The adrenocortical hormones

Question 1

How many adrenal glands do we have and where are they located?

Answer 1

2, located on the superior poles of the kidneys.

Question 2

What are the two distinct parts of the adrenal gland?

Answer 2

The adrenal medulla and the adrenal cortex

Question 3

Describe the adrenal medulla.

Answer 3

The central part of adrenal gland.
It is regulated by the sympathetic nervous system
Its major secretion is epinephrine (E)
Its minor secretion is norepinephrine (NE)

Question 4

Describe the adrenal cortex.

Answer 4

The adrenal cortex secretes corticosteroids which include more than 30 types of hormones. They are synthesized from cholesterol. These hormones are grouped into mineralocorticoids, glucocorticoids, androgens.

Question 5

What are the different adrenal cortex.

Answer 5

Inner layer: Zona reticularis
Middle layer: Zona fasciculata
Outer layer: Zona glomerulosa

Question 6

Describe mineralocorticoids.

Answer 6

Aldosterone is the principal mineralcorticoid
Secreted from outer layer (zona glomerulosa)
Affect electrolytes Na, K ions in extracellular fluid.
Mineralcorticoids have a weak glucocorticoid effect

Question 7

Describe glucocorticoids

Answer 7

Cortisol is the principal glucocorticoid
Secreted from both middle layer (zona fasciculata ) and inner layer (zona reticularis ).
Mainly increase glucose concentration in the blood
Glucocorticoids have a weak mineralcorticoid effect

Question 8

Describe androgens

Answer 8

These are sex hormones but play a minimal role as compared to estrogen and testosterone.
They are secreted from middle layer and inner layer
Have similar effects on body as testosterone

Question 9

True or False. All the adrenocortical hormones are steroid-based compounds.

Answer 9

True

Question 10

What are the steps to adrenocortical hormone synthesis

Answer 10

They are formed mainly from cholesterol:

Low-density lipoprotein (LDL) in blood contains cholesterol.
LDL-cholesterol is absorbed from blood by endocytosis through cell membrane.
The cell membrane of adrenal cortex promotes endocytosis.
Small amounts of cholesterol are also synthesized in the cortical cell from acetyl-coA.
Cholesterol becomes pregnenolone, which is a precursor to many hormones.

Question 11

Are adrenocortical hormones hydrophilic or hydrophobic?

Answer 11

they are hydrophobic so they rely on carrier proteins to get them around

Question 12

What happens to cortisol in the blood?

Answer 12

About 94% of the cortisol binds with globulin (aka cortisol-binding globulin or transcortin)
6% floats freely in the blood. They are in a dynamic equilibrium.

Question 13

What happens to aldosterone in the blood?

Answer 13

About 50% of aldosterone binds with plasma proteins, the rest float freely in the blood. This is also a dynamic equilibrium.

Question 14

What is the mineralocorticoid function of aldosterone?

Answer 14

It involves the concept of sodium and potassium balance. A membrane ‘wants’ to maintain an equal electrical charge across the membrane. An imbalance can create energy, and also affect osmosis (transport of water).

Question 15

What is the effect of aldosterone on transport of sodium and potassium?

Answer 15

Aldosterone promotes transport of Na+ and K+ ions through renal tubular walls and in the cortex and collecting ducts. The cells that do this are called the principal cells.
That increases the reabsorption of Na+ which means that Na+ is conserved in extracellular fluid. It decreases the loss of Na+ into urine.
When sodium is reabsorbed it increase the excretion of K+ into urine.
When sodium is reabsorbed it also caused water to be reabsorbed by osmosis.

Question 16

What is the cascade of events that explain the cellular mechanism of aldosterone action that increases sodium reabsorption

Answer 16

The lipid soluble aldosterone can diffuse readily into the principal epithelial cells,  binds with a receptor in the tubular cell, diffuses into the nucleus, ==> Causes the formation Channel proteins and Na-K ATPase pump ==> now Na+ can be reabsorbed, K+ excreted.
Channel proteins are inserted into luminal membrane of principal cell and result in rapid diffusion of Na+ ions from lumen side, into cell cytoplasm. The luminal side is the one pointing inwards, where the kidney filtrate (urine) is located.

Na-K ATPase enzyme works together with membrane transport proteins to pump Na+ and K+ at the basolateral membrane of renal principal cells. Basolateral is the side of the tubule cell that faces outwards, to the interstitial fluid. The interstitial fluid is connected to the blood circulation.

Question 17

What is the effect of aldosterone on extracellular fluid volume and arterial pressure?

Answer 17

Aldosterone causes Na ions to be conserved ==> tendency of increasing concentration of sodium ==> simultaneous osmotic absorption of water by principal cells ==> keep the concentration of Na constant ( very little rise ) in extracellular fluid ==> absorption of water increases the volume of extracellular fluid ==> increase blood pressure ==> cause great increase of excretion of both water and salt (sodium chloride) from kidney at hypertension ( called pressure diuresis ).

Question 18

What is the effect of aldosterone on sweat glands, salivary glands and intestinal absorption?

Answer 18

Aldosterone increase reabsorption of NaCl and secretion of K ions by principal cells to conserve body salt when water is secreted by sweat gland and salivary gland.

Enhance NaCl absorption by intestine especially in the colon to prevent salt loss in the stools.

Question 19

What happens with a lack of aldosterone?

Answer 19

Lack of Aldosterone causes loss of salt (Na) in urine ==> decrease sodium-chloride in extracellular fluid and the volume of fluid ==> great reduction of total volume of extracellular fluid (dehydration) and diminished cardiac output ==> low blood pressure ==> circulatory shock ==> cause death in few days.

Question 20

How can chronically low or defective aldosterone due to a genetic mutation be treated before it leads to death?

Answer 20

by providing supplemental aldosterone or mineralocorticoids.

Question 21

What happens if aldosterone is not working?

Answer 21

Causes high levels of K+ concentration in extracellular fluids and blood which can lead to cardiac toxicity.

Question 22

What is hyperkalemia?

Answer 22

When K+ levels reach 60-100% above normal levels. Symptoms include: weakness of heart contraction, arrhythmia

Question 23

What happens if there is a chronic excess of aldosterone?

Answer 23

excess aldosterone causes massive retention of Na+ and water reabsorption, which increases blood pressure and may trigger pressure diaresis.

It causes excessive loss of K+ from extracellular fluid which can lead to a serious decrease of K+ concentration in blood. This is called hypokalemia.

When K+ concentration fall below 1/2 to 1/3 normal it prevents transmission of normal action potential in the nerve which develops severe muscle weakness.

Question 24

What are the four factors regulating aldosterone secretion? (List them in order of relevance)

Answer 24

1. A small increase of K+ concentration in extracellular fluid will increase aldosterone secretion.
2. An increase of activity of renin-angiotensin system will increase aldosterone secretion
   3a. An increase of Na+ concentration in extracellular fluid decreases aldosterone secretion.
   3b. A 10 to 20% decrease of Na ion concentration can double aldosterone secretion.
3. When adrenocoticotropic hormone (ACTH) is secreted from anterior pituitary it causes aldosterone secretion. This is the most minor factor, however, if there is a total absence of ACTH, like a genetic disease, it can significantly reduce aldosterone secretion.

Question 25

What happens to cortisol concentration throughout the day.

Answer 25

It increases until it reaches a peak around midday and slowly starts to decrease back to its level upon waking up.

Question 26

Cortisol stimulates gluconeogenesis. What is gluconeogenesis?

Answer 26

Formation of glucose from amino acids and other substances by the liver.

Question 27

What is the cascade of events by which cortisol stimulates gluconeogenesis?

Answer 27

Cortisol binds with receptor in the cytoplasm of hepatic cells ==> diffuses into liver cell nucleus and activates DNA transcription ==> formation of messenger RNA ==> increase the enzymes needed to convert amino acids into glucose in hepatic (liver) cells.

Question 28

Cortisol mobilizes amino acids from muscles. What does mobilize mean in this case?

Answer 28

The proteins are digested into amino acids. This is a catabolic effect

Question 29

Why does cortisol cause a moderate decrease in the utilization of glucose by cells?

Answer 29

because cortisol antagonizes insulin. It also depresses the oxidation of nicotinamide-adenine dinucleotide (NADH) to form NAD+ and NADH. Those must be oxidized to allow the use of glucose by cells. Cells can not effectively use glucose for energy.

Question 30

What happens if the cortisol is in excess for a long time?

Answer 30

glucose will accumulate in the blood and can be 50% more above normal. This is called adrenal diabetes

Question 31

Cortisol works on the body to produce and conserve carbohydrates which allows for what?

Answer 31

allows the body to have carbohydrate reserves, which can be used if epinephrine or glucagon are present.

Question 32

What is the effect of cortisol on protein metabolism?

Answer 32

Cortisol reduces the protein stores in all body cell due to catabolic effects.

Cortisol prevents amino acids from entering extra-hepatic cells (all the non-liver cells).

Except, protein will increase in the liver because cortisol promotes uptake of amino acids into liver for gluconeogeneis, thus, cortisol promotes large amounts of liver enzymes that are needed for gluconeogenesis.

In the end, most proteins in muscles and other tissues are decreased by cortisol except for liver proteins which are increased.

Question 33

What is the effect of cortisol on fat metabolism?

Answer 33

Cortisol promotes mobilization of fatty acids from adipose tissue.
The triglycerides are digested into free fatty acids and glycerol ==> increases the concentration of free fatty acids in plasma ==> increases oxidation of fatty acids in cells into acetylCoA ==> increases use of fatty acids for metabolic energy ==> allows for long-term conservation of body glucose and glycogen.

Question 34

What can happen if there is excess cortisol?

Answer 34

Even though cortisol promotes fat burning, if there is too much cortisol it can make a person hungry all the time and cause weight gains

Question 35

An anti-inflammatory effect of cortisol happens when tissue is damaged by trauma or infection and tissue becomes inflamed. What are the different stages of inflammation?

Answer 35

Chemicals release from the damaged tissue cell and activate inflammation process. The chemicals include histamine, bradykinin, proteolytic enzyme, prostaglandins and leukotrienes.

Blood flow is increased in the inflamed area (called erythema).

Large amount of plasma leak out of the capillaries into damaged area because of the increased capillary permeability.

Leukocytes infiltrate through the area.

At the end of inflammation, there is growth of fibrous tissue for the healing process.

Question 36

Cortisol has two basic anti-inflammatory functions, what are they?

Answer 36

It can block the early stage of inflammation and if inflammation has already begun, cortisol blocks most of factors that promote inflammation and causes rapid resolution of inflammation, and increases healing rate.

Question 37

How does cortisol block the early stage of inflammation?

Answer 37

Most of the proteolytic enzymes that cause inflammation are stored in lysosomes in the tissue cell. Cortisol can make the membrane of lysosome cell much more difficult to be ruptured ==> greatly decrease the release of proteolytic enzymes into the inflamed area.

Cortisol decreases the permeability of capillaries because of the reduced release of proteolytic enzymes ==> reduce loss of plasma into damaged tissue area.

Cortisol decreases the mobility of white blood cell into inflamed area ==> decrease phagocytosis of the damaged tissues.

Reduce the release of interleukin-1 from white blood cell ==> suppresses the hypothalamic temperature control system ==> lower the fever.

Question 38

If inflammation has already begun how does cortisol act to diminish the effects?

Answer 38

a) Cortisol causes mobilization of amino acids and promote the use of them to repair damaged tissues, to increase glucose and fatty acids for cellular energy.
b) Plays an important role in combating rheumatoid arthritis, rheumatic fever, and acute glomerulonephritis.

Question 39

What are the other effects of cortisol?

Answer 39

• reduces allergic reaction by reducing inflammation
• prevents immunological rejection of transplanted heart, kidney and other tissues by reducing the release of lymphocytes and antibodies.
  -Increase production of RBOs and promotes healing of tissues

Question 40

What is the secretion of cortisol primarily regulated by?

Answer 40

regulated by ACTH ( corticotropin or adrenocorticotropin ) which is secreted by anterior pituitary gland in response to corticotropin releasing hormone (CRH).

Question 41

What is the secretion of cortisol primarily regulated by?

Answer 41

regulated by ACTH ( corticotropin or adrenocorticotropin ) which is secreted by anterior pituitary gland in response to corticotropin releasing hormone (CRH).

Question 42

What is the pathway to the release of adrenocorticotropin?

Answer 42

The neurons of hypothalamus release corticotropin-releasing hormone (CRH) through hypophysial portal system in median eminence to anterior pituitary, which causes secretion of ACTH from anterior pituitary. ACTH acts on the adrenal cortex to synthesize adrenocortical hormones and cause them to be secreted.

Question 43

True or False.
Cortisol has a direct negative feedback effect on the hypothalamus to decrease formation of CRH. Cortisol also has a direct negative feedback on the anterior pituitary gland to decrease the formation of ACTH.

Answer 43

True

Question 44

What are the different types of stresses that can cause an immediate increase in ACTH secretion by the anterior pituitary?

Answer 44

• Pain
• Trauma
• Infection
• Intense heat or cold
• Injection of norepinephrine
• Surgery
• Injection of necrotizing chemicals beneath skin
• Debilitating disease
• Psychological

Question 45

Hypoadrenalism (i.e. Addison’s disease) is a primary adrenal insufficiency. What does it entail?

Answer 45

This could be due to atrophy (small size), loss, or injury to the adrenal glands. Can be caused most often by autoimmune disease, but also by infections like tuberculosis or cancer that destroys the glands. Can be a side effect of chemotherapy treatments.

Question 46

What are the causes of secondary adrenal insufficiency?

Answer 46

Causes vary, could be genetic mutation, birth defect, infection of pituitary, or some problem with hypothalamus or CRH.

Question 47

What is the difference between primary and secondary adrenal insufficiencies?

Answer 47

Primary adrenal insufficiency: the adrenal gland does not make enough adrenal hormones
Secondary: defective pituitary gland which does not secrete enough ACTH

Question 48

What happens if the primary or secondary adrenal insufficiency are chronic?

Answer 48

If there is a lack of mineralocorticoids such as aldosterone, the sodium ions are excreted into urine, which causes loss of water by osmosis. If its untreated blood pressure and dehydration can be fatal. Also, there is compensatory increase in potassium in the blood that can lead to hyperkalemia.

If there is a lack of glucocorticoids such as cortisol, then in between it is difficult to maintain blood glucose levels since gluconeogenesis is impaired. Stress of infection can be deadly because cortisol normally suppresses inflammation and promotes healing.

If the medulla is defective, then the lack of catecholamines such as adrenaline will alter mood and make hypoglycemia more likely. Adrenaline is able to mobilize glucose in times of need, so lacking it is dangerous.

Melanin deposition is increased. Melanin has various functions including skin pigmentation. Because cortisol is low, the pituitary over produces ACTH, which also provides more MSH (melanin stimulating hormone) which gets unevenly distributed in skin, creating a spotty appearance in the skin. This would not occur if the patient has an ACTH deficiency.

Question 49

What are the various treatments for adrenal insufficiency?

Answer 49

Daily supplement with synthetic mineralocorticoids and glucocorticoids
In cases of trauma, extra glucocorticoids must be given
Corticosteroids given to suppress the immune system if it is autoimmune in nature
allergic reactions may need more medication to control inflammation

Question 50

What is hyperadrenalism and what causes it?

Answer 50

for example Cushing’s Syndrome, Conn’s syndrome
It is defined by hypersecretion of adrenal hormones. The cause may be adenoma tumor which produces adrenal hormones out of control. May be in glands or elsewhere in body. Or, an abnormal function of the hypothalamus-pituitary axis that makes more ACTH than needed.

Question 51

What effects does hyperadrenalism have on the body?

Answer 51

Excessive Glucocorticoids (cortisol): high blood sugar leading to pituitary diabetes, and loss of protein from muscle, and redistribution of fat into the torso
Excessive Androgens: over masculinizing effects

Question 52

What are the treatments available to treat hyperadrenalism?

Answer 52

The treatment for hyperadrenalism is to try and remove or destroy the tumour. Medications can include drugs that block steroid hormone synthesis, or drugs that block the effect of the hormones.