Continuous

Discontinuous

1. Peptides and proteins
2. Amino acid derivatives
3. Steroids
4. Fatty acid derivatives-Eicosanoids

Steroid Ring

within there structure

Amino Acid Derivatives

(tyrosine->NE)

Fatty Acid Derivatives

(Eicosanoids)

Polypeptides

• synthesized and stored in vesicles by the R ER
• they are made into nonactive large proteins called preprohormones
• they are cleaved into prohormones and stored in Golgi apparatus
• when needed, released into cytosol
• prohormone splits into its pro- and the actual -hormone

Calcium

• Sometimes the influx of Ca++ is driven by membrane depolarization, sometimes it is driven by second messenger systems such as cyclic AMP

Thyroid Hormones

Catecholamines (tyrosine->DOPA->Dopamine->NE)

Tryptophan

Glutamic Acid

3-cyclohexyl rings

1-cyclopentyl ring

No; once made they simply diffuse through the membranes because they are very LIPID SOLUBLE

(NDMRs can be steroid-based)

• Glucocorticoids; cortisol is the major one in most mammals
• Mineralcorticoids; aldosterone (Na+=reabsorption; excrete K+)
• Androgens; testosterone
• Estrogens; Estradiol and estrone
• Progesterones (progestins); progesterone

• Bind to cell membranes
• Make things happen in cell's cytoplasm
• Increase or decrease cell nucleus activity (transcription)
• Impact the function of ion channels
• Stimulate or inhibit G-protein second messenger systems
• Activate or deactivate genes
• Act as enzymes

• AKA the hypophysis
• 1cm weighs 1 gm
• Sits at the base of the brain in the sella turcica
• Connected to the hypothalamus via the pituitary stalk

Hypothalamus

Stores

Antidiuretic Hormone (Vasopressin)

Oxytocin

• Thyrotropin releasing hormone
• Gonatotropin releasing hormone
• Corticotropin releasing hormone
• Growth Hormone releasing hormone
• Growth Hormone inhibiting Hormone (Somatostatin)
• Prolacting inhibiting hormone

Thyroxine (93%)

Triiodothyronine (7%)

The thyroid gland contains chambers lined with _____ _____ cells.

Iodine; 1mg/week needed to prevent iodine deficiency

absorbed in the GI tract

Thyroglobulin

Tyrosine

Thyroxine & Triiodothyronine

T4

Retinoid X

• Inc. CO
• Inc. tissue and blood flow
• Inc. HR
• Inc. heart strength
• Inc. RR

• Inc. mitochondria
• Inc. Na+-K+-ATPase
• Inc. O2 consumption
• Inc. glucose absorption
• Inc. gluconeogenesis
• Inc. glycogenolysis
• Inc. lipolysis
• Inc. protein synthesis
• Inc. BMR

• Growth and cell maturation (constant replacement)
• Inc. in ALL metabolic processes (generation of heat)
• Major player in heart and vascular function
• Reproduction
• Mental status

Direct

T3

Thyrotropin Releasing Hormone

Anterior

Thyroid Stimulating Hormone

Increased

• Cleaving of the thyroid hormones in storage from the thyroglobin protein
• Inc. iodine pump activity
• Inc. iodination of tyrosine (inc. iodine+tyrosine=T3 and T4)
• Inc. number of thyroid gland cells
• Inc. SIZE of thyroid gland cells (Goiter; hypertrophy)

1. Graves' disease
2. Toxic multinodular goiter
3. Toxic adenoma
4. Metastatic thyroid carcinoma
5. Too much iodine

• Increased risk for HEARTBURN, pancreatitis (inc. insulin production), low Vitamin D (positioning issues), risk for prostate, colon and breast CA (portal), DIFFICUTLY SWALLOWING (airway!!!)

1. Anxious, restless, emotionally unstable, irritability
2. Skin feels warm, moist, face flushed (vasodilated)
3. Hair is fine, nails are soft and fragile
4. Eyes have wide-eyed stare with retracted eyelids (bug eyes)
5. C/o heat intolerance (Inc. MR)
6. Fatigue/insomnia-always revved up
7. Osteoporosis d/t high bone turn over
8. Diarrhea, weight loss
9. Inc. cardiac workload (high metabolic demand)
10. Arrhythmias are common (atrial)
11. Inc. CO and contractility

Graves Disease

• Accounts for 60-80% of all hyperthyroid conditions
• Antibody posing as TSH=OVER PRODUCTION of T3/T4
• More prevalent in women (40-60 yo)
• 3 fold increase in postpartum women

• Adenomas can secrete large thyroid hormones
• Exogenous iodine (radiocontrast dye/iodine/shellfish allergies)
• Administration of thyroid replacement
• AMIODARONE-is an iodine rich antiarrhythmic which can produce HYPER or HYPO-thyroidism (negative feedback loop)

Usually detected on routine lab screen.  Most have few symptoms. 

The thyroid function test show an ELEVATED T3 and T4 but REDUCED TSH (tx @<0.1mU/L).  At this point, atrial fibrillation may occur increasing risk for stroke an embolic events.

With Graves, the thyroid stimulating immunoglobulins (antibodies) will be detected.  Graves is associated with other autoimmune disorders such as rheumatoid arthritis, myasthenia gravis, systemic lupus erythematosus and DM

• Radioactive iodine (2-4 mos to work); Hypothyroidism is common side effect (pregnancy and lactation contraindications)
• Thyroidectomy; if antithyroid drugs/radioacitve iodine don't work; pregnant; child; exceptionally large goiter; SHOULD BE TREATED W/ DRUGS UNTIL EUTHYROID (6-7 weeks)!; may have difficult airway; injury to recurrent laryngeal nerve, neck hematomas, hypoparathyroid complications
• Thioamides; propylthiouracil (PTU) inhibit thyroid hormone synthesis by interfering with iodine and tyrosine interaction; also inhibits conversion of T4 to T3; HEPATITIS side effect
• Beta adrenergic blockers; blocks SNS from T3 T4
• Potassium iodide; Iodide in high concentrations inhibit the release of the hormones from a hyperfunctioning gland.  Effect is IMMEDIATE and lasts for weeks

Potassium Iodide

Has to be coupled with other therapies because although levels are reduced, storage of thyroid hormone increases

(Chernobyl; protects thyroid from nuclear radiation accidents)

YES!

cocaine, epi, ketamine, etomodate, desflurane

HYPERCARBIA and HYPOXIA inc. SNS

• IDEALLY EUTHYROID
• Must take meds DOS
• SNS control (ventilate/oxygenate)
• Direct acting vasopressors (catecholamine depleted)
• Exophthalmos-Protect eyes
• CORE TEMP

Thyroid Storm

• Diagnosis based on symptoms
• Thyroid fxn tests may not be that high
• URGENT and AGGRESSIVE TX

Treatment for Thyroid Storm

(20% mortality rate)

• Address life-threatening symptoms
• severe dehydration, cardiovascular instability, tachy, arrythmias, extreme anxiety, ALOC, EXCESSIVE HEAT production

1. Cooling blankets, ice packs, cool humidified O2
2. IV fluid and glucose administration (often develop hypoglycemia)
3. Propranolol, labetalol or esmolol to dec. HR
4. Dexamethasone or cortisol
5. Antithyroid drugs
6. Vasopressors (Direct acting such as phenylephrine)

1. Radioactive iodine or surgery to ablate gland
2. Idiopathic where antibodies destroy the TSH binding sites
3. Hashimotoes Thyroiditis-d/t autoimmune destruction of the receptors and leads to a large goiter (associated w/ other autoimmune disorders)
4. Iodine deficiency
5. Nodular goiter

Hypothalamus

or

Pituitary gland

Symptoms of Hypothyroidism

(slow and progressive)

• Fatigue, lethargy, apathy, listlesness
• Slowed speech, dull intellect
• Cold intolerance, decreased sweating
• Weight gain
• Dry thick skin, brittle hair
• Large tongue, deep hoarse voice
• Edema in the periorbital area and legs
• Ventricular dyrhythmias, bradycardia, inc. SVR, cool skin, dec. cardiac contractility, baroreceptor fxn reduced
• Pericardial effusions common
• Hypercholestremia
• Ventilatory response to hypoxia nd hypercarbia is REDUCED!
• Ileus (portal)
• Uterine bleeding (portal)

Cretinism

(seen in other countries d/t US neonatal screening)

Goiter

Causes:  Iodine deficiency, drugs, defect in the synthesis of thyroid hormones

Size is determined by deficiency length of time

Normals are often normal because thyroid gland has enlarged enough to compensate

Tx: 

• Give thyroxine (3-6 mos improvement)

• Surgery

• Meds DOS
• Postpone electives until EUTHYROID
• AIRWAY if goiter
• Depressed response to hypoxia and hypercarbia
• Sensitive to opioids and NDMRs
• Decrease # of beta receptors
• May need additional doses of steroids
• Body temp and warming (PRONE TO HYPOthermia)

Myxedema Coma (mortality approaches 50%)

seen in elderly women w/ hx of hypothyroidism

MEDICAL EMERGENCY

HYPOTHERMIA (80 degrees Farenheit)

d/t defective hypothalmic regulation

• Hypothermia
• Delirium
• Hypoventilation
• Dilutional Hyponatermia
• Bradycardia
• CHF

IV Thyroxine and Triiodothyronine

Correct lyte imbalances, mech. vent., warming device

Hydrocortisone (tx of adrenal suppression usually associated w/ this condition)

Negative feedback

Ca++; LOW calcium levels result in an INCREASED release of parathormone and Hypercalcemia suppresses its release

1. Impacting GI absorption
2. Renal tubule absorption
3. Bone uptake and release

99%

41%

40%

Rest rides along w/ citrate and bicarbonate

Acidosis-Inc. Ionized

Alkalosis-Dec. Ionized

Deminerlaization

Rickets

Osteomalacia "brittle bones"

Calcitonin released from the ______ gland weakly antagonizes _____ hormone.  Calcitonin promotes deposits of ____ into the bones decreasing calcium concentrations in extracellular fluid.

Thyroid

Parathyroid

Ca++

• Circumoral parasthesia, restlessness, neuromuscular irritability
• Chvosteks sign: Facial muscle twitching w/ manual tapping over the area of the facial nerve by the mandibular angle
• Trousseaus:  Carpopedal spasm after 3 minutes of limb ischemia d/t a tourniquet
• Inspiratory stridor refelects neuromuscular instability

• Temporary hypocalcemia can occur after thyroidectomy (few hours to few days post op).  Once out of "shock" it fxns
• Aline and preop Ca++ levels
• Laryngeal muscles are sensitive to tetanic spasm and laryngospasm is dangerous
• Cardiac dysrhythmias (delayed repolarization), dec. contractility
• Avoid hyperventilation (dec. ionized Ca++=more binding to albumin)
• Treat emergently w/ 10% CaCl- or calcium glutamate

CaCl-=contains 27mg/ml of elemental Ca++

Glutamate=9mg/ml of elemental Ca++ (better PIV)

Plateau

dec. Ca++= depolarization longer

inc. Ca++= repolarize faster

1. Hyperparathyroidism or
2. PTH secreting adenoma or cancer somewhere often associated w/ metastasis to bone

"STONES, BONES and GRONES"

1. Develop kidney stones, gall stones, pancreatitis
2. Absorption of bones (pain)
3. Peptic ulcers, nausea and vomiting, dehydration
4. Bradyarrhythmias

1. VERY dehydrated
2. Aline (PTH and Ca++ frequent draws)
3. Unpredictable NDMR rxn
4. Positioning
5. Prophylactic antiemetics!

SNS

It secretes the hormones EPI and NE

• Mineralcorticoids
• Glucocorticoids
• Androgens

Corticotropin Releasing Hormone

Adrenal Corticotropic Hormone (ACTH)

1. Zonus glomerulosa:  This is the outer most layer and is THIN.  Contains enzyme aldosterone synthase.  This area is responsible for the production of the mineralcorticoids-aldosterone.  Responds most to concentration of  K+  and Angiotensin II
2. Zonus fasciculata:  This is the largest zone and sits in the middle.  This zone is regulated by ACTH (adrenal corticotropin hormone) which responds to the hypothalmic (corticotropin releasing hormone) and the AP (ACTH) axis which leads to the production and release of glucocorticoids-cortisol and corticosterone.  Small amount of adrogens too.
3. Zonus reticularis:  Is the inner layer and secretes androgens (dehydroepiandrosterone-DHEA) as well as estrogen.  This layer is controlled by ACTH and other unknown fxs.
4. Below the cortex lies the medulla

Aldosterone

Cortisol also has mineralcorticoid activity

• Potassium ion concentration in the extracellular fluid-increases release
• Levels of angiotensin II-increases release
• Increased sodium concentration in the plasma-decreases release
• Adrenal cortical hormone (ACTH) from the AP-increase release

• Usually d/t a tumor that secretes aldosterone-like substance
• More common in women
• Associated w/ pheochromocytoma, hyperparathyroidism, or acromegaly
• Can also occur when the renis system is elevated or out of whack

1. HEADACHE-lots of Na+=H2O=cerebral edema
2. HTN-Inc. circulatory volume
3. Hypokalemia-Reabsorb Na+ and excrete K+
4. Metabolic alkalosis; H+ moving into cell; tx. hyperventilate
5. ECG=T-wave changes; PVCs

1. Supplement K+
2. Give competitive aldosterone antagonist (spironolactone)
3. Potassium-sparing diuretics (Lasix)
4. May require adrenal gland removal
5. IF renin system was culprit=ACE-Inhibitor

• Responsible for utilization of proteins, carbs and fats
• Responsible for management of stress and controlling immune response to infection
• Cortisol is released in response to Corticotropin Releasing Horomone

Cortisol AKA hydrocortisone

Very small amount is corticosterone

15-30mg

MORNING

Buffalo hump

Moon face

1. Trauma
2. Infection
3. Instense heat or cold
4. Sympathetic drugs (NE, epi)
5. SURGERY
6. Injection of painful substance
7. Restraining
8. Disease

If you were cortisol depleted and then placed under stress, what could potentially happen?

• Cortisol facilitates catecholamine synthesis
• Modulates Beta receptor synthesis, regulation, coupling and responsiveness to catecholamines
• Contributes to normal vascular permeability, tone and cardiac contractility
• Delayed SNS response
• Dec. CO/neg. inotrope
• Dec. BP/Vasodilate

"steroids trick the body into thinking it doesn't have and infection even though it does"

• Stages of inflammation
• Cortisol stabilizes lysosome membranes
• Decreases permeability of capillaries
• Decreases WBC migration and phagocytosis
• Suppresses lymphocyte reproduction
• Stops fever by reducing the release of interleukin 1 from WBCs which impacts the hypothalamus and causes a rise in body temp

• Very similar to melanocyte stimulating hormone, lipotropin and endorphin
• When ACTH is released from AP, these are also
• Under normal circumstances they play no role unless in LARGE amounts (problem)

• Too much cortisol
• Most common cause is secreting tumor
• Associated w/ OAT/SMALL CELL CARCINOMA (Eaton Lambert)=very little NDMR; prolonged paralysis

1. Hyperglycemia
2. Rapid weight gain
3. Water retention
4. HTN
5. Edema
6. Hypokalemia (Wash out)
7. Amenorrhea or abn bleeding post menopause
8. Weakness
9. Depression;insomnia
10. Bruising
11. Telangiectasias (dilated vessels of face and other body parts)
12. Moon face/buffalo hump
13. Tx is transsphenoidal microadenomectomy, pituitary radiation and bilateral adrenalectomy

1. Addison's Disease-problem is the adrenal glands are not able to generate enough glucocorticoids, mineral corticoids, or androgens.  MOST COMMON CAUSE is autoimmune destruction of gland
2. Iatrogenic-NUMBER 1 CAUSE OF HYPOTHALAMIC-PITUITARY AXIS DYSFUNCTION d/t steroid administration; or radiation removal of pituitary

• Fatigue, weakness, anorexia, vomiting, cutaneous, and mucosal hyperpigmentation, hypotension, hypovolemia, hyponatremia, hyperkalemia
• Tx-supplement with corticosteroids and mineral corticoids

Adrenal insufficiency w/in 24 hours

Takes 6-12 mos for patients adrenals to recover following long-term therapy

This can effect body's natural ability to raise ACTH levels in response to surgery

• Patients taking less than 5 mg of prednisone/day for any length of time (years) DO NOT demonstrate HPA axis suppression-SHOULD CONTINUE NORMAL DOSE
• Timing of dose is important because cortisol secretions are diurnal w/ MAX dose in MORNING; bedtime doses have a negative feedback response
• Consider replacement if:
• Pt taking > 5mg for more than 2 wks in previous 12 mos (5 mg of prednisone=20mg hydrocortisone)
• Patient was on steroids for more than 2-3 wks
• The patient received steroids w/in past 12 mos

15-30mg

300mg

• Minor surgery=25mg/day (for 1 day)
• Moderate/Joint Replacement=50-75mg/day (1-2 day)
• Major (thoracotomy, tumor resec, CPB)=100-150mg/day (for 2-3 days)

20mg solucortef

25mg cortisone

4mg solumedrol

0.75mg dexamethasone

IN OR=

100mg hydrocortisone=25mg prednisone=3.75 mg dexamethasone

NONE, all others do

Dexamethasone also has the longest 1/2 life

and is the least likely to produce HPA axis suppression

1. Huge epiglottis and tongue
2. Inc. length of the mandible
3. Plypoid masses in the pharynx
4. Hoarseness and abn vocal cord movement
5. Cricoarytenoid joints may be stretched and impair vocal cord movement (REVIEW MUSCLES)
6. Stridor, dyspnea
7. Peripheral neuropathy d/t nerve trapping and limb growth
8. Aline-poor distal flow
9. DM?
10. Tx for tumor removal

Posterior Pituitary

Adrenal Medulla (catecholamines)

Antidiuretic Hormone

Oxytocin (Pitocin) is regulated by + feedback loop; Both have antidiuretic effect and retain volume

POTENT vasoconstrictive

AKA Vasopressin-difference is the DOSE

15-25%

1. Stretch receptors in the atria. Excited by overfilling.  When blood volume decreases, they are UNEXCITED.  Lack of excitement results in release of ADH
2. Decreases stretch receptor stimulation of the baroreceptors of the carotid and aorta results in profound ADH release (REVIEW AFFERENT and EFFERENT limbs)

• Absence of vasopressin d/t
• destruction of the posterior pituitary (neurogenic DI)
• failure of renal tubes to respond to ADH (nephrogenic DI)
• Sevoflurane-like polyuria diuresis

1. Polydipsia
2. Inc. serum osmolarity
3. Dec. urine osmolarity
4. High urine output

• Inappropriate secretion of ADH (TOO MUCH), occurs as a result of tumors, hypothyroidism, porphyria and small cell lung carcinomas.  This also occurs after GA!

• Dec. serum osmolarity
• Hyponatremia
• Inc. urine osmolarity
• Symptoms often associated w/ hyponatremia

Which nerve causes afferent and efferent changes in Baroreceptor reflex?