Endocrinology 2

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Endocrinology 2

• Lecture Notes

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Adrenal Glands

• We have 2 adrenal glands located above the
  kidneys.
• The adrenal gland is divided into 3 portions, the
  adrenal cortex the adrenal medulla.
• The adrenal cortex is further divided into 3
  layers
• Zona glomerulosa ? releases aldosteron
• Zona fasciculata ? releases cortisol
• Zona reticularis ? releases sex steroids

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Adrenal Medulla

• Adrenal medulla cells secrete catecholamines
  (epinephrine norepinephrine, 4 1 ratio , more
  epinephrine secretion)
• It is innervated by sympathetic nerve fibers,
  activated by stress, meaning that it will support
  the sympathetic nervous system
• Secretion is initiated by stimulation of
  preganglionic sympathetic neurons

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Adrenal Medulla

• Effects are very similar to those caused by
  stimulation of sympathetic nervous system, they
  last 10 times longer.
• Activation of adrenal medulla along with the
  sympathetic nervous system prepares the body for
  greater physical performance (fight-or-flight)

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Effects of Fight-or-Flight

• Increase heart rate
• Vasoconstricts arterioles to most tissues
• Vasodilates arterioles to muscles, lungs and
  heart
• Dilate pupils so more light reaches retina
• Stimulates ventilation
• Increases glycogenolysis in the liver to provide
  energy
• Stimulate glucagon ? increases blood glucose
  level
• Inhibits insulin ? prevent the uptake of glucose
  from blood
• Increases lipolysis in adipose tissue to provide
  energy
• Increases efficiency of muscle contraction
• Increases sweating ? heat loss

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Adrenal Cortex

• Secrets steroid hormones called corticosteroids
  including
• Mineralocorticoids (aldosterone)
• Glucocortecoids (cortisol)
• Sex steroids (estrogens, androgens)

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Adrenal Cortex

• Mineralocorticoids (aldosterone)
• Zona glomerulosa ? aldosterone ? kidneys ?
  regulates Na and K balance in body fluids
• Glucocortecoids (cortisol? catabolic hormone)
• ACTH stimulates the zona fasciculata ? cortisol
  is released ? acts on liver, muscle adipose
  tissue to regulate carbohydrate, prootein and fat
  metabolism? leading to
• Increase in serum glucose
• Increase in serum fatty acid
• Increase in serum amino acid
• Sex steroids (estrogens, androgens)
• Weak andorgens secreted by different zones of
  adrenal cortex (Zona reticularis)
• Not the main sex steroids, the main sex steroids
  are provided by the gonads, these are supplement
  of sex steroids secreted by gonads.

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Adrenal Cortex Secretion Abnormalities

• Cushings Disease
• Cause hypersecretion of corticosteroids
  (cortisol) as a result of
• Tumor of adrenal cortex (Cushing's syndrome)
• Oversecretion of ACTH from anterior pituitary (
  Cushing's disease)

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Important!Cushings Disease is Different From
Cushings Syndrome

• Cushings Syndrom
• One cause for Cushings syndrome is exogenous
  glucocorticoids. Meaning that a person take
  corisol exogenously by injections or tablets to
  treat various diseases.
• Another cause for Cushings syndrome is a tumor
  of the adrenal gland, the patient will have high
  production of cortisol ? it will inhibit ACTH
  through negative feedback mechanism.
• In these two cases the person is said to have
  Cushings syndrome

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Important!Cushings Disease is Different From
Cushings Syndrome

• Cushings Disease
• A patient has high secretion of ACTH from the
  anterior pituitary ? high ACTH will stimulate the
  adrenal gland to produce cortisol

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Important!Cushings Disease is Different From
Cushings Syndrome

• If you take a serum sample from a Cushings
  Disease patient he will have
• High levels of ACTH High level of cortisol
• If you take a serum sample from a Cushings
  Syndrom patient he will have
• Low levels of ACTH High level of cortisol

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Important!Cushings Disease is Different From
Cushings Syndrome

• Changes in the body are the same in the two cases
  EXCEPT
• The hyperpigmentation in Cushings Disease
  patients because of excess ACTH
• ACTH is a melanocyte stimulating hormone, it
  stimulates the melanocyte , so the patient will
  have a darker skin

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Cushings Disease and Cushings Syndrome

• Characterized by
• Hyperglycemia because cortisol is a catabolic
  hormone?it will cause the breakdown of
  carbohydrates ? increase level if glucose in the
  circulation
• Hypertension because cortisol can stimulate Na
  and water retention
• Muscular weakness due to the breakdown of
  protiens
• Thin arms and legs

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Cushings Disease and Cushings Syndrome

• Those patients will also have red cheeks because
  cortisol stimulates erythropoietin which is the
  hormone that causes the production of red blood
  cells from the bone marrow.
• The patients also have purple abdominal striae,
  the look like stretch marks but they are wider
  and purple in color
• Hirsutism a side effect of the stimulation of
  ACTH is the stimulation of the androgens
  production, and thats why growth of excessive
  hair happens

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Addisons Disease

• Cause
• Inadequate secretion of cortisol and aldosterone
• Characterized by
• Hypoglycemia because of low cortisol.
• Na loss and K retention because of low
  aldosterone.
• Dehydration because of Na and water loss.
• Hypotension because of Na and water loss.
• Rapid wieght loss because cortisol is one of the
  hormones that stimulates the appetite.
• Generalized weakness.
• High ACTH causes hyperpigmentation.
• May lead to death if not treated with
  corticosteroids.

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Adrenogenital Syndrome

• Cause
• Hypersecretion of adrenal sex hormones,
  particularly androgens
• In young children ? premature puberty and
  enlarged genitals
• In mature women ? growth of beard (Hirsutism)
  boldness (similar to male boldness)

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Thyroid Gland

• Thyroid gland does not have a certain tissue to
  act on it acts all over the body
• It secretes
• Thyroxine (T4)
• Triiodothyronine (T3)
• Calcitonin ? responsible for phosphate and Ca
  metabolism.

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Hypothyroidism

• 1- Iodine-deficiency (endemic goitre, meaning it
  happens in a certain geographic area)
• A form of hypothyroidism, caused by the lack of
  adequate iodine in the died

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Hypothyroidism

• 2- Cretinism
• New born infants born in areas of low iodine
  intake and endemic goitre.
• Symptoms include mental retardation, short
  stature, puffy face and hands, deaf mutism, etc.

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Hypothyroidism

• 2- Cretinism
• Happens becase the mother doesnt provide enough
  thyroid hormone to the fetus during the first 3
  months.
• Thyroid hormone is important for the development
  of CNS
• During the first 3 months the fetus can not
  produce thyroid hormone but depends on the mother
• After the first 3 month the baby is able to
  produce thyroid hormone on its own
• But, if the baby was deprived from thyroid
  hormone during the first 3 months, he will still
  develop cretinism because the damage is done

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Hypothyroidism

• 3- Infantile hypothyroidism
• Occurs during childhood
• Symptoms include
• Retarded growth because thyroid hormone is needed
  for the action of growth hormone.
• Abnormal bone development.
• General lethargy.
• Low body temperature because of low BMR .

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Hypothyroidism

• 4- Hashimoto thyroditis
• Form of hypothyroidism .
• Characterized by a goitre, high concentration of
  antibodies, which are directed against
  thyroglobulin and thyroid peroxidase.
• The progressive destruction of thyroid follicular
  tissue results in hypothyroidism.

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Hypothyroidism

• 5- Myxoedema
• Hypothyroidism in adulthood
• Symptoms include
• Edema
• Low basal metabolic rate
• Cold intolerance
• Lethargy
• Weight gain tendency

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Whats Happening in The Case of Iodine-deficiency
Hypothyroidism?

1. We have TRH stimulating the pituitary.
2. TSH is secreted stimulating the thyroid gland.
3. The thyroid glad is trying to produce T3 T4 but
   it cant because of inadequate iodine (We need
   iodine for the formation of T3 T4).
4. We will have low levels of T3 T4.
5. Low negative feedback will lead to high TSH.
6. TSH will act on the thyroid gland causing it
   hypertrophy (become bigger in size) producing a
   goitre.

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Goitres can occur in both hypothyroidism and
hyperthyroidism
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HyperthyroidismGraves Disease (Toxic Goitre)

• It is an autoimmune disease caused by antibodies
  that are similar in structure to TSH, so they act
  like causing the growth of the thyroid associated
  with hypersecretion of thyroxine.
• The antibodies will bind to the TSH receptors on
  the thyroid gland
• Then they will stimulate thyroid hormone
  production the growth of the gland.

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HyperthyroidismGraves Disease (Toxic Goitre)

• Clinical symptoms include
• High metabolic rate
• High heart rate
• Wight loss
• Excessive sweating
• Heat intolerance
• Exopthalamus (bulging of the eyes because of
  edema in tissues of eye sochet)

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Regulation of Calcium Phosphate

• Ca phosphate concentration in plasma is
  affected by
• Bone resorption taking Ca and phosphate out of
  the bone into the circulation.
• Bone absorption taking Ca and phosphate into
  the bone.
• intestinal absorption
• Urinary excretion

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Regulation of Calcium Phosphate

• Regulation of plasma calcium and phosphate by
• Parathyroid hormone
• Calcitriol (Dihydroxyvitamin D3)
• Calcitonin

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Parathyroid Hormone (PTH)

• Usually 4 parathyroid glands
• PTH is secreted by the parathyroid gland whenever
  the plasma concentration of Ca begins to fall
• PTH promotes a rise in blood calcium levels by
  acting on
• The bones ( causing bone resorption)
• kidneys ( causing reabsorption)
• Intestines (indirectly)

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Parathyroid Hormone (PTH)

• The stimulus of PTH secretion is low Ca.
• PTH will be released.
• It will act on the bone causing an increase in
  bone resorption.
• Ca will go from the bone to blood circulation.
• It will also cause an increase in Ca
  reabsorption from the kidney.
• It will promote formation of 1,25
  dihydroxyvitamin D3 by acting on the kidney.

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Calcitriol (1,25 Dihydroxyvitamin D3)

• Production starts in the skin where Vitamin D3
  (prehormone) is produced from precursor molecule
  7-dehydrocholestrol under influence of sunlight.
• Actions
• Activity stimulated by PTH
• Helps to raise plasma concentration of Ca and
  phosphate by stimulating
• Intestinal absorption of Ca and phosphate (main
  function)
• Resorption of bones
• Renal reabsorption of calcium and phosphate

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Calcitonin

• Calcium lowering hormone
• Secreted by the parafollicular cell in the
  thyroid gland
• It antagonizes the hypercalcemic effect of
  calcitriol and PTH
• Is stimulated by high plasma Ca and phosphate
  levels and acts to lower Ca levels by
• Inhibitong bone resorption ( cause bone
  absorption)
• Stimulating the urinary excretion of Ca and
  phosphate by inhibiting their reabsorption by the
  kidneys

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Rickets

• A disease in which the Bones become weaker

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Action of Insulin

• After approximately ½ an hour of having a meal we
  have the peak of glucose level.
• This will stimulate the secretion of insulin.
• Insulin will cause the glucose to be converted
  into glycogen (glycogenesis) in the muscles.
• Insulin will stimulate the uptake of glucose in
  the liver to convert it into glycogen and also
  into triglycerides (lipogesesis).
• Glucose is also taken into the adipose tissue and
  converted into triglycerides.

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Action of Glucagon

• When we have low levels of glucose in the
  circulation glucagon is secreted.
• It will act in the muscle causing the breakdown
  of protein into amino acids.
• It will act on adipose tissue to cause the
  breakdown of triglycerides into fatty acids.
• Amino acids fatty acids will be converted in
  the liver into glucose.
• Glucagon will also aid in the breakdown of
  glycogen into glucose.
• In the end youll have higher glucose level in
  the circulation

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Abnormalities

• Diabetes Mellitus is characterized by
• Fasting hyperglycemia
• Glucose in the urine
• Types of Diabetes Mellitus
• Type 1 diabetes
• 10 of cases
• Also known as insulin dependent diabetes mellitus
  
• Caused by lack of insulin secretion as a result
  of destruction of the beta cells
• Also known as juvenile-onset diabetes

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Abnormalities

• Types of Diabetes Mellitus
• Type 2 diabetes
• 90 of cases
• Patients are usually over weight
• Also known as insulin independent diabetes
  mellitus
• Large amount of insulin secretion however,
  decreased tissue sensitivity to insulin secreted
• Also known as maturity-onset diabetes

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Long Term Complications of Diabetes Mellitus

• Strokes
• Retinopathy
• Blindness
• Hypertension
• Renal failure
• Impotence (in males)
• Skin infections that might lead to Gangrene
• Vascular diseases

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End of The Second Lecture