pathophysiology II unit III review xdd

endocrine system functions and controls

• reproduction

• growth and development

• maintenance of electrolyte, water, nutrient balance

• regulation of metabolism

• mobilization of defenses

• food intake and digestion

amine hormone class

synthesized from: tyrosine or tryptophan

• stored before release

• polar and non-polar

• membrane and nuclear membrane acting

ex: norepinephrine (adrenaline), thyroxin, triiodothyronine, catecholamines

peptide hormone class

synthesized from: pro-hormones (req. cleavage)

• stored in vesicles

• polar → free travel in blood

• membrane binding and transduction of signal (second messengers)

ex: insulin, glucagon, prolactin, ACTH, oxytocin

steroid (lipid based) hormone class

synthesized from: cholesterol or arachidonic acid

• released immediately due to hydrophobicity

• non-polar → requires protein binding to travel in the blood

• binds intracellular receptors to change gene expression directly

ex: testosterone, progesterone, cortisol, estrogen

three ways to control hormone release?

1. humoral stimuli

2. neural stimuli

3. hormonal stimuli

humoral stimuli mechanism

ion/nutrient levels in the blood → impacts secretion of hormones

• ex: glucose levels in blood stimulate insulin secretion

blood osmolarity humoral stimuli example

high blood osmolarity (low water content)

• hypo-thalamus releases ADH (vasopressin) from posterior pit.

  • ADH increases aquaporins in lumen side of kidney duct for increased water reabsorption → dilutes blood and decreases blood osmolarity

Calcium levels humoral stimuli example

Normal Pathway: When calcium is present in the blood

• CaSR is bound by calcium → Gq11 phospholipase activation → release of intracellular Ca2+

  • intracellular Ca2+ blocks PTH synthesis

  • Kidney CaSR bound = decreased Ca2+ reabsorption

Decreased Blood Calcium Pathway:

• CaSR remains unbound and inactivated → no release of intracellular Ca2+ → PTH is freed

  • PTH synthesized = rise of Calcium in the blood

permissiveness

one hormone must be present for another hormone to be fully expressed

• hormone 1 allows/enhances effects of hormone 2

syngergism

hormone 1 and hormone 2 effects sum together allowing for greater activity

antagonism

hormone 1 opposes hormone 2 action

what are the three things target cells depend on for activation?

1. blood levels of the hormone

2. relative number of receptors on/in the target cell

3. affinity of binding between hormone and receptor

types of desensitization

1. homologous: only agonist-activated receptors are desensitized

2. heterologous: both agonist-activated and non-activated receptors are inactivated

situation where biological response to ligand is diminished when given continuously

mechanism of desensitization

1. down regulation of receptors

2. receptor modification (phosphate, acetyl → inactive)

3. receptor endocytosis (internalized receptor)

4. inhibition of signal transduction

functions of the hypothalamus

1. homeostasis; food intake, metabolism, water, temperature, sleep

2. endocrine control; growth, stress

3. autonomic control; sensory processing

4. limbic function; memory and emotion

hypothalamus-anterior connection

tropic hormones secreted from hypothalamus into:

• primary capillary plexus

  • portal veins to anterior pituitary

    • AP releases hormones into secondary capillary plexus where they reach systemic circulation

hypothalamus-posterior connection

oxytocin and ADH are synthesized in the hypothalamus:

• transported down hypothalamic-hypophyseal axon tract → posterior pituitary

• oxy and ADH stored in terminals in PP

• released when hypothalamic nerve signals arrive

oxytocin

nonapeptide; stimulates uterine contractions during childbirth and milk let down (positive suckling feedback)

• posterior pituitary

antidiuretic hormone (ADH) ((vasopressin))

• osmotic balance

• blood pressure

• sodium homeostasis

released when:

• blood high osmolarity

• drop in blood pressure

• decreased circulating blood volume

ADH mechanisms

1. binds V1a → vasoconstriction increases blood pressure

2. binds V2 on principal cells of collecting duct

   1. increased aquaporin migration to lumen membrane (increased water retention)

inappropriate ADH syndrome

• excess ADH = excess water reabsorption

• no edema occurs → euvolemic

  • body counters increased fluid by increasing sodium secretion

    • dilutional hyponatremia

tropic anterior pituitary hormones

1. TSH

2. ACTH

3. FSH

4. LH

What factors regulate the level of concentration of circulating hormones?

1. rate of release

2. speed of metabolism (inactivation and removal from the body)

growth hormone effects

growth of all cells, skeletal muscle and bone targets

• promotes protein synthesis

• promotes burning fat for fuel

• direct effects: metabolic and anti-insulin

• indirect effects: growth promotion

GH stimulates secretion of insulin-like growth factors (IGF-1)

gonadotropins

FSH and LH post-puberty from anterior pituitary

FSH: stimulates gamete (sperm/egg production)

LH: gonadal hormones

Stimulated by gonadotropin releasing hormone from hypothalamus during puberty

Prolactin

Secreted from lactotrophs of anterior pituitary

a.    Promotes growth of mammary glands

b.    Stimulates milk production

c.     Release is controlled by prolactin releasing hormone and prolactin inhibiting hormone (dopamine)

d.    Suckling triggers prolactin positive feedback loop

Hypothalamus Pituitary Adrenal Axis

1. hypothalamus releases corticotropin releasing hormone (CRH)

2. anterior pituitary releases ACTH

3. adrenal cortex releases cortisol

Adrenal Gland Overview

Cortex (outer)

• corticosteroids (aldosterone, cortisol)

• sex hormones (androgens)

Medulla (inner)

• catecholamines (epinephrine, norepinephrine)

Adrenal Cortex Layers

Outermost:

• Zona Glomerulosa = Mineralocrticoids (aldosterone)

• Zona Fasciculata = Glucocorticoids

• Zona Reticularis = Sex Hormones

mineralocorticoids

Secreted from glomerulosa of adrenal cortex (aldosterone)

• regulate Na+ and K+ levels

Na+ = ECF volume, blood pressure, blood volume

K+ = resting membrane potential of cells

Aldosterone Mech

Mineralcorticoid- Kidney Increased Water Retention

• stimulates Na+ reabsorption

• stimulates K+ elimination

CYP11B2

aldosterone synthase

• only found in the zona glomerulosa

How does Aldosterone Reglate Na+/H2O reabsorption

• activation of intracellular mineralocorticoid receptor

  • increased gene transcription of:

  • Na+ channels

  • Na+/K+ ATPase

more Na+ reabsorption from urine

more intracellular K+ for excretion

regulators of aldosterone release

1. angiotensin II

2. ACTH

3. increased plasma K+ (hyperkalemia)

4. Atrial Natriuretic Peptide (ANP); inhibits renin and aldosterone secretion to decrease blood pressure

Aldosterone Renin-Angiotensin Mechanism

drop in blood pressure → kidneys release renin

• renin stimulates angiotensin II release

  • angiotensin II stimulates the release of aldosterone

primary aldosteronism

excess aldosterone production by the adrenal gland (tumors)

• excessive Na+ → hypertension

• depleted K+ due to excessive excretion → abnormal muscle and neuron function

secondary hyperaldosteronism

excessive activation of renin-angiotensin-aldosterone (RAA)

• caused by kidney artery stenosis

• increased renin → increased angiotensin II → increased aldosterone

vasoconstriction and increased blood volume = hypertension

Glucocorticoids

Zona fasciculata adrenal cortex: stimulated by ACTH

Cortisol Primary Effect: gluconeogenesis to promote rise in blood glucose levels

• keeps blood sugar levels constant

• maintains blood pressure (vasoconstriction)

Cushing’s Syndrome

Hyper secretion of Cortisol

• depressed cartilage/bone formation

• inflammation suppression

• immune system suppression

• moon face/neck hump

low ACTH low CRH levels (increased cortisol neg feedback)

Addison’s Disease

Hypo cortisol syndrome

• decreased glucose and Na+

• weight loss, dehydration

increased ACTH increased CRH levels (unresponsive cortisol levels)

Chromaffin cells

cells of adrenal medulla

• epinephrine (80%)

• norepinephrine (20%)

increased vasoconstriction

increased heart rate

increased blood glucose levels

blood diversion; brain, muscles, heart

epinephrine stimulations

• metabolic activities

• bronchial dilation

• blood flow to skeletal muscle and heart

norepi stimulations

• peripheral vasoconstriction

• blood pressure

regulation of growth hormone release

stimulation: GHRH binds somatotrophs AP

• tetrodotoxin insenstive Na+

• Ca2+ intracellular increases

  • exocytosis of growth hormone granules

inhibition: Somatostatin binds somatotrophs AP

• opens K+ channel influx

• hyperpolarize prevents growth hormone release

regulator hormones of growth hormone…

stimulators:

• Ghrelin; hunger hormone of GI system

• Testosterone

inhibitors:

• Leptin; from adipocytes

• Estrogen

growth hormone receptor layout

cytokine receptor family

• dimer when bound by GH

• binding = activates janus kinase (JAK2)

  • JAK2 promotes tyrosine phosphorylation of itself + messengers

GH Receptor JAK2 Pathways

• G-Protein PLC-DAG Pathway

• IRS-PI3K Pathway

• STAT Pathway

• RAS-MAPk Pathway

role of GH in metabolism

1. Protein Metabolism

   1. increased AA uptake

   2. increased protein synthesis

2. Fat Metabolism

   1. Triglyceride Breakdown

3. Carbohydrate Metabolism

   1. Gluconeogenesis

   2. suppress insulin to prevent peripheral glucose uptake (deplete blood-glucose levels)