Lecture 14: Endocrine System (Exam 3) Flashcards

1
Q

What endocrine organs did we focus on in the endocrine lecture?

A

Hypothalamus and pituitary
Thyroid
Parathyroid
- Phosphate and Calcium metabolism
Adrenal gland

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2
Q

What is homeostasis?

A

-multiple layers of control with feedback
-balance

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3
Q

Briefly describe hormone interaction

A

Hypothalamus
GHRH affects GH
Somatotostain affects TSH and GH
TRH affects TSH and PRL
dopamine effects dopamine
GnRH affects LH/FSH

Adenohypophysis
GH affects multiple organs
TSH affects thyroid
PRL affects reproductive organs
LH/FSH affects reproductive organs

Target of Organs
Multiple
thyroid (can feedback hypothalamus)
reproductive organs

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4
Q

What endocrine diseases are covered in this lecture?

A

Hypothalamus/Pituitary
-Diabetes Insipidus
-SIADH (syndrome of inappropriate ADH secretion)
-Sheehan Syndrome

Thyroid
-Goiter
-Thyroiditis
-Graves Disease

Adrenal Gland
-Addison Disease
-Cushing Syndrome
-Pheochromocytoma

Parathyroid
-Osteomalacia
-Hypercalcemia

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5
Q

Describe the interactions of the hypothalamus

A

Hypothalamus
-releasing hormones act on adenohypophysis
-Neurohypophysis is the end of neurons that are in the hypothalamus

Neurohypophysis (posterior pituitary)
-Diabetes Insipidus decrease
-SIADH

Adenohypophysis (anterior pituitary) (through the blood, acidophils, and basophils)
-Adenomas increase
-Sheehan syndrome decreases

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6
Q

What is Diabetes insipidus?

A

Deficient ADH production
-by the neurohypophysis
-results in excess water excretion
-serum Na+ and osmolarity increase

-caused by head trauma, tumors, inflammation of the hypothalamus/pituitary

ADH and oxytocin are hormones that accumulate in the neurohypophysis

Two types:
- insufficient ADH–>Central DI
-ADH insensitivity –> Nephrogenic DI

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7
Q

Describe CDI clinically

A

Sx:
Frequent Urination
-Extreme thirst
-Can cause life-threatening dehydration

Treatments
-Mild CDI
-drink more water
More severe
-Vasopressin can be prescribed

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8
Q

What is SIADH?

A

Syndrome of inappropriate (comes from outside the pituitary) ADH secretion
-more frequently by ADH-secreting tumors (SCLC)
-also certain drugs, CNS disorders

Excess ADH
-Excessive water resorption
-Dilutes blood –> hyponatremia

Clinically:
-Hyponatremia
-Cerebral edema (blood volume does not change, so no peripheral edema)
-neurologic dysfunction (think water intoxication)

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9
Q

What is water intoxication?

A

Water poisoning or fatal hyponatremia
-urine excretion can be increased to 16ml/min when large quantities of hypotonic fluid are ingested

-if ingestion exceeds this, or continues for too long, cells will swell due to water uptake to cope with hypotonic ECF

Symptoms
-swelling of CNS neurons
-Convulsions, coma (can kill)

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9
Q

What is water intoxication?

A

Water poisoning or fatal hyponatremia
-urine excretion can be increased to 16ml/min when large quantities of hypotonic fluid are ingested

-if ingestion exceeds this, or continues for too long, cells will swell due to water uptake to cope with hypotonic ECF

Symptoms
-swelling of CNS neurons
-Convulsions, coma (can kill)

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10
Q

What is Sheehan Syndrome?

A

During pregnancy, the anterior pituitary (where FSH and LH are produced) undergoes hypertrophy
-Will nearly double in size

-Hormones of pregnancy
-Progesterone produced by corpus luteum
-blocks the development of additional follicles
-HCG stimulates the production
LH and Prolactin-adenohypophysis
-Support function of the corpus luteum
-Prolactin inhibits GnRH release; inhibited by estrogen and progesterone until parturition
-Prolactin release stimulated by estrogen

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11
Q

What is Ischemic Necrosis of the adenohypophysis?

A

-excessive cell numbers without increased blood flow causes minor anoxia
-more sensitive to low blood pressure
-Hypovolemic shock due to hemmorrage
-infarct will develop in the anterior pituitary
-Necrosis leading to fibrosis

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12
Q

What are symptoms of Sheehan symptoms?

A

Ischemic tissue is replaced by fibrosis nodules
-Causes postpartum hypopituitarism

Symptoms include:
-Amenorrhea (FSH/LH)
-Infertility (FSH/LH)
Lactation failure (Prolactin)
-Hypothyroidism (Thyroid-stimulating hormone)
Pallor (loss of melanocyte stimulation) POMC (MSH)

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13
Q

Describe how adrenal hormones move/work

A

-release into nearby blood vessels
-steroid hormones in the cortex
-peptide hormones (catecholamines) in the medulla
-Release induced by nerve signal

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14
Q

What are the diesease that are focused in the adrenal gland?

A

Addison Disease
-primary chronic adrenocortical insufficiency

Cushing Syndrome
-aka hypercortisolism
-exogenous and endogenous causes

Pheochromocytoma
-medullary tumor

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15
Q

What is Addison’s disease?

A

_progressive destruction of the adrenal cortex
-extensive mononuclear infiltrate
-Loss of most of the cortical cells

-60%-70%: autoimmune adrenalitis
-infections: tuberculosis or fungal
-AIDS
-Metastatic cancer

-Gross appearance of gland varies
-Autoimmune: shrunken
-Infection: inflammatory reaction
-Cancer: enlarged with tumor

Sx: 90% of the adrenal gland is lost still noticed
First: progressive weakness and easily fatigued

  • Lack of aldosterone (aldosterone increases Na+ reabsorption, increases K+ secretion, and H+ secretion) increase leads to loss of sodium and retention of potassium
    -Volume depletion and hypotension

**Lack of glucocorticoids (glucocorticoids produce hyperglycemia, glucosuria, secondary diabetes, and suppress the immune system) leads to hypoglycemia and lack of gluconeogenesis
-Cortisol increases gluconeogenesis
-Stress causes an adrenal crisis that can be fatal
-Adrenal crisis: continuous vomiting, abdominal pain, hypotension, vascular collapse, and coma

GI disturbances (cortisol helps break down fat, carbohydrates, and protein)
-Anorexia, nausea, vomiting, weight loss, diarrhea

Skin hyperpigmentation
-increase in POMC due to lack of cortical hormones
-Trying to make more ACTH (no negative feedback)
-POMC contains MSH fragments
-Stimulate melanocytes to produce melanin

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16
Q

What is Autoimmune adenalitis?

A

The immune system destroys steroid-producing cells in the adrenal cortex
-Autoantibodies to enzymes involved in steroid synthesis

-Associated with autoimmune polyendocrine syndromes (APS)
-Multiple diseases that involve the destruction of endocrine tissue (multiple organs)
-Best understood is APSI
-Autoantibodies to IL-7 and IL-22 (produced by T helper cells)
-Mutation is in a single gene on chromosome 22
-gene product (AIRE) is involved in protein expression in the thymus needed to remove T cells reactive to adrenal cortex antigens

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17
Q

What is Cushing’s Syndrome?

A

Pituitary adenoma
-monoclonal microadenomas
-excessive ACTH secretion will produce bilateral adrenal hyperplasia

Chronic exposure to high blood glucocorticoid levels
-most common cause is excess ACTH secretion by the adenohypophysis
-tumor in the anterior pituitary

Iatrogenic
- medial administration of glucocorticoids to treat the non-endocrine disorder
-immune suppression for autoimmune, transplant patients
-see adrenal atrophy

Endogenous (non-iatrogenic)

4 types
Pituitary Cushing Syndrome
-adrenal hyperplasia
Adrenal Cushing syndrome
-Tumor or nodular hyperplasia
Paraneoplastic Cushing syndrome
-see adrenal hyperplasia
Iatrogenic Cushing syndrome
neg. feedback: High GC/Low ACTH

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18
Q

What are the possible changes you will possibly see in the adrenal gland?

A

depending on the cause:
1.) cortical atrophy (iatrogenic Cushing syndrome)
-exogenous GC decreases ACTH
-lack of stimulation results in atrophy
2.) Diffuse hyperplasia (Cushing’s Disease)
3.) Nodular hyperplasia (ACTH-independent)
-adrenal gland is not dependent on ACTH but the adrenal gland secretes its own ACTH
4.) Adenoma/carcinoma
-causative; tumors that produce cortisol

Treatment:
removal of the adrenal gland if in one
eliminate the cause

19
Q

What are the possible changes you will possibly see in the pituitary gland?

A

-regardless of the cause
-corticotropic basophils become paler, and fill with keratin filaments (Crooke hyaline change)

20
Q

What is endogenous Cushing’s

A

ACTH dependent
-Cushing’s Disease
-ACTH-secreting pituitary adenoma
-Ectopic ACTH syndrome
-spontaneous
-most often-small cell lung carcinoma or bronchial carcinoid tumors

ACTH independent
-Adrenocortical tumor (produce ACTH or ACTH-like peptide)

21
Q

What is the effect of high cortisol levels?

A

-Suppress CRH secretion (hypothalamus)
-Suppress ACTH secretion (pituitary)
-also inhibit GH, TSH, and gonadotropin release
-affects insulin production and gluconeogenesis in the liver

22
Q

What are the symptoms of Cushing’s Disease?

A

-Hypertension
-Weight gain
-centralized (trunk, posterior neck)
-Selective atrophy of fast-twitch muscle fibers, resulting in proximal limb weakness

Glucocorticoids produce
-Hyperglycemia, glucosuria, secondary diabetes (induce gluconeogenesis, decrease glucose uptake)
-Suppress the immune system

23
Q

What is Cushing’s Catabolism?

A

Promotes catabolism of
-Collagen
-Inhibits fibroblast function
-Bone
Leads to
-Fragile skin with poor wound healing
-Striae on the skin (especially the abdomen)
-Similar to stretch marks
-Osteoporosis

24
Q

What is Pheochromocytoma?

A

-tumor of the chromaffin cells in the adrenal cells in the adrenal medulla (known to secrete norepinephrine)
-will affect tissues with adrenoreceptors (Cardiovascular, GI, Eyes)

Sx:
Tachycardia and “pounding heart”
-Beta-1 receptors in the heart increased rate and contractility
-Cold hands/feet
-Alpha-1 receptors in vessels produce vasoconstriction
-Feeling hot
-Cannot dissipate heat

-Throbbing headache
-Severe HTN due to increased HR, contractility, vasoconstriction

-Nausea and vomiting
-Decreased blood flow, smooth muscle relaxation

-Visual disturbances
-Alpha-1/beta receptors dilate pupil

25
Q

What are the diseases that were covered about the thyroid?

A

Goiter
-enlarged thyroid gland

Thyroiditis
-inflammation

Graves Disease
-Most Common cause of persistent hyperthyroidism
-Women are affected 10X as frequently as men

26
Q

Describe Thyroid hormone production

A

Thyroglobulin
-the storage form of thyroid hormone
-produced in RER
-Glycosylated
-Exocytosed into the follicular lumen

Iodide from blood
- Transported by symporter
-Oxidized after release into lumen

27
Q

What is Goiter?

A

-Impaired synthesis of thyroid hormones
-usually due to iodine insufficiency

Low T3/T4 levels
-induce TRH release
-induces TSH release
-TSH induces thyroid hypertrophy

28
Q

What are the two types of Goiter?

A

Simple (diffuse, non-toxic)
-Endemic
-More than 10% of the population
-Usually related to diet
-Sporadic
-More common in women at puberty or shortly after

Multinuclear
-Repeated episodes of hypertrophy

29
Q

What are the dietary causes of Goiters?

A

insufficient Iodine
-more common in mountainous regions (access to saltwater)
-supplementation has reduced

Goitrogenic Food intake
-Certain vegetables (cruciferous, including cabbage, cauliflower, and cassava root)
-Cassava contains a thiocyanate that inhibits iodine transport

30
Q

What are the consequences of Goiters?

A

Compressive syndrome
-airway obstruction
-compression of large.blood vessels
- difficulty swallowing (dysphagia)

31
Q

What is Thyroiditis?

A

any inflammation of the thyroid
- 3 common types
-Hashimoto
-Granulomatous
-Subacute Lymphocyte

32
Q

What is Hashimoto Thyroiditis?

A

-Autoimmune disorder; strong genetic component
- Ab’s against thyroglobulin and thyroid peroxidase

Cause unknown; possibilities
- Abnormalities in regulatory T cells
-Exposure of thyroid antigens (normally sequestered)

**mononuclear infiltrate
**Atrophic follicles
**Hurthle cells (very eosinophilic)

33
Q

What is hypothyroidism?

A

inflammation –> enlargement of the thyroid
-destruction of parenchyma–> lack of T3/T4 production

Sx:
mimic depression
slower metabolism
cold intolerance
decreased sympathetic nerve activity –> constipation, decreased sweating
-decreased blood flow–> skin cool

Serum TSH increased
Serum T4 decreased

34
Q

What is Graves disease?

A

Autoimmune disorder
-genetic susceptibility has been linked to mutations in immune function genes

Clinical findings
-Hyperthyroidism (diffuse hypertrophy)
-Exophthalmos
-Localized infiltrative dermopathy
-on the shins
-less common

35
Q

What is the autoimmune response in Graves disease?

A

antibodies actually stimulate the thyroid
-Failure to recognize thyroid antigens as self
-Most frequently, TSH receptor

Common autoantibodies
-IgG that acts as an agonist for TSH receptor (stimulates T3/T4)
-Thyroid growth stimulating IgGs
-follicular cell hyperplasia
-TSH-binding inhibitors IgGs
-May actually decrease activity

36
Q

What are the function and clinical presentation of TSH?

A

Thyroid-stimulating hormone
-Aka Thyrotropin
-Released induced by TRH
-Thyrotropin Releasing hormone

Clinical Presentation
Thyroid Hypertrophy
-Treatment: destroy excess tissue

Extra-thyroidal (beta-adrenergic effects)
- Generalized lymphoid hyperplasia
-Heart hypertrophy/ischemia
-Exophthalmos- edema in the tissue surrounding the eyeball (also, fibrosis, lymphocyte infiltrates)

Dermal thickening due to lymphocyte infiltration n

37
Q

What is PTH release?

A

-parathyroid hormone
- Chief cells have a calcium receptor
-G protein-coupled receptor
-Detects blood calcium levels
-When calcium binds, inhibits PTH release
-If calcium levels are low, PTH release proceeds

**PSH in bone stimulates osteoclasts/ in kidneys it will decrease Ca2+ excretion, and maintain Po4 (a balance that is release from bone)

37
Q

What is PTH release?

A

-parathyroid hormone
- Chief cells have a calcium receptor
-G protein-coupled receptor
-Detects blood calcium levels
-When calcium binds, inhibits PTH release
-If calcium levels are low, PTH release proceeds

**PSH in bone stimulates osteoclasts/ in kidneys it will decrease Ca2+ excretion, and maintain Po4 (a balance that is release from bone)

38
Q

What is parathyroid disease?

A

Osteomalacia (secondary hyperparathyroidism)
-a skeletal disease associated with Vitamin D deficiency

Hypoparathyroidism-uncommon, usually associated with surgical removal, APSI mutation

Hypercalcemia
-Clinically apparent is most often due to malignancy
-Asymptomatic is associated with hyperparathyroidism

39
Q

What is osteomalacia?

A

excess of persistent osteoid

Failure to mineralize
Vitamin D deficiency
-Lack of sun exposure
-children of women with frequent pregnancies followed by lactation

Hypocalcemia
-renal disorders
-Malabsorption (causes calcium deficiency absorption)

40
Q

How is osteomalacia clinically presented?

A

-soft bones
-prone to breaks
-similar to osteoporosis
-in children- rickets

Treatment: Vitamin D supplementation (in milk)

41
Q

What is hypercalcemia?

A

-primary hyperparathyroidism
- 95%- solitary parathyroid adenoma
- increased PTH production increases blood calcium by promoting resorption from bone

Secondary Hyperparathyroidism
-Most common- chronic renal failure
-Vit D conversion
- re-absorption

Any hypocalcemia will cause

42
Q

What are the morphologic changes with hyperparathyroidism in Bone?

A

Increased number of osteoclasts
-erode bone matrix
-mobilize calcium salts
Similar to osteoporosis (thinner trabeculae)

Advanced disease
-The cortex of bone is thinned
-Marrow contains fibrosis and clumps of irregular cells that mimic neoplasms

43
Q

What are the morphologic changes with hyperparathyroidism in the Kidney?

A

-Favors formation of kidney stones
-calcification of interstitium and tubules