The Endocrine SystemThe Endocrine System

PathophysiologyPathophysiology

A & P Review of Endocrine SystemA & P Review of Endocrine System

Mechanism of Hormone ActionMechanism of Hormone Action• Hormones play an important function in regulation & control of body functions &

metabolism• Hormones exert control that is slower acting but of longer duration than nerve

impulses• Hormones secreted by endocrine glands go to a target organ • How do specific hormones know where to go?

– Receptors in the cell are specific for certain hormones» Thus get “lock & key effect”

• 2 types of hormones• Protein derivative hormones (from amino acids or polypeptides)

» water soluble, thus need plasma membrane receptor» then need second messenger for hormone to exert its action

» this action occurs in the cytoplasm

• Lipid derivative hormones (primarily steroids)

» Fat soluble, thus pass right through the cell membrane

» bind with receptor in the nucleus

» this complex triggers DNA to make a specific protein

Regulation of Hormonal SecretionRegulation of Hormonal Secretion

• The control of hormonal secretion is “homeostatic feedback”• Another name for this is: “negative feedback”

• Remember negative feedback reverses the direction of change back to physiologic normal

» if hormone level too high----- the gland is shut down» if hormone level too low ------the gland is stimulated

• Positive feedback augments the direction of change» if hormone level high ----- the gland is stimulated» if hormone level too low---- the gland is shut down, even further

• Most endocrine diseases are centered around:– TOO MUCH = hypersecretion--- from glandular hyperplasia or a

functional tumor (adenoma or carcinoma)– TOO LITTLE = hyposecretion – from glandular atrophy or a

destructive carcinoma

ProstaglandinsProstaglandins

• Written as PG; called “tissue hormones”– they are substances produced locally by specific tissues

– they travel only short distances & thus have a localized effect

– 2 types: Inflammatory (bad) & non-inflammatory (housekeeping or good)

• Prostaglandins & leukotrienes = usually enhance inflammation

• Prostacyclins & thromboxanes = work in opposition to platelet aggregation

– they are lipids called eicosanoids• The major eicosanoid fatty acid precursor = arachidonic acid

– This is a essential fatty acid; thus from diet

» Omega 3 fatty acids produce non-inflammatory PG’s

» Omega 6 fatty acids produce inflammatory PG’s

– their synthesis begins when a cell membrane is disrupted e.g. injury» the disrupted cell membrane releases certain lipids into the

cytoplasm that begins PG synthesis

• Mech of action of PG’s• COX = cyclooxygenase = enzyme that synthesizes prostaglandins

• 2 forms: COX-I & COX-II• COX-I = results in products (prostaglandins) that act on stomach,

platelets, & vascular endothelium (prostacyclins)

• These prostaglandins are involved in homeostatic activities• Also called “housekeeping” activities• These include:

1. Maintaining GI mucosal barrier2. Maintaining platelet function (checks & balances via prostacyclin

& thromboxane)3. Maintaining vascular homeostasis

• COX-II = results in products(prostaglandins) that are inflammatory chemical mediators

• Get organ smooth muscle contraction (constrict bronchi)• Vasodilation • Pain

• Anti- prostaglandins (NSAID’s)• Non-selective NSAID’s inhibit COX I & COX II• Selective COX II agents exert their actions primarily on the inflammatory

process ( they inhibit it)

Pituitary GlandPituitary Gland

• 2 glands

– Anterior pituitary• Adenohypophysis

– Posterior pituitary• Neurohypophysis

• Extension of hypothalamus

Diseases of the PituitaryDiseases of the Pituitary

• TSH– hypersecretion = hyperthyroidism

– hyposecretion = hypothyroisism

• ACTH– hyposecretion = Addison’s disease

– hypersecretion = Cushing’s disease

• FSH– hyposecretion

• M = poor sperm production

• F = low estrogen, amenorrhea

– hypersecretion

• F = menopause

• LH– hyposecretion

• F = no ovulation

• M = low testosterone

• MSH– hypersecretion = excess pigment

• GH– hypersecretion

• during growth = giantism

• after growth = acromegaly

– hyposecretion = dwarfism

• PRL– hypersecretion = galactorrhea,

infertility

– hyposecretion = poor milk production

• ADH– Hypersecretion = SIADH

• Syndrome of inappropriate ADH secretion

– hyposecretion = diabetes insipidus

• General facts – Main cause of pituitary diseases = benign adenomas

• Age: 30 – 50 years old

– Symptoms fall into 2 main categories:

• Pressure symptoms from glandular enlargement

» Headache, seizures, drowsiness, visual defects

• Hormonal effects

» Usually stimulatory if functional tumor

» May be inhibitory (non-functional with pressure necrosis)

– Most common hormonally active adenomas = prolactinoma

Diseases of the PituitaryDiseases of the Pituitary

Specific Pituitary DiseasesSpecific Pituitary Diseases

Giantism– If congenital may be accompanied by mental retardation &/or sexual retardation– If occurs after puberty ---- called acromegaly

• Get enlarged hands & feet, protruding mandible– Etiology usually pituitary adenoma

Dwarfism– If congenital get mental retardation(+/-) & no secondary sexual characteristics– Tx = GH

Prolactinoma– Most common pituitary functional tumor– Get high prolactin levels

• In women get galactorrhea, amenorrhea, infertility• In men get impotency, oligospermia, decrease libido

Diabetes Insipidus– Symptoms = polyuria & polydipsia

– Get large amounts of dilute urine & dehydration– Etiol:

• head injury or surgery = temporary condition• Nephrogenic tubular insensitivity to ADH = permanent condition

– Tx = replacement therapy with ADH

SIADH– Get too much ADH secretion & get retention of fluid– Etiol :

– Some cancers especially oat cell lung cancer (very common cancer)– Post op (temporary, only last 1 week)– Stress – Psychiatric diseases

– Pathophysiology = hypoosolarity & hyponatremia– Symptoms related to low serum sodium

– First = fatigue & weakness– Then G-I sx– Then twitchings, convulsions, & coma

HypothalmusHypothalmus

• Three things it does relating to the endocrine system– (1) it makes the posterior pituitary hormones

» oxytocin (OT)» antidiuretic hormone (ADH) * nb: diabetes insipidus & SIADH

– (2) it controls the anterior pituitary by means of hormones it makes– This physiology used in pharmacology

» Releasing Hormones* exp = GnRH (gonadotropin

releasing hormone)» Inhibiting Hormones

– (3) It controls sympathetic output of adrenal medulla

see next slide

Thyroid GlandThyroid Gland

• 3 hormones• Thyroxine (T4) = more abundant than T3, but less potent• Triiodothyronine (T3) = more potent than T4• Calcitonin

– Functions:• Thyroid hormones (T4 & T3) function = increase metabolic rate

• Calcitonin

– lowers serum calcium by preventing the bones from giving it up

– works in harmony with the parathyroid & parathormone

• Disease states Goiter – may be euthyroid, hyper or hypo

hyperthyoidism• Grave’s disease = one specific type;autoimmune etiol;

get exophthalmos

hypothyroidism• cretinism = congenital type

• myxedema = adult type;get edema of face & tongue

• Hashimoto’s disease = autoimmune; chronic inflam. produces fibrosis of thyroid

Thyroid cancer Key cause = radiation exposure

Goiter• By definition just means thyroid enlargement

• Pathophysiology = excess TSH

• If have goiter, patient may be» Normothyroid

» Hypothroid

» Hyperthyroid

• 3 clinical types• Endemic goiter --- from lack of iodine in diet (hypothyroid)

» See next slide

• From goitrogens --- from drugs (e.g. lithium) & foods (e.g. cabbage)– These prevent T3 & T4 production

• Toxic goiter --- hyperthyoidism

– Note: if goiter present & patient hyperthyroid but not toxic ----think of Grave’s disease

Endemic goiter; hypothyroidism

Hyperthyroidism• 2 types: with exophthalmos & without exopthalmos• Graves disease

• Autoimmune • Most common form of hyperthyroidism• Get goiter

• Symptoms = “motor running fast”– Tachycardia, systolic hypertension, palpitations, insomnia, – heat produces discomfort– Exophthalmos (+/-)

• Complication = thyrotoxicosis or thyroid storm• Treatment

• Radioactive iodine• Surgery• Antithyroid drugs

Hypothyroidism• Commonest problem of thyroid

• 3 forms• Hashimoto’s thyroiditis---- autoimmune

• Myxedema --- adult severe hypothyroidism

– Myxedema = nonpitting edema of puffy face & thick tongue

– In early mild form --- symptoms subtle; hard to diagnose

– Muscle weakness (hung-up reflex)

– Mental apathy

– Dry skin

– Likes heat (always cold)

• Cretinism ---- congenital

– short stature, thick tongue, protruding abdomen, mental retardation

– Lack of hair (axillary)

Parathyroid GlandsParathyroid Glands

• Normally 4 glands located on posterior surface of thyroid• may have up to 8 glands

• produces hormone: Parathormone (PTH)– it increases calcium in blood by breaking down bone to release calcium– it works in conjunction & opposite calcitonin– Effects of parathormone:

– 3 key effects: 2 on bone & 1 on kidneys» 1. Acutely --- breaks bone down & increases serum Ca++» 2. Chronically --- get bone remodeling; i.e. bone is broken down &

reformed

» 3. In kidneys resorbs Ca++ & secretes phosphorus– Tissue effects of calcium:

• Skeletal muscle ------- no effect• Cardiac muscle ------- low weakens contraction; high strengthens contraction

(arrhythmias)• Nerve conduction ----- low increases excitability (get twitching, spasm, tetany)

high decreases excitability

– Hyperparathyroidism = hypersecretion = hypercalcemia• symptoms = SOUP, cardiac irritibility, osteoporosis, skeletal muscle

weakness due to decrease excitability of nerves

• Primary hyperparathyroidism

– Etiology ---- adenoma

• Secondary Hyperparathyroidism more common

– Etiology = decrease serum calcium secondary to:

» Renal disease

• Hypoparathyroidism = hyposecretion = hypocalcemia • symptoms =

– hyperexcitible neuromuscular system & get twitching, spasms, & tetany

– Skeletal muscle contraction power = same; no change– Cardiac muscle = weak contraction

• Etiol– Metastatic cancer --- raises calcium in blood & thus shuts off gland– Immobility – causes bone to release calcium

PancreasPancreas• Pancreas is both endocrine & exocrine gland

– exocrine = digestive enzymes secreted via duct into duodenum– endocrine located in Islets of Langerhans

• Cells of the islets– alpha cells produce glucagon

» it raises blood sugar by increasing liver glycogenolysis– beta cells produce insulin & amylin

» Insulin lowers blood sugar by escorting glucose into the cells

» Amylin contributes to postprandial glucose control* slows gastric emptying* regulates appetite centrally* see comment on “good

health” --- next slide

• Insulin– Anabolic hormone (a type of growth factor)

• Promotes synthesis of proteins, nucleic acids, & fats

• This occurs in liver, muscle, & adipose tissue

• Permits primarily glucose & ,also, amino acids into the cytosol

– Certain cells do not need insulin to get their glucose supply

» Brain

» RBC’s

» G-I tract epithelial cells can absorb glucose from diet

– Theory of good health, longevity, & prevention of “aging” diseases

• Good health = slow rises & falls of insulin production

• Bad health = peaks & valleys production of insulin

• “Glycemic index” & food

Diabetes Mellitus– Def: a disease that involves an “insulin deficit”

– Get hyperglycemia

– Get lack of available glucose in cells for mitochondria to make ATP

– Thus, mitochondria use fats to generate ATP

– Side effect = ketone body formation

– Pathophysiology (with associated symptoms/signs of the disease)

– Hyperglycemia

– Glucosuria

– Polyuria

– Polydipsia

– Polyphagia

-- & then—

– Fat catabolism

2 types (90% = type II & 10% = type I)

• Insulin Dependent Diabetes Mellitus(IDDM) = Type I

– autoimmune; get decreased production of insulin

• Non Insulin Dependent Diabetes Mellitus(NIDDM) = Type II

– get cellular insensitivity to insulin

– Current epidemic in USA ; incidence --- 10% of adults

– Major risk factor = obesity

– Alzheimer’s disease & insulin cellular insensitivity

• Etiology = autoimmune process; ? triggered by an infection early in life• Complications ---- divided into acute & chronic

– Acute complications– Diabetic Coma ---- lethargy, dry (dehydrated)– Insulin Shock ---- anxiety, sweating

– Chronic complications– Vascular complications – get macro & microangiopathy

» Macroangiography

* MI’s; CVA’s, peripheral vascular disease» Microangiography

* Kidneys ---- ruins glomerular capillary basement membrane

*Eyes ------ get diabetic retinopathy which leads to blindness

Adrenal CortexAdrenal Cortex• Has 3 distinct layers or zones

– from outside towards middle:

• Zona Glomerulosa– secretes mineralcorticoids (Aldosterone)

» Retain sodium (water follows sodium)» Usually gets rid of potassium &

hydrogen

• Zona Fasiculata– secretes glucocorticoids (Cortisol)

» Secreted in response to stress» Causes gluconeogenesis &

hyperglycemia» Causes protein catabolism

* thus, delays healing

» Is anti-inflammatory» Maintains BP by sensitizing vessels to

ANS

• Zona Reticularis» secretes sex hormones (steroids)

Diseases of the Adrenal Cortex– even though there are 3 different classes of hormones, most diseases affect primarily

the glucocorticoids

– Hypersecretion – Commonest problem = involves glucocorticoids; but some diseases may

have a combination of components

– Of glucocorticoids = Cushing disease– Commonest etiology = pituitary adenoma secreting ACTH

– Other etiol:

– ectopic ACTH secreting tumor (oat cell lung cancer, etc)

*called paraneoplastic syndrome

– Adrenal adenoma

– Taking “steroids” (exogenous)

– Of mineralcorticoids = hyperaldosteronism

– Commonest etiol = adrenal adenoma

– Note that 5-10% of people with hypertension have them

– Of sex steroids = feminization or virilization

– Clinical picture depends on sex

– Commonest etiol = adenoma & associated with Cushing disease

• Cushing Disease (MOODIAH)– Moon face– Obesity & edema from salt

& water retention

– Osteoporosis– Diabetes– Infections– Atherosclerosis– Hypertension

• Etiol– Pituitary adenoma– Adrenal adenoma– Ectopic paraneoplastic

syndrome– Iatrogenic

• Only cause that produces adrenal atrophy & resultant poor response to stress see next slide

Etiol– Pituitary adenoma– Adrenal adenoma– Ectopic

paraneoplastic syndrome

– Iatrogenic• Only cause that

produces adrenal atrophy & resultant poor response to stress

– Hyposecretion– Usually affects both glucocorticoids & mineralocorticoids

• Addison Disease = primary adrenal insufficiency• Commonest etiol = autoimmune destruction of adrenal cortex

• Get increased levels of ACTH

• In secondary hypocortisolism get low levels of ACTH

• Commonest etiol = exogenous glucocorticoids

Diagnostic clinical difference:

• Increase ACTH & Addison disease = skin pigmentation (bronze color)

• Decrease ACTH & Addison disease = no skin pigmentation

• Clinical features

– get hypotension, fatigue, weakness, & weight loss

* severe hypotension = shock = life threatening

– get dehydration & hyperkalemia* (from lack of aldosterone)

– get bronze skin color & pigmentation ( if increase of ACTH)

– Vitiligo from autoimmune destruction of melanocytes

Adrenal MedullaAdrenal Medulla

• Works in conjunction with sympathetic nervous system

• Involved in the “stress response”

• Makes catecholamines

• Key ones are norepinephrine (20%) & epinephrine (80%)

• Epinephrine is 10 times more potent in producing direct metabolic effects

* note that norepinephrine is more potent as neurotransmitter

• Diseases of Adrenal Medulla

– Pheochromocytoma• Benign tumor of adrenal medulla

• Cells of medulla called pheochromocytes

• Greek = dusky color

• Secretes epinephrine

• Get hypertension

Stress ResponseStress Response

• Def: A systemic generalized response to a change (stressor) either internal or external

– Stressors:

– Physical

– Psychological

– Real

– Imagined

– Anticipated

• Stressors are normal component of life

• Can be positive ---- stimulate growth & development

• Can be negative ---- if severe and/or not properly dealt with

• Note possible complications– Hypertension

• CHF

• Kidney failure

– CNS

• Stroke via vasospasm

• Depression– Fatigue

• Insomnia

• Tension headache

– Infections ---- see picture

– Digestive

• Stress ulcers

• GERD

• N&V; diarrhea

• IBS

– Diabetes mellitus