Homeostasis & Endocrinology

The Endocrine System

The endocrine system consists of glands widely separated from each other with no physical connections;

Endocrine glands secret hormones (chemical messengers);

Gland send those hormones into the bloodstream so they can travel to other body parts.

Hormones target tissues and organs that may be quite distant - influence mood, growth, development, metabolism, organs and reproduction

Homeostasis

Homeostasis is the maintenance of a relatively constant internal environment adjusting body’s system physiological responses when conditions change.

• Homeostatic set-points are determined by genetics, age, gender, health status & environment

• Internal environment is maintained close to an optimal point even though the external environment may change dramatically.

• Crucial to survival

• Environment is unpredictable

• All body systems must react to fluctuations in the environment to resist change

• Pathology emerges when homeostatic mechanisms break down

• Two general mechanisms:

- Intrinsic (auto) regulation: Cells regulating own millieu

- Extrinsic regulation: Nervous & endocrine systems maintain this.

NEGATIVE:

Primary mechanism of homeostatic regulation, providing long-term control over internal conditions by opposing change

Negative feedback resists physiological deflections away from the body’s setpoint.

POSITIVE:

Initial stimulus produces a response that exaggerates/amplifies the change

Seldom encountered (blood clotting cascade, childbirth)

Negative feedback

Primary mechanism of homeostatic regulation, providing long-term control over internal conditions by opposing change. Is used to keep a variable close to the optimum level and maintain homeostasis.

Has three components:

• A sensor that detects a change in the internal environment

• A control centre that instructs a response to counteract the change

• An effector that gets activated to produce a physiological response that brings conditions back to the optimum level

Negative feedback: regulation of body temperature

When body temperature rises above normal:

The hypothalamus senses the change and causes

• blood vessels to dilate and

• sweat glands to secrete, so that temperature returns to normal.

When the body temperature is above normal, the control center directs the blood vessels of the skin to dilate. This allows more blood to flow near the surface of the body, where heat can be lost to the environment.

In addition, the nervous system activates the sweat glands, and the evaporation of sweat helps lower body temperature. Gradually body temperature decreases to 98.6°F.

Negative feedback: regulation of body temperature

When body temperature falls below normal:

• The hypothalamus senses the change and causes blood vessels to constrict.

• In addition, shivering may occur to bring temperature back to normal. In this way, the original stimulus is resolved, or corrected

The control center directs the blood vessels of the skin to constrict. This conserves heat.

If body temperature falls even lower, the control center sends nerve impulses to the skeletal muscles and shivering occurs.

Shivering generates heat, and gradually body temperature rises to 98.6°F. When the temperature rises to normal, the control center is inactivated.

Positive feedback

Positive feedback is a mechanism by which the body responds to a change by amplifying it.

• It brings about rapid change in the same direction as the stimulus.

• Positive feedback does not maintain homeostasis.

• Only few biological functions demonstrate positive feedback. Examples: childbirth, bloodclotting.

• Positive feedback may also occur in disease. Example: fever that rises

above 42oC.

• Note that positive feedback does not last forever, once the relevant biological process is complete other controls cut off the positive feedback loop and restore balance.

When a woman is giving birth, the head of the baby begins to press against the uterus cervix (entrance to the womb),stimulating sensory receptors there. These nerve signals reach the hypothalamus in the brain, which causes the pituitary gland to secrete and release the hormone oxytocin.

Oxytocin travels in the blood and causes the uterus to contract and the baby’s head is forced further downwards.

This is a positive feedback mechanism which stops soon after the baby is delivered when distension of the uterine cervix is greatly reduced.

Hormones

Endogenous bioactive substances which are distributed throughout the body via the bloodstream, to induce physiological changes in specific target cells

Most hormones are distributed by the bloodstream to target cells. Target cells have receptors for the hormones, and a hormone combines with a receptor like a key fits a lock.

A hormone e.g. insulin, is a chemical signal that travels in the cardiovascular system from the pancreas to the liver where is causes liver cells to store glucose as glycogen

Mechanism of action of water-soluble hormones

• Non water soluble

• Pass through plasma membrane initiating a 2-step process

• Activated hormone-receptor complex formed within the cell

• Complex binds to DNA & activates specific genes

• Gene activation leads to production of key proteins

Endocrine glands vs. exocrine glands

Gland - one or more cells that secrete a substance

• Unicellular – one cell (Goblet cells)

• Multicellular – more than one cells

• Exocrine glands have ducts (tubes) to carry the secretion away to the site of function

- sweat, oil and gastric glands

• Endocrine gland are ductless, they secrete hormones that enter capillaries and circulate through the body to the target organs

- thyroid gland

- adrenal glands

- pituitary gland

Pancreas: exocrine (digestive enzymes) and endocrine (insulin & glucagone) gland

Coordination & Cellular Communication

Compare & contrast

• Endocrine & nervous systems work in parallel to control homeostasis, growth & maturation

• Nervous system coordinates rapid responses to stimuli using electrical conduction

• Endocrine system maintains long term control using chemical signals

Hypothalamus and the pituitary gland

• The hypothalamus is the part of the brain that controls the endocrine system known as the master switchboard.

• The pituitary gland and the hypothalamus act as a unit, regulating the activity of most of the other endocrine glands.

• The pituitary gland is called the master gland because regulates the activity of the endocrine glands.

• The pituitary gland lies below the hypothalamus, to which it is attached by a stalk.

• It is the size of a pea, weighs about 500 mg and consists of two main parts that originate from different types of cells.

1. The anterior pituitary (adenohypophysis) is an upgrowth of glandular epithelium from the pharynx

2. The posterior pituitary (neurohypophysis) a downgrowth of nervous tissue from the brain.

There is a network of nerve fibres between the hypothalamus and the posterior pituitary.

The Thyroid Gland

• The gland is composed of largely spherical follicles

Follicle: a small secretory cavity, sac, or gland.

• These secrete and store thyroglobulin the precursor hormone of T3 and T4

• Parafollicular cells (found between the follicles as single or small groups) secrete the hormone calcitonin.

T3, T4 and their negative feedback regulation

T3 & T4 (amines) regulate

• oxygen use and basal metabolic rate

• cellular metabolism

• growth and development

• Secretion of thyroid-releasing hormone (TRH) is stimulated by exercise, stress, malnutrition, low plasma glucose levels and sleep.

• TRH secretion by the hypothalamus stimulates the anterior pituitary to produce the thyroid-stimulating hormone (TSH).

• TSH stimulates the thyroid to release of T3 & T4 to the blood stream.

• T3 and T4 which gives feedback to inhibit the release of TRH & TSH: TSH secretion depends on the plasma levels of T3 and T4 because these hormones that control the sensitivity of the anterior pituitary to TRH. Through the negative feedback mechanism, increased levels of T3 and T4 decrease TSH secretion and vice versa.

Defects in T3 and T4 production

• Iodine is essential for the formation of the thyroid hormones, (enlargement of thyroxine (T4) and tri-iodothyronine (T3). thyroid gland)

• T4 contains four and T3 three iodine atoms.

• Main dietary sources of iodine are seafood, vegetables grown in iodine-rich soil and iodinated table salt. The thyroid gland selectively takes up iodine from the blood, a process called iodine trapping

Hypothyroidism:

A condition in which the thyroid does not release enough T4 and T3 hormones The metabolic rate slows and weight increases. Prevalent in older adults & five times more common in females than males.

• iodine deficiency

• autoimmune disease – Hashimoto: autoimmune antibodies bind thyroglobulin and prevent production of T3 and T4

Hyperthyroidism:

The body tissues are exposed to excessive levels of T3 and T4:

• Toxic nodular goitre

• Adenoma

• Graves’disease

• autoimmune disorder: an antibody binds to TSH receptors and stimulate secretion of excess thyroxine.

• leads to increased release T3 and T4 levels.

Calcium Homeostasis in the blood

Parathyroid hormone (PTH)

• increases release of calcium and phosphate from bones to the blood

• increases absorption of calcium and phosphate by the small intestine

• increases reabsorption of calcium by the kidneys

• activates vitamin D that stimulates calcium absorption

Calcitonin (peptide): increases calcium deposition in the bones

• Metabolises calcium and its secretion from kidneys.

• Decreases the reabsorption of calcium (and phosphate) from the bones to the blood

→ reduces blood levels of Ca2+

• Accelerates Ca2+ and phosphates uptake of into the bone extracellular matrix.

The opposing functions of calcitonin and PTH

When the blood calcium level is high, Parafollicular cells in the thyroid gland secretes calcitonin.

Calcitonin promotes the uptake of calcium ions (Ca2+)by the bones.

Blood calcium level returns to normal.

When the blood calcium level is low, the parathyroid glands release

parathyroid hormone (PTH). PTH causes

• the bones to release calcium ions (Ca2+)

• the intestines absorb Ca2+

• the kidneys to reabsorb Ca2+ and activate vitamin D.

The blood calcium level returns to normal.

Adrenal Gland: location and anatomy

Two adrenal glands sit atop the kidneys.

Each adrenal gland consists of

• an outer portion called the adrenal cortex

• an inner portion called the adrenal medulla

These portions have no functional connection with one another.

The hypothalamus exerts control over the activity of both portions of the adrenal glands.

Adrenal Gland: the hormones

Adrenal medulla: secretes epinephrine (adrenaline) and norepinephrine (noradrenaline), which help the body respond to short-term stress (e.g. fight or flight) • water-soluble hormones

Adrenal cortex: mineralocorticoids (e.g. aldosterone) and glucocorticoids (e.g. cortisol) enable the body to survive prolonged long-term stress.

• steroid hormones

It also secretes small amounts of sex hormones

Response to different types of stress

The hypothalamus controls both portions of the adrenal glands.

• Hypothalamus initiates nerve impulses that travel by way of the brain stem, spinal cord, and sympathetic nerve fibers to the adrenal medulla, which then secretes its hormones.

Rapid & short-term stress response

• Hypothalamus releases the cortocotrophin

hormone (CRH) and activates the anterior

pituitary gland to secrete the adrenocortocotrophic (ACTH), which in turn

stimulates the adrenal cortex.

Slower but long-term stress response

Regulation of blood pressure & the hormones

When a high blood sodium level accompanies a high blood volume, the heart secretes atrial natriuretic hormone (ANH). ANH causes the kidneys to excrete sodium ions (Na+), and water follows. The blood volume and pressure return to normal.

Keep in mind: blood volume and blood composition go hand in hand!!!

When blood sodium levels (Na+) are low, the low blood pressure causes the kidneys to secrete renin. Renin leads to secretion of aldosterone from the adrenal cortex. Aldosterone causes kidneys to reabsorb sodium ions (Na+) and water follows, so that blood volume and pressure return to normal.

Functions of cortisol

Glucocorticoids and cortisol mobilize energy reserves

and building blocks to cope with stress

• increase blood glucose levels

• mobilises amino acids and fatty acids for energy production

• decrease use of glucose for energy (except for the brain)

• increases conversion of glucose to glycogen in the liver for energy storage

• constrict blood vessels

• suppressed immune system leaves a person vulnerable to illness.

Cushing’s syndrome: excess glucocorticoids

Hypersecretion of adrenal cortex hormones.

• Excess of cortisol: tendency toward diabetes mellitus due to glucose mobilization

• Excess of adrenal male sex hormones: masculinization in females, increase in body hair, deepening of the voice, and beard growth.

• Excess of aldosterone: reabsorption of sodium and water by the kidneys, hypertension and face swelling.

Addison disease: hyposecretion of glucocorticoids

Hyposecretion of glucocorticoids & aldosterone

• Autoimmune disorder or pathogens that destruct adrenal cortex.

• decreased sodium in the blood • low blood pressure, dehydration, arrhythmias.

• mental lethargy, anorexia, nausea and vomiting, weight loss, hypoglycemia, and muscular weakness.

• “bronzing” of the skin

The pancreas

• An elongated gland, about the size of

a hand

• A multifunctional organ with function

in digestive and endocrine system.

• Is both an exocrine (digestive) gland and endocrine gland

Pancreas is endocrine & exocrine gland

• hormone-producing cells of the pancreas

• scattered throughout the gland

• pancreatic hormones are secreted directly into the bloodstream and circulate throughout the body.

Pancreatic islets secrete hormones

There are three main types of cells in the pancreatic

islets:

• α (alpha) cells secrete glucagon

• β (beta) cells secrete insulin

Blood glucose regulation

After a meal rich in carbohydrates, glucose enters the circulation at the small intestine. The resulting rise in blood sugar triggers cells in the pancreas to secrete insulin, which stimulates cells throughout the body to absorb glucose from the bloodstream.

As cells take up sugar, the blood glucose concentration declines, and insulin secretion slows. If blood sugar dips too low, however, other pancreatic cells secrete glucagon, which stimulates target cells in the liver to release stored glucose into the bloodstream

Diabetes Mellitus (DM)

The most common endocrine disorder

Caused by absence or relative deficiency of insulin (production) or resistance to insulin (use).

Signs of diabetes

• hyperglycemia (primary): glucose accumulates to dangerously high levels in the bloodstream

• varying degrees of disruption of carbohydrate and fat metabolism.

Two types of diabetes mellitus:

• Type 1 is called insulin-dependent diabetes and its onset is usually in childhood (juvenile onset).

• Type 2 is called non–insulin-dependent diabetes, and its onset is usually later in life (maturity onset).