Lec 15 - Hypothalamic-Pituitary Axis, ADH + Oxytocin

What does the endocrine system comprise of

All hormones and hormone glands that help regulate systems in the body

Use of hormones

Regulates growth, development, metabolism, reproduction, mood regulation and other functions

What components of the body can respond to hormoens

All components

Tropic hormone

hormones that target other endocrine glands

Where are most tropic hormones produced/secreted

Anterior pituitary gland

Trophic hormone

Hormones that stimulate growth in target tissues

Non-tropic hormones

Directly stimulate target cells to induce effects

Location of hypothalamu

Below thalamus, above brainstem

Role of hypothalamus

Controls and informs the endocrine system through the pituitary gland

Role of neuroendicrine system

Links CNS and endocrine glands

Hypothalmic pituitary axis role

Sense homeostatic status of the body

Anterior pituitary role

Glandular tissue - releases hormones

What controls secretion of the anterior pituitary

Hypothalamus secretion

Role of posterior pituitary

Mainly neural tissue. Will store the hormones ADH and oxytocin in neurosecretory cell bodies (Herring bodies)

Positive feedback

Product of reaction causes more product to be made

Negative feedback

Product of reaction inhibits product from bein made

What type of hormones does the pituitary gland secrete

Both tropic and non tropic

Does the posterior pituitary release hormones?

No - only stores them

Are oxytocin/ADH tropic or non tropic hormoens

Non tropic: both effect a target tissue

Oxytocin structure

9 amino acid peptide

Oxytocin functions

- Uterine contractions during labor

- Milk secretion let down during breast feeding

- Socio-behavioral functions

Oxytocin social-bheavioural functions

- Decreases stress/anxiety

- Influences eating behaviors and metabolism

- Promotes feeling of love and positive feelings

Effect of low levels of oxytocin

Depression, including post-partum depression

Oxytocin feedback and regulation

Positive feedback loop: stimulates its own release

What is Pitocin

Synthetic oxytocin used to induce labor

Oxytocin clinical testing/indications

Not performed

How to boost oxytocin

Exercise, listening to music, group activities, cuddling, promoting sense of belonging/wellbeing

Why are Oxytocin assays not used

Expensive

ADH (vasopressin) structure

9 AA peptide

ADH functions

Water balance and blood pressure

How does ADH effect water balance

- Increases permeabilility of collecting ducts and distal tubules to allow for more water reabsorption in times of high blood osmolality

ADH levels in low osmolality

ADH secretion decreased to expel water and increase urination

Effect of ADH on blood pressire

When blood volume decreases, ADH helps retain water and maintain blood pressure

- Causes vasoconstriction

When is ADH testing ordered?

When patient has:

- Water balance issues

- Kidney diseases

- heart issues or vasculature issues (blood pressure)

Limitations of ADH testing

- ADH rapidly cleared from body

- Poor stability in vitro

- Low plasma concentrations (pmol/L)

Since ADH is so hard to test, what is used as a surrogate marker?

Copeptin - produced in equimilar amounts with ADH

Copeptin testing

Copeptin testing must be approved via a clinical biochemist approving testing. All testing is referred to Calgary lab?

Which of the following would signal hypothalamus/pituitary to release ADH?

A. Low blood pressure

B. High blood pressure

C. High blood osmolality

A or C

ADH deficiency can be caused by

Insufficient production, ADH resistance, or inability to secrete ADH

What does ADH deficiency result in

Diabetes insipidus

Symptoms of diabetes insipidus

Polyuria (large amounts of urine), Polydipsia (feelings of being thirsty)

Effect of diabetes insipidus in children

Lots of bed wetting

Weight loss

Vomiting

Fever

Vision + Sleeping problems

Central diabetes insipidus

Hypothalamus or posterior pituitary does not produce or release ADH

What causes diabetes insipidus

Head injury, brain tumor, surgery, genetics, infections

Copeptin levels in central diabetes Insipidus

Decreased (ADH not released)

How to treat central diabetes insipidus

Treat with synthetic ADH (desmopressin)

Nephrogenic diabetes insipidus

Kidneys are resistant to ADH action, which causes increased fluid loss

What causes Nephrogenic diabetes insipidus

Genetics, CKD, Lithium toxicity, hypercalcemia

Copeptin levels in nepheogenic diabetes insipidus

Normal or High (ADH released, but not working. Body signals for more)

How to treat nephrogenic diabetes insipidus

Diuretics (decrease urine output), low salt diets. Desmopressin DOES NOT woek

Main test method for diabetes insipidus

Water deprivation test

Psychogenic polydipsia

compulsive water drinking. Causes increased urine volume, and decreased urine + serum osmolarity

Water deprivation test

• Make patients fast for 8-10 hours with no food or water

• Measure Serum osmolality

○ >1000 mOsm, no DI

○ If 300 or lower, give synthetic desmopressin

§ If values come back to normal, we have central DI (we cannot produce it, but kidneys respond

§ No change in values = nephrogenic (no matter the type of ADH, kidneys do not respond)

Testing for ADH deficiency

- Patient symptoms (excessive urination and thirst)

- Serum and urine osmolality

- Serum glucose

- Copeptin

- Water deprivation test

Syndrome of Inappropriate ADH (SIADH)

Increased ADH secretion, causing low plasma/serum osmolality, hyponatremia.

Possible effect of SIADH on body

Edema - swelling of brain and neuron dysfunction

Urine output of SIADH patient

Low urine but high osmolality (very concentrated)

Causes of SIADH

- CNS Disorders (stroke, trauma, tumor)

- Drugs/medications

- Infections

- Genetics

- Hormonal imbalances (hypothyroidism, adrenal insufficiency)

Patient symptoms of SIADH

Swelling, confusion, seizures

How to treat SIADH

Fluid restriction, Hypertonic saline, ADH antagonists to block ADH action on kidneys

Serum osmolarity of SIADH patient

Low - lots of water