Download MBBS Glucocorticoids Lecture PPT

Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Glucocorticoids Lecture PPT


Glucocorticoids

1. Cortisol accounts for 95% of all glucocorticoid

activity, very potent.

2. Corticosterone about 4% , less potent .

3. Cortisone almost as potent as cortisol

4. Prednisone (synthetic, 4 times as potent as

cortisol)

5. Methylprednisone (synthetic, 5 times as potent

as cortisol)

6. Dexamethasone (synthetic, 30 times as potent

as cortisol)

Cholesterol

ACTH Cholesterol desmolase
Pregnenolone
17 -hydroxylase
17-hydroxypregnenolone
3 HSD
17-hydroxyprogesterone
21-hydroxylase
11-deoxycortisol
11 -hydroxylase
cortisol

Transport of Glucocorticoids

? Cortisol is bound in the circulation to an

globulin called transcortin/CBG, minor degree

to albumin.

? Half life is 30-60 min that of corticosterone is

50min

? Bound steroids are physiologically inactive.
? CBG is synthesized in liver ,production ed by

estrogen ,&es in cirrhosis and nephrosis .
Interrelationship of free & bound form
? Why pregnant women have high plasma

cortisol level without symptoms of

glucocorticoid excess?

? Why some patients of nephrosis have low

total plasma cortisol without symptoms of

glucocorticoid deficiency ?
Metabolism & Excretion of

Glucocorticoids

? Principal site of glucocorticoid catabolism is

liver.

? They are conjugated to glucuronic acid and

lesser extent to sulfates.

? About 25% of these conjugates are excreted in

the bile and then in the feces and remaining

excreted in the urine.
Degradation of cortisol

Cortisol

Dihydrocortisol

Tetrahydrocortisol

Tetrahydrocortisol glucuronide

Excretion in urine
Mechanism of cortisol action

? Glucocorticoids bind with receptor to form

hormone receptor complex which activate

DNA to form mRNA.

? mRNA causes synthesis of proteins which alter

cell function.

Physiological effects of Glucocorticoids

? 95% of glucocorticoid activity of the

adrenocortical secretion results from

secretion of cortisol/hydrocortisone.
Effects of Cortisol on Carbohydrate

Metabolism

Stimulation of Gluconeognesis
? es enzymes for gluconeogenesis .
? Mobilisation of amino acids from extrahepatic tissue.
? ed hepatic giycogenesis.
? ed glucose utilization by cells.
? in blood glucose level.

WHAT IS ADRENAL DIABETES ?
Effects Of Cortisol On Protein & Fat

Metabolism

?Reduction in Cellular Protein.
?es Liver and Plasma proteins.
?es blood amino acid levels by mobilising

amino acid from non-hepatic tissue.

1.Mobilisation of fatty acids.

2.Typical obesity of excess

cortisol
Effect of cortisol on fat metabolism

? Mobilisation of fatty acid : from adipose tissue

? es the conc. of frs in starvation ee fatty

acidsin the plasma

? Enhances the oxidation fatty acids in cell.

?Above two mechanism utilizes fatty acid

during starvation or other stresses
On Food Intake and Fat Distribution

? Cortisol es appetite by stimulating

neuropeptide Y secretion from hypothalamus.

? It stimulates lipogenesis by activating

lipoprotein lipase and G-6-PD activity of

adipocytes in some parts of body.

? So cortisol excess leads to maldistribution pf

fat.

? Cortisol also es leptin synthesis.
?Why cortisol excess leads to truncal obesity,

moon face &buffalo hump
Effects on musculoskeletal system

? Cortisol increases performance of cardiac &

skeletal muscle.

? The inotropic effect is due to synthesis of Ach

at neuromuscular junction .

? However, excess cortisol promotes proteolysis

, therefore it decreases muscle mass &

strength.

Anti-Inflammatory & Anti- Allergic

Effects(On pharmacological dose)
Blocks early stages of Inflammation BY:

? Stabilising Lysosomal Membrane.

?es Permeability of Capillaries.

?es Migration of wbc into inflammed site.

?Suppress immune system :T cells

?Attenuates fever by ing IL-1.

Suppress Allergic Manifestations By ing Release of

Histamine by Mast cells & Basophils.
? What is the role of cortisol in shock and anaphylaxis ?
?Why cortisol should be given with antibiotics ?

Effects on blood cells & lymphatic

organs

? Glucocorticoid es the no. of circulating

eosinophils by increasing their sequestration

in the spleen and lungs

? Also lowers no. of basophils.
? es no. of neutrophils,platlets and rbcs.
? es circulating lymphocyte by inhibiting their

mitotic activity and size of lymph node.

? es secretion of cytokines like IL-2.

On bone

? Glucocorticoid stimulate bone resorbtion (by

stimulating osteoclasts) .

? Inhibits bone formation by ing collagen

synthesis and inhibits conversion of

osteoprogenitor cells to osteoblast.

? It es absorbtion of calcium & es synthesis of

active vit.D

? So prolonged use of glucocorticoids will lead to

osteoporosis
Effect on nervous system

? Glucocorticoids are essential for normal

functioning of nervous system.

? Insufficiency will lead to personality changes

like irritability, and lack of concentration.

? Sensitivity to olfaction and taste stimuli

increases in adrenal insufficiency.
Effect on Kidney & Water metabolism

? Cortisol es GFR so essential for rapid

clearance of water load.

? It achieves this partly by inhibiting ADH

secretion.

?Why water intoxication occur when glucose

solution is infused in cortisol defcit patients ?

?What is glucose fever ?
On Vascular Response

? Presence of glucocorticoids is essential for

constrictor action of adrenaline and nor

adrenaline.

? So vascular collapse occurs in adrenal

insufficiency.
Other Effects

? Large dose of glucocorticoids inhibits growth

es GH secretion, es TSH secretion.

? During fetal life glucocorticoids acclerates

maturation of surfactant in the lungs.
Permissive Action

Requirement of Glucocorticoids For Action

Of Other Hormones e.g

?Catecholamines :Lipolytic Effect

Pressure Response

Bronchodilatation

?Glucagon & Thyroid hormone-Calorigenic

effect
Resistance to stress

? The most important function of of cortisol is to

protect the body against stress.

? Stress is defined as any change in the

environment that changes an existing optimal

steady state.

? Stress activates processes at the molecular,

cellular or systemic level that tends to

maintain homeostasis.
Stress

Hypothalamus ,CRH

Anterior pituitary, ACTH

Adrenal cortex, , cortisol

FFA release Vascular reactivity

Calorie supply Maintenence of BP & blood vol.
Regulation Of Cortisol Secretion

? ACTH stimulates cortisol secretion by ing

cAMP

? ACTH not only produces prompt increase in

glucocorticoids but also es the sensitivity of

adrenal to subsequent dose of ACTH.

Regulation Of Cortisol by ACTH

Hormone From Pituitary Gland

? ACTH stimulates cortisol secretion.
? ACTH activates Adrenocortical cells to produce
steroids by ing cAMP.
? Inhibitory effect of cortisol on the

Hypothalamus and on the Anterior Pituitary to

es ACTH secretion.

ACTH

? ACTH is a single chain polypeptide containing 39

amino acids.

? It origin from proopiomelanocortin ( POMC) in

the pitutary.

? Both basal secretion of glucocorticoids and ed

secretion provoked by stress are dependent on

ACTH.

? ACTH is secreted in irregular bursts throughout

the day and plasma cortisol tends to rise and fall

in response to these bursts.
? In humans ,the bursts are frequent in early

morning, & 75% between 4a.m and 10a.m.

? Bursts are least frequent in evening.
? The diurnal ACTH rhythm is located in

suprachiasmatic nuclei of the hypothalamus.

? Free glucocorticoids inhibits ACTH seretion.
? In chronic adrenal insufficiency the rate of ACTH

synthesis is markedly increased.

? Hence steroid therapy should not be abruptly

stopped.


This post was last modified on 30 November 2021