs?
A

Hyperaldosteronism (Primary)

  • Due to sporadic bilateral adrenal hyperplasia
  • Adrenal adenoma (Conn syndrome) and adrenal carcinoma are less common causes
  • Clinical Signs:
    1. High aldosterone and low renin
    2. Hypertension (due to sodium retention)
    3. Decreased or normal K+
    4. Metabolic alkalosis
    5. No oedema due to aldosterone escape mechanism

Hyperaldosteronism (Secondary)

  • Seen with activation of RAAS
  • Due to renovascular hypertension, juxtaglomerular cell tumours (renin- producing) and oedema (e.g. cirrhosis, heart failure or nephrotic syndrome)
  • Clinical Signs
    • As above
    • High aldosterone and high renin
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57
Q

What are the Clinical Features of Conn Syndrome?

A
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58
Q

Adrenal Gland Pathology: Congenital Adrenal Hyperplasia

  • 21-hydroxylase deficiency?
  • Clinical Signs? (3)
A

Congenital Adrenal Hyperplasia

  • Excess sex steroids with hyperplasia of both adrenal glands
  • Inherited 21-hydroxylase deficiency is most common cause
  • 21-hydroxylase is required for the production of aldosterone and corticosteroids
  • In enzyme deficiency, steroidogenesis is predominantly shunted toward sex-steroid production (which does not require 21-hydroxylase)
  • Deficiency of cortisol leads to increased ACTH secretion (lack of negative feedback), which results in bilateral adrenal hyperplasia
  • Clinical Signs:
    1. Salt wasting with hyponatremia, hyperkalemia, and hypovolemia (due to lack of aldosterone)
    2. Life-threatening hypotension (due to lack of cortisol)
    3. Clitoral enlargement (females) or precocious puberty (males) due to excess androgens
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59
Q

Adrenal Gland Pathology: Neuroblastoma

  • Epidemiology?
  • Origin?
  • Where does it occur?
  • Histological features?
  • Associated with overexpression of which oncogene?
  • Clinical Features? (5)
A

Neuroblastoma

  • Most common tumour of the adrenal medulla in children, usually < 4 years old
  • Originates from neural crest cells
  • Occurs anywhere along the sympathetic chain
  • Histology shows Homer-Wright rosettes characteristic of neuroblastoma and medulloblastoma
  • Associated with overexpression of N-myc oncogene
  • Clinical Signs
    1. Abdominal distension
    2. Firm, irregular mass that can cross the midline
    3. Less likely to develop hypertension than with pheochromocytoma
    4. Can also present with opsoclonus-myoclonus syndrome (“dancing eyes-dancing feet”)
    5. Increased HVA and VMA (catecholamine metabolites) in urine
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60
Q

Adrenal Gland Pathology: Pheochromocytoma

  • Epidemiology?
  • Which cells does it derive from?
  • Associated with which germ-line mutations?
  • Rule of 10s?
  • Clinical Features? (5)
A

Pheochromocytoma

  • Most common tumor of the adrenal medulla in adults
  • Derived from chromaffin cells (arise from neural crest)
  • May be associated with germline mutations (NF-1, VHL, RET [MEN 2A, 2B])
  • Rule of 10s
  • Clinical Signs
    1. Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension
    2. Episodic hyperadrenergic symptoms (5Ps)
    3. Pressure, pain, perspiration, palpitations and pallor
    4. Symptoms occur in “spells” (relapse and remit)
    5. Increased catecholamines and
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61
Q

Adrenal Gland Pathology: Pheochromocytoma

  • Episodic hyperadrenergic symptoms (5 Ps)?
  • Rule of 10s?
A
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62
Q

Pharmacology of Adrenal Disorders: Hyperaldosteronism

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects?
A

Pharmacology of Adrenal Disorders: Hyperaldosteronism

  • Treatment: Aldosterone receptor antagonist
  • Mechanism: Synthetic aldosterone receptor antagonist which acts on distal tubules
    to inhibit Na+ reabsorption (water excretion), K+ secretion and H+ secretion. Weak diuretics.
  • Examples: Spironolactone
  • Indications: Primary hyperaldosteronism, refractory oedema associated with secondary hyperaldosteronism e.g. cirrhosis of the liver and resistance hypertension (adjunct)
  • Side Effects: Gastric problems especially peptic ulcers, hyperkalaemia, nausea and lethargy. As a consequence of its similarity to the sex hormones, it can cause gynecomastia in males and menstrual irregularities in females.
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63
Q

Pharmacology of Adrenal Disorders: Hypoaldosteronism

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects?
A

Pharmacology of Adrenal Disorders: Hypoaldosteronism

  • Treatment: Synthetic mineralocorticoid
  • Mechanism: Mineralocorticoid replacement therapy
  • Examples: Fludrocortisone
  • Indications: Primary adrenal insufficiency and salt-losing congenital adrenal hyperplasia
  • Side Effects: Sodium and water retention, oedema, hypokalaemia, hypertension, hypokalaemic alkalosis and heart failure
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64
Q

Pharmacology of Adrenal Disorders: Hypocortisolism

  • Treatment?
  • Mechanism?
  • Examples?
  • Indications?
  • Side Effects?
A

Pharmacology of Adrenal Disorders: Hypocortisolism

  • Treatment: Corticosteroid
  • Mechanism: Glucocorticoid replacement therapy
  • Examples: Hydrocortisone or cortisone
  • Indications: Adrenal insufficiency (primary or secondary)
  • Side Effects: Hypertension, oedema, osteoporosis, impaired wound healing, hypokalaemia, peptic ulcers, glaucoma, increased appetite, weight gain, emotional disturbance, hirsutism and impaired glucose tolerance
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65
Q

Discuss the correct approach to a patient with a suspected endocrine disease - History protocol?

A
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66
Q

Discuss the correct approach to a patient with a suspected endocrine disease - Examination protocol?

A
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67
Q

Clinical Features of Excess GH (Acromegaly)?

  • High GH Adult
  • High GH Child
  • Adenoma?
A

Clinical Features of Excess GH (Acromegaly)

  • High GH Adult: Large tongue (macroglossia), hands and feet, deep husky voice, heavy facial features (enlarged nose, thickened lips, prominent brow and protruded jaw), diaphoresis (excessive sweating), impaired glucose tolerance (insulin resistance and T2DM), skin tags, thickened oily skin, dental changes (separation of lower teeth), bilateral carpal tunnel, cardiovascular problems (enlarged heart), joint aches and pains, hirsutism, weight gain, sleep apnoea, high blood pressure, fatigue.
  • High GH Child: Gigantism and increased linear bone growth
  • Adenoma: Headache, vision deficits and mass effect (i.e. altered menstrual cycle, erectile dysfunction and low sex drive)
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68
Q

What are the Clinical Features of Deficient GH?

  • Low GH Adult?
  • Low GH Child?
A

Clinical Features of Deficient GH

  • Low GH Adult: Increased body fat mass, reduced muscle mass, reduced bone density and osteoporosis
  • Low GH Child: Slow growth, failure to thrive, short stature, delayed puberty, hypoglycaemia and obesity
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69
Q

What are the Clinical Features of Deficient FSH and LH?

  • Males vs females?
A

Low FSH and LH: Amenorrhea, hypogonadism, low libido, infertility, erectile dysfunction, reduced muscle mass (males), delayed puberty, mood swings, vaginal dryness, hot flushes and osteoporosis (females)

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70
Q

What are the Clinical Features of Hyperprolactinemia?

  • High prolactin?
  • Adenoma?
A

Clinical Features of Hyperprolactinemia

  • High Prolactin: Galactorrhea, gynecomastia, amenorrhea, low libido, erectile dysfunction, infertility and hypogonadism (high prolactin and negative feedback on GnRH and sex hormones).
  • Adenoma: Headache, vision deficits and mass effect
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71
Q

What are the Clinical Features of Cushings (Hypercotisolism)?

  • High cortisol?
  • High sex hormones?
A

Hypercortisolism (Cushing Syndrome)

High Cortisol: Hypertension (increased adrenergic receptor activity), weight gain (due to high glucose and fat storage), moon facies, malar flush, proximal myopathy and muscle weakness (cortisol breaks down muscle producing AAs for gluconeogenesis), abdominal striae, thin wrinkled skin and purpura (due to impaired synthesis of collagen with thinning of skin), truncal obesity, buffalo hump, osteoporosis, hyperglycaemia (insulin resistance), amenorrhea and infertility (negative feedback on GnRH), immunosuppression and impaired wound healing

High Sex Hormones (Adrenal Cortex): Acne, oily skin and hirsutism (due to high ACTH)

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72
Q

What are the Clinical Features of Deficient Cortisol (Primary Adrenal Insufficiency)?

  • Low cortisol?
  • Low aldosterone?
  • Low sex hormones?
A

Deficient Cortisol (Primary Adrenal Insufficiency)

  • Low Cortisol: Postural hypotension, weight loss, malaise, fatigue, weakness, hypoglycaemia, hyperpigmentation of skin and mucosa (due to increased MSH, a byproduct of ACTH production from POMC) and vomiting and diarrhea
  • Low Aldosterone (Also Occurs with Addison’s): Hyponatremia (decreased aldosterone), hyperkalemia (decreased aldosterone), hypovolemia, hypotension and metabolic acidosis (low pH and HCO3-)
  • Low Sex Hormones (Also Occurs with Addison’s): Low libido and axillary and pubic hair
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73
Q

Clinical Features of Deficient Cortisol (Secondary Adrenal Insufficiency)?

A

Clinical Features of Deficient Cortisol (Secondary Adrenal Insufficiency)

Low Cortisol: As above BUT no skin/mucosal hyperpigmentation (no excess MSH from excess ACTH production) and no hyperkalemia (aldosterone synthesis preserved due to intact RAAS axis)

74
Q

Clinical features of Hypothyroidism and Hyperthyroidism?

A

Low TH: Cold intolerance (decreased heat production), weight gain, reduced appetite, hypoactivity, lethargy, fatigue, weakness, depressed mood, constipation, delayed reflexes, myopathy (proximal muscle weakness and increased CK), myxedema (facial/periorbital), dry and cool skin, coarse and brittle hair, bradycardia and dyspnea on exertion.

High TH: Heat intolerance (increased heat production), weight loss, increased appetite, hyperactivity, anxiety, insomnia, hand tremor, diarrhea, brisk reflexes, thyrotoxic myopathy (proximal muscle weakness and normal CK), pretibial myxedema (Graves disease), periorbital oedema, warm moist skin, fine hair, chest pain, palpitations, and arrhythmias (increased number and sensitivity of β-adrenergic receptors)

75
Q

Clinical Features of Deficient ADH (Central Diabetes Insipidus)?

Clinical Features of Excess ADH (SIADH)?

A

Deficient ADH (Central Diabetes Insipidus) - Low ADH: Polydipsia (intense thirst), polyuria, nocturia and inability to concentrate urine, dehydration, tachycardia, hypotension, hypovolaemia, insomnia, weight loss, hypernatraemia and serum hyper-osmolality

Excess ADH (SIADH) - High ADH: Low urinary output and concentrated urine, hyponatraemia, serum hypo- osmolality, nausea and vomiting, cramps or tremors, irritability, depressed mood or memory impairment, confusion, seizures and coma

76
Q

Review the anatomy of the eye and the physiology of vision

  • What are the 2 components of the outermost layer?
A

Outermost Layer (Outer Fibrous Tunic):

  1. Sclera: Tough connective tissue coat over majority of outside of eye (whites of eye)
  2. Cornea: Transparent structure in front of eye which allows light to enter (immunoprivileged site)
77
Q

Review the anatomy of the eye and the physiology of vision

  • What are the 4 components of the middle layer?
A

Middle Layer (Intermediate Vascular Tunic):

  1. Choroid: Vascular, pigmented layer under sclera which provides blood to retina and stops reflection of light that reaches back of eye (tunnel vision)
  2. Lens: Focuses light on the retina
  3. Ciliary Body: Contains ciliary muscles which attach to lens by zonular fibres and change the shape of the lens to focus light
  4. Iris: Located in front of lens which regulates amount of light entering eye by adjusting diameter of pupil
78
Q

Review the anatomy of the eye and the physiology of vision

  • What are the 3 components of the inner layer?
A

Inner Layer (Neural Tissue):

  1. Retina: Neural tissue that detects light
  2. Fovea: Where light from centre of visual field strikes retina (area of greatest visual acuity)
  3. Optic Disc (Papilla): Where optic nerve and blood vessels supplying eye pass through retina. No photoreceptor cells making it a blind spot. Overlapping visual fields cover the blind spots in each eye (perceptual closure accounts for any other missing information)
79
Q

Review the anatomy of the eye and the physiology of vision

  • What are the 3 internal chambers of the eye?
A

Internal Chambers of Eye: Lens and ciliary body separate eye into two chambers

  1. Anterior Chamber: Contains clear, watery (aqueous) fluid which supplies nutrients to cornea and lens
  2. Posterior Chamber: Consists of a small space directly posterior to the iris but anterior to the lens
  3. Vitreous Chamber: Contains firm, jelly like material (vitreous humour) which maintains spherical structure of eye. Consistency maintains internal pressure required to keep the eye’s shape.
80
Q

Muscles of the Eye

  • Where do the extraocular muscles originate and insert?
  • What is the function of the muscles of the eye?
  • Conjugate eye movements?
  • Disconjugate eye movements?
  • Saccadic eye movements?
  • Smooth-Pursuit Movements?
  • Vergence Movements?
A

Muscles of the Eye:

  • Extraocular Muscles: Originate from walls of orbit and insert in the outer surface of the eyeball (see below)
  • Function: Maintain the shape of the eyeball, hold it in the orbit and allows for eye movement
  • Conjugate Eye Movements: Both eyes move in same direction (binocular vision)
  • Disconjugate Eye Movements: Both eyes move in different directions
  • Saccadic Movements: Shift fovea rapidly to new visual target (conjugate movement)
  • Smooth-Pursuit Movements: Keep image of moving target on fovea (conjugate movement)
  • Vergence Movements: Align fovea of each eye with targets located at different distances from the observer (disconjugate movement). When viewing distant object, eyes diverge and close objects are not in focus. When viewing a near object, eyes converge and distant objects are not in focus.
81
Q

What are the 6 extraocular muscles and their actions?

  • Where do the rectus muscles originate and insert?
  • Superior oblique - origin & insertion?
  • Lateral oblique - origin & insertion?
A

Extraocular Muscles

  1. Lateral Rectus → Move eyes in horizontal plane away from nose (abduction)
  2. Medial Rectus → Move eyes in horizontal plane towards nose (adduction)
  3. Superior Rectus → Elevation, adduction and intorsion (medial rotation)
  4. Inferior Rectus → Depression, adduction and extorsion (lateral rotation)
  5. Superior Oblique → Depression, abduction and intorsion
  6. Inferior Oblique → Elevation, abduction and extorsion

NB: All rectus muscles originate from common tendinous ring (annulus of Zinn) and insert onto sclera of eye. Superior oblique originates from sphenoid bone and inserts posteriorly onto the eyeball. Lateral oblique originates from orbital surface of maxilla and inserts laterally onto the eyeball.

82
Q

Which nerves innervate the eyes?

  • Where is the horizontal gaze centre located?
  • Where is the vertical gaze centre located?
  • Where is the interneuron pathway located?
A

Nerves of the Eye:

Cranial Nerves: CN II, III, IV and VI (see below)

Horizontal Gaze Centre: Located in paramedian pontine reticular formation (PPRF)

Vertical Gaze Centre: Located in rostral midbrain formation

Interneuron Pathway: Medial longitudinal fasciculus in pons is a very important interneuron pathway between abducens nucleus in the pons and oculomotor nucleus in the midbrain (CN III and VI) which allows for conjugate eye movements

83
Q

Physiology of Vision:

  • What are visual fields?
  • What is visual acuity?
  • What is accommodation?
    • Near vision?
    • Distant vision?
A

Physiology of Vision:

  • Visual Fields: The angle of view, or the space that can be viewed by the retina when the eye is fixated straight ahead (normally 120 degrees)
  • Visual Acuity: The ability of the eye to distinguish detail, depends upon the spacing of the photoreceptors in the retina, and the precision of the eye’s refraction
  • Accommodation: Focus on near and distant objects (accommodate) by changing the shape of the lens due to the ciliary body (under PNS control)
    • Near Vision: Ciliary muscles contract causing the lens to round up
    • Distant Vision: Ciliary muscles relax and the suspensory ligaments pull the lens into a flatter shape
84
Q

Physiology of Vision: Regulation of Light

  • Bright light?
  • Dim Light?
  • Fight or Flight response?
  • Innervation?
A

Regulation of Light: Contraction or relaxation of inner circular muscle of iris smooth muscle regulates how much light enters eye

  • Bright Light: PNS stimulation contracts inner circular muscle, causing pupillary constriction, decreasing amount of light entering eye
  • Dim Light: Lack of PNS stimulation allows relaxation of inner circular muscle and pupillary dilation, increasing amount of light entering eye
  • Fight or Flight Response: SNS stimulation contracts outer radial muscle, causing pupillary dilation, increasing amount of light entering eye
  • Innervation: Oculomotor nerve (CN III) fibres which originate in the Edinger Westphal nucleus of the midbrain
85
Q

Physiology of Vision: Refraction of Light Waves

  • Which wavelengths are detected by humans?
  • What happens to light when it enters the eye?
A

Refraction of Light Waves: The bending of a wave when it enters a medium

  • Visible light detected by human ranges from 750nm to 350 nm (between infrared and UV rays)
  • Both cornea and lens have convex surfaces, causing light waves entering eye to converge onto retina
  • A given point in visual field comes to focus on a single point on retina
  • Focus mainly due to the cornea as the lens is responsible for fine adjustments
  • Passage of light waves through convex lens causes retinal image to be inverted and reversed
  • Light rays strike the curved surface of the cornea, pass through to the aqueous humour and slow down and refract (bend) at the lens to converge onto the retina
  • Light rays that enter the centre of the eye pass straight to the retina
  • Focal distance (m) is calculated from the lens to the focal point and is expressed in dioptres (1/m) e.g. A 3 dioptre lens brings parallel rays of light to focus at 1/3m
86
Q

Physiology of Vision: Phototransduction

  • 7 Steps?
A

Phototransduction: Photoreceptors depolarise in response to absence of stimuli or scotopic conditions (darkness). On exposure to light, retinal dissociates from opsin, initiating a sequence of reactions that decrease levels of cGMP inside cells, causing hyperpolarisation of photoreceptors and activation of bipolar cells (rods turn off, which turns on bipolar cells allowing nerve conduction).

  1. Activation of the receptor protein (rhodopsin in rods)
  2. Activated receptor protein (rhodopsin) stimulates G-protein transducin and GTP is converted to GDP in the process
  3. In turn, activated transducin activates the effector protein phosphodiesterase which converts cGMP to GMP
  4. Falling concentrations of cGMP cause the transduction channels to close, decreasing Na+ current and causing hyperpolarisation of the photoreceptor (due to ongoing efflux of K +)
  5. Hyperpolarisation of the cell causes voltage-gated calcium channels to close
  6. As the calcium levels in the photoreceptor cell drops, the amount of the neurotransmitter glutamate that is released by the cell also drops. This is because calcium is required for the glutamate -containing vesicles to fuse with cell membrane and release their contents.
  7. This reduces glutamate release which thus reduces the inhibition of retinal ganglion cells (activates them), leading to excitation of these nerve (glutamate normally has inhibitory effect here)
87
Q

What is the Neural Pathway of Vision?

  • 6 steps?
  • Which lobes of the brain do the optic radiations pass through and hence are vulnerable in stroke?
A

Neural Pathway:

  1. From ganglion cells, signals travel in optic nerve (CN II) and the optic nerves exits the eye at optic disc
  2. The optic nerves combine in the optic chiasm
  3. Proportion of nerve fibres cross over to opposite side of brain
  4. Information from right and left sides of visual field are processed in left and right sides of brain, respectively (nasal retina goes to opposite side, temporal retina goes to same side)
  5. Almost all ganglion cell axons synapse in the lateral geniculate nucleus (thalamus). Signals are then sent to the primary visual cortex.
  6. The remainder branch off to synapse in the superior colliculi and the pretectal area (cranial nerve nuclei areas) for direct eye movements.

NB: Optic radiations travel through the temporal and parietal lobes and so can be vulnerable to strokes

88
Q

Integration of Vision

  • Where is the primary visual cortex?
  • Ventral stream?
  • Dorsal stream?
  • Parietal Visual Cortical Areas?
  • Temporal Visual Areas?
A

Integration of Vision: At primary visual cortex

  • Primary Visual Cortex: The primary cortical region that receives, integrates and processes visual information that is relayed from the retinas.
  • Ventral Stream: Critical for visual perception (vision for perception)
  • Dorsal Stream: Mediates the visual control of skilled actions (vision for action)
  • Parietal Visual Cortical Areas: Deal with motion and spatial reasoning
  • Temporal Visual Areas: Process complex perception of patterns and forms into recognisable objects
89
Q

Disorders of Visual Pathway: Retina

  • 4 causes?
  • 2 defects?
A

Disorders of Visual Pathway: Retina

  • Causes
    1. Retinitis Pigmentosa
    2. Diseases of the retina
    3. Retinal detachment
    4. Retinal vessel occlusion
  • Defects
    1. Central Scotoma: A partial loss of vision or blind spot in an otherwise normal visual field seen with macula lesions (due to trauma or age)
    2. Peripheral Scotoma: Occurs with macula lesions involving fovea sparing
90
Q

Disorders of Visual Pathway: Retinitis pigmentosa?

A

Retinitis Pigmentosa: Inherited retinal degeneration. Painless, progressive vision loss beginning with night blindness (rods affected first). Bone spicule-shaped deposits around macula. Tunnel vision.

91
Q

Disorders of Visual Pathway: Retinal Detachment?

  • Pathogenesis?
A

Retinal Detachment: Separation of neurosensory layer of retina (photoreceptor layer with rods and cones) from outermost pigmented epithelium (normally shields excess light and supports retina) causing degeneration of photoreceptors and vision loss.

92
Q

Disorders of Visual Pathway: Retinal Detachment?

  • Clinical Findings?
A
93
Q

Disorders of Visual Pathway: Central Retinal Artery Occlusion?

  • Pathogenesis & Clinical Findings?
A

Central Retinal Artery Occlusion: Acute, painless monocular vision loss. Retina cloudy with attenuated vessels and “cherry-red” spot at fovea.

94
Q

Disorders of Visual Pathway: Central Retinal Vein Occlusion

  • Pathogenesis & Clinical Findings?
A

Retinal Vein Occlusion: Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis. Retinal hemorrhage and venous engorgement and oedema in affected area.

95
Q

Disorders of Visual Pathway: Optic Nerve

  • 5 Causes?
  • 4 Defects?
A

Disorders of Visual Pathway: Optic Nerve

  • Causes
    1. Optic neuritis (MS)
    2. Optic atrophy
    3. Retinal vessel occlusion
    4. Anterior ischemic optic neuropathy
    5. Papilledema
  • Defects
    1. Ipsilateral blindness (anopia) or scotoma
    2. Centrocecal Scotoma: Loss of vision in the fovea centralis region and a blind spot
    3. Pupillary Light Reflex: Loss of afferent limb.
    4. Absent direct pupillary light reflex. Consensual light reflex maintained.
96
Q

Disorders of Visual Pathway: Optic Chiasm

  • 4 Causes?
  • 2 Defects?
A

Disorders of Visual Pathway: Optic Chiasm

  • Causes
    1. Pituitary adenoma
    2. Craniopharyngioma
    3. Parasellar aneurysm of the internal carotid artery
    4. Meningioma
  • Defects
    1. Bitemporal heteronymous hemianopsia (middle lesions)
    2. Binasal hemianopsia (bilateral lesions)
97
Q

Disorders of Visual Pathway: Optic Tract

  • Cause?
  • Defect?
A

Disorders of Visual Pathway: Optic Tract

  • Cause → MCA infarction
  • Defect → Contralateral homonymous hemianopsia
98
Q

Disorders of Visual Pathway: Lateral Geniculate Nucleus

  • Cause?
  • Defect?
A

Disorders of Visual Pathway: Lateral Geniculate Nucleus

  • Cause: MCA infarction (MCA → Anterior choroidal artery → Posterior cerebral artery → Lateral choroidal artery)
  • Defect: Contralateral homonymous hemianopsia
99
Q

Disorders of Visual Pathway: Optic Radiations

  • Cause?
    • Lobes?
  • 2 Defects?
A

Disorders of Visual Pathway: Optic Radiations

  • Cause → MCA infarction
    • Upper quadrantanopsia indicates temporal lobe lesion
    • Lower quadrantanopsia indicates parietal lobe lesion
  • Defects
    1. Contralateral upper homonymous quadrantanopsia (anterior/lateral bundle lesions)
    2. Contralateral lower homonymous quadrantanopsia (posterior/medial lesions)
100
Q

Pathologies of the Eye: Conjunctivitis?

A

Conjunctivitis: Inflammation of the conjunctiva causing red eyes due to viral or bacterial infection or allergy.

101
Q

Pathologies of the Eye: Myopia?

A

Myopia (Near-Sightedness): Eye too long for refractive power of cornea (too curved) and lens and light is focused in front of retina. People have good near vision but poor distance vision. Correct with concave (diverging) lens.

102
Q

Pathologies of the Eye: Hyperopia?

A

Hyperopia (Far-Sightedness): Eye too short for refractive power of cornea (too little curvature) and lens and light is focused behind retina. Distant objects can be seen clearly, but close ones do not come into proper focus. Correct with convex (converging) lenses.

103
Q

Pathologies of the Eye: Astigmatism?

A

Astigmatism: Abnormal curvature of cornea causing different refractive power at different axes. Correct with cylindrical lens.

104
Q

Pathologies of the Eye: Presbyopia?

A

Presbyopia: Aging-related impaired accommodation (focusing on near objects), primarily due to decreased lens elasticity, changes in lens curvature and decreased strength of the ciliary muscle. Patients often need “reading glasses” (magnifiers).

105
Q

Pathologies of the Eye: Cataracts?

A

Cataracts: Painless, often bilateral, opacification (clouding) of lens, often resulting in decreased vision (due to UV or trauma).

106
Q

Pathologies of the Eye: Glaucoma?

A

Glaucoma: Optic disc atrophy with characteristic cupping (thinning of outer rim of optic nerve), usually with elevated intraocular pressure (IOP) and progressive peripheral visual field loss if untreated.

107
Q

Pathologies of the Eye: Uveitis?

A

Uveitis: Inflammation of uvea with specific name based on location within affected eye. Anterior uveitis is iritis and posterior uveitis is choroiditis and/or retinitis.

108
Q

Pathologies of the Eye: Age-Related Macular Degeneration?

A

Age-Related Macular Degeneration: Degeneration of macula (central area of retina). Causes distortion (metamorphopsia) and eventual loss of central vision (scotomas).

109
Q

Pathologies of the Eye: Diabetic Retinopathy?

A

Diabetic Retinopathy: Retinal damage due to chronic hyperglycemia due to microvasculature effects.

110
Q

Pathologies of the Eye: Diabetic Papilloedema?

A

Papilloedema: Optic disc swelling (usually bilateral) due to raised ICP. Enlarged blind spot and elevated optic disc with blurred margins.

111
Q

Pathologies of the Eye: Grave’s Ophthalmopathy?

A

Grave’s Ophthalmopathy: Autoimmune inflammatory disorder of the orbit and periorbital tissues, characterised by upper eyelid retraction, lid lag, swelling, erythema, conjunctivitis, and bulging eyes (exophthalmos). Most commonly occurs with Grave’s disease. Autoantibodies target the fibroblasts in the eye muscles, and those fibroblasts can differentiate into adipocytes. Fat cells and muscles expand and become inflamed. Veins become compressed, and are unable to drain fluid, causing oedema.

112
Q

Discuss the association between visual field defects and endocrine disorders

A
113
Q

Cells & Layers of the Retina

  • Pigmented Epithelium?
  • Photoreceptors?
  • Horizontal Cells?
  • Bipolar Cells?
  • Amacrine Cells?
  • Ganglion Cells?
A

Cells and Layers of the Retina:

  • Pigmented Epithelium: A layer of dark tissue beneath the photoreceptors which absorbs excess light so the photoreceptors can give a clearer signal. Moves nutrients to (and waste from) the photoreceptors to the choroid. Also blood retinal barrier.
  • Photoreceptors: Specialised cells that respond to light and enable phototransduction
  • Horizontal Cells: Laterally interconnecting neurons summate inputs from photoreceptors
  • Bipolar Cells: Responsible for 30% of input to retinal ganglion cells (regulated by am acrine cells)
  • Amacrine Cells: Responsible for 70% of input to retinal ganglion cells
  • Ganglion Cells: Receive visual information from photoreceptors via bipolar cells and amacrine cell and transmit it to the thalamus and visual cortex
114
Q

Photoreceptors (Rods and Cones)

  • Distribution?
  • Rods?
  • Cones?
  • Outer Segment?
  • Inner Segment?
  • Synaptic Terminal?
  • Rhodopsin?
A

Photoreceptors (Rods and Cones): Convert a light signal into a nerve signal (i.e. an electrical impulse).

  • Distribution: Uneven across the retina
  • Rods: Provide ability to see black and white in low light conditions. High sensitivity to light but low visual acuity. 100 million per retina.
  • Cones: Provide ability to see colour (red, blue and green), but only in bright light. Low sensitivity to light but high visual acuity. 3 million per retina.
  • Outer Segment: Has disks that contain photopigment
  • Inner Segment: Contains the nucleus
  • Synaptic Terminal: Contains stores of neurotransmitter used for communicating with nerves
  • Rhodopsin: Light sensitive pigment located in disks in outer segment. Comprises protein called opsin, which is bound to vitamin A derivative called retinal.
115
Q

Anatomy of the Eye

  • What is the fovea?
  • What is the macula?
  • Optic disc?
  • Retinal blood supply?
    • Arterial supply?
    • Venous drainage?
A

Anatomy of the Eye

  • Fovea: Region of highest visual acuity and contains 100% cones at highest density to ensure that most light is processed. Directed towards whatever focus of visual attention. Ratio of photoreceptors to ganglion cells is about 2:1. Percentage of rods increase towards the periphery.
  • Macula: Area around the fovea which has a pale yellow pigmentation
  • Optic Disc (Papilla): Where optic nerve and blood vessels supplying eye pass through retina.
  • Retinal Blood Supply:
    • Arterial Supply: Central retinal artery (first branch of ophthalmic artery) enters eye at optic disk. Branches are end arteries so if blocked that part of the retina dies.
    • Venous Drainage: Central retinal vein into cavernous sinus and/or superior ophthalmic vein
116
Q

How do we assess vision? Which defect will it detect?

A
117
Q

4 Grades of Hypertensive Retinopathy?

A

Grades of Hypertensive Retinopathy

  • Grade 1: Silver wiring of arteries
  • Grade 2: PLUS AV nipping/nicking
  • Grade 3: PLUS hemorrhages (flame- shaped) and exudates (cotton-wool spots or hard lipid residues)
  • Grade 4: PLUS papilloedema
118
Q

4 Categories of Diabetic Retinopathy Severity?

A

Categories of Diabetic Retinopathy Severity

  • Category 1 → Mild Non-Proliferative: Micro-aneurysms
  • Category 2 → Moderate Non-Proliferative: Multiple retinal hemorrhages
  • Category 3 → Severe Non-Proliferative: Starts to form new vessels with exudate formation
  • Category 4 → Proliferative: Neovascularization (fragile new vessels)
    * Non-Proliferative can have cotton wool spots (white and fluffy), hard exudates (yellow and waxy), flame hemorrhages and micro-aneurysms
119
Q
A
120
Q
A

Microaneurysms are localised outpouchings of capillaries that leak plasma constituents into the retina. They may be clinically indistinguishable from small dot and blot haemorrhages (see below).

121
Q
A

Dot and blot haemorrhages arise from bleeding capillaries in the middle layers of the retina.

They may look like microaneurysms if small enough. It is not particularly important to be able to distinguish between small haemorrhages and microaneurysms as they are both parts of pre-proliferative retinopathy.

122
Q
A

Cotton wool spots

Cotton wool spots appear as small, fluffy, whitish superficial lesions.

They are accumulations of dead nerve cells from ischaemic damage.

123
Q

Identify the topography of the structures in the anterior neck

  • Which 6 structures are you looking for?
A

Topography of Anterior Neck:

  1. Superficial (Investing) Fascia
  2. Pretracheal Fascia
  3. Infrahyoid Muscles
  4. Thyroid Gland
  5. Trachea
  6. Oesophagus
124
Q
A
125
Q

Cross section of the neck?

A
126
Q

Anatomy of the Thyroid Gland?

A

Anatomy of Thyroid Gland:

  • A butterfly-shaped gland located just inferior to the larynx (voice box)
  • Composed of right and left lateral lobes, one on either side of the trachea
  • Lobes connected by an isthmus anterior to the trachea
  • About 50% of thyroid glands have a small third lobe, called the pyramidal lobe, that extends superiorly from the isthmus
  • Normal mass is about 30g
127
Q

Histology of the Thyroid Gland?

A

Histology of Thyroid Gland:

  • Gland composed of microscopic spherical sacs called thyroid follicles
  • The wall of each follicle consists primarily of follicular cells, most of which extend to the lumen
  • A basement membrane surrounds each follicle
  • When the follicular cells are inactive their shape is low cuboidal to squamous, but under the influence of TSH
  • they become active in secretion and range from cuboidal to low columnar in shape
  • Parafollicular cells or C cells lie between the thyroid follicles
128
Q

Anatomy and Histology of the Parathyroid Gland?

A

Relation to Parathyroid Gland:

  • Four small glands on posterior side of thyroid gland
  • Disc-like glands embedded in the thyroid gland (dorsal surface)
129
Q

5 Functions of the Thyroid Hormones (T3/T4)?

A

Function of Thyroid Hormones (T3 and T4):

  1. Increase Basal Metabolic Rate: Increase the rate of oxygen consumption under standard or basal conditions (awake, at rest, and fasting), by stimulating the use of cellular oxygen to produce ATP. When the basal metabolic rate increases, cellular metabolism of carbohydrates, lipids, and proteins increases. Exceptions are adult brain, testes, uterus, lymph nodes, spleen (and anterior pituitary, turn off TSH production).
  2. Increase Temperature: Play an important role in the maintenance of normal body temperature. Stimulate synthesis of additional Na+/K+ ATPase pumps which use large amounts of ATP. As cells produce and use more ATP, more heat is given off, and body temperature rises. This phenomenon is called the calorigenic effect.
  3. Increase Metabolism: Stimulate protein synthesis and increase the use of glucose and fatty acids for ATP production. They also increase lipolysis and enhance cholesterol excretion, thus reducing blood cholesterol level.
  4. Increase Catecholamines: Enhance some actions of noradrenaline and adrenaline because they upregulate beta receptors. This increases heart rate, contractility, cardiac output, stroke volume and blood pressure.
  5. Increase Growth: Together with human growth hormone and insulin, thyroid hormones accelerate body growth, particularly the growth of the nervous and skeletal systems. Deficiency of thyroid hormones
    during fetal development, infancy, or childhood causes severe mental retardation and stunted bone growth.
130
Q

Triiodothyronine (T3) & Thyroxine / Tetraiodothyronine (T4)

  • Synthesis?
  • 7 Functions?
A

Thyroxine / Tetraiodothyronine (T4)

  • Synthesis → Follicular Cells of Thyroid Gland
  • Functions
    1. Increase basal metabolic rate
    2. Stimulate synthesis of proteins
    3. Increase use of glucose and fatty acids for ATP production
    4. Increase lipolysis
    5. Enhance cholesterol excretion
    6. Accelerate body growth
    7. Contribute to development of nervous system
131
Q

Calcitonin

  • Synthesis?
  • 2 Functions?
A

Calcitonin

  • Synthesis → Parafollicular Cells of Thyroid Gland
  • 2 Functions
    1. Lowers blood levels of Ca2+ and HPO42- by inhibiting bone resorption by osteoclasts and by accelerating uptake of calcium and phosphates into bone extracellular matrix
    2. Inhibits osteoclasts which decreases bone resorption
132
Q

Parathyroid Hormone

  • Synthesis?
  • 4 Functions?
A

Parathyroid Hormone

  • Synthesis → Chief Cells of Parathyroid Gland
  • Functions
    1. Increases blood Ca2+ and Mg2+ levels and decreases blood HPO42- levels
    2. Promotes Ca2+ release into the blood by increasing bone resorption by osteoclasts (increases RANKL and decreases OPG which increases osteoclast numbers)
    3. Increases Ca2+ reabsorption (DCT regulated reabsorption) and HPO42- excretion by kidneys, reducing the amount lost in the urine
    4. Promotes formation of calcitriol (active form of
      vitamin D by kidneys), which increases rate of dietary Ca 2+ and Mg2+ absorption at small intestine, reducing the amount lost in the faeces
133
Q

8 Steps in Thyroid Hormone Production?

A

Synthesis of Thyroid Hormones:

  1. Iodide Trapping: Thyroid follicular cells trap iodide ions (I-) by actively transporting them from the blood into the cytosol. The thyroid gland normally contains most of the iodide in the body.
  2. Synthesis of Thyroglobulin: While the follicular cells are trapping I-, they are also synthesising thyroglobulin (TGB), a large glycoprotein that is produced in the rough endoplasmic reticulum, modified in the Golgi complex, and packaged into secretory vesicles. The vesicles then undergo exocytosis, which releases TGB into the lumen of the follicle.
  3. Oxidation of Iodide: Some of the amino acids in TGB are tyrosines that will become iodinated. However, negatively charged iodide ions cannot bind to tyrosine until they undergo oxidation (removal of electrons) to iodine (I2). As the iodide ions are being oxidised, they pass through the membrane into the lumen of the follicle.
  4. Iodination of Tyrosine: As iodine molecules (I2) form, they react with tyrosines that are part of TGB molecules. Binding of one iodine atom yields monoiodotyrosine (T1), and a second iodination produces diiodotyrosine (T2). The TGB with attached iodine atoms, a sticky material that accumulates and is stored in the lumen of the thyroid follicle, is termed colloid.
  5. Coupling of T1 and T2: Two T2 molecules join to form T4, or one T1 and one T2 join to form T3.
  6. Pinocytosis and Digestion of Colloid: Droplets of colloid reenter follicular cells by pinocytosis and merge with lysosomes. Digestive enzymes in the lysosomes break down TGB, cleaving off molecules of T3 and T4.
  7. Secretion of Thyroid Hormones: T3 and T4 are lipid soluble, and so diffuse through the plasma membrane into interstitial fluid and then into the blood. T4 normally is secreted in greater quantity than T3, but T3 is several times more potent. After T4 enters a body cell, most of it is converted to T3 by removal of one iodine.
  8. Transport in the Blood. More than 99% of both the T3 and the T4 combine with transport proteins in the blood, mainly thyroxine-binding globulin (TBG) and travel to site of action.
134
Q

Regulation of Thyroid and Parathyroid Hormones

  • T3 & T4? (3)
  • Calcitonin?
  • PTH?
A

Regulation of Thyroid and Parathyroid Hormones:

  • Thyroid Hormones (T3 and T4)
    1. Secretion is increased by thyrotropin-releasing hormone (TRH), which stimulates release of thyroid-stimulating hormone (TSH) in response to low thyroid hormone levels, low metabolic rate, cold, pregnancy, and high altitudes
    2. TRH and TSH secretions are inhibited in response to high thyroid hormone levels
    3. High iodine level suppresses T3/T4 secretion
  • Calcitonin
    1. High blood Ca2+ levels stimulate secretion
    2. Low blood Ca2+ levels inhibit secretion
  • Parathyroid Hormone
    1. Low blood Ca2+ levels stimulate secretion
    2. High blood Ca2+ levels inhibit secretion
135
Q

5 Steps in Hormones and Expression of Target Genes?

A

Hormones and Expression of Target Genes:

  1. Hormone travels in blood to distant sites of action
  2. Hormone binds to receptors on target organ
  3. Binding elicits specific signal transduction pathway (via second messengers)
  4. Produces cellular response and changes in gene expression (nucleus)
  5. Results in specific cellular function
136
Q

3 Types of Transmembrane Receptors?

A

Transmembrane Receptors: Receptors that span the cell membrane

  1. Enzyme-linked receptors: Intracellular component is an enzyme that is activated by binding (insulin receptor activates protein kinase)
  2. Ion channel-linked receptors: Binding of a ligand opens/closes an ion channel (neurotransmitter)
  3. G protein-coupled receptors: Binding of first messenger activates secondary messenger to elicit cellular response (adrenaline)
137
Q

7 Steps in the activation of G protein-coupled receptors?

A

Activation of G protein-coupled receptors

  1. Hormone binds to a specific receptor
  2. The bound receptor causes replacement of the GDP bound to Gs by GTP, activating Gs
  3. Gs (alpha subunit) moves to adenyl cyclase and activates it
  4. Adenyl cyclase catalyzes the formation of cAMP from ATP
  5. cAMP activates protein kinase A (PKA)
  6. Phosphorylation of cellular proteins by PKA causes cellular response
  7. cAMP is degraded, reversing the activation of PKA
138
Q

4 Hormones that act on Transmembrane Receptors?

A

Hormones that act on Transmembrane Receptors

  1. Peptide hormones
  2. Catecholamines (monoamines)
  3. GFs
  4. Water-soluble hormones
139
Q

What are Intracellular receptors?

  • Nuclear receptors?
  • 4 steps in activation pathway?
  • Which 3 hormones use intracellular receptors?
A

Intracellular Receptors: Receptors found within the cytoplasm or nucleus of a cell

Nuclear receptors: Ligands bind to receptor (cytoplasmic/nuclear) causing a conformational change, allowing complex to interact with DNA and increase/decrease transcription of a specific gene(s)

  1. Steroid passes through plasma membrane and binds to receptor in cytoplasm
  2. Activated receptor binds to specific regulatory sequence of DNA (hormone response elements)
  3. Binding to DNA modifies the rate of transcription of the associated gene
  4. Modified transcription leads to modified translation of regulated gene product

Hormones:

  1. Steroid hormones
  2. Thyroid hormones
  3. Lipid-soluble hormones
140
Q

Signaling pathways of endocrine hormones?

A
141
Q

Thyroid Gland Pathology: Thyroglossal Duct Cyst?

A

Thyroid Gland Pathology: Thyroglossal Duct Cyst

  • Cystic dilation of thyroglossal duct remnant
  • Thyroid develops at the base of tongue and then travels along the thyroglossal duct to the anterior neck
  • Thyroglossal duct normally involutes however a persistent duct may undergo cystic dilation
  • Presents as an anterior neck mass that moves during swallowing

The thyroid anlage begins in the region of the foramen cecum at the base of the tongue; as the gland develops, it descends to its definitive midline location in the anterior neck. Remnants of this developmental process may persist, resulting in 1- to 4-cm cysts that are lined by stratified squamous epithelium when located near the base of the tongue or by pseudostratified columnar epithelium in lower locations. Transitional epithelial differentiation patterns also occur. The fibrous cyst wall often includes lymphoid aggregates or thyroid remnants. Malignant transformation of the lining epithelium is exceedingly rare. The definitive treatment is surgical excision.

142
Q

Thyroid Gland Pathology: Lingual Thyroid?

A

Thyroid Gland Pathology: Lingual Thyroid

  • Persistence of thyroid tissue at the base of tongue
  • Presents as a base of tongue mass

The thyroid gland consists of two lateral lobes connected by a thin isthmus, usually located below and anterior to the larynx. It develops embryologically from an evagination of the pharyngeal epithelium that descends from the foramen cecum at the base of the tongue to its normal position in the anterior neck. This pattern of descent explains the occasional presence of ectopic thyroid tissue at the base of the tongue (lingual thyroid) or at other sites high in the neck.

143
Q

6 Hypothyroidism Pathologies?

A

Hypothyroidism Pathologies

  1. Cretinism
  2. Myxedema
  3. Hashimoto Thyroiditis
  4. Subacute Granulomatous Thyroiditis (de Quervain)
  5. Riedel Thyroiditis
  6. Other
144
Q

Hypothyroidism Pathology: Cretinism?

A

Hypothyroidism Pathology: Cretinism

  • Hypothyroidism in neonates and infants (congenital)
  • Severe fetal hypothyroidism due to maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis, iodine deficiency or dyshormonogenetic goiter (due to congenital defect in thyroid hormone production, most commonly thyroid peroxidase)
  • Clinically manifests as pot-bellied, pale, puffy-faced child with protruding umbilicus, protuberant (enlarged) tongue and poor brain development (6 P’s), short stature with skeletal abnormalities and coarse facial features
145
Q

Hypothyroidism Pathology: Myxedema?

A

Hypothyroidism Pathology: Myxedema

  • Hypothyroidism in older children or adults
  • Most common causes are iodine deficiency and Hashimoto thyroiditis
  • Other causes include drugs (lithium) and surgical removal or radio-ablation of the thyroid
  • Clinical features are based on decreased basal metabolic rate and decreased sympathetic nervous system activity (general hypothyroidism features)
146
Q

Hypothyroidism Pathology: Hashimoto Thyroiditis?

  • Cause?
  • Mechanism?
  • Histological findings?
  • Clinical manifestations?
A

Hypothyroidism Pathology: Hashimoto Thyroiditis

  • Most common cause of hypothyroidism in iodine-sufficient regions
  • Autoimmune destruction of the thyroid gland, associated with HLA-DRS and antithyroid peroxidase (antimicrosomal) and antithyroglobulin antibodies
  • Progressive depletion of thyroid epithelial cells, replaced by mononuclear cell infiltration and fibrosis
  • Associated with increased risk of non-Hodgkin lymphoma (typically of B-cell origin)
  • May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture
  • Histologic findings include Hürthle cells (eosinophilic metaplasia of cells that line follicles) and chronic lymphoid aggregates with germinal centers
  • Clinically manifests as moderately enlarged, nontender thyroid
147
Q

Hypothyroidism Pathology: Hashimoto Thyroiditis?

  • Natural history and clinical findings?
A
148
Q

Hypothyroidism Pathology: Subacute Granulomatous Thyroiditis (de Quervain)?

  • What?
  • Histological findings?
  • Clinical findings?
A

Subacute Granulomatous Thyroiditis (de Quervain)

  • Self-limited disease often following a flu-like illness (such as viral infection)
  • May be hyperthyroid early in course, followed by hypothyroidism
  • Histological findings include granulomatous inflammation
  • Clinically manifests as raised ESR, jaw pain and very tender thyroid (de Quervain is associated with pain)
149
Q

Pathogenesis of Hashimoto’s?

A
150
Q

Hypothyroidism Pathology: Riedel Thyroiditis

A

Hypothyroidism Pathology: Riedel Thyroiditis

  • Chronic inflammation with extensive fibrosis of the thyroid gland
  • Thyroid replaced by fibrous tissue with inflammatory infiltrate
  • Fibrosis may extend to local structures (trachea, esophagus), mimicking anaplastic carcinoma.
  • One third are hypothyroid
  • Considered a manifestation of IgG4-related systemic disease (i.e. autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis).
  • Clinical manifests as fixed (‘hard as wood’) nontender thyroid and painless goiter
151
Q

Thyroiditis : Pathogenesis and clinical findings?

A
152
Q

7 Hyperthyroidism Pathologies?

A

Hyperthyroidism Pathologies

  1. Graves Disease (Diffuse Toxic Hyperplasia)
  2. Multinodular Goiter
  3. Thyroid Storm (Thyrotoxicosis Crisis)
  4. Jod-Basedow Phenomenon
  5. Hyperfunctioning adenoma or carcinoma (see below)
  6. TSH-secreting pituitary adenoma (secondary hyperthyroidism)
  7. Struma ovarii (ovarian teratoma with ectopic thyroid)
153
Q

Hyperthyroidism Pathology: Graves Disease (Diffuse Toxic Hyperplasia)?

  • Mechanism?
  • Epidemiology?
  • Histological findings?
  • Lab findings?
  • Treatment?
  • Complications?
A

Hyperthyroidism Pathology: Graves Disease (Diffuse Toxic Hyperplasia)

  • Most common cause of hyperthyroidism
  • Autoantibody (IgG) that stimulates TSH receptor (type II hypersensitivity)
  • Leads to increased synthesis and release of thyroid hormone
  • Classically occurs in women of childbearing age (20-40 years)
  • Histological findings include irregular follicles with scalloped colloid (colloid that has been removed for secretion into blood) and chronic inflammation
  • Laboratory findings include increased total and free T4 and decreased TSH, hypocholesterolemia and increased serum glucose
  • Treatment involves B-blockers, thioamide, and radioiodine ablation
  • Thyroid storm is a potentially fatal complication
154
Q

Hyperthyroidism Pathology: Graves Disease (Diffuse Toxic Hyperplasia)

  • Clinical Findings?
A

Clinical features of Graves

  1. Hyperthyroidism
  2. Diffuse goiter (constant TSH stimulation leads to thyroid hyperplasia and hypertrophy)
  3. Exophthalmos and pretibial myxedema (fibroblasts behind the orbit and overlying the shin express the TSH receptor and activation results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis and oedema)
155
Q

Hyperthyroidism Pathology: Multinodular Goiter?

A

Hyperthyroidism Pathology: Multinodular Goiter

  • Enlarged thyroid gland with multiple nodules
  • Due to relative iodine deficiency
  • Usually nontoxic (euthyroid)
  • Rarely, regions become TSH-independent leading to T4 release and hyperthyroidism (toxic goiter)

With time, recurrent episodes of hyperplasia and involution combine to produce a more irregular enlargement of the thyroid, termed multinodular goiter. Virtually all long-standing simple goiters convert into multinodular goiters. Multi- nodular goiters produce the most extreme thyroid enlarge- ments and are more frequently mistaken for neoplasms than any other form of thyroid disease. Because they derive from simple goiter, they occur in both sporadic and endemic forms, having the same female-to-male distribution and presumably the same origins but affecting older individuals because they are late complications.

156
Q

Hyperthyroidism Pathology: Thyroid Storm (Thyrotoxicosis Crisis)

  • What?
  • Clinical features?
  • Tx?
A

Hyperthyroidism Pathology: Thyroid Storm (Thyrotoxicosis Crisis)

  • Uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/untreated and then significantly worsens in the setting of acute stress such as infection, trauma or surgery
  • Due to elevated catecholamines and massive hormone excess
  • Presents with agitation, delirium, fever, diarrhea, coma, tachyarrhythmia (cause of death), hyperthermia, vomiting and hypovolaemic shock. May see raised LFTs.
  • Treat with 4Ps including β-blockers (Propranolol), Propylthiouracil, corticosteroids (Prednisolone) and Potassium iodide (Lugol iodine)
157
Q

Hyperthyroidism Pathology: Jod-Basedow Phenomenon?

A

Hyperthyroidism Pathology: Jod-Basedow Phenomenon

  • Thyrotoxicosis if a patient with iodine deficiency and partially autonomous thyroid tissue (autonomous nodule) is made iodine replete
  • Opposite of Wolff-Chaikoff effect
158
Q

7 Thyroid Neoplasm Pathologies?

A

Thyroid Neoplasm Pathologies

  1. Thyroid Adenoma
  2. Thyroid Cancer
  3. Papillary Carcinoma (75-85% of cases)
  4. Follicular Carcinoma (10-20% of cases)
  5. Medullary Carcinoma (5% of cases)
  6. Undifferentiated / Anaplastic Carcinoma (<5% of cases)
  7. Lymphoma
159
Q

Morphology and Histology of Multinodular goiter?

A

Multinodular goiter.

(A) Gross morphology demonstrating a coarsely nodular gland containing areas of fibrosis and cystic change.

(B) Photomicrograph of a hyperplastic nodule with compressed residual thyroid parenchyma on the periphery. Note the absence of a prominent capsule, a distinguishing feature from follicular neoplasms.

160
Q

Thyroid Neoplasm Pathology: Thyroid Adenoma?

A

Thyroid Neoplasm Pathology: Thyroid Adenoma

  • Benign solitary growth of the thyroid (commonest neoplasm)
  • Most are nonfunctional
  • Rarely cause hyperthyroidism via autonomous thyroid hormone production (“toxic”)
  • Most common histology is follicular with absence of capsular or vascular invasion (unlike follicular carcinoma).
161
Q

Thyroid Neoplasm Pathology: Thyroid Cancer

  • Diagnosis?
  • Treatment?
  • Complications of surgery?
A

Thyroid Neoplasm Pathology: Thyroid Cancer

  • Typically diagnosed with fine needle aspiration
  • Treated with thyroidectomy
  • Complications of surgery include hoarseness (due to recurrent laryngeal nerve damage), hypocalcemia (due to removal of parathyroid glands) and transection of recurrent and superior laryngeal nerves (during ligation of inferior thyroid artery and superior laryngeal artery, respectively)
162
Q

5 Types of Thyroid Cancer?

A
163
Q

4 Causes of Smooth/Diffuse Goitre?

4 Causes of Nodular Goitre?

A
164
Q

3 Causes of Graves?

A

Causes of Graves Disease:

  1. B and T lymphocyte-mediated autoimmune disorder
  2. Genetic predisposition given that 50% of patients with Graves disease have a family history of autoimmune disorders (Type 1 DM, Hashimoto’s disease, pernicious anemia, myasthenia gravis)
  3. May be triggered by surgery/trauma of the thyroid gland and possibly severe psychological stress
165
Q

Pathophysiology of Graves Disease (6 steps)?

A

Pathophysiology of Graves Disease:

  1. TSH-receptor stimulating IgG immunoglobulin (type II hypersensitivity reaction)
  2. Autoantibody acts as an agonist on TSH receptors and activates thyroid
  3. Leads to increased synthesis and release of thyroid hormone (hyperthyroidism)
  4. Constant TSH stimulation leads to thyroid hyperplasia and hypertrophy (diffuse goiter)
  5. Autoantibody also acts on orbital fibroblasts causing fibroblast proliferation, hyaluronic acid synthesis and differentiation of fibroblasts to adipocytes (opthalmopathy with exophthalmus)
  6. Autoantibody also acts on dermal fibroblasts (shin) and causes deposition of glycosaminoglycans in connective tissue (pretibial myxedema)
166
Q

4 Clinical Features of Graves Disease?

A

Clinical Features of Graves Disease:

  1. Symptoms of hyperthyroidism
  2. Diffuse Goiter: Smooth, uniformly enlarged goiter and bruit may be heard at the superior poles of the lobes
  3. Ophthalmopathy: Exophthalmos, ocular motility disturbances, lid retraction and conjunctival conditions
  4. Dermopathy (Pretibial Myxedema): Non-pitting oedema and firm plaques on the anterior/lateral aspects of both legs
167
Q

Diagnosis of Graves Disease? (4)

A

Diagnosis of Graves Disease: Often apparent on clinical examination and is confirmed through detection of specific thyroid antibodies

  • 1) Blood Test: Reduced/undetectable TSH and raised T3/T4
  • 2) Thyroid Antibodies
    • ↑ TRAbs (specific)
    • ↑ anti-TPO and anti-Tg (nonspecific)
  • 3) Thyroid Scintigraphy
    • A nuclear medicine procedure that produces a visual display of functional thyroid tissue based on the selective uptake of various radionuclides by thyroid tissue
    • Indicated if TRAbs are low to establish a diagnosis
    • Shows a diffuse uptake of radioactive iodine (123I)
    • Contraindicated in pregnancy
  • 4) Thyroid Ultrasound (With Colour Doppler)
    • Indicated in pregnant women if TRAbs are low
    • Shows an enlarged, hypervascular thyroid
168
Q

Treatment of Graves Disease

  • Goal?
  • Role of beta-blockers?
  • 3 Antithyroid drugs?
    *
A

Treatment of Graves Disease:

  • Goal: To inhibit the production of thyroid hormones and to block the effect of the hormones on the body
  • β-blockers: Rapid control of hyperthyroidism symptoms
  • Antithyroid Drugs:
    1. Carbimazole: Block thyroid hormone synthesis
    2. Propylthiouracil: Block thyroid hormone synthesis and also inhibits peripheral conversion of T4 to T3
      1. Patients with a small goiter and mild hyperthyroidism may undergo remission on antithyroid drugs alone (in about 50% of cases)
      2. Once remission is achieved, drugs are slowly tapered and stop
  • Radioactive Iodine Ablation:
    • First-line therapy in nonpregnant patients with small goiters
    • Second-line therapy in patients who relapse after long-term therapy with antithyroid drugs
  • Surgery: Near-total thyroidectomy is rarely done in Graves disease
  • Complications of Therapy:
    1. Permanent hypothyroidism after radioactive iodine ablation or surgery (requires lifelong thyroid replacement therapy)
    2. New-onset/exacerbation of Graves ophthalmopathy after radioactive iodine ablation
    3. Hoarseness due to transection of recurrent laryngeal nerve
    4. Hypocalcaemia due to removal of parathyroid gland
169
Q

Hyperthyroidism medications

  • What are they?
  • Types?
A
170
Q

Hyperthyroidism medications

  • Clinical concerns?
A
171
Q

List 11 Autoimmune Diseases and their Autoantibody?

A

Autoimmune Diseases

  1. Autoimmune Hepatitis (Liver) → Anti-smooth muscle
  2. Antiphospholipid Syndrome → Anti-phospholipid
  3. Coeliac Disease (GI Tract) → Anti-endomysial IgA, Anti-gliadin IgA, Anti-tissue transglutaminase IgA
  4. Diabetes Mellitus Type 1 (Pancreas) → Anti-glutamic acid decarboxylase
  5. Goodpasture’s Syndrome → Anti-glomerular basement membrane
  6. Graves Disease (Thyroid) → Anti-TSH receptor
  7. Hashimoto’s Thyroiditis (Thyroid) → Anti-thyroid peroxidase (microsomal) & Anti-thyroglobulin
  8. Myasthenia Gravis (Nerves and Muscles) → Anti-acetylcholine receptor
  9. Pernicious Anaemia (Stomach) → Anti-intrinsic factor & Anti-parietal cell
  10. Primary Biliary Cirrhosis (Liver) → Anti-mitochondrial
  11. Systemic Lupus Erythematous (SLE) → Anti-nuclear antibodies (ANA), Anti-dsDNA & Anti-Sm (Smith antigen)
172
Q

Clarify that Graves’ disease is an organ-specific autoimmune disease

  • Autoantibody?
  • Receptor?
  • Locations of TSH Receptors? (3)
A

Graves as Autoimmune Disease:

  • Autoantibody: TSH-receptor stimulating IgG immunoglobulin (TRAbs) which acts as an agonist on TSH receptors and activates thyroid gland and extra-thyroid tissues
  • Receptor: Thyroid stimulating hormone receptor (TSHR), a G protein-coupled receptor
  • Location of TSH Receptors:
    1. Thyroid follicular cells (main location)
    2. Retro-orbital fibroblasts and adipose tissue
    3. Pretibial space fibroblasts and adipose tissue
173
Q
A
174
Q

Pathogenesis and Clinical Findings of Hyperthyroidism?

A
175
Q

Pathogenesis and Clinical Findings of Hypothyroidism?

A
176
Q

Develop skills in the use of an interpreter to facilitate communication with non-English speaking patients, including Aboriginal peoples.

  • How to work with an interpreter?
A
177
Q

Develop skills in the use of an interpreter to facilitate communication with non-English speaking patients, including Aboriginal peoples

  • How to determine if you need an interpreter?
A
178
Q

Develop skills in the use of an interpreter to facilitate communication with non-English speaking patients, including Aboriginal peoples

  • Decision making tree about interpreters?
A
179
Q

Develop skills in explaining a diagnosis and prognosis, and in explaining treatment and follow-up.

  • What is Murtagh’s 10-Point Plan for Consultation?
A

Murtagh’s 10-Point Plan for Consultation:

  1. Tell the patient the diagnosis, or if not possible, describe the problem as it relates to the presenting symptoms (signpost, explain in simple terms without medical jargon, pace the information and use resources)
  2. Establish the patient’s knowledge of the diagnosis
  3. Establish the patient’s attitude to the diagnosis and management
  4. Educate the patient about diagnosis
  5. Develop a management plan for the presenting problem (immediate, long-term and preventive)
  6. Explore other preventive opportunities (immunisation, screening tools and smoking, alcohol and safe sex advice)
  7. Reinforce the information
    1. Use the patient’s own results (e.g. X-rays and ECGs)
    2. Encourage the patient to participate in the decision making and in accepting some degree of responsibility for his or her own management
  8. Provide take-away information (patient instruction leaflets, diagrams and resource contacts)
  9. Evaluate the consultation
  10. Arrange follow-up and document
180
Q

Endocrine Investigations

  • How to we test for Addison’s Disease (Primary Adrenal Insufficiency)?
A
  • Acute adrenal insufficiency: Make a clinical diagnosis and defer detailed testing until after empiric glucocorticoids are given.
  • Chronic adrenal insufficiency: Use stepwise endocrine testing in all patients.
    1. Morning cortisol
    2. Morning ACTH
    3. ACTH stimulation test
  • Primary adrenal insufficiency: Screen for hypoaldosteronism and hypoandrogenism.
  • Secondary and tertiary adrenal insufficiency: Differentiating between the two is often not required, as it does not influence management.
  • All patients: Investigate for an underlying cause.

YR2 BCS Study Points SEM 1 (7 decks)

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