PSIO107 FINAL

Nervous System

* Neuron transmits nerve down the axon to the neurotransmitter
* neurotransmitter releases the impulse into the synapse
* the post-synaptic cell responds to that nerve impulse
* **rapid response but transient effects**

Endocrine System

* Glandular cells secrete hormone into the bloodstream
* through the bloodstream, throughout the whole body maybe before they find their receptors. **target cells have to have receptors for hormones to find them**
* Target cells respond to the hormone, **hormones have no effect on other cells of the body**
* **slow response but long-term effects**

Endocrine grands

ductless, secrete hormones into blood (or CSF)

Hormones

* act on target cells (require specific receptors to have effects)
* slow onset (minutes-hours), long-term effects (days-weeks)

Endocrine Organs

Hormone Action

Chemistry

* hormones can be __water-soluble__ or **lipid soluble**
* hydrophilic
* Amine, peptide, protein, glycoprotein (all amino acid-based)
* Hydrophobic (lipophilic)
* steroid (cholesterol) or prostaglandin (fatty acid-based)

Synthesis and Packaging of Hydrophilic hormones

1. Proteins are packaged in secretory vesicles for exocytosis
2. vesicle becomes lysosome
3. Vesicle inserted into the plasma membrane

if we want to secrete a hormone, it needs to be stimulated, proteins can be generated and stored in vesicles so that the hormones are ready to be released when needed

Hormone Action

* hormone chem plays role in location of receptors on target cells
* hormones act in small quantity, but have big effect
* hormones act in minuet quantities, because they are amplified
* only the “free” (unbound) fraction of hormone in plasma is regulated
* plasma concentration is determined by:
* secretion rate, production rate, clearance rate, metabolism rate

* Endocrine disorders arise when:

* hormone production is too low (hyposecretion)
* hormone production is too high (hypersecretion)
* hormone receptors are absent (insensitivity)

Control Mechanisms: most hormones…

are regulating via negative feedback mechanisms

* ex: high blood glucose stimulates insulin secretion, which results in cell uptake and storage of glucose (lowering blood glucose concentration)

Control Mechanisms: some hormones…

are part of positive feedback mechanisms

* ex: cervical stretch receptors signal the brain to release oxytocin, which results in uterine contraction (effectively causing more stretch as the baby’s head is forced against the cervix)

Hypothalamus

integration center

* body temp
* thirst and urine output
* appetite
* Anterior pituitary hormones (produces 6 hormones)
* posterior pituitary hormones (**produces oxytocin and ADH**)

stimulus from the hypothalamus that influences the posterior pituitary

Anterior pituitary hormones

Bridge to endocrine system

* Stimulates or inhibits A.P. hormone secretion via “releasing -” and “inhibiting hormones”
* Synthesizes P.P. hormones

circadian rhythm: **biological clocks**

approximate 24 hour cycles for body functions

* ex: temperature, gene expression, behavior, hormone secretion
* pineal gland secretes melatonin to synchronize

circadian rhythm: **Melatonin**

Secreted during periods of darkness

* Light/dark cycle entrains biological rhythms

Proposed roles

* Can induce natural sleep
* Inhibits sex hormones
* Puberty initiated by drop in melatonin levels
* In other species → seasonal breeding, hibernation, migration cycles
* Birth control
* High levels shut down ovulation
* Antoxidant
* Slows aging process
* Enhance immunity
* Also slows regression of thymus

Pituitary Gland

consists of two separate tissues

* anterior pituitary is gland tissue (true gland tissue)
* posterior pituitary is neural tissue (extension of NS)

Posterior Pituitary (Neurohypophysis) secrets two hormones: **Antidiuretic Hormone (ADH) (Vasopressin)**

* targets kidney → stimulates water reabsorption
* targets blood vessels → stimulates vasoconstriction

__Helps with regulation of blood pressure via negative feedback__

\*This hormone acts w/ many other mechanisms during hypovolemia and/or hypotension

Posterior Pituitary (Neuro**hypophysis(means pituitary)**) secrets two hormones: **Oxytocin**

* targets uterine smooth muscle (myometrium)
* targets myoepithelial cells lining milk ducts

__participates in parturition and milk ejection via positive feedback__

Anterior pituitary (Adenohypophysis): six secreted hormones (all negative feedback mechanisms) involved in growth, metabolism, or reproduction

Prolactin (PRL)

Growth Hormone (GH)

Thyroid-Stimulating Hormone (TSH)

Adrenocorticotropic Hormone (ACTH)

Follicle-Stimulating Hormone (FSH)

Luteinizing Hormone (LH)

Hypothalamic-Anterior Pituitary Axis

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Prolactin

* promotes milk production (secretion) from mammary glands
* also inhibits ovulation
* ‘nature’s contraceptive
* **feedback loop*\*

Growth Hormone

* metabolic hormone
* promotes growth of tissues (indirectly)
* bone and muscle, and most soft tissues
* If hyposecretion:
* in kids = dwarfism
* in adults = muscle weakness, metabolic issues
* If hypersecretion:
* in children = gigantism
* in adults = acromegaly
* **feedback loop*\*

Growth Hormone (Important Points)

**ON EXAM*\*

Pathway of control of growth and development

* GHRH stimulates GH secretion
* GH stimulates IGF-1 (negative feedback control)
* GH acts __directly__ on tissues to stimulate __metabolism__
* GH acts __indirectly__ to promote __growth-related actions__
* via IGF-1

Thyroid Gland

Major histological structure = follicle

* cells forming follicle are called follicular cells
* help produce __thyroid hormone__ in the colloid
* thyroxine (tetraiodothyronine, T4)
* Triiodothyronine (T3)
* Iodine
* sequestered in thyroid gland
* required for T3/T4 synthesis

Hyperthyroidism

too much TSH

or, thyroid tumor

or, TSI

* thyroid tumor (primary hyperthyroidism)
* excessive tropic hormones (secondary)
* or, most common
* symptoms:
* elevated metabolic rate
* heat tolerance
* weight loss (but increase food intake)
* increased heart rate
* excess mental alertness
* exophthalmos

Hypothyroidism

too little TSH

or, other thyroid dysfunction

* thyroid gland failure (primary hypothyroidism)
* deficiency of tropic hormones (secondary)
* Symptoms:
* Reduced metabolic rate
* cold intolerance
* weight gain
* reduced cardiac output
* lethargy (fatigue)
* Edema

Thyroid Gland Metabolism

ATP production and utilization

Thermogenesis O2 consumption

Growth: muscle, bone, nervous

Password

IGF1

Parathyroid Gland

produces __parathyroid hormone__

* reverses low blood calcium levels
* stimulates osteoclasts to remove calcium from bone
* stimulates kidney to reabsorb calcium
* stimulates kidney to increase Vit. D activation
* promotes intestinal uptake of calcium

PTH Hypersecretion

Hyperparathyroidism

* hypersecreting tumor
* symptoms may vary w/ magnitude of problem
* **hypercalcemia and hypophosphatemia**
* decrease muscle and nervous tissue excitability
* muscle weakness
* neurological disorders
* decrease alertness, poor memory, depression
* cardiac arrhythmias
* **Thinning of bone**
* deformities
* factures
* **incidence of Ca2+: containing kidney stones**
* decrease renal function
* pain
* **peptic ulcers, nausea, and constipation**

PTH Hyposecretion

Hypoparathyroidism

* surgical removal → most common cause
* autoimmune destruction

**-Hypocalcemia and Hyperphosphatemia**

* increase muscle and neuron excitability
* Muscle cramps and twitches
* Tingling and pins-and-needles sensation
* Irritability and paranoia
* death (in absence of PTH)

Vitamin D deficiency

impaired Ca2+ absorption

* PTH maintains plasma Ca2+ at expense of bones
* Softened bones deform
* Rickets (in children)
* Osteomalacia (in adults)

Endocrine Pancreas

Glucose-sensing cells called pancreatic islets (islets of Langerhans) form the endocrine pancreas

* alpha islets are sensitive to low blood glucose
* secrete __glucagon__
* Beta islets are sensitive to high blood glucose
* secrete __insulin__

Insulin actions

targets the liver, adipose, and muscle to promote the storage of glucose

* glucose transporters are stimulated
* glucose is phosphorylated to keep it in the cell
* glucose-6-phosphate (G6P) is linked together to form __glycogen__

Feedback loop

Glucose Transport

1. **Passive facilitated diffusion into cell (through GLUT)**
2. glucose → glucose-6-phosphate


1. phosphorylation


1. traps glucose inside cell
2. keeps intracellular glucose concentration low

Insulin triggers glucose transporter (GLUT-4) recruitment in body celss

Glucose transporters

GLUT-1

* Blood-brain barrier

GLUT-2

* __B-islets,__ kidney, liver and intestinal cells

GLUT-3

* Neurons

GLUT-4

* most cells of body
* __**only transporter that is sensitive to insulin**__

GLUT-1

transports to blood-brain barrier

GLUT-2

transport to __B-islets,__ kidney, liver and intestinal cells

GLUT-3

transport to neurons

GLUT-4

Most cells of body

__**Only transporter that is**__

__**sensitive to insulin**__

transporter recruitment

* pool of internal vesicles containing GLUT-4
* Insulin binds to receptor
* signaling cascade induces vesicles to fuse w/ plasma membrane
* 10-30 fold increase glucose uptake
* decrease insulin → endocytosis of GLUT-4 and return to intracellur pool

Tissues not dependent on insulin:

* Brain
* Skeletal muscle cells
* liver

Tissues not dependent on insulin: brain

freely permeable to glucose

* GLUT-1 and GLUT-3

Tissues not dependent on insulin: Skeletal cells

__Not dependent__ __**on insulin**__ during exercise

* __***____muscle contraction triggers insertion of GLUT-4__ (in absence of insulin)\*

dependent on insulin at rest

Tissues not dependent on insulin: liver

does not use GLUT-4

**But** insulin does enhance carbohydrate metabolism

* stimulates glucose phosphorylation

Glucagon action

essentially the opposite of insulin

glucagon does not affect muscle tissue

primary target is the liver

* promotes cleavage of glycogen into G6P
* G6P is dephosphorylated
* Free glucose molecules diffuse out of hepatocytes

Insulin deficiency: Diabetes Mellitus: Type 1

* insulin dependent
* pancreas does not produce enough insulin
* develops rapidly
* usually diagnosed in childhood

Insulin deficiency: Diabetes Mellitus: Type 2

* adult onset diabetes
* insulin receptors not responsive to insulin, or pancreas not secreting enough to meet needs
* develops slowly
* obesity is factor
* can be controlled w/ diet

Insulin deficiency: gestational diabetes

* develops in women who are pregnant
* correlates w/ type 2 development later in life
* baby could develop diabetes later in life

acute complications

osmotic diuresis, electrolyte imbalance, ketoacidosis, circulatory failure, cell shrinking, nervous malfunction → Diabetic coma

Chronic complications

* manifest after 15-20years
* degeneration of vascular tissues
* blood vessel legions
* kidney failure
* blindness
* gangrenous
* heart disease
* strokes
* degeneration in nervous system
* nerve lesions result in neuropathies
* brain dysfunction
* spinal cord dysfunction
* peripheral nerve dysfunction
* pain, numbness, tingling in extremities
* renal failure
* dialisis → 2 year life expectency

Insulin excess

characterized by hypoglycemia arising two ways

* diabetic patient injects too much insulin
* insulin shock
* Hypersecretion of insulin
* beta cell tumor
* beta cell over-responsive to glucose
* reactive hypoglycemia

Insulin excess: consequences

primarily effects brain

* decrease glucose → brain starves
* tremor, fatigue, sleepiness, inability to concentrate
* unconsciousness
* death
* Treatment
* limit glucose intake

Adrenal Gland

Consists of two endocrine glands

* adrenal cortex
* Adrenal medulla

Adrenal gland: adrenal cortex

* regulated via hypothalamic-pituitary-adrenal axis
* secretes cortical hormones (steroids)
* Mineralocorticoid
* aldosterone
* Glucocorticoid
* cortisol
* Gonadocorticoid
* DHEA
* Androgen

Adrenal gland: Adrenal medulla

* part of sympathetic NS
* secrets catecholamines
* epinephrine (adrenaline)(80%)
* Norepinephrine (20%)

Cortical hormones: Gonadocorticoid (sex hormones)

* primarily the androgen __**dehydroepiandrosterone**__ (__**DHEA**__), but also some estrogen


* Not important as a major source of androgen in males (they have testosterone; 1000X more potent)
* **In women, DHEA is important** for sex drive and pubic/axillary hair growth
* stimulated via ACTH

Cortical Hormones: Mineralocorticoids = __**Aldosterone**__

* targets kidney, resulting in sodium reabsorption
* stimulated via low blood pressure/volume regulation
* if salt is recovered from urine, water follows follows passively
* also stimulates potassium excretion, to maintain ionic equilibrium

Cortical Hormones: glucocorticoids = __**cortisol**__

Chronic stress hormone, targets glucose metabolism in many tissues

* Liver: stimulates conversion of proteins/lipids into glucose (**gluconeogenesis)**
* muscle: promotes utilization of fatty acids as an energy source

Control: CRH → ACTH → Cortisol

Aldosterone

Mineralocorticoids

* **from: Zona glomerulosa**
* aldosterone
* conservation of sodium
* water retention by osmosis

Cortisol

Cortisol is critical for survival during prolonged fasts

* increase blood glucose concentrations, at expense of protein and fat stores
* **increase gluconeogenesis**
* **increase amino acids**
* **increase blood fatty acids**
* permissive to other hormones
* Ex: catecholamine induced vasoconstriction
* →if unavailable during stressful condition → shock
* **PROTECTS AGAINST STRESS**
* mechanism largely unknown
* helpful in surgery patients (demand to have surgery in morning)
* Pharmacological actions
* decrease inflammation and immune response

Adrenocortical Dysfunction: Hypersecretion: Aldosterone

* Adrenal tumor of aldosterone-secreting cells (**Conn’s syndrome)**
* primary hyperaldosteronism
* High activity of renin-angiotensin-aldosterone system
* secondary hyperaldosteronism

→ __**Exaggerated effects**__: **Na+ retention, K+ depletion, increase BP**

Adrenocortical Dysfunction: Hypersecretion: Cortisol

* overstimulation by CRH and/or ACTH
* Adrenal tumor of cortisol-secreting cells
* ACTH-secreting tumors located outside pituitary

→ __**Exaggerated effects of cortisol:**__

* **excessive gluconeogenesis**

**→ excess glucose and protein shortage: Hyperglycemia and glucosuria**

→ **some of excess glucose deposited as body fat → “buffalo hump” and “moon face”: Cushing’s Syndrome**
* Muscle weakness, fatigue, skin streaks, bruising, poor wound healing, bone fracture

Adrenocortical insufficiency: Primary insufficiency

Addison’s disease

* __All sones exhibit reduced secretion__
* Likely autoimmune destruction
* Aldosterone deficiency is most life-threatening
* hyperkalemia (K+ retention)
* abnormal ECG
* Hyponatremia (Na+ loss)
* hypotension

Adrenocortical insufficiency: Secondary insufficiency

* Pituitary or hypothalamic abnormalities → decrease ACTH secretion
* cortisol is deficient
* poor response to stress
* hypoglycemia (decrease gluconeogenesis)
* loss of permissiveness
* hyperpigmentation (excessive ACTH → binds alpha MSH → skin darkening)

Adrenal Medulla (refer back to nervous system section)

Considered part of the sympathetic branch of the autonomic nervous system

* Innervated by sympathetic neurons
* “fight-or-fight”
* Major hormone for short-duration stress responses
* Promotes long-lasting effects than nervous input to tissues, alone.
* Aimed at promoting an increase in blood glucose and fatty acids
* Glucose available for brain use
* Fatty acids for liver (gluconeogenesis) and muscles (energy)

Integrated Stress Response

Testes

* produce testosterone from Leydig cells
* control: GnRH → LH → Testosterone

Ovaries

* Produce estrogen and progesterone
* Control: GnRH → FSH → Estrogen and GnRH → LH → Progesterone
* Estrogen and progesterone both have effects on the uterus, promoting a healthy environment for gestation

Functions of the Reproduction system: For both males and females

* produce gametes
* Oocytes and spermatocytes
* requires hormone production, also
* deliver gametes to the site of fertilization
* ampulla of the fallopian tube

Functions of the Reproduction system: female specific

* prepare uterus for implantation
* requires hormones
* protection of fetus
* allow fetal growth and development (gestation)
* parturition (give birth)
* lactation

Anatomy of the Male Reproductive System: Male reproductive structures

External Genitalia

* Penis
* Corpus cavernosum
* corpus spongiosum
* urethra
* Scrotum
* Testes
* Seminiferous Tubules
* Epididymis

Internal Genitalia

* ductus deferens (vas deferens)
* ejaculatory duct
* urethra
* accessory sex glands
* seminal vesicles
* prostate gland
* bulbourethral glands

Testes

contain seminiferous tubules

* site of **spermatogenesis**
* requires two cell types for production
* **interstitial cells of Leydig**
* Testosterone
* **Sertoli cells**
* Nurture the process
* Temperature sensitive

Spermatogensis

cremaster is in the groin

* begins at puberty
* continues throughout life
* **one** primary spermatocyte produces **four** sperm cells
* 2-month development period
* Several hundred million produced per day

Sperm

structure of sperm fits its function of delivering male genetic material

* a mobile, trimmed-down cell

Accessory Sex Glands

* Seminal Vesicles
* Provide majority (60%) of semen fluid volume
* Helps dilute thick mass of sperm cells
* Fructose, prostaglandins, fibrinogen
* Prostate Gland
* Alkaline fluid, clotting enzymes, prostate-specific antigen
* Bulbourethral Glands
* Mucus-Like secretion

Semen consists of: Sperm, Seminal fluid, Prostate Fluid, Bulbourethral fluid

* 2-6mL total/ejaculation
* \~66 million sperm/mL
* Total range: 120-400 million sperm

male repro loop

Anatomy of the female Reproductive System: External Genitalia (Vulva)

* Opening of the vagina = vestibule
* Urethral opening
* Labia minora and majora
* Clitoris
* Mons pubis

Anatomy of the female Reproductive System: Internal Genitalia

* Vagina
* Uterus
* Cervix
* Fallopian tubes
* Ovary
* Site of oogenesis

Uterus

* Body is pear-shaped
* Cervix is cylindrical
* Walls consist of myometrium and endometrium
* Cervical canal
* Entrance for sperm
* Exit for fetus

Accessory Glands

Mammary glands

* lactation

Ovaries

* Site of oogenesis- production of oocyte
* Suspended from pelvic cavity wall and attached to uterus
* Fallopian tube held close, with fimbria hovering over ovary
* Oocytes are released in process of ovulaton

Oogenesis

Begins during development of female fetus

* produces primary oocytes

Process arrests by birth (during meiotic division)

* process resumes at puberty
* one viable oocyte per 28 days
* process is lost by menopause

The Ovarian Cycle

Repeating cycle divided into two parts, separated by ovulation

* Follicular phase
* Luteal phase

The Ovarian Cycle: Follicular phase

* Growth of follicle
* Resumption of meiotic divisions
* One of several develops to ovulation
* Characterized by rising levels of estrogen
* High estrogen triggers LH surge, resulting in ovulation

The Ovarian Cycle: Luteal phase

* high LH concentration triggers luteinization of follicular remnants
* characterized by progesterone secretion

The Uterine Cycle

* Correlates w/ the Ovarian Cycle
* Hormones produced by ovary drive uterine changes
* **Estrogen** promotes endometrial lining thickening and development of glandular tissues and vessels (proliferation)
* **Progesterone** promotes glandular secretion (secretory) and maintenance of the endometrial lining and vessels. Also, inhibits myometrial contractions
* Withdrawal of E and P triggers **menses** (the shedding of the thick endometrial lining)
* Prostaglandin production promotes vasoconstriction

Correlation between Ovarian and Uterine Cycles

The Human Response Cycle

* Excitement/ Arousal phase
* Plateau Phase
* Orgasmic Phase
* Resolution Phase

Male Sex Act

Sexual Response cycle

* Excitement phase
* Excretion and increase sexual awareness
* Plateau phase
* increase HR, increase BP, increase Resp. Rate, increase muscle tension
* Orgasmic phase
* Ejaculation
* emission
* delivery of prostatic, sperm, and sem. ves. fluids into urethra
* Expulsion
* Semen in urethra → sk. muscle contraction in base of penis
* increase sexual excitement → collective experience of intense physical pleasure
* Resolution
* refractory period
* return to pre-arousal state

Female Sex Act

Sexual response cycle

* excitement phase
* plateau phase
* Orgasmic phase
* Resolution

Female Sex Act: Sexual Response cycle: Excitement phase

* Erection and ↑ sexual awareness
* Nipples erect, breasts enlarge
* “sex flsh” → ↑ blood flow through skin

Female Sex Act: Sexual Response cycle: Plateau phase

* ↑ HR, ↑ BP, ↑ Resp. Rate, ↑ muscle tension, vasocongeston in vagina → ↓ vaginal capacity
* Tenting effect
* Uterus raises, lifting cervix

Female Sex Act: Sexual Response cycle: Orgasmic phase

* Rhythmic contractions of pelvic musculature
* 0.8 second intervals
* ↑ sexual excitement → collective experience of intense physical pleasure

Female Sex Act: Sexual Response cycle: Resolution

* No refractory period → repeated orgasms
* up to 12 successive organisms
* Return to pre-arousal state

Lubrication

* Vasocongeston → forces fluid into vaginal lumen
* Mucus secretion from vestibular glands (outer vagina)
* Mucus from male

Fertilization: Primary site = ampulla

Oviduct cups around ovary

* Fimbriae “sweep” ovulated oocyte into lumen
* Cilia contribute
* Peristaltic contractions and ciliary action move oocyte toward ampulla

Fertilization: Sperm transport

* Cervical mucus thins (↑ E2)
* For 2-3 days
* Dispersal via uterine contractions
* Retrograde peristalsis
* Possible chemotaxis