The Endocrine System

Blood Sugar Levels-An Endocrine Case

Debbie, a 57-year-old female has been feeling tired and losing weight, despite eating more and feeling hungry

She also states that she is always thirsty and urinating more freely than usual

Classic symptoms of Diabetes Mellitus:

• Fatigue, weight loss without trying, appetite increase, thirst, frequent urinating

• Polydipsia= increased thirst/drinking

• Polyphagia= increased eating

• Polyuria= increased urinating

• *Poly means “many or lots”

Clinical Test #1: Urinalysis

• A sample of urine is tested with a dipstick

• Checking to see if excess glucose is in the urine

• If too much glucose is in the urine, it means there is so much in the blood that it is “spilling” over into the kidneys and into urine

• Debbie had increased glucose in her urine…not looking good…

Clinical Test #2: Serum Blood Glucose Test

• Serum/plasma= liquid fluid of blood minus blood cells

• Patient fasts for 8 hours before the test

• Vial of blood is drawn and the level of glucose in plasma is measured

• Normal: 70-100mg/dl*

• Debbie’s results: 112mg/dl, a “prediabetes” level

• Not the worst, but not too good either…

Clinical Test #3: Oral Glucose Tolerance Test (OGTT)*

• The patient chugs a liquid with 100g of glucose (yuck!)

• Over the next 3 hours, 5 vital of blood are drawn

• Normal: blood glucose rises fast, then falls to below 140 mg/dl within 2 hours

• Debbie’s: very slow glucose fall and at 2 hours, she was at 150 mg/dl

• 3 tests have now shown abnormal amounts of glucose in Debbie's blood. She is told that she has Type 2 Diabetes Mellitus

Now think about the honest question…

• Did I learn enough about the endocrine system in class to help Debbie?

Clinical Questions to learn:

1. What are some symptoms of Diabetes Mellitus (DM)?

2. What are 3 tests we can order to check for Diabetes?

3. Normal blood sugar levels are ___ to ___ mg/dl.

4. A normal OGTT should be below ___ mg/dl within 2 hours.

Endocrine System Overview

Endocrine system= system of glands that secrete hormones to control the body's functions

• Endo= “within/inside”; -crine= “to secrete”

• Hormone= chemical signals or “messengers” secreted by glands

• Hormon/hormein= to excite or stimulate”

• Endocrine glands secrete hormones directly into the blood

• Blood carries hormones all over the body to different organs and cells

Major glands of the Endocrine System:

• Hypothalamus (brain)

• Pituitary Gland (brain)

• Pineal gland (brain)

• Thyroid (neck)

• Parathyroid glands (neck)

• Pancreas (abdomen)

• Thymus (chest-thoracic)

• Adrenal glands (abdomen)

• Testes/Overies (pelvis)

The endocrine system controls and integrates: 

• Reproduction

• Growth and development

• Maintenance of electrolyte, water, and nutrient balance of blood

• Regulation of cellular metabolism and energy balance

• Mobilization of body defenses

Endocrine and Nervous Systems

Endocrine + Nervous systems- 2 main control systems of body

The endocrine system acts with nervous system to coordinate and integrate activity of body cells

Influences metabolic activities via hormones transported in blood 

Responses slower but longer than nervous system

Endocrinology: medical study of hormones and endocrine organs

Compare and contrast

Endocrine System Overview

Exocrine glands

• Have ducts

• Produce non-hormonal sub-stances (ex: sweat, saliva)

• Secrete projects into ducts to carry secretion to outside surface or into an organ cavity

Endocrine glands

• Produce hormones

• Lack ducts

• Secrete directly into blood

Some glands have exocrine and endocrine functions

• Pancreas, gonads, placenta-all do both

1. Secrete things direct into the bloodstream (endo)

2. Secrete things out into ducts into organs or body surfaces (exo)

Some other tissues and organs have small pockets of endocrine cells that produce hormones

• Adipose (fat) calls; thymus, and cells in walls of small intestine, stomach, kidneys, and heart

Endocrine Hormones

Hormones: chemical messengers of endocrine system

• Travel long distances in blood

We have 2 main chemical classes of hormones:

1. Water-based/soluble hormones:

• Amine hormones

• Peptide/protein hormones

• Eicosanoid hormones

• **Require receptor protein on surface-cant enter cell

2. Lipid-based/soluble hormones:

• Synthesized from cholesterol

• Steroid hormones and thyroid hormones

• Bind to receptor inside the cell (lipids diffuse easily through membrane)

Hormone Function on Cell

Hormones act in one of two ways, depending on their chemical nature and receptor location

1. Water-soluble hormones (all amino acid-based hormones except thyroid hormone)

• Cannot enter the cell (Eater and lipids (fats) DONT MIX)

• Act on plasma membrane receptors

• Act via G-protein second messengers system (signal transduction cascade)

2. Lipid-soluble hormones (steroid and thyroid hormones)

• Can easily enter cell- float through cell membrane lipids

• Act on intracellular receptors that directly activate genes

Water-Soluble Hormones

Amine, peptide, and protein hormones use the G-protein “second messenger” cell pathway:

1. peptide/protein hormone (1st messenger) binds to receptor on cells plasma membrane

2. Binding leads to activation of an enzyme inside the cell that changes ATP  into cAMP (2nd messenger)

3. cAMP activates a series of enzymes called a “cascade”

4. Cell responds to enzyme-activated proteins and does what the hormone wants to happen

Lipid-Soluble Hormones

1. Lipid-based hormone diffuses right through the plasma membrane

• Its lipid-soluble (steroid hormones and thyroid hormones)

2. Receptor-hormone complex enters nucleus and binds to specific regions of DNA

3. Initiates DNA transcription to produce mRNA

4. mRNA moves to Ribosomes, then translated into specific protein 

• Proteins synthesized have various functions

• Examples: metabolic activities, structural purposes, or exported from cell

Pharmacology “Flash”

What's the big deal if I learn about water-soluble vs. lipid-soluble hormones?

• Lipid-soluble hormones can be taken by mouth since they can easily cross the intestinal lining and not get damaged in the stomach

• Steroids and thyroid hormones

• Water-soluble hormones (amines, peptides, proteins) get broken down by stomach acid and digestive enzymes that break peptide bonds

• This is why Insulin (protein) has to be injected

Target Cells and Hormones

Through hormones circulate systematically, only cells with receptors for that hormone are affected (target cells)

• Target cell has a specific receptor for a specific hormone

• Hormone + receptor protein, “lock and key” idea

• Only when a specific hormone locks to a specific receptor protein on the target cell will the cell respond

• Ex: Thyroid hormone does nothing to the ovaries because ovaries have no receptors for thyroid hormone!

Hypothalamus

Located in the brain

• Forms the Diencephalon with the Thalamus

• Hypothalamus + thalamus = Diencephalon

• Connects to the Pituitary Gland by a “stalk” or column of tissue called the infundibulum

• Function: controls and manages the Pituitary gland by sending “releasing hormones or inhibiting hormones” (RH’s or IH’s)

Tells the Pituitary when and what hormone to secrete into the body's bloodstream

Sends:

• 7 hormones by blood to the anterior Pituitary Gland

• 2 hormones down nerve axons to the posterior Pituitary Gland

The hypothalamus is called a “neurosecretory” organ- it is a major part of the brain (neuro) but it secretes specific hormones for the endocrine system (secretory)

Pituitary Gland

Sits in a special notch in the sphenoid bone called the “sella turcica”

Has 2 parts: an anterior and posterior lobe

• Anterior pituitary- “adenohypophysis”

• (ADD-in-O-Hi-POF-e-sis)

• Posterior Pituitary- “neurohypophysis”

• (NEURO-Hi_POF-e-sis)

Each part secrets a different series of hormones when triggered by the hypothalamus to do it

Hormones from the Anterior Pituitary (adenohypophysis)

• GH- “growth hormone, somatotropin”

• Directly boosts mitosis and protein synthesis in most body cells (bone, muscle, cartilage, and organs)

• TSH_ “thyroid stimulating hormone”

• Stimulates thyroid gland to release thyroid hormones to regulate metabolic rates of cells/organs

• ACTH- “edrenocorticotropic hormone, corticotropin”

• Stimulates the adrenal gland cortex to release “glucocorticoid hormones”- help the body overcome stress

• FSH- “follicle-stimulating hormone”

• Stimulates egg (follicle) production in ovaries and sperm production in testes

• LH- “luteinizing hormone”

• Kicks off the menstrual cycle/ovulation each month and triggers sperm growth in the testes

• Prolactin

• Stimulates milk production in breasts after pregnancy

Posterior Pituitary Hormones (neurohypophysis)

• Oxytocin (“mama hormone”)

• Stimulates hard uterine contractions for birth

• Activates milk release and muscles to secrete milk from mama’s breast- aka “milk let-down reflex”

• ADH (“vasopressin”)- Anti Diuretic Hormone

1. Controls fluid regulation in the body

• This causes the body to absorb and hold onto more H20 in the blood

2. Kidney function control

• Decreases urine output- prevents water loss

• Makes kidneys absorb more H20 back into the body

• Makes urine more concentrated

3. Blood pressure (BP) control (raises BP)

• Senses low BP and low blood volume (blood loss)

• Causes kidneys to absorb more H2O back into the blood and constricts blood vessels (vasoconstriction)

Clinical Significance

Hypersecretion of GH is usually caused by anterior pituitary tumor

• In children results in gigantism

• Can reach heights of 8 feet!

• In adults results in acromegaly

• Overgrowth of hands, feet, and face

Hyposecretion of GH

• In children results in pituitary dwarfism

• May reach a height of only 4 feet

• A genetic defect, born without one, or an unknown reason

• In adults usually causes no problems

Pineal Gland

Produces serotonin during the day (wake-up hormone)

Produces melatonin at night (sleepy time hormone)

Thyroid Gland

Largest endocrine organ of the body

Found in the anterior neck, superior to the suprasternal notch of the sternum

Has two large lobes connected by a “bridge” or tissue called the “isthmus”

• Gives it a “bowtie” shape

The thyroid is wrapped around the anterior and lateral parts of the trachea

Secretes 3 hormones:

1. T3- triiodothyronine

2. T4- tetraiodothyronine or “thyroxine”

• *together T3 and T4 are called “TH”- thyroid hormone

3. Calcitonin

T3 and T4- major regulators of the metabolic rate of body tissues

• Increase heart rate, raises BP

• Increase respiration rate

• Boost body temp

• Stimulate bone, teeth, nails, and hair growth in adults

Calcitonin: 

• Controls blood calcium levels in the body 

• Triggers the moving of calcium from the blood into the bone for osteogenic cell growth

• Helps infants and kids make strong bones

• Helps a pregnant/breastfeeding mom move calcium into her bones to deposit strong bone growth and repair or into her milk for baby

• Generally, calcitonin lowers blood calcium levels so it can be used to help bone or mama’s milk

Clinical Significance

Hypothyroidism

• Hyposecretion of TH (T3 and T4) in adults

• Symptoms include low metabolic rate (weight gain), thick and/or dry skin, cold intolerance, mental sluggishness, lethargy, hair loss

• Can lead to myxedema- a severe form of Hypothyroidism + “puffiness”/swelling

• If due to lack of iodine, a pointer may develop

• Lack of iodine decreases TH levels, which triggers increased TSH secretion, triggering the thyroid to synthesize more and more unusable thyroid hormone

• Thyroid enlarges

TH is critical for normal growth and brain development in early childhood

• Congenital hypothyroidism is usually caused by poor development of the thyroid gland

• Hormone treatment must happen in the first 2 months of life or intellectual disability results

Hyperthyroidism

• Hypersecretion of TH: The most common type is Graves’ disease

• Autoimmune disease: the body makes abnormal antibodies directed against thyroid cells

• Antibodies mimic TSH, stimulating TH release

• Symptoms include: elevated metabolic rate- weight loss despite adequate food, sweating, rapid and irregular heartbeats, hyperactivity, insomnia

• Exophthalmos may result: eyes protrude as tissue behind the eyes becomes edematous and fibrous

• Treatments include surgical removal of thyroid or radioactive iodine to destroy active thyroid cells

Pharm Flash-Thyroid

Treatment for both Hypo and Hyperthyroidism:

• Synthetic T4 (tetraiodothyronine or “Thyroxine”)

• Levothyroxine (Synthroid, Levothroid, Levoxyl)

• Taken as oral tablets or capsules

Parathyroid Glands

Usually 4, yellowish, rice-grain-sized glands on the posterior surfaces bilaterally of the Thyroid

Secretes “parathormone”:

• Functions to raise blood calcium levels

1. Boosts osteoclast activity- raises calcium in the blood from the osteoclasts “eating” and breaking down bone tissue

2. Blocks excretion of calcium into the urine at the kidneys

3. Stimulates Vitamin D formation- increases the calcium, magnesium, and phosphorus absorbed by digested goods in the intestine

Adrenal Gland

Bilateral, pyramid-shaped organs on top of both kidneys (suprarenal glands)

Due to the heavy influence of the hypothalamus and pituitary glands on the adrenals, endocrinologists refer to the

• “Hypothalamic- pituitary- adrenal- axis” or the HPA axis

2 main parts: 

• Outer cortex

• Secretes 3 groups of hormones:

• Mineralocorticoids

• Glucocorticoids

• Gnadocorticoids (sex hormones

• Inner medulla

• Secretes 2 main hormones: 

• Epinephrine

• Norepinephrine

• Work with the sympathetic nervous system from “fight or flight” responses

Three layers of cortical cells produce different corticosteroid 

• Zona glomerulosa- Mineralocorticoids

• Aldosterone- holds onto body salt and water in the body

• Acts on kidneys to increase blood fluid volume and BP

• Zona fasciculata- Glucocorticoids

• Cortisol and corticosterone

• Reduces inflammation, triggers Gluconeogenesis (break down of proteins and fats to make glucose during stress/illness)

• Zona recticularis- Gonadocorticoids

• Androgens and Estrogens

• Promote testes and ovaries to make testosterone and estrogen

Adrenal Medulla

Medullary cells synthesize catecholamines epinephrine (80%) and norepinephrine (20%)

Effects of catecholamines:

• Vasoconstriction

• Increased heart rate (tachycardia)

• Increased blood glucose levels (hyperglycemia)

• Blood is diverted to the brain, heart, and skeletal muscle

Epinephrine is more of a stimulator of metabolic activities

• Example: bronchodilation, and blood flow to skeletal muscles and heart

• Norepinephrine has more of an influence on peripheral vasoconstriction and blood pressure

Clinical Significance

Hypersecretion

• Leads to symptoms of uncontrolled sympathetic nervous system:

• Hyperglycemia, increased metabolic rate, tachycardia, palpitations, hypertension, intense nervousness, and sweating

• This can be due to pheochromocytoma, a tumor of the adrenal medulla

Pancreas

“Chicken tender” shaped gland located partially posterior to the stomach

Both an Endocrine and Exocrine gland

• Endocrine= insulin and glucagon

• Exocrine= digestive enzymes

• More on that later in March

Consists of 3 atomic parts:

• Head- fitted in the curve of the small intestine

• Body- extends posterior to the stomach

• Tail- points to the Spleen in the LUQ

Has both exocrine and endocrine cells

• Acinar cells (exocrine) produce pancreatic digestive enzymes

• Islets of Langerhans”: contain endocrine cells like “little islands” within the Acinar cell clusters

• Alpha cells produce glucagon (increase blood sugar)

• Beta cells produce insulin (decrease blood sugar)

Insulin

• Secreted when blood glucose levels increase

• Insulin lowers blood glucose levels in three ways:

• Increases membrane transport of glucose into muscle and organ cells for energy

• Inhibits breakdown of glycogen to glucose (at liver)

• “Glycogenolysis”

• Inhibits conversion of amino acids or fats to glucose (liver)

• “Gluconeogenesis”

Glucagon

• Triggered by low blood glucose levels, rising amino acid levels, or sympathetic nervous system

• Raises blood glucose levels by targeting the liver to:

• Break down glycogen into glucose

• Glycogenolysis

• Synthesize glucose from lactic acid and other noncarbohydrates

• Gluconeogenesis

• Release glucose into the blood

Clinical Significance

Diabetes mellitus (DM) can be due to:

• Hyposecretion of insulin: type 1 DM

• Hypoactivity of insulin: Type 2 DM

• “Shutting down” of insulin receptors due to too much sugar and constant insulin usage

• This leads to the clinical term “insulin resistance”

Three cardinal signs of DM:

• Polyuria: huge urine output

• Glucose acts as osmotic diuretic

• Polydipsia: excessive thirst

• From water loss due to polyuria

• Polyphagia: excessive hunger and food consumption

• Cells cannot take up glucose and are “starving”

Clinical Significance

When sugars cannot be used as fuel, as in DM, fats are used

Fatty acid metabolism results in the formation of ketones

Ketones are acidic, and their build-up in blood can cause diabetic ketoacidosis (DKA)

Untreated ketoacidosis causes:

• Hyperpnea (excessive fast/deep breathing)

• Disrupted heart activity and O2 transport

• Severe depression of nervous system that can possibly lead to coma and death

Ovaries and Placenta

Female gender/reproductive organ

Ovaries produce estrogens and progesterone

• Estrogen

• Maturation of reproductive organs

• Appearance of secondary sexual characteristics

• With progesterone, causes breast development and cyclic changes in the uterine mucosa

• menstruation

Placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG) 

• hCG helps thicken the uterine lining to support a growing embryo and stops menstruation

Testes

Testes produce testosterone

• Initiates maturation of male reproductive organs

• Causes appearance of male secondary sexual characteristics and sex drive

• Necessary for normal sperm production

Endocrine Review

Major hormones of the:

• Hypothalamus

• Anterior pituitary (adenohypophysis)

• Posterior pituitary (neurohypophysis)

• Remember the “HPA” axis

• Hypothal-pituitary-Adrenal axis