PSIO 241 CH 17 cont..

adrenal androgens

• Major hormone is dehydroepiandrosterone (DHEA)

– Only adrenal sex hormone that has any biological importance

– Overpowered by testicular testosterone in males

– Physiologically significant in females where it governs

• Growth of pubic and axillary hair

• Enhancement of pubertal growth spurt

• Development and maintenance of female sex drive

Cushing’s disease

ACTH overproduction from a pituitary adenoma (Cushing’s disease) leading to excess cortisol

Cushing’s syndrome

– Adrenal tumors secrete cortisol independent of ACTH

– ACTH-secreting tumors located in places other than the pituitary

– Both cause  excess cortisol

cortisol hyper secretion

• Central obesity, affecting face, neck, trunk, and **abdomen**

• “Moon face” and “buffalo hump” 

• **Protein depletion** due to excessive protein catabolism

• Limited or no inflammatory response

• Bone breakdown

• Skin with wide purple striae located around abdomen and hips 

primary insufficiency

• **Addison’s disease**; autoimmune disease that affects entire gland: 

– **Aldosterone deficiency**

– **Cortisol deficien**cy

secondary insufficiency

– Occurs because of pituitary or hypothalamic issue resulting in a deficiency in **ACTH production**

– **Only cortisol is deficient** because aldosterone release not under control of pituitary

Addison’s disease

**Cortisol deficiency :**

• weakness, fatigue, anorexia, weight loss, hypotension, hyponatremia, **hypoglycemia**

• increased ACTH leads to **hyperpigmentation of skin** and mucous membranes

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**Aldosterone deficiency:**

• sodium wasting and **hyponatremia**, potassium retention and **hyperkalemia**,  **hypotension**

Conn’s syndrome

• Most common cause: **small adenoma producing excess aldosterone**

• **Sodium retention** fluid, and circulating blood volume

• Increased vasoconstriction and TPR

• **Potassium loss**

• Since blood pressure elevated, plasma renin and angiotensin II levels **are low** 

Adrenal Androgen Hypersecretion

• Adrenogenital syndrome-excess DHEA secretion, symptoms seen only in females or prepubertal males

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– __Adult females__

•**Hirsutism-**male pattern of body hair

•Deepening of voice, more muscular arms and legs; breasts become smaller, and menstruation may cease

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– __Newborn females__

• Have male-type external genitalia

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– __Prepubertal males__

Precocious (early) puberty

hormones of the adrenal medulla

• Secretion of the adrenal medulla is 20% norepinephrine and 80% epinephrine.

•Half-life of the catecholamines is **only about 2 minutes**

• Most circulating norepinephrine arises from postganglionic sympathetic neurons

• **adrenal medulla is not essential for life**

• Epinephrine is a stress hormone and rapidly increases in response to **exercise, exposure to cold, emergencies, and hypoglycemia.**

pheochromocytoma

• **Most consistent feature is hypertension**. Symptoms include headache, diaphoresis, palpitations, and anxiety. Increased metabolic rate and hyperglycemia also occur.

• Characterized by __***episodic release***__ of hormone, acute hypertensive crisis, followed by hypotensive periods

• Treat with alpha blocker followed by surgical removal

exocrine cells

secrete digestive enzymes and bicarbonate into ducts that empty into the duodenum

endocrine cells

are found in pancreatic islets and release hormones into venous blood

beta cells

insulin secretion, insulin lowers blood glucose

alpha cells

glucagon secretion, glucagon raises blood glucose

insulin

secreted along with **C-peptide**

C-peptide

**the best marker for endogenous insulin release** (β cell function). 

proinsulin

Insulin and the cleaved connecting C-peptide are packaged together in secretory granules as _

equimolar quantities 

when the β cell is stimulated, they are released in **_ into the blood**. 

plasma glucose

the most important controller of insulin secretion is _

steps of insulin secretion

• Glucose enters the cell via GLUT1,3 transporters, is then metabolized, causing a rise in intracellular ATP that **closes ATP sensitive K+ channels**.

• Closure of the ATP-sensitive K+ channels **results in depolarization**, causing **voltage-gated Ca2+ channels to open.**

• The rise in cytosolic Ca2+ **causes exocytosis** of the vesicles, which then **secrete insulin** and **C-peptide** into the blood.

Glut-1, 2, and 3

_ transporters do **NOT** require insulin activity. These tissues can take up glucose with or without insulin.

GLUT-1

predominately in the red blood cells, brain, muscle, and adipose tissue

GLUT-2

in the membrane of hepatocytes and the pancreas, kidneys, and small intestine

GLUT-3

function in the brain

GLUT-4

low glucose affinity, in muscle and adipose tissue, and its function depends on insulin

activation of the insulin receptor by insulin

• promotes glucose uptake in **muscle and adipocytes** via translocation of **GLUT4** vesicles to the plasma membrane

• promotes glucose uptake in **liver** by altering **enzyme activity**

in the presence of insulin

**muscle cells and adipose tissue:** have more GLUT-4 proteins in their membrane; can take up more glucose out of the blood and put them in the cells

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**liver:** alters its enzyme activity; uptake of more glucose from the blood

absence of insulin

liver, skeletal muscle, and adipose tissue have trouble up taking glucose; therefore elevate glucose levels in the blood

specific actions of insulin

• induces glycogen synthesis

• induces protein synthesis

(antibolic hormone)

• induces lipogenesis

• promotes growth (protein synthesis)

• promotes K+ uptake by cells

• **Insulin means storage**

glucagon

• **Elevates blood glucose levels**

• Secreted in response to a direct effect of a fall in blood glucose on pancreatic α cells

•Stimulates liver to dump glucose into blood via **glycogenolysis or gluconeogenesis**

raise blood glucose levels

1st hormone body releases- glucagon

2nd- cortisol/growth hormone

3rd- epinephrine

diabetes mellitus

• Most common of all endocrine disorders

• Prominent feature is elevated blood glucose

• Two major types:

– **Type I diabetes; insulin dependent DM**  

– **Type II diabetes; non-insulin dependent DM**

type I diabetes

characterized by lack of insulin secretion

type II

characterized by normal or increased insulin secretion but reduced sensitivity of target cells

symptoms of diabetes mellitus

1. Hyperglycemia
2. Glucosuria
3. Polyuria
4. Polydipsia
5. Polyphagia
6. Increased fat metabolism and weight loss (in type I only) and this can lead to **ketosis/metabolic acidosis**

chronic symptoms of diabetes

Microvascular disease affecting nerves, heart, eye, loss of pain perception, kidney

diabetic ketoacidosis

without insulin (Type I) **excessive lipolysis** provides fatty acids to liver to be converted to ketone bodies (acids)

\- loses weight fast

• Blood pH and bicarbonate decrease **: metabolic acidosis** 

• **Increased alveolar ventilation** to compensate for acidosis (Kussmaul breathing) to rid the body of the acid, CO2

• **Acidic urine** to compensate for acidosis

control of calcium homeostasis

• Plasma Ca2+ must be closely regulated to prevent changes in neuromuscular excitability

• Also plays vital role in several essential activities:

• Excitation-contraction coupling in cardiac and smooth muscle

• NT secretion

• Clotting of blood

changes in calcium levels

– **Hyper**calcemia reduces excitability (blocks VG-sodium channels)

– **Hypo**calcemia can produce severe overexcitability and can cause fatal spastic contractions of respiratory muscles

bone

99% of total calcium

mostly as complex calcium phosphate salts (hydroxyapatites)

interstitial fluid (calcium)

* 0.1% of total calcium
* mostly Ca 2+
* 1.5 mM

intracellular fluid (calcium)

1% of total calcium

Ca 2+ and protein bound calcium

plasma

cellular level

calcium concentration gradient allows rapid calcium entry into cells when channels open to promote rapid physiological responses

hormones that regulate plasma concentration of calcium and phosphate

1. **Parathyroid hormone (PTH)-**elevates plasma concentration of Ca2+ **and** lowers plasma phosphate
2. **Calcitonin**- decreases plasma concentration of Ca2+
3. **Vitamin D**-raises both plasma calcium and phosphate to promote **bone deposition**

parathyroid hormone

function is to **elevate free calcium**, it also **lowers phosphate** so that the ratio stays below the ossification threshold and  plasma calcium levels rise

vitamin D

function is to **promote bone formation**, so it **raises both calcium and phosphate** to exceed the threshold and bone is formed

hypercalcemia of primary hyperparathyroidism

• Initiating factor is primary **hypersecretion of PTH** (adenoma) 

• Consequences include increased plasma calcium, decreased plasma phosphate

• **Neural tissue less likely to depolarize** (lethargy, confusion, and constipation)

• Bone manifestation is **osteitis fibrosa cystica**

calcitonin

• Hormone produced by C cells of thyroid gland

• Secreted in response to increase in plasma Ca2+

• **Unimportant except during hypercalcemia**

• May play a role in protecting skeletal integrity during times of calcium demand (pregnancy and lactation

parathyroid hormone

• **Function of PTH is to increase free calcium**, targets kidney (fast) bone (slow) 


1. Increases Ca2+ reabsorption in **distal tubule of the kidney**
2. Inhibits phosphate (Pi) reabsorption in **proximal tubule of the kidney.**
3. Stimulates the 1-alpha-hydroxylase enzyme **in kidney, converting inactive vitamin D to its active form.**
4. Causes bone resorption, releasing Ca2+ and Pi into the blood.

vitamin D

Acts to raise plasma Ca2+ AND PO-4 ; promotes __bone deposition__

– Increases absorption of Ca2+ and PO-4 in **intestinal mucosa**

– Resulting high concentrations of Ca2+ and PO-4 in extracellular fluid exceed solubility product, **precipitation of bone salts into bone matrix**

– Enhances PTH’s action at renal distal tubule, calcium reabsorption