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Endocrinology 2. Lecture Notes. 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

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endocrinology 2

Endocrinology 2

Lecture Notes

adrenal glands
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
adrenal medulla
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
adrenal medulla4
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)
effects of fight or flight
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
adrenal cortex
Adrenal Cortex
  • Secrets steroid hormones called corticosteroids including:
    • Mineralocorticoids (aldosterone)
    • Glucocortecoids (cortisol)
    • Sex steroids (estrogens, androgens)
adrenal cortex7
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.
adrenal cortex secretion abnormalities
Adrenal Cortex Secretion Abnormalities

Cushing’s 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)
important cushing s disease is different from cushing s syndrome
Important!Cushing’s Disease is Different From Cushing’s Syndrome

Cushing’s Syndrom:

  • One cause for Cushing’s syndrome is exogenous glucocorticoids. Meaning that a person take corisol exogenously by injections or tablets to treat various diseases.
  • Another cause for Cushing’s 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 Cushing’s syndrome

important cushing s disease is different from cushing s syndrome10
Important!Cushing’s Disease is Different From Cushing’s Syndrome

Cushing’s Disease:

  • A patient has high secretion of ACTH from the anterior pituitary  high ACTH will stimulate the adrenal gland to produce cortisol
important cushing s disease is different from cushing s syndrome11
Important!Cushing’s Disease is Different From Cushing’s Syndrome

If you take a serum sample from a Cushing’s Disease patient he will have :

High levels of ACTH + High level of cortisol

If you take a serum sample from a Cushing’s Syndrom patient he will have :

Low levels of ACTH + High level of cortisol

important cushing s disease is different from cushing s syndrome12
Important!Cushing’s Disease is Different From Cushing’s Syndrome

Changes in the body are the same in the two cases EXCEPT:

  • The hyperpigmentation in Cushing’s Disease patients because of excess ACTH
  • ACTH is a melanocyte stimulating hormone, it stimulates the melanocyte , so the patient will have a darker skin
cushing s disease and cushing s syndrome
Cushing’s Disease and Cushing’s 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
cushing s disease and cushing s syndrome14
Cushing’s Disease and Cushing’s 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 that’s why growth of excessive hair happens
addison s disease
Addison’s 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.
adrenogenital syndrome
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)
thyroid gland
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.
hypothyroidism
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

hypothyroidism19
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….

hypothyroidism20
Hypothyroidism

2- Cretinism:

  • Happens becase the mother doesn’t 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
hypothyroidism21
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 .
hypothyroidism22
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.
hypothyroidism23
Hypothyroidism

5- Myxoedema:

  • Hypothyroidism in adulthood
    • Symptoms include:
    • Edema
    • Low basal metabolic rate
    • Cold intolerance
    • Lethargy
    • Weight gain tendency
what s happening in the case of iodine deficiency hypothyroidism
What’s Happening in The Case of Iodine-deficiency Hypothyroidism?
  • We have TRH stimulating the pituitary.
  • TSH is secreted stimulating the thyroid gland.
  • The thyroid glad is trying to produce T3 & T4 but it can’t because of inadequate iodine (We need iodine for the formation of T3 & T4).
  • We will have low levels of T3 & T4.
  • Low negative feedback will lead to high TSH.
  • TSH will act on the thyroid gland causing it hypertrophy (become bigger in size) producing a goitre.
hyperthyroidism grave s disease toxic goitre
HyperthyroidismGrave’s 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.
hyperthyroidism grave s disease toxic goitre27
HyperthyroidismGrave’s 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)
regulation of calcium phosphate
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
regulation of calcium phosphate29
Regulation of Calcium & Phosphate
  • Regulation of plasma calcium and phosphate by:
    • Parathyroid hormone
    • Calcitriol (Dihydroxyvitamin D3)
    • Calcitonin
parathyroid hormone pth
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)
parathyroid hormone pth31
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.
calcitriol 1 25 dihydroxyvitamin d3
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
calcitonin
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
rickets
Rickets
  • A disease in which the Bones become weaker
action of insulin
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.
action of glucagon
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 you’ll have higher glucose level in the circulation
abnormalities
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
abnormalities38
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
long term complications of diabetes mellitus
Long Term Complications of Diabetes Mellitus
  • Strokes
  • Retinopathy
  • Blindness
  • Hypertension
  • Renal failure
  • Impotence (in males)
  • Skin infections that might lead to Gangrene
  • Vascular diseases