What do hormones do?

What are the 3 classes of hormones?

Play a key role in regulating almost all of the body's functions.

Protein and polypeptide hormones

Steroid hormones

Amino acid tyrosine hormones

Where are protein and polypeptide hormones made?  What are some examples?

What are examples of steroid hormones?

What are examples of amino acid tyrosine hormones?

Pituitary (anterior and posterior), pancreas, parathyroid.  Examples: insulin, glucagon, parathyroid hormone.

Adrenal cortex hormones (cortisol and progesterone), sex hormones, placental hormones (estrogen, progesterone)

Norepinephrine, epinephrine, thyroid.

Where are polypeptide hormones synthesized and stored?

How are they made?

What happens when they are needed?

What drives the influx of calcium?

In vesicles by the rough endoplasmic reticulum.  They are made as large proteins called preprohormones.  The are cleaved into prohormones, and placed in the storage vesicles by the Golgi apparatus.

When needed, they are released by a mechanism driven by the influx of calcium into the cytosol.  The prohormone splits into its pro part and the actual hormone.

Sometimes it's depolarization of the cell membrane, sometimes it's by second messenger systems such as cAMP.

What are steroid hormones made from?

What is the structure of a steroid hormone?

Are steroid hormones stored?

What happens once they are made?

Cholesterol.

3 cyclohexyl rings and 1 cyclopentyl ring.

They are not stored.

They are very lipid soluble, so once made, they simply diffuse through the membrane.

Where are thyroid hormones made?  How are they stored?

Where are epi and norepi made?  How are they stored?

What class of hormones are they?

They are synthesized and stored in the thyroid gland, bound to a protein called thyroglobin.

Formed in the adrenal medulla, stored in vesicles.

Amino acid tyrine

How much circulating hormone is usually present?

How long does it take for hormones to be released?

What type of feedback do hormones rely on?

VERY small amounts are circulating--some as little as a picogram, to at most a few micrograms.

Following stimuli, most are released within seconds, but others take longer.

Most rely on negative feedback, from either the hormone itself, or a product of the hormone.  A few use positive feedback (labor)

Where do hormones bind?

What are some effects of hormones?

Some bind on the cell membrane (receptors are mostly specific for protein, peptide, and catecholamine hormones), cytoplasm (steroids), or in the cell nucleus (thyroid).

*Ion channels

*G-protein receptors

*Enzyme-linked receptors

*Activation of genes

What is the other name for the pituitary?

How big is it?

Where is it located?

What structure is it connected to, and how is it connected?

Hypophysis (anterior pituitary = adenohypophysis, posterior = neurohypophysis)

1 cm, weighs 1 gm

Sits at the base of the brain in the sella turcica

Connected to the hypothalmus via the pituitary stalk.

Growth hormone

Adrenocorticotropin

Thyroid stimulating hormone

Prolactin

Follicle-stimulating hormone

Luteinizing hormone

What does growth hormone do?

What does adrenocorticotropin do?

What does thyroid stimulating hormone do?

Impacts nearly all body tissues by affecting protein formation, cell multiplication, and cell differentiation.

Controls the secretion of adrenocortical hormones.

Controls the rate of secretion of thyroxine and triiodothyronine, which controls most of the body's intracellular reactions.

What does prolactin do?

What do follicle-stimulating and luteinizing hormones do?

Promotes mammary gland development and milk production.

Controls ovary and testes growth and their reproductive activities.

Does the posterior pituitary synthesize hormones?

What hormones are released from the posterior pituitary, and what do they do?

No--they are synthesized in the hypothalamus.  The posterior pituitary is a "holding tank."

Antidiuretic hormone, which controls the rate of water excretion

Oxytocin, helps express milk and helps in the delivery of child

1.  Pain

2.  Anxiety

3. Hypoxia

4.  Stress

5.  Hyperthermia

6.  Positive pressure ventilation

7.  Beta agonists

8.  Histamine releasing drugs

What type of vascular flow does the anterior pituitary have?

Where does blood first enter?  Where does it go next?

It is highly vascular, with an extensive capillary system.

The blood first enters a capillary system of the hypothalamus.  It then flows through small hypothalamic hypophysial portal blood vessels into the anterior pituitary sinus.

What are the hypothalamus hormones? (6)

Where do these hormones act?

Thyrotropin releasing hormone

Gonadotropin releasing hormone

Corticotropin releasing hormone

Growth hormone releasing hormone

Growth hormone inhibiting hormone (somatostatin)

Prolactin inhibiting hormone

They act on the anterior pituitary.

Where is the thyroid located?

What hormones does it excrete?

What is the percentage released of the hormones?  What happens in the tissue?

Immediately below the larynx on each side of the trachea.

Excretes thyroxine (T4) and triiodothyronin (T3).

T4--93%, T3--7%, but almost all of the thyroxine is converted to triiodothyronine in the tissue.

How do thyroxine and triiodothyronine differ?

What does the thyroid gland contain?

The action is nearly the same, but the rate of onset and the intensity of action is different.  Triiodothyronine is 4X more potent, but has a shorter half-life and shorter duration of action.

Closed follicles lined with cuboidal epithelial cells

What is required for normal thyroxine production?

How much is needed to prevent deficiency?

Where is this absorbed?

How is it transported?

Iodine.

1 mg/week

Absorbed from the GI tract.

Iodine is transported from the blood into the thyroid glandular cells.  The membrane of the thyroid cell has the specific ability to pump the iodide actively to the interior of the cell, known as iodide trapping.  The concentration of the amount of iodide trapped is controlled by the TSH.

What is the huge protein containing many tyrosine amino acids called?  Where is this made?

How are thyroid hormones made?  Where are they located?

How are the individual hormones made?

Thyroglobin, made in the endoplasmic reticulum and Golgi apparatus.

The tyrosine binds with the iodide to form the thyroid hormones.  They remain connected to the thyroglobin once made, and are stored here.

The iodized thyroglobin is then oxidized by peroxide to form T3 and T4.

What must happen for the thyroid hormones to enter the blood?

What happens when they enter the blood?

The hormones must be cleaved from the thyroglobin molecule.

Over 90% of the thyroxine and over 99% of the triiodothyronine bind to thyroxine binding globulin, and to a lesser extent, albumin.  This ensures the release to the tissue is slow and controlled.

Do thyroid hormones easily cross membranes?

What happens to much of the thyroxine?

Where are thyroid hormone receptors located?  What happens when T3 attaches?

Yes.

Much of it is deiodinated to form T3.

Either attached to the DNA genetic strands or located in proximity to them.  It forms a heterodimer with retinoid X receptor at specific thyroid hormone response elements on the DNA.  This leads to either increases or decreases in transcription of genes that lead to formation of proteins, thus producing the thyroid response of the cell.

1.  Increases biochemical reactions

2.  Increases total body oxygen consumption

3.  Increases heat production through metabolism

4.  Increases blood flow to tissue

What does TSH do?

What controls the release of TSH?  How does this work?

Binds and activates the cAMP second messenger system, increasing all processes of the thyroid.

Thyrotropin releasing hormone from the hypothalamus.  TRH activates the phospholipase second messenger system in the anterior pituitary.

1.  Cleaving of the thyroid hormones in storage from the thyroglobin protein

2.  Increased iodide pump activity

3.  Increased iodination of tyrosine to form T3 and T4

4.  Increased number of thyroid gland cells

5.  Increased SIZE of thyroid gland cells.

What are some causes of hyperthyroidism?

What happens to the thyroid gland?

What happens to the function?

Toxic goiter (Graves disease)

Thyrotoxicosis

Thyroid Storm

The thyroid gland increases in size 2-3X.  In addition to the number of cells and the increased size of the cells, the output also increases dramatically.

Hyperthyroidism is the hyperfunctioning of the thyroid gland resulting in excessive thyroid hormone output.

Anxious, restless, emotionally unstable

Skin feels warm, moist, flushed face

Hair is fine, nails are soft

Eyes wide, retracted eyelids

Heat intolerance

Fatigue, insomnia

Osteoporosis (high bone turnover)

Diarrhea, weight loss

Increased cardiac workload (high met. demand)

Arrhythmias (atrial)

Increased cardiac output and contractility

How is hyperthyroidism usually detected?  What type of symptoms are they usually having at this point?

What do tests show?  Why?

When does treatment start?

Routine lab screening--few symptoms.

Thyroid function tests show an elevated T3 and T4 but low TSH, d/t negative feedback.

Treatment does not usually occur until the TSH drops below 0.1 mU/L.  This is the point where A-fib may occur and increases risk for embolic events or stroke.

How does a goiter form?

What causes a goiter?

Results from a compensatory hypertrophy and hyperplasia of thyroid tissue d/t a reduction in thyroid hormone output.

1.  Iodine deficiency

2.  Some drugs are goiter producing

3.  Defect in the synthesis of the thyroid hormones, producing hypothyroidism.

What determines the size of a goiter?

What would the thyroid levels be on someone with a goiter?  Why?

What is the treatment?

How long the deficiency has been allowed to continue.

They are often normal, because the thyroid gland has enlarged enough to compensate for the low hormone output.

To give thyroxine, which improves most cases within 3-6 months.  Otherwise surgery is an option.

What would be an anesthetic concern for someone with a goiter?

What would the respiratory loop look like?

AIRWAY!!!

Fixed central lesion--poor flow on both inspiration and expiration

What is the leading cause of hyperthyroidism?  What is another name?

Who is most often affected?

What is the etiology?

Graves disease, or toxic goiter.  Females between the ages of 20-40.

Thought to be autoimmune, with thyroid stimulating antibodies that bind the the TSH receptors in the thyroid, activating the cAMP system and stimulating thyroid growth and output.  This results in a hypersecretion of T3 and T4.

What is the common triad of Graves disease?

What happens to the thyroid?  What can happen in severe cases?

1.  Exophthalmos

2.  Hyperthyroidism

3.  Dermopathy (lumpy, reddish skin over the legs and feet)

It becomes very enlarged.  It can cause dysphagia, choking sensations, inspiratory stridor, superior vena cava obstruction syndrome.  The gland becomes nodular.  Radioactive iodine uptake in these nodules is increased.  CT helps differentiate Graves nodules from tumors.

What happens when iodide is in high concentration?  When does the effect start?

Why must this therapy be coupled with others?

What happens if the patient is not responsive to drug therapy or if relapse occurs?

What is the remission with this treatment?

What commonly occurs after this treatment?

What does this treatment replace?

Ablation with radioactive iodine.

80-98%

Hypothyroidism

Thyroidectomy 

1.  Hypothyroidism

2.  Hemorrhage with tracheal compression

3.  Recurrent laryngeal nerve(s) damage

4.  Damage to the motor branch of the superior laryngeal nerve

5.  Inadvertent removal of the parathyroid gland

1.  All patients should be euthyroid for 6-8 weeks before surgery

2.  Potassium iodide is given 7-14 days before surgery to reduce the gland's vascularity and hormone release

3.  Beta blockers are effective at controlling the cardiovascular effects, esp. tachycardia.

What is the preferred treatment for hyperthyroidism if mom is pregnant?

Why?

Drug therapy is preferred.  The antithyroid drugs do NOT cross the placenta.

Radioactive iodine is contraindicated and iodine treatment causes goiter in the infant with hypothyroidism.  Propanolol is associated with intrauterine growth retardation.  If mom does not respond to therapy, a subtotal thyroidectomy is the only choice.

What is thyroid storm?

What might cause it to happen?

You must address the life-threatening symptoms.

1.  Severe dehydration, CV instability, tachycardia

2.  Extreme anxiety, altered LOC

3.  Excessive heat production.

1.  Cooling blankets, ice packs, cool humidified oxygen

2.  IV fluid and glucose administration

3.  Propanolol, labetalol, or esmolol to decrease HR

4.  Dexamethasone or cortisol

5.  Antithyroid drugs

6.  Vasopressors (direct acting--phenylephrine)

What lab values are usually associated with thyroid tumor?

What is a risk of a large tumor?

What might be done to shrink the tumor?

Usually normal

Compromised airway

Radiation or chemotherapy

What lab values are associated with primary hypothyroidism?

What is the most common cause?

What is the 2nd most common cause?

What is Hashimotoes thyroiditis?

A low T3 and T4 level despite an increase in the TSH.

Radioactive iodine or surgery to ablate the gland.

Idiopathic, where antibodies destroy the TSH binding sites.

The autoimmune destruction of the TSH receptors, leading to a large goiter.

What is the cause of secondary hypothyroidism?

How do the symptoms of hypothyroidism present?

Problem with the hypothalamus or pituitary gland.

In an adult, the symptoms are slow and progressive.

1.  Fatigue, lethargy, apathy, listlessness

2.  Slowed speech, dull intelect

3.  Cold intolerance, decreased sweating

4.  Weight gain  5.  Dry, thick skin, brittle hair  6.  Large tongue, deep hoarse voice

7.  Edema in the periorbital area and legs

8.  Vent. dysrhythmias, bradycardia, increased SVR, cool skin, decreased cardiac contractility, reduced baroreceptor function  9.  Pericardial effusions

10.  Hypercholesterolemia

11.  Ventilatory response to hypoxia and hypercarbia is reduced.  Pleural effusions.

12.  Ileus  13. Uterine bleeding 

What is myxedema coma?

What is the most common symptom?

What is the associated mortality?

A severe form of hypothyroidism most commonly seen in elderly women with a history of hypothyroidism.  Considered a medical emergency.

HYPOTHERMIA (80 degrees F), due to defective hypothalamic regulation.

50%

What are the symptoms of myxedema coma?

What is the treatment?

1.  Hypothermia

2.  Delirium

3.  Hypoventilation

4.  Dilutional hyponatremia

5.  Bradycardia

Treatment is IV thyroxine or triiodothyronine.  Correct electrolyte imbalances, mechanical ventilation, warming devices.  Hydrocortisone to treat the adrenal suppression usually associated with this condition.

How many parathyroid glands do we have?

How big are they?  Where are they located?

What kind of hormone do they produce?

What is the release dependent on?

4, about the size of a pea, located in the upper and lower poles of the thyroid gland.

Parathormone is a polypeptide hormone.

It is released by a negative feedback system that is dependent on the plasma calcium concentration.  LOW calcium results in an INCREASED release of parathormone, hypercalcemia suppresses the release.

How does parathormone impact calcium levels?

What are the two electrolytes controlled by the parathyroid gland?

1.  Impacting GI absorption

2.  Impacting renal tubule reapsorption

3.  Impacting bone uptake and release

Calcium and phospate

What causes primary hyperparathyroidism?

What are the hallmarks?

What is an indicator of a benign condition?

Excessive parathormone secretion due to a benign adenoma, carcinoma, or hyperplasia of the parathyroid gland.  Benign cases account for 90% of hyperparathyroid cases.

1.  Elevated total serum calcium

2.  Elevated ionized calcium

When calcium levels increase gradually.  When levels increase dramatically, this indicates cancer.

What are the most common early symptoms?

What is treatment aimed at?

What is used with severe hypercalcemia?

What is the definitive treatment?

What is the most common complication of that treatment?

Vomiting and dehydration

Treatment is aimed at at treating the symptoms with saline infusion, and then the addition of a loop diuretic (inhibits sodium and calcium reabsorption in the loop).  Drugs that bind to calcium can be used.

Hemodialysis

Removal of the parathyroids.  Hypocalcemia!

What complication is associated with hyperparathyroidism?  Why?  What is the implication for anesthesia?

What causes secondary parathyroidism?

What is an example?

Occurs when there is a disease process that reduces the serum calcium levels.  The parathyroid gland then reacts by pumping out more parathyroid hormone.

ESRD patient cannot rid themselves of phosphorous and cannot hydroxylize vitamin D, which is required for calcium absorption from the gut.  The resulting hypocalcemia results in hyperplasia of the parathyroid glands.

What is calcitonin?

Where is it released from?

What does it do?

Calcitonin is the opposite of the parathyroid.

It is released from the thyroid gland and weakly antagonizes parathyroid hormone.

Calcitonin promotes deposits of calcium into the bones, decreasing calcium concentrations in ECF.

What causes hypoparathyroidism?

What are the signs?

Most common cause is due to surgical removal with a thyroidectomy

Circumoral parasthesia, restlessness, neuromuscular irritability.

Chvosteks sign: facial muscle twitching with manual tapping over the area of the facial nerve by the mandibular angle.

Trousseaus: carpopedal spasm after 3 minutes of limb ischemia due to a tourniquet.

Inspiratory stridor reflects neuromuscular irritability.

Where is the adrenal gland located?

What are the two parts?

How are they different?

Lies on the superior pole of the kidney.

Adrenal cortes, Adrenal medulla.

The adrenal medulla is functionally related to the sympathetic nervous system.  It secretes the hormones epinephrine and norepinephrine in response to sympathetic stimulation.

The adrenal cortex has a separate set of hormones called the corticosteroids, which are synthesized from cholesterol.

Mineralcorticoids

Glucocorticoids

Androgens

3 distinct layers

Zonus glomerulosa: the outermost layer.

Zonus fasciculata: the middle layer, largest zone.

Zonus reticularis: inner layer.

What does the zonus glomerulosa contain?

What is this area responsible for?

What does it respond most to?

An enzyme called aldosterone synthase.

This area is responsible for the production of the mineralcorticoids--specifically aldosterone.

Responds MOST to the potassium concentration and the concentration of angiotensin II.

What regulates the zonus fasciculata?

What does this respond to?

What does it release?

What does the zonus reticularis secrete?

What is it controlled by?

Where is the medulla in relation to the cortex?

androgens--dehydroepi androsterone (DHEA) as well as estrogen.

Controlled by ACTH and other unknown factors.

The medulla lies below the cortex.

What is the major mineralcorticoid?

What are the 4 stimuli that causes the release?

What also has mineralcorticoid activity?

Aldosterone

1.  The potassium ion concentration in the ECF (increases release)

2.  The levels of angiotensin II (increases release)

3.  Increased sodium concentration in the plasma (decreases release)

4.  ACTH from the anterior pituitary

Cortisol

What is Conn's syndrome?

What usually causes it?

Who is most likely to have it?

What is it associated with?

Hyperaldosteronism

Usually due to a tumor that is secreting an aldosterone-like substance

Women

Associated with pheochromocytoma, hyperparathyroidism, or acromegaly.  Can also occur when the renin system is elevated our out of whack.

1.  Headache (brain swelling)

2.  Hypertension (too much fluid)

3.  Hypokalemia (too much excreted)

4.  Metabolic alkalosis

5.  EKG: U waves, flattened T, prolonged PR, PVCs

What is the treatment for Conn's syndrome?

1.  Supplement potassium

2.  Give competitive aldosterone antagonist (spironolactone)

3.  Potassium sparing diuretics

4.  May require adrenal gland removal

5.  If the renin system is to blame, use of an ACE inhibitor is indicated.

What do glucocorticoids do?

What form are the majority of glucocorticoids in?

Responsible for utilization of proteins, carbohydrates, and fats.  Responsible for management of stress and controlling the immune response to infection.

90% in the form of cortisol, or hydrocortisone.  A small amount is corticosterone.

How does cortisol impact glucose levels?

What other effects does cortisol have?

It causes mobilization of amino acids from muscle cells for gluconeogenesis, as well as glucose production from fats and carbs.  At the same time, it inhibits uptake of glucose into cells.  This all contributes to elevated serum glucose levels.

It increases the appetite.  It also produces an imbalance of fat deposits resulting in buffalo humps or moon face.

What is the effect of stress on the anterior pituitary?  What does this do?

What are some stressors?

Stress of any type increases the production of ACTH by the anterior pituitary, which leads to a large release of cortisol.

Trauma, infection, intense heat or cold, sympathetic drugs (epi, norepi), surgery!!, injection of a painful substance, restraining, disease.

Facilitates catecholamine synthesis

Modulates Beta receptor synthesis, regulation, coupling, and responsiveness to the catecholamines

Contributes to normal vascular permeability, tone, and cardiac contractility

Cortisol stabilizes lysosome membranes

Decreases permeability of capillaries

Decreases WBC migration and phagocytosis

Suppresses lymphocyte reproduction

Stops fever by reducing the release of interleukin I from WBCs, which impacts the hypothalamus and causes a rise in temperature

What is ACTH's structure similar to?

What happens when ACTH is released?

What happens when large amounts are released?

Melanocyte stimulating hormone, lipotropin, and endorphin.

When ACTH is released, these substances are also released.

When large amounts are released, the similar structures can also act as ACTH, leading to a hugh increase, leading to problems.

What is Cushing's disease?

What is the most common cause?

What else is it associated with?

What is the treatment?

Too much cortisol released.

Secreting tumor (benign or malignant).

Also associated with oat cell carcinoma.

Transsphedoidal microadenomectomy, pituitary radiation, and/or bilateral adrenalectomy.

1.  Hyperglycemia 2.  Rapid weight gain

3.  Water retention  4.  Hypertension

5.  Edema  6.  Hypokalemia

7.  Amenorrhea or abnormal bleeding

8.  Weakness  9.  Depression, insomnia

10.  Bruising  11.  Telangiectasias (dilated vessels)

12.  Moon face, buffalo hump

What are the types of adrenal insufficiency?

What happens?  What is the cause?

1.  Addison's disease

2.  Iatrogenic

In Addison's disease, the problem is the adrenal glands are not able to generate enough glucocorticoids, mineralcorticoids, or androgens.  The most common cause is an autoimmune destruction of the adrenal glands.

In iatrogenic, the number one cause is HYPOTHALAMIC-PITUITARY AXIS DYSFUNCTION due to STEROID ADMINISTRATION!!  Other causes are radiation or removal of the pituitary.

What are the symptoms of Addison's disease?

What is the treatment?

Fatigue, weakness, anorexia, vomiting, cutaneous and mucosal hyperpigmentation, hypotension, hypovolemia, hyponatremia, hyperkalemia.

Supplement with corticosteroids and mineralcorticoids.

What happens in Hypothalamic-Pituitary Axis supression?

What happens to ACTH release during surgery?  What is this dependent on?

What happens to cortisol levels during surgery?

With prolonged steroid exposure, the adrenal gland atrophies, resulting in little or no response when cortisol levels are required to meet a demand.

It increases, depending on the depth of surgery, the severity, and the length of the case.  

Increases substantially.  The ACTH levels remain high into the post-op time frame.

What happens if a patient is on long-term steroids, and they are suddenly stopped?

How long does it take the adrenal response to recover following steroid use?

What if a patient is taking a small dose (< 5 mg/day)?

Adrenal insufficiency may occur within 24 hours.

It take 6-12 MONTHS for a patient's adrenals to recover following LONG TERM steroid therapy.

They do not demonstrate HPA axis suppression, and do not require pre-op supplementation--BUT THEY SHOULD CONTINUE TO GET THEIR NORMAL DAILY DOSE!!

What dose of steroids is thought to have potential HPA axis suppression?

How much cortisol to adults make daily?

What is the recommended dosing?

> 5 mg of prednisone by ANY route for more than 2 weeks in the previous 12 months.

About 20 mg, without stress

Give 100 mg of hydrocortisone every 8 hours starting the evening and morning before surgery.

What is acromegaly?

What is the usual cause?

What does xray show?

What symptoms do patients have?  

Excessive growth hormone in adults.

Adenoma in the pituitary.

Skull xray shows a large sella turcica.

The adenoma produces pressure resulting in headache and papilledema due to an increased ICP.  Visual disturbances occur.

What are the airway implications of acromegaly?

What are other symptoms?

What is the treatment?

Huge epiglottis and tongue

Increased length of mandible

Plypoid masses in the pharynx

Hoarseness and abnormal vocal cord movement (stretching)

Cricoarytenoid joints may be stretched and impair vocal cord movement

Stridor, dyspnea

Peripheral neuropathy d/t nerve trapping and growth of limbs.

May have DM.

Removal of the tumor.

Adrenal medulla (epi, NE)

Posterior pituitary (ADH, oxytocin)