The Endocrine System Pathophysiology. A & P Review of Endocrine System.
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Transcript of The Endocrine System Pathophysiology. A & 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
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