ADRENCORTICAL ADRENCORTICAL HORMONESHORMONES

Dr Nida SohailDr Nida Sohail

AldosteroneAldosterone

• Reabsorbing Reabsorbing sodium (Na+)sodium (Na+) ions and water into the blood ions and water into the blood• Secreting Secreting potassium (K+)potassium (K+) ions into the urine. ions into the urine. • H+H+ secretion by intercalated cells in the collecting duct secretion by intercalated cells in the collecting duct• Regulating plasma Regulating plasma HCO3HCO3−− levels and its acid/base levels and its acid/base

balance.balance.• Increases ECFIncreases ECF volume volume• Increases Blood Increases Blood pressurepressure• Small affect on plasma NaSmall affect on plasma Na• Affects Na and K transport in Affects Na and K transport in sweat, salivary and sweat, salivary and

intestinal epithelialintestinal epithelial cells cells

Adrenal CortexAdrenal Cortex: : Zona GlomerulosaZona Glomerulosa

Plasma protein-Plasma protein-bound cortisolbound cortisol

AdrenalsAdrenals Free cortisol Free cortisol in plasmain plasma

Tissue Tissue cortisolcortisol

Anterior Anterior pituitarypituitary

Interrelationships Between Free & Bound Cortisol

BiologicalBiologicaleffectseffects

ACTH

Metabolic Effects of CortisolMetabolic Effects of Cortisol

Glycogen

Glucose-P

Glucoseprecursors

Glucose

AminoacidsProtein

+

Free fattyacids

Glycerol

Stimulate

Inhibit

MuscleLiver

Adiposetissue

GlucoseFree fatty acidsAmino acids

Glucose

Plasma

Provision of Energy by Glucocorticoid Provision of Energy by Glucocorticoid ReleaseRelease

EFFECTS OF CORTISOLEFFECTS OF CORTISOL

• CarbohydratesCarbohydrates• Stimulate gluconeogenesis Stimulate gluconeogenesis ((↑ enzymes, mobilize a.a.↑ enzymes, mobilize a.a.))• Decrease glucose utilization Decrease glucose utilization (↓ rate by decreasing NADPH (↓ rate by decreasing NADPH

oxidation)oxidation) by cells by cells• Adrenal Diabetes (elevates plasma glucose) (impairs insulin Adrenal Diabetes (elevates plasma glucose) (impairs insulin

action by action by ↑ fatty acids↑ fatty acids ) )• ProteinsProteins

• Reduction in cellular protein (Reduction in cellular protein (↓↓aa transport, aa transport, ↓↓RNA formation)RNA formation)• Increased proteins in liver and plasmaIncreased proteins in liver and plasma• Increased blood amino acids (more to liver less to other tissues)Increased blood amino acids (more to liver less to other tissues)

EFFECTS OF CORTISOLEFFECTS OF CORTISOL

• FatsFats• Mobilization of Fatty AcidsMobilization of Fatty Acids• Obesity caused by cortisolObesity caused by cortisol

• STRESSSTRESS• Trauma, infection, extreme temperature, surgery etc.Trauma, infection, extreme temperature, surgery etc.

• AllergyAllergy• Blocks inflammation in allergyBlocks inflammation in allergy

• InfectionsInfections• Decreases eosinophils and lymphocytesDecreases eosinophils and lymphocytes• Atrophy of lymphoid tissueAtrophy of lymphoid tissue

EFFECTS OF CORTISOLEFFECTS OF CORTISOL

• InflammationInflammation• Stages: chemical releaseStages: chemical release→ erythema → edema → → erythema → edema →

local leucocytosis → fibrous tissue growthlocal leucocytosis → fibrous tissue growth• CORTISOL blocks start of or stops inflammationCORTISOL blocks start of or stops inflammation• Lysozyme stabilizationLysozyme stabilization• Decreases capillary permeabilityDecreases capillary permeability• Decreases WBC migrationDecreases WBC migration• Suppresses immunity (lymphocytes)Suppresses immunity (lymphocytes)• Decreases IL-1Decreases IL-1• Resolution of inflammationResolution of inflammation

ACTIONS OF CORTISOLACTIONS OF CORTISOL• Increase lipolysis Increase lipolysis • Increase glyconeogenesisIncrease glyconeogenesis• Decrease peripheral glucose utilizationDecrease peripheral glucose utilization• Protein catabolic hormoneProtein catabolic hormone• Modulate fibroblast proliferation and function - mostly inhibitionModulate fibroblast proliferation and function - mostly inhibition• Inhibit extracellular matrix synthesis - collagenInhibit extracellular matrix synthesis - collagen• Decrease osteoblastic functionDecrease osteoblastic function• Aid in maintenance of blood pressure - increase vascular sensitivity to Aid in maintenance of blood pressure - increase vascular sensitivity to

catacholaminescatacholamines• Inhibition of ADH secretion, or action upon renal tubular cellsInhibition of ADH secretion, or action upon renal tubular cells• Increase GFR Increase GFR • Anti-inflammatory - inhibit synthesis of prostaglandins, leukotrienes, Anti-inflammatory - inhibit synthesis of prostaglandins, leukotrienes,

stablize lysozymesstablize lysozymes• Suppress lymphocyte proliferation, actions of cytokines Suppress lymphocyte proliferation, actions of cytokines • Stablization of microvascular integrityStablization of microvascular integrity

Hypothalamohypophyseal-Adrenal Axis

HypothalamusHypothalamus

CorticotropeCorticotrope

Adrenal CortexAdrenal Cortex

GlucocorticoidsGlucocorticoids

CRHCRH

ACTHACTH+

+

__

__

CORTISOLCORTISOLAXISAXIS

ABNORMALITIESABNORMALITIES

• ALDOSTERONEALDOSTERONE• CORTISOLCORTISOL• ANDROGENSANDROGENS

Pathophysiology of the Adrenal Cortex

• Cushing’s syndrome

• Cushing’s disease

• Addison’s disease

• Conn’s syndrome

• Apparent mineralocorticoid excess

• Congenital adrenal hyperplasia

21 - Hydroxylase deficiency

11 - Hydroxylase deficiency

Causes of Cushing’s Syndrome

• Adrenal hyperplasia

• Adrenal neoplasia

• Iatrogenic

– Pituitary ACTH

– Nonpituitary tumors (ectopic)

– Adenoma– Carcinoma

hypothalamic dysfunctionpituitary tumors (Cushing’s disease)

ACTHCRH

CORTISOL CORTISOL AXISAXIS

Thank youThank you

AllahumMa inni lima anzalta AllahumMa inni lima anzalta ilayya min khairin faqirilayya min khairin faqir