Adrenal Gland Final 2

8/7/2019 Adrenal Gland Final 2

1/8

SUBJECT: PHYSIOLOGY TOPIC: Adrenal GlandLECTURER: DR. VIC MENDOZADATE: FEBRUARY 2011

Adrenal Gland

Remember: the blood supply of the adrenalgland is designed in such a way that the

blood passing through the cortex will also be

the same blood that will pass through the

medulla

o This means that the medulla is alsoexposed to the hormones produced

by the adrenal cortex!

EmbryologicallyThe cortex is mesodermal, whereas the

medulla is neuroectodermalin origin.

Adrenal Cortex

About 8090% of the weight of the gland Secretes 3 classes of steroid hormones [not

stored but synthesized as needed]

o Because there is no storage, thereare no preformed hormones that

can be secreted right away.

Although it takes longer, steroid

hormones have a longerlasting

effect compared to other hormones

anyway.

Glucocorticoids, mineralocorticoids and sexhormones

Recall Histology: 3 layers of the cortexo Zona Glomerulosa, Fasciculata and

Reticularis

o Glomerulosa: synthesis andsecretion ofmineralocorticoids

o Fasciculata: glucocorticoidso Reticularis: sex hormones

Also, recall that the ratelimiting step in theformation of steroid hormones is the

conversion of cholesterol to pregnenolone.

Mineralocorticoids

For regulation of water and sodium,potassium ion concentrations

Regulation of normal acidbase balance Main mineralocorticoid: ALDOSTERONE

Aldosterone

A steroid hormone responsible forregulating sodium reabsorption in the distal

tubule and the cortical collecting duct

Target cells: Principal [P] Cells Stimulates the synthesis of Na/KATPase

pump

Furthermore, ALDOSTERONE:

Promotes the retention of sodium and water[handinhand]

o Chloride is also retained togetherwith bicarbonate

(This consequently affects acidbase

balance.)

Promotes the loss of potassium through thekidneys and hydrogen ion

(These are also responsible for how Aldosterone

affects acidbase balance)


2/8

Direct stimulators:o Increased extracellular potassiumo Decreased osmolality

Indirect stimulators [RAAS]o Decreased blood pressure

Reduction in kidney perfusion thus

resulting in INCREASED Renin

production, which acts on

Angiotensinogen to eventually yield

Angiotensin II. This can then stimulate

the adrenal cortex to produce more

aldosterone.

o Decreased macula densa blood flow RAAS: Renin AngiotensinAldosterone System

Glucocorticoids

3 classes of glucocorticoids:o Cortisol [major glucocorticoid!]o Corticosteroneo Cortisone

CORTISOLo A steroid hormone that is plasma

bound to corticosteroid binding

globulin [CBG or transcortin]

o Essential for lifeo Net effects of cortisol are catabolic:

prevents hypoglycemia

(very low glucose in the bloodstream)

A person cannot survive for a long time

without glucocorticoids in the body.

If adrenal glands are removed, there will be a

need for exogenous supply

Net effects of cortisol are catabolic

They circulate bound to a globulin but being steroid

hormones, they are capable of crossing cell

membranes. When they detach to CBG, they can

cross the cell membrane because of receptors insidethe cell membrane. Once they enter the nucleus of

the cell, they can promote transcription.


3/8

Physiological actions:

(how it prevents hypoglycemia)

Promotes gluconeogenesis[primarily amino acids coming from catabolism

of skeletal muscle thus providing substrates for

gluconeogenesis]

Promotes breakdown of skeletal muscleprotein

Enhances fat breakdown [lipolysis] Suppresses immune system

[at pharmacological doses: reduces phagocytic

actions of WBCs]

Breakdown of bone matrix[High doses; like when exogenous glucocorticoids

had been administered. Fracture is therefore a

sideeffect of prolonged use of high dose

glucocorticoids.] Reduces fever Suppresses allergic reactions Widespread therapeutic use

[Primarily because it CAN suppress immune

response. Disease entities promoted by

inflammation will be affected, such as bronchial

asthma or lupus, or patients who have

undergone a transplant. Suppression of immune

system is needed so that the body will not reject

the transplanted organ.]

Decreases formation of connective tissue[Thus weakening it. Eg capillaries with CT in its

walls. High doses of glucocort can cause the

supporting CT to disappear leading to easy

bruisability]

Enhance vascular responsiveness tocatecholamines

Inhibit bone formation Increase GFR

[Can promote free water clearance in the

kidneys] Decrease REM sleep

[Modulates wakefulness of a particular person]

Influences brain function: states of cortisolexcess or deficiency cause mood changes

and memory and learning alterations

Cortisol Effects:

Regulation of Cortisol Release

Cortisol release is regulated by the ACTH[secreted by the anterior pituitary; pulsatile

secretion; diurnal rhythm]

Release follows a daily patternCircadianSince ACTH secretion is pulsatile, it follows that

cortisol seems to have a similar pattern.

Negative feedback by cortisol inhibits thesecretion of ACTH and CRH [regulation of

their relationship]

Cortisol also promotes negative feedback tothe hypothalamus

CRH acts on Anterior Pituitary; it stimulatessecretion of ACTH


4/8

**About 10 pulses all throughout the day. Just

before waking up in the morning, there is this big,

big pulse (increase in secretion). This increase in

secretion represents more than half the total

secretion of ACTH in 24 hours.

** Levels of ACTH are actually lower during sleeping

hours, and then the big,big spike, then eventually

goes down. Though its generally really higher during

the day than at night.

ACTH promote secretion of glucocorticoids

Main effects is on the ratelimiting step:transformation of cholesterol to

pregnenolone and from there, it proceeds

Hypothalamus will produce CRH which influences

anterior pituitary Production of ACTH then acts

on adrenal to release further cortisol and this will act

on anterior pituitary decreasing the release of ACTH

Enhanced secretion can be caused by anyform ofstress:

o Physical traumao Infectiono Extreme heat and coldo Exercise to the point of exhaustiono Extreme mental anxiety

Stress and the Adrenal Cortex

Glucocorticoids act for the human organismto adapt to stress

Any form of stress are first perceived by thebrain and other sensory receptors

o The hypothalamus is stimulated torelease CRH

o With high levels of CRH, it willinfluence anterior pituitary to

release more ACTH which will, again,

increase secretion of cortisol from

the adrenal cortex

o Cortisol in bloodstream increasesmetabolism of carbohydrate, fat,

and protein

o Metabolic processing alleviate theeffects of stress therefore reducing

stress

**HypothalamicPituitaryAdrenal Axis


5/8

**Please refer to the Powerpoint if figures are not

clear.

Clinical Correlation:

HyperadrenalismCushings Syndromeo Caused by exogenous

glucocorticoids and by tumours

[adrenal or pituitary] which produce

enhanced levels of glucocorticoids

o Zg tumor increases aldosterone Increase in sodium and

blood pressure

o Zr tumor increases cortisol Excess protein catabolism,

redistribution of fat

omoonfacie [picture]

striae are blood vessels thatare seen because of thinning

out of connective tissue

Addisons Diseaseo Underactivity of the adrenal cortex

[hypoadrenalism] results in

decreased output of glucocrticoids

and aldosterone

o Results from infection, intake ofcertain drugs, etc

o Adrenal cortex is unable to produceenough hormones to supply the

needs of the body

o Plasma sodium decreases and maylead to circulatory collapse

o Symptoms: decreased blood sodium

skin color becomes bronze[crossreaction of ACTH and

MSH; excess ACTH levels]

**MSH is responsible for pigmentation of skin

anemia [RBC deficiency] weakness and fatigue increase in blood potassium

o The only way to survive is to providewith exogenous glucocorticoids [in

the form of drugs]

o

Ex: JFKs suntan might be because ofAddisons disease

Gonadocorticoids

Adrenal sex hormones normally have only avery slight effect on the sex organs

o Because the most important sourceof sex hormones are testis and

ovaries

Consist mainly of androgens and estrogens DHEA in females are main source of

androgens

*note the different layers: remember Endocrine

Histology

*Glucocorticoids have some sodiumretaining

capability [like Mineralocorticoids]


6/8

*Mineralocoritcoids have some glucocorticoid

properties

*PTH is essential to life!

ADRENAL MEDULLA

Embryologically derived frompheochromoblasts [neruoectodermal in

origin]

Differentiate into modified neuronal cellso More of a gland than nerveo Chromaffin cells

Acts like sympathetic ganglion Extension of the sympathetic nervous

system [SNS]

Acts as peripheral amplifier of SNS

Activated by same stimuli as the SNSo Ex: exercise, cold, stress,

hemorrhage

Cells of adrenal medulla synthesize, store,and secrete two types of catecholamines

o Main neurotransmitter in adrenalmedulla is epinephrine

o 80% of secretion of adrenal medullais in the form of epinehphrine

o

Norepinephrine o Small amount ofdopamine can also

be secreted by the medulla [but is

not really counted as one of the

types of cathecolamines]

The hormones produce effects similar tostimulation by the sympathetic nervous

system.

Conversion of norepinephrine toepinephrine requires another

hormone/substance which is cortisol! Cortisol enhances phenylethanolamineN

methyltransferase [PNMT] which is an

enzyme that converts norepinephrine to

epinephrine

Influences blood vessels in the same waythat the peripheral nervous system affects

the vessels

RECEPTORS

o Effectors on which epinephrine andnorepinephrine act and can be grouped

based on their response to each hormone

o Effector organs may contain their cellmembranes

o alpha receptorso beta receptorso or both

o Even though epinephrine or norepinephrinebind to alpha and beta receptors, they do

not evoke same response

o Beta receptor activation linked tostimulating cAMP

oAlpha receptor activation is linked toinhibiting cAMP

Receptor Response

Norepinephrine interacts predominantlywith alpha receptors

Beta receptors have higher affinity forepinephrine

Response of cell haing alpha receptors maybe different completely from the response

of cells with beta receptors for the sametransmitters or hormones

GENRAL RULE:

Tansmitters trigger the receptors, but it isthe receptor that defines the nature of the

response!

EFFECTS OF CATECHOLAMINES

See Figure 1 Last Page


7/8

Catecholamine Synthesis

Elimination of Catecholamines

Stress and Adrenal Medulla [See ppt!]

Fright, fight, or flight response Secretion of epinephrine causes intense

effects that last a very short time

o liver enzymes inactivateepinephrine in about 3 minutes

After epinephrine has been released:

Some blood vessels constrict and othersdilate redistributing blood to the brain andmuscles

Digestion is halted during the emergency bythe diversion of blood from the stomach and

intestines to the skeletal muscle

Other effects:

Blood pressure rises Heart rate increases Blood clotting time reduces RR increase Bronchioles dilate Enzymes in liver Release of epinephrine favors survival of

body

**The figure above shows integrated responses to

stress mediated by the sympathetic nervous system

and the hypothalamopituitaryadrenocortical axis.

**Negative feedback by cortisol can limit an over

response that might be harmful to humans.

CLINICAL:

Pheochromocytoma

A catecholaminesecreting tumour ofchromaffin cells of the adrenal medulla

Adrenal pheochromocytoma (90%) Paraganglioma a catecholamine secreting

tumour of the sympathetic paraganglia

Extraadrenal pheochromocytomaSigns and Symptoms:

Treatment resistant hypertension (95%) Headache Sweating Palpitations Chest pain Anxiety

Classic Triad!


8/8

Glucose intolerance Increased metabolic rate

Diagnosis and Treatment:

Diagnosed by high plasma catecholaminesand increased metabolites in urine

Glucagon stimulation causes a 3foldincrease of plasma catecholamines

No test for adrenal or extraadrenaltreatment is surgical resection

END OF TRANSCRIPTION

Actions of Catecholamine Hormones:

Adrenal Gland Final 2

Documents