Question

Analyze the mechanisms of impairment that can lead to altered hormonal and metabolic regulation

Answer 1

hormones

Chemicals made by cells that can affect the growth and/or function of other target tissues/organs

• Are involved in:
- Metabolism

- Growth and development

- Muscle/Fat distribution

- Fluid/Electrolyte balance

- Sexual development

- Reproduction

- Stress response

ypothalamic-pituitary axis controls the synthesis and secretion of many hormones

Terms in this set (69)

objectives

Define and use the key terms listed in the chapter.

• Identify features that characterize hormones.

• Discuss the role of the hypothalamic-pituitary axis in regulating
hormone levels.

• Identify pathways for mediating cell-to-cell communication.

• Describe the role of the neuroendocrine system in the stress response.

• Analyze the mechanisms of impairment that can lead to altered hormonal and metabolic regulation.

• Discuss common measures to diagnose and treat hormone dysfunction.

• Apply concepts of altered hormonal and metabolic regulation to select clinical models.

hormones

Chemicals made by cells that can affect the growth and/or function of other target tissues/organs

• Are involved in:
- Metabolism

- Growth and development

- Muscle/Fat distribution

- Fluid/Electrolyte balance

- Sexual development

- Reproduction

- Stress response

don't have to memorize entire table
just know hormones we talk about in class and applications

characteristics of hormones

-Control via the hypothalamic-pituitary axis: hormone synthesis and release is controlled by tissues and organs

• Feedback (positive and negative loops): hormones listen and adjust based on negative and positive loops

• Patterns: hormones exhibit predictable patterns of secretion, metabolism, and elimination

• Receptor binding: to exert an effect hormones must locate and attach onto target tissues

• Action on target organs and glands

1. Act on target organs to achieve an effect

2. Act on glands to produce another hormone

control: they work together in communication
with one another and control hormones in your body

all metabolism with through they interact with broken down by the liver (hormone)

sometimes we don't have to even break them down some have half-life through apoptosis

can act on glands to produce another hormone

the endocrine system

The collective group of cells capable of secreting hormones.

• Note: Cells of the endocrine system are not the only tissues capable of secreting hormones!

-pancreas and thyroid

- Examples:

• Immune cells secrete cytokines,
which act as hormones.

• Neurons release neurotransmitters which act as hormones.

hypothalamic-pituitary axis

controls the synthesis and secretion of many hormones

hypothalamus: releasing hormones

-Growth hormone-releasing
hormone

• Thyrotropin-releasing hormone

• Corticotropin-releasing hormone

• Gonadotropin-releasing hormone

hypothalamus: inhibiting hormones

Somatostatin (inhibits GH and TSH)

• Dopamine (inhibits prolactin)

pituitary

Made up of two lobes:

- Anterior

• Receives signals from the hypothalamus via circulation

• Under negative feedback regulation

- Posterior

• Direct neural connection

• Not under negative feedback regulation

anterior: lutenizing hormone, adrenocorticotropin, growth hormone, prolactin PL, thyroid stimulating hormone, and folicle stimulating hormone

things go from the hypothalamus

anterior: negative if hormone level
is high we are going to prevent it from being released and vise versa

posterior: positive

-oxytocin, and antidiuretic hormone


talking to anterior and posterior pituitary through the blood vessels and shows where it releases and where it works in the body


could have two step or three step process on releasing the hormone

stimulating hormone: stimulate an end organ to release the actual hormone (know there is going to be a third step)

antidiuretic: conserving water-keeping

water in your body and it causes more urine to be released not being absorbed

anterior: sends messages from the hypothalamus to the blood vessels

posterior: uses neurons

the hypothalamic-pituitary axis

1. Hypothalamus produces a releasing
hormone.

- Travels to anterior pituitary and is activated to produce a trophic hormone which is released to the body to act on a target organ to secrete a final hormone that is released to the body.

- Example: Thyrotropin releasing hormone - thyroid stimulating hormone - Thyroid hormone

feedback

"The modification or control of a process or system by its results of effects"

• The hypothalamus is constantly receiving input in the form of neurotransmitters, chemical mediators, or injury.

• Feedback can be positive or negative

positive feedback loop

-The presence of a hormone stimulates an increased production of hormone until there is an interruption of the cycle.

• Positive feedback loops are less common than negative feedback loops

posterior: oxytoxin makes stretching of cervix and when baby is born stretching stops

negative feedback loop

Two mechanisms:

1. Low levels of hormone stimulate additional release of hormone.

2. High levels of hormone inhibit the release of hormone

things get to high: try to decrease it

things get to low: stimulate to increase

t3 and t4 low: increase hormones because we need more to be produced

-affected by environmental and body temperature, stress, nutrition, and the presence of specific body substances

example of negative feedback loop

circulating thyroid hormone levels (T3+T4) alert the hypothalamus and anterior pituitary to increase or decrease thyrotropin-releasing hormone and thyroid stimulating hormone

example of positive feedback loop

oxytocin levels during labor and delivery increase release of additional oxytocin until the birth of the baby which decreases stretching of the cervix and the cycle is interrupted

patterns of hormone secretion, metabolism, and elimination

-diurnal patterns of secretion

-cyclic patterns of secretion

diurnal: daily pattern (cortisol level) increase in morning, decrease in evening and shoot back up why you are sleeping

cyclic: ovulation: estrogen level goes up and down over a month and lutenizing hormone goes low and increases during ovulation

receptor binding

Hormones MUST bind to a receptor in order to elicit a response
-a surface receptor requires a second messenger to elicit a response from the cell and without the appropriate receptor, the hormone moves along and has no impact on that cell

-cell surface

-intracellular

can sit and cause an enzyme

or can have a direct effect on nucleus of cell and cause protein synthesis

cell-to-cell communication

paracrine: hormone producing cell and go from cell to cell with receptors on those cells
-hormones are produced in a cell, secreted, and act directly on nearby receptive cells

autocrine: can make hormones by itself and has receptors to communicate to make them
-the same as the paracrine pathway except that the receptor cells also are secretory cells so in essence the cell is able to produce the hormone and exert an effect on itself

cell-to-cell communication: synaptic vs neuroendocrine

synaptic: travels across synaptic cleft between cells
-hormones are produced in the neuron, secreted, and travel along the axon to the synapse where they are released and makeup by a nearby neurons with the appropriate receptors to exert an effect

neuroendocrine: neuron cells produce hormone and entered into the blood stream
-hormones are produced in a neuron, secreted, travel along the axon to the synapse, are released, are taken up into the vascular system, and travel to distant cells with the appropriate receptors to exert an effect


endocrine: hormones are produced in a cell, secreted, and travel through blood vessels to distant cells, attach to receptors, and act on that cell

historical background: Dr. Hans Selye

Worked to discover a new sex hormone.

- Injected ovarian extracts into rats

- Witnessed

• Enlargement of the adrenal cortex

• Thymic atrophy

• Development of bleeding ulcers in the stomach and
duodenal lining

- Witnessed these changes with many agents and called these stimuli stressors.

stress

-threat to homeostasis

-real vs perceived

-good vs bad

-stressor is the stimulus that invokes the stress response

-body's reaction to harmful forces (stressors) capable of disturbing homeostasis

stress requires balance

-good thing if its in balance and keeps you motivated

neurologic response to stress

-autonomic nervous system

-cerebral cortex: regulates cognitive activities such as intense focus, planning, attention, and persistence

-limbic system: regulates emotional activities such as fear, anxiety, anger, and excitement, and stimulates the reticular activating system

-thalamus: intensifies sensory input related to the stressor such as vision, hearing, and smell

-hypothalamus: release hormones to initiate the neuroendocrine response; acts on the autonomic nervous system

-reticular activating system: increases alertness and muscle tension and contributes to stimulation of autonomic nervous system

stress response

-is a specific physiological response to a nonspecific threat.

•Is initiated by the central nervous system and the endocrine system.

-autonomic sympathetic nervous system takes over

autonomic nervous system

increases heart rate

-increase blood pressure

-increase respiratory rate

-increase pupil dilation

-increase sweating

-blood flow is increased to the muscles, heart, and lungs in preparation of "fight or flight"

-gastric function decreased to shunt blood to vital organs

-altered blood flow, decreased oxygenation to gastric tissues, and prolonged cortisol exposure may result in stress ulcers of the gastrointestinal tract

hypothalamic-pituirary-adrenal axis

corticotropin: is the one that is very important in stress model

cortisol: negative

Hypothalamus secretes corticotropin-releasing hormone

(CRH) CRH acts on the pituitary gland to induce the production of adrenocorticotropic hormone (ACTH)

ACTH acts on the adrenal cortex to induce the release of cortisol

stress hormones

norepinephrine: neurotransmitter

-stress stimulates the release of CRH from the hypothalamus and then CRH stimulates the pituitary to secrete adrenocorticotropic hormone which in turn stimulates the adrenal glands to secrete cortisol

cortex is outer layer, medulla is inner layer ( in charge or norepeniphre and epinephrine) and cortex is in charge of hormones

catecholamines: norepinephrine, epinephrine, dopamine
-triggered by the sympathetic nervous system which also acts on the adrenal glands
-induce a neurologic response to receptive organs

-release from presynaptic neurons

-epinephrine: secreted by adrenal medulla


-glucocorticoids (steroid hormone)

-cortisol: needed to increase metabolism and regulate blood glucose levels for energy and also acts as a potent anti-inflammatory

stress response 2

alteration in glucose fat and alteration: get fat
autonomic and hormones causing these symptoms

selye's general adaptation syndrome

-term used to describe this neuroendocrine response and the corresponding physiology changes

-Alarm stage
-catecholamines and cortisol are released in response to stimulation of the sympathetic nervous system, the hypothalamic pituitary axis, and the adrenal glands
-fight or flight stage

- Stressor triggers the hypothalamic-pituitary-adrenal (HPA) axis.

- Activation of the sympathetic nervous system (SNS).


• Resistance (adaptation) stage

- Begins with the actions of adrenal hormones.
• Cortisol, epinephrine, and norepinephrine

-cortisol levels decrease though negative feedback mechanisms and excess cortisol is helpful in early stages but later on hypercortisolism is detrimental leading to exhaustion of inflammatory and immune responses





•Exhaustion stage (allostatic overload)

- Occurs only if stress continues and adaptation is not
successful.

-characteriszes by energy depletion and degeneration of cells, tissues, organs, and organ systems

-stress begins in brain stem

altered hormone function

-Impairment of endocrine gland

• Lack of/excessive hormone synthesis

• Impaired receptor binding

• Impaired feedback mechanisms

• Impaired cell response to hormones

hypopituitarism

-Gradual onset

- Fatigue

- Weakness

- Anorexia

- Sexual dysfunction

- Growth impairment

- Dry skin

- Constipation

- Cold intolerance

-generic term indicating decreased secretion of one or more pituitary hormones that could be caused from damage to the hypothalamic-pituitary axis due to infection, inflammation, tumors, degeneration, hypoxia, hemorrhage, or genetic defects that lead to problems with the production and secretion of multiple hormones

hyperpituitarism

-a wide range of manifestations, depending on hormones elevated

too much hormone is being released by the pituitary

-know these hormones

glucose intolerance: usually end up with diabetes

-excess of pituitary hormone secretion

diagnosing altered hormone function

-History and physical examination

• Laboratory tests

- Serum and urine hormone levels

- Hormone suppression and stimulation tests

- Serum electrolyte, glucose, and calcium levels

• Imaging studies

• Genetic testing

treating altered hormone function

-Dependent on cause

• Hormone excesses

- Removal of tumor secreting ectopic hormone

• Production of hormone from an alternate site

• Escape of negative feedback regulation

- Removal of part or all of endocrine gland

- Medications that block effects of hormone

• Hormone deficits

- Medications that stimulate release or replace hormone

-cut back thyroid gland

panhypopituitarism

decrease in pituitary hormones

syndrome of inappropriate antidiuretic hormone (SIADH): pathophysiology

-Excess production and release of ADH

-condition of excessive production and release of ADH despite changes in serum osmolality and blood volume

• Most common cause:tumor secreting ectopic ADH

• ADH promotes water retention intracellularly

• Water accumulates in cells, altering function

• Sodium is diluted in extracellular space

• Result:hypotonic hyponatremia

syndrome of inappropriate antidiuretic hormone

too much of antidiuretic hormone(too little urine)

-intracellular because low solutes compared to inside of cell which alters their function (too much water in the cells)

hypotonic: amount of solute in your serum

antidiuretic hormone

-excess: fluid retention, low urine output, hyponatremia

-deficit: excessive water losses through the urine, leading to nausea, vomiting, fatigue, muscle thirst, dehydration, can progress to shock twitching; can progress to convulsions and death

glucocorticoids (cortisol)

-excess: truncal obesity, moon face, buffalo hump, glucose intolerance, atrophic skin, striae, osteoporosis, psychological changes, poor wound healing, increased infections

-deficit: hypoglycemia,anorexia, nausea, vomiting, fatigue, weakness, weight loss, poor stress response

growth hormone

excess: before puberty (gigantism) excessive skeletal growth
-after puberty (acromegaly)


deficit: short stature, obesity, immature facial features, delayed puberty, hypoglycemia

aldosterone (mineralocorticoids)

excess: hypertension, hypokalemia, hypernatremia, muscle weakness fatigue, polyuria, polydipsia, metabolic alkalosis


deficit: weakness, nausea, anorexia, hyponatremia, hyperkalemia, dehydration, hypotension, shock, death

thyroid hormone

excess: hyper metabolism, weight loss, diarrhea, exopthalamos, anxiety, goiter

deficit: hypo metabolism, weight gain, constipation, goiter, dry skin, coarse hair

parathyroid hormone

excess: hypercalcemia, excessive osteoclastic activity and bone resorption, pathologic fractures, formation of renal calculi

deficit: hypocalcemia, muscle spasms, hyperreflexia, seizures, bone deformities

SIADH: clinical manifestations

-Decreased urine output (concentrated)

• Severity of symptoms depends on serum sodium levels

- Anorexia, nausea, vomiting, headache

- Irritability, disorientation,
cramps, weakness

- Psychosis, gait disturbances, seizures, coma

pretty dark yellow pee

normal sodium 135-145

too much water and not enough sodium

lower sodium: more severe symptoms

SIADH: diagnostic criteria

-Hyponatremia (serum sodium <135 mEq/L)

• Hypotonicity (plasma osmolality <280 mOsm/kg)

• Decreased urine volume

• Highly concentrated urine with a high sodium content

• Absence of renal, adrenal, or thyroid abnormalities

water is 1.000

hypotonicity for the blood

: don't have much solute in it so youre going to be closer to water

SIADH: treatment

- Remove cause

• Water restriction

• Isotonic or hypertonic IV fluid replacement

• Pharmacologic treatment

diabetes insipidus

-a condition of insufficient ADH that results in the inability of the body to concentrate or retain water


-most common cause: impairment of hypothalamic osmoreceptors after trauma or surgery to a region at or near the hypothalamus

diabetes insipidus: pathophysiology

-Insufficient ADH

• Inability to concentrate or retain
water

• Causes

- Insufficient ADH production or secretion

- Inadequate kidney response to ADH also called nephrogenic DI - Water intoxication

-ingestion of extremely large volumes of fluids and decreasing ADH levels; water intoxication can sometimes be attributed to a psychiatric disturbance

not enough diuretic hormone youre going to be secreting more water

diabetes insipidus: clinical manifestations

-Polyuria: large volume urine output

• Excessive thirst

• Dehydration

• Shock

• Death if untreated

diabetes insipidus: diagnostic criteria

-history and physical examination

-lab tests
-serum solute concentration

-ADH levels

-urine-specific gravity

-urine osmolality

urine specific: low more like water because you are peeing out so much water

diabetes insipidus: treatment

-treat cause

-hydration

-pharmacologic treatment

-desmopression (synthetic vasopressin analog that acts as an antidiuretic)

hyperthyroidism

work on the pituitary and pituitary will release
TSH which works on the thyroid to make hormones T3 and T2

too much T4 or T3, negative feedback loop so won't release TSH

low thyroid hormones: high TSH because we want more

high thyroid: TSH goes low


-state of excessive thyroid hormone and can result from excessive stimulation to the thyroid gland, diseases of the thyroid gland, or excess production of tSH by a pituitary adenoma

hyperthyroidism: pathophysiology

Condition of excess thyroid hormone due to:

- Excess stimulation of thyroid gland - Disease of thyroid gland

- Excess production of TSH

• Graves disease: most common form in U.S.

- Autoimmune disorder of unknown etiology

• Type II Hypersensitivity

- IgG binds to TSH receptors on thyrocytes

negative feedback is blocked by IgG by having an autoimmune disorder

females at higher risk

graves disease: pathophysiology

-an excessive stimulation of the thyroid gland, is the most common cause of hyperthyroidism and is the most common autoimmune condition in the US

-triggering event is unknown: maybe genetic and environmental

-IgG antibodies bind to the TSH receptor on thymocytes (thyroid cells) and stimulate excessive thyroid hormone secretion causing a state of thyrotoxicosis

-thyrotoxic crisis: thyroid storm or sudden, severe worsening of hyperthyroidism that may result in death

graves disease: clinical manifestations

• Goiter (enlargement of the thyroid gland)

• Weight loss

• Agitation

• Restlessness

• Sweating

• Heat intolerance

• Diarrhea

• Tachycardia

• Palpitations

• Tremors

• Fine hair, oily skin

• Irregular menstrual cycle

• Weakness

• Exophthalmos: protrusion of the eyeballs

exphthalamos: right behind their eyes they have excess inflammation that protude the eye ball (bulging out) and treating they don't usually go down

graves disease: diagnostic criteria

History and physical examination

• Laboratory tests

- Serum TSH, T3, and T4 levels

- Free thyroxine level and increased uptake of
radioactive iodine by the thyroid gland confirm diagnosis

TSH will be low

t3 and t4: high

iodine: soak it up (t3 and t4)

graves disease: treatment

Pharmacologic treatment

- Medications that block thyroid hormone
production

- Oral thyroid hormone replacement therapy

• Destruction of all or part of gland with radioactive iodine

• Surgical removal of all or part of gland

replace thyroid gland somehow

medication rest of lives

can go from hyper to hypo to treat it

hypothyroidism: pathophysiology

Congenital or acquired deficiency of thyroid hormone (TH) from:

- Lack of thyroid gland development

- Deficient synthesis of TH

- Destruction of thyroid gland

- Impaired secretion of TSH or TRH

• Many potential causes such as autoimmunity, genetic defects, injury to gland, iodine deficiency

doesn't affect fetus in utero because mom can produce enough

problem after baby is born where they have to produce their own

in babies it can cause brain damage because thyroid hormone can have a lot to do with brain development

screen for it with all babies (T3 and T4)-state mandated test they can't refuse it

cretinism

lack of thyroid hormone in an infant; if untreated, leads to mental retardation

hypothyroidism: clinical manifestations

-Fatigue, weakness, lethargy, weight gain

• Cold intolerance

• Constipation

• Dry skin, course hair

• Impaired reproduction

• Impaired memory

• Goiter, myxedema

myxedema: swelling in the tissues but doesn't pit because of all the solute in it

hypothyroidism: diagnostic criteria

-History and physical examination

• Laboratory studies

- TSH

- Free T4

- Total T3 and T4 uptake

- Thyroid autoantibodies

- Antithyroglobulin

low T4, super high TSH working so hard to stimulate this thyroid to produce more

hypothyroidism: treatment

-lifelong thyroid hormone replacement therapy

cushing syndrome

-refers to a condition of prolonged exposure to elevated levels of either endogenous (from the adrenal cortex or cortisol-producing tumors) or exogenous glucocorticoids (as when taking glucocorticoids drugs)

cushing syndrome: pathophysiology

-Excess glucocorticoids secreted from adrenal cortex

• Affects metabolic function, stress response, inflammatory and immune responses

• Causes

- Long-term administration of exogenous glucocorticoids (prednisone)

- Tumors of the pituitary gland that stimulate excess ACTH production

-tumors of the adrenal gland that stimulates excess cortisol production

-ectopic production of ACTH and CRH from a tumor at a distance site such as small cell carcinoma of the lung

too much: excess fat in middle, get sick more

too much prenitzone

cushing syndrome: clinical manifestations

-Metabolic alterations

• Obesity of trunk, face, and upper back

• Glucose intolerance

• Suppression of inflammation/immunity

• Behavioral changes

• Impaired stress response

cushing syndrome: diagnostic criteria

-Cortisol levels in 24-hour urine

• Imaging studies to detect tumors

has diurnal effect: different times different amount of urine

cushing syndrome: treatment

-Remove cause of excess cortisol secretion

• Gradually taper exogenous glucocorticoid
medications

• Surgical removal of tumors, chemotherapy,
radiation

-decrease prenitzone slowly

addison disease: pathophysiology

-Autoimmune destruction of the adrenal cortex

• Adrenal gland cannot produce glucocorticoids, mineralocorticoids, or androgens due to tumors, hemorrhage, trauma, radiation, or surgical removal

• ACTH levels increase to stimulate secretion of adrenal hormones from the adrenal glands

-autoimmune destruction of the layers of the adrenal cortex is the most common cause for this

-destruction least to the inability of the adrenal gland to produce any glucocorticoids, mineralocorticoids, and androgens resulting in ACTH levels elevated to increase the secretion

-too little glucocorticoids

-adrenal glands aren't working

addison disease: clinical manifestations

-Darker pigmentation of skin (high ACTH)

• Glucocorticoid deficiency

- Hypoglycemia, weakness, poor stress response, fatigue, anorexia, nausea, vomiting, weight loss, personality changes

• Mineralocorticoid deficiency

- Dehydration, hyponatremia, hyperkalemia, hypotension, weakness, fatigue, shock

-lady again because autoimmune disease higher risk

addison disease: diagnostic criteria

-History and physical examination

• Hyponatremia, hyperkalemia

• Serum corticosteroid levels remain depressed after administration of ACTH

give ACTH should help them secrete more glucocorticoid

addison disease: treatment

-Fluid replacement

• Pharmacologic treatment

- Hydrocortisone

- Oral glucocorticoid and mineralocorticoid replacement

• Dietary change

- Increased sodium intake due to excess sodium losses (sweating)