PHGY 216 Midterm Exam - Modules 1-3

MODULE 1 - Endocrine Physiology

Section 01: Principles of Endocrinology

Endocrine is comprised of many different glands
Major regulatory system
Glands = A specialized cell, group of cells, or organ that secretes substances to be used by or eliminated from the body.
Hormones = chemical substances secreted into the blood that exert a physiological effect

6 main functions of the endocrine system:

Maintain a constant internal environment via regulation of metabolism and water/electrolyte balance
Adaptive stress response
Growth and development
Reproduction
Red blood cell production
Integrating with the autonomic nervous system in regulating both the circulation and digestive functions

Hydrophilic and Lipophilic hormones

Hydrophilic hormones: highly water soluble, low lipid solubility, unbound to carrier molecules. Tend to be peptides or proteins, and even amines.
Types of amine hormones = catecholamines and thyroid hormones
Lipophilic hormones: highly soluble in lipids, low water solubility, and require a carrier molecule. Include the amine thyroid hormones and the steroid hormones.
Hormones are dynamically unbinding and rebinding at any moment.

Dissolved in Plasma = Peptide Hormones
Bound to Carrier Molecules or Proteins = Steroid and thyroid hormones
Both = Catecholamines

Hydrophilic Hormone synthesis steps:

Synthesis = Large precursor proteins called preprohormones are synthesized by ER ribosomes
Packaging = When travelling through ER and Golgi complex, the preprohormones are processed into active hormones and packaged into secretory vesicles
Storage = The hormone-containing secretory vesicles can be stored until the cell receives the signal
Secretion = The signal triggers exocytosis of the vesicle, which releases the hormones

Lipophilic Hormone synthesis:

**Cuz steroid hormones are so lipophilic, they are not stored but released while being synthesized.

Free lipophilic diffuses across the membrane to interact with receptors
The receptor complex (H-R) binds to hormones in the DNA
Binding to DNA activates genes and produces mRNA
mRNA leaves nucleus
mRNA binds to a ribosome and proteins synthesize
The synthesized proteins lead to the cellular response of the hormone

Peptide hormone and catecholamines:

Binds to the receptor surface

Activates second messenger systems
Amplifies initial signal
Cyclic AMP (cAMP) and Calcium second messenger systems

Steroid and thyroid hormones:

Pass through the plasma and nuclear membranes
Produces effects by regulating gene transcription and protein synthesis

Section 02: Hypothalamic-Pituitary Axis

Pituitary gland = small gland in a bony cavity in the skull
Posterior pituitary gland = neural-like tissues, also called neurohypophysis. Connected to the hypothalamus via neural pathways.
Anterior pituitary gland = glandular epithelial tissues, also called adenopophysis. Connected to hypothalamus via hypothalamic-hypophyseal portal system.

Growth Hormone (GH): body growth and metabolism
Adrenocorticotropic Hormone (ACTH): stimulates secretion of cortisol
Luteinizing Hormone (LH): In males testosterone, in females estrogen and progesterone. Also responsible for ovulation.
Thyroid-Stimulating Hormone (TSH): stimulates release of thyroid hormones
Follicle-Stimulating hormone (FSH): In females, stimulates growth of ovarian follicles. In males, sperm production.
Prolactin (PRL): not tropic. In females, breast development and milk. In males, but physiological purpose not clear…

Hypothalamus = controls hormone release

In the posterior pituitary lobe, it contains supraoptic and paraventricular nucleus. Axons project down the pituitary stalk.
In the anterior pituitary lobe, the hypothalamus secretes hormones into the portal where they are carried to the anterior PL, which inhibits or promotes the release of hormones
Can monitor the blood and respond to circulating chemicals
Stress and emotion can lead to hypothalamic hormonal release
Involved in a three-hormone hierarchic chain of command
In response to stress, the hypothalamus increases its secretion of CRH
CRH then stimulates the anterior pituitary to release ACTH
ACTH then acts on the adrenal cortex to release cortisol
Cortisol then acts in a negative feedback fashion to reduce the secretion of regulatory hormones from the hypothalamus and anterior pituitary

Vasopressin = enhances the retention of water by the kidneys and causes contraction of the arterioles
Oxytocin = stimulating the contraction of uterine smooth muscle cells during birth and promoting milk ejection
Tropic hormones = Once released, these hormones stimulate other endocrine glands to release their hormones

Hypothalamic-Hypophyseal Portal System (H-HPS)Steps:

Hypophysiotropic hormones produced by neurosecretory neurons in the hypothalamus enter in hypothalamic capillaries
The hypothalamic capillaries join together to create the H-HPS, a link to the anterior pituitary
Portal system branches into the capillaries of the anterior pituitary
The hypophysiotropic hormones control the release of anterior pituitary hormones
When stimulated by the hormone the anterior pituitary secretes a given hormone into these capillaries
The anterior pituitary capillaries rejoin to form a vein, through which the anterior pituitary hormones leave for distribution in the body by circulation

Regulation of Anterior Pituitary

Thyrotropin-Releasing Hormone (TRH): Stimulates the release of TSH and prolactin
Gonadotropin-Releasing Hormone (GnRH): Stimulates the release of FSH and LH
Growth Hormone Inhibiting Hormone (GHIH): Inhibits the release of growth hormone and TSH
Corticotropin-Releasing Hormone (CRH): Stimulates the release of ACTH (corticotropin)
Growth Hormone Releasing Hormone (GHRH): Stimulates the release of growth hormone
Prolactin-Releasing Hormone (PRH): Stimulates the release of prolactin
Prolactin-Inhibiting Hormone (PIH): Inhibits the release of prolactin

Section 03: The Thyroid Gland

The thyroid gland is located over the trachea just below the larynx.
Consists of 2 lobes (no difference between the lobes, the entire gland serves the same function)
Thyroid gland cellular structure: Follicular cells are arranged to form hollow spheres throughout the gland. The gland contains C cells that secrete calcitonin. It also contains the colloid, which is made up of proteins and stores the thyroid hormones.

Thyroid hormones

The two hormones exert the same physiological effect (but dif speeds and intensities)
Tertaiodothyronine = 4 iodine molecule, 90% of the hormones secreted
Triiodothyronine = 3 iodine molecules, 10% secreted
The body needs 1 mg of iodine a week to ensure sufficient levels of thyroid hormone
Thyroid gland extracts iodine from the blood

Synthesis of thyroid hormones

Thyroglobulin is produced in the follicular cell by the ER-Golhi complex and taken to the colloid by exocytosis
Iodide is taken up by follicular cells (iodide trapping).
Iodide is then transferred into the colloid of the follicular lumen
Iodide is converted into a highly reactive state which attaches to tyrosine (iodide organification). This attachment produces monoiodotyrosine and a second diiodotyrosine.
A coupling process that combines MIT and DIT to form the thyroid hormones. Either one MIT and one DIT (T3) OR two DITs (T4) couplings. (No coupling of two MITs)

Release of thyroid hormones

The follicular cells engulf a portion of the thyroglobulin-containing colloid by phagocytosis and create hormone-filled vesicles
The lysosomes fuse with the vesicles and digestive enzymes release the MIT, DIT, T3 and T4.
The T3 and T4 immediately cross the plasma membrane to the blood where they bind to plama proteins.

Effects of thyroid hormones

Metabolic rate and heat production: increases metabolic rate and heat production
Intermediary metabolism: influences enzymes in fuel metabolism, the effect differs in terms of the amount of thyroid hormone present.
Sympathomimetic: increase a target cell’s response to catecholamine
Cardiovascular system: increase both heart rate and strength of contraction to increase cardiac output
Growth: stimulates the release of both growth hormone and insulin-like growth factor

*The release of both TSH and TRH are under negative feedback control

Hypothyroidism

Hypothyroidism = low thyroid or underactive thyroid, a disorder of the endocrine. Occurs when the thyroid gland does not secrete enough thyroid hormone into the blood.
Primary failure of the thyroid gland = dysfunction originating in the endocrine gland itself (Hasimoto’s thyroiditis)
Secondary failure of the thyroid gland = occurs when the hypothalamus and/or pituitary fails to secrete enough TRH and/or TSH. Low levels of T3 or T4.
Inadequate dietary supply of iodine = low T3 and T4 and elevated TSH. (most common)
Common symptoms = cold intolerance, slower reflexes, reduced mental alertness, easy to fatigue, slow weak heart rate, weight gain

Hyperthyroidism

Hyperthyroidism = increased levels of thyroid hormone
Secondary to excess hypothalamic or anterior pituitary secretions = are generally observed when there’s a tumour in the hypothalamus or in the anterior pituitary.
Thyroid tumour = a tumour in thyroid gland itself, increased thyroid hormone secretion (T3 and T4), decreased TSH
Graves’ disease = autoimmune system disease in which the body produces a long-acting thyroid stimulator that targets and activates TSH receptors
Common symptoms = increased HR, excessive heat, muscle weakness, mood swings, elevated basal metabolic rate

*** Goiter = a symptom from both hypo and hyperthyroidism. It’s an enlarged thyroid gland.

Section 04: The Adrenal Glands

Located at the top of kidneys
They are two endocrine organs
Outer layers are called the cortex → Secretes steroid hormones
Inner layer is called the medulla → Secretes catecholamines

Adrenal Cortex

Has 3 zones = zona glomerulosa, zona fasciculata and zona reticularis
Mineralocorticoids = influence electrolyte balance (zona glomerulosa)

Without this, we would die in days because of circulatory shock
The most common one produced is aldosterone

Glucocorticoids = glucose, lipid & protein metabolism (zona zona fasciculata & reticularis)

Is a cortisol
Produces glucose from non-carb precursors
Inhibits glucose uptake by mot tissues and breaks down lipid stores for fuel
Plays a key role in the adaptation to stress
Under negative feedback regulation involving the hypothalamus and anterior pituitary
Cortisol has a diurnal pattern (high during day, low at night)
Stress can override the normal patterns of cortisol secretion

Sex hormones = similar to hormones in gonads (zona zona fasciculata & reticularis)

Androgens → Male sex hormones (in testes)
Estrogen → Female sex hormones (in ovaries)
Adrenal cortex secretes low levels of androgen and estorgens
The most important one is dehydroepiandrosterone (DHEA), its responsible for growth of hair, and sex drive in women

Adrenal Medulla

Catecholamines are synthesized by the adrenomedullary secretory cells
With proper stimulation, the granules undergo exocytosis to release epi and norepi into blood
Norepi binds to Beta1 receptors near postganglionic sympathetic nerve terminals
Epinephrine = hormone and neurotransmitter

Epi binds to all alpha and Beta1 & 2 receptors
Causes increased heart rate, the strength of contraction, increased cardiac output, dilation of the respiratory airways to increase oxygen intake
Also has effects on carbs and fat metabolism
Enhances liver glycogenolysis

Stress response

Sympathetic Nervous System & Spinephrine: permits the body to overcome anything from preventing escape from the situation.

Increased muscle strength, mental activity, blood pressure, cellular metabolism and blood flow.

Insulin and Glucagon: increases blood glucose, breaks down glycogen stores to produce glucose and decreases insulin secretion.
CRH-ACTH-Cortisol System: involved in the integrated stress response

Increases blood levels of glucose, fatty acids and amino acids to provide energy
It may play a role in resisting stress

Renin-Angiotensin-Aldosterone System: Increases blood pressure

During stress, there’s an increase in vasopressin and angiotensin II, which help increase blood pressure in emergencies

Hyperadrenalism

Hyperadrenalism = when the adrenal glands secrete excessive hormones

Cortisol hypersecretion = occurs during overstimulation of the adrenal cortex by CRH/ACTH

Increase in circulating cortisol and plasma glucose
Physical features: “buffalo hump” and moon face

Adrenal androgen hypersecretion = symptoms depend on age and sex

Adult females → masculine body hair, possible deepening of voice, more muscular, breast size decrease, period stops
Adult males → little to no effects
Newborn females → male-type external genitalia, clit enlarges and looks like a pp
Pre-puberty males → precocious pseudo-puberty

Hyperaldosteronism = excessive mineralocorticoid secretion either by an aldosterone-secreting tumour or abnormally high activity of the renin-angiotensin-aldosterone system

Adrenocortical insufficiency

If you were to lose 1 adrenal gland, the other would undergo hypertrophy and hyperplasia

Primary adrenocortical insufficiency: under-secreting caused by autoimmune destruction
Secondary adrenocortical insufficiency: problem in the hypothalamus or anterior pituitary gland, characterized by reduced ACTH and cortisol deficiency

Common symptoms = severe fatigue, vomiting, irritability, nausea depression, etc…

Section 05: Endocrine Control of fuel Metabolism

Metabolism = sum of all chemical reactions that occur in all organisms
Anabolic reactions = synthesis of larger organic molecules from smaller organic molecules (used for repair growth and storage.
Catabolic reactions = breakdown of larger organic molecules into smaller molecules.

Storage and energy sources

Excess glucose, stored in liver and skeletal muscle (stored as glycogen)
Excess fatty acids, stored in adipose tissues (stored as triglycerides)
Excess amino acids, used for proteins or converted to glucose and fatty acids

Glycerol → comes from the backbone of triglycerides and can be converted to glucose
Lactic acid → formed by glycolysis and can be converted to glucose
Ketone bodies → produced in the liver in times of glucose shortages

Metabolic states

Absorptive state → anabolism dominates (as ingested food is digested and absorbed in circulation)
Postabosrptive state → catabolism dominates (hours after ingesting food, becomes energy source)

The pancreas

Both endocrine and exocrine functions
The endocrine functions of the pancreas are localized to the islets of Langerhans, which are clusters of cell found in the pancreas

Alpha cells: produce and secrete glucagon
Beta cells: produce and secrete insulin
Delta cells: produced and secrete somatostatin
PP cells: secrete pancreatic polypeptide

Source of somatostatin (produced in the digestive tract and inhibits digestion)

Also released by the hypothalamus (inhibits secretion of GH nd TSH)

Factors that increase blood glucose → glucose absorption from the digestive tract and hepatic glucose production
Factors that decrease blood glucose → urinary excretion of glucose and transport of glucose into cells

Insulin

Insulin = small peptide hormone produced by the pancreas
Insulin secretion has a negative feedback system

Effects on carbohydrates:

Increase the uptake of glucose into most cells
Inhibit glycogenolysis in the liver
Stimulate glycogenesis in skeletal muscle and the liver
Inhibit gluconeogenesis in the liver

Effects on fats:

Increase GLUT-4 recruitment to increase glucose uptake
Enhances the activity of the enzymes in triglyceride synthesis
Enhances the entry of fatty acids in fat tissue cells
Inhibits lipolysis

Effects on Proteins:

Promotes the uptake of amino acids
Enhances the activity of the enzymes involved in protein synthesis
Inhibits the degradation of proteins

Glucagon

Glucagon = major pancreatic hormone involved in the postabsorptive state

Effects on carbohydrates:

Increases hepatic glucose by decreasing glycogen synthesis
Enhances both glycogenesis and glycogenolysis

Effects on fats:

Promotes lipolysis
Inhibiting fat storage
Enhances the formation of ketone bodies in the liver

Effects on Proteins:

Promotes protein catabolism in the liver

Section 06: Growth and Calcium Metabolism

Two main periods of rapid growth

First two years of life
Puberty

Growth in males and females is supported by GH (most abundant) and androgens

Growth hormones

GH is mediated through other peptides known as somatomedins aka IGFs
IGF-I

GH stimulates the synthesis and release of IGF-I
Primarily in the liver
May have paracrine actions
Mediates most of the growth-promoting actions of growth hormone

IGF-II

GH doesn't stimulate the production of IGF-II
Important during fetal development
Produced in adults

GH also has a diurnal pattern of secretion
Negative feedback loops participate in the regulation of GH secretion
If there is a GH deficiency during childhood, the result is dwarfism
If excess GH occurs in childhood the result is gigantism.
Acromegaly = marked coarsening of the jaw and cheekbones, the hands and feet enlarge, and extremities become thickened

Metabolic actions ofGH

Increased rate of protein synthesis
Increased fatty acid mobilization and use
Decreased rate of glucose use by body tissues

Soft tissue actions of GH

Increase the number of cells (cell division)
Increase cell size by promoting protein synthesis

Bones

Highly vascularized and dynamics; always being remodelled because of osteoblasts and osteoclasts
Osteoblasts = deposit new bone
Osteoclasts = dissolve bone
Bone growth in thickness:

Adding new bone to the outer layer of existing bone (osteoblasts)
While osteoclasts remove bone on the inside so that the marrow cavity increases

Bone growth in length:

Only occurs at the ends between the knob at the bed and the shaft of the bone
Cartilage-forming (chondrocytes) cells stack onto each other (causing the bone to elongate)
Osteoclasts then remove the dead chondrocytes and the calcified matric and start depositing bone through ossification
At the end of adolescence, sex hormones cause the plates to completely ossify

Calcium

Calcium is under hormonal control
Can be ingested bu generally stored in bones
3 hormones that regulate calcium concentration = PTH, Calcitonin and Vitamin D
Parathyroid hormone (PTH): hormone secreted by parathyroid glands

4 small glands on the back of the thyroid gland
Essential for lids
In the kidneys, PTH stimulates reabsorption
The release of PTH increases in response to decreasing plasma concentrations

Calcitonin: secreted by the thyroid gland

Acts on osteoclasts to decrease their activity
Prevents the release of calcium from the bone

Vitamin D

Functions as a hormone, it can be produced by the skin
Activated by two subsequent steps, the first occurs in the liver and the second in the kidneys, the setos add a hydroxyl group to the compound
Increases calcium absorption in the intestine

MODULE 2 - Reproductive Physiology

Section 01: Introduction to Reproductive Physiology

Gametes = Reproductive, or germ cells, each containing a half set of chromosomes
Gonads = Wheee the gametes and primary sex hormones are produced

Females → ovaries
Males → testes

Male reproductive functions

Production of sperm (happens in the testes)
Delivery of sperm (happens during sex)

Female reproductive functions

Production of eggs (happens in the ovaries)
Reception of sperm (happens in the vagina)
Transport of ovum and sperm to a common site for fertilization (happens in fallopian tubes)
Maintenance of the developing fetus (happens in the uterus
Birth of baby
Nourishing the baby by milk production

Sexual differentiation

Sexual differentiation = embryonic development of both external genitalia and reproductive tract
Genetic → sex is determined by the combination of sex chromosomes at conception
Gonadal → sex is determined by the presence or absence of a Y chromosome
Phenotypic → apparent anatomical sex is dependent on the gonadal sex
For the first 3 weeks of gestation, the reproductive systems of male and female embryos are identical
Testosterone stimulates the Wolffian ducts which develop into the male reproductive system
Testosterone is then converted into dihydrotestosterone (which develops the male external genitalia)
In the absence of testosterone, the wolffian ducts degrade and the mullerian ducts develop into the female reproductive tract and external genetalia.

Section 02: Male Reproductive Physiology

In most males, the testes will descend into the scrotum in the last months of fetal life
If they don’t ever descend, this could result in sterility
The location of the testes is physiologically important to spermatogenesis
When balls are cold, the cremaster and dartos muscles contract to lift the balls closer to the body

Testosterone

Effects before birth = masculinization of the reproductive tract, genitalia, and dropping of balls
Effects on sex-specific tissues after birth = promotes spermatogenesis, and maturation of the reproductive system
Other reproductive effect = develops a sex drive at puberty and controls the secretion of GTH
Effects on secondary sexual characteristics = voice deepens, body hair, muscle growth
Non-reproductive actions = promote bone growth, may induce aggressive behaviour

Spermatogenesis

Spermatogenesis = process in which diploid primordial germ cells are converted into motile sperm cells (haploid)
Mitotic proliferation = continuously dividing to create new germ cells, the sperm-forming daughter cell will undergo mitotic divisions twice more to produce 4 identical primary spermatocytes
Meiosis = forms 2 secondary spermatocytes. For each spermatogonia, 16 spermatids can be produced
Packaging = maturation of spermatids into spermatozoa, stripped down of all non-essentials (cytosol and most organelles)

Spermatozoa

Head = consists of the nucleus
Acrosome = Enzyme-packed vesicle at the tip of the head that is needed to penetrate the egg
Midpiece = Packed full of mitochondria to provide energy for locomotion
Tail = movement of this provides propulsion

Function of Sertoli cells

Forms the blood-testes barrier
Nourish sperm cells
Absorbe developing sperm cytoplasm and remove defective germ cells
Secrete seminiferous fluid into the lumen to flush released sperm into the epididymis for storage
Secrete androgen-binding protein that helps to concentrate testosterone in the lumen
The site of action of testosterone and FSH to regulate spermatogenesis

Epididymis and ductus deferens:

After sperm is produced, they are psuhed into the epididymis
The epididymal ducts from each testis converge to form the ductus deferens
The ductus deferens empties into the urethra

Male accessory sex glands

Semen = a mixture of accessory gland secretion and sperm
Seminal vesicles = Their purpose is to provide the bulk of the semen
The prostate gland = secretes an alkaline fluid to neutralize the acidic environment of the vagina and secretes clotting enzymes which helps it stay in the female reproductive tract
Bulbourethral glands = secrete a clear substance during sexual arousal (helps lube the urethra)

Section 03: Female Reproductive Physiology

Oogensis

Oogenesis = the steps of ova formation
Prenatal = Oogenesis begins in the female fetus around seven weeks into gestation. Primordial germ cells, which later become oogonia, colonize the ovary.
Antral = During each menstrual cycle, secondary follicles develop under the influence of hormones. Fluid-filled spaces between granulosa cells merge to form a central fluid-filled space called the antrum.
Pre-ovulatory = The follicle prepares to release an egg.
Ovulation = An egg is released from a mature follicle on the ovary's surface.
Fertilization = If fertilization occurs, the sperm penetrates the zona pellucida surrounding the ootid. The sperm and ootid cell membranes and haploid pronuclei fuse to produce a diploid zygote. If fertilization doesn't occur, the secondary oocyte degenerates and is expelled during menstruation

Cycles

Two cycles → the ovarian and uterine cycles
The ovarian cycle:

At the beginning of puberty, it alternates between the follicular phase and the luteal phase
Follicular phase = prepares a mature egg (lasts the first 14 days)

Begins proliferation of granulosa cells, divide to form layers around the oocyte
Primary follicle forms (zona pellucida)
As it gets bigger, it becomes a secondary follicle (secretes estrogens)
Antrum is formed
The follicles develop into a mature follicle and undergoes mitotic division
Ovulation occurs and the ovum is released

Luteal phase = prepares the reproductive tract for potential implantation

The remaining follicular cells form the corpus luteum, very active in secreting hormones like progesterone
If the egg is not fertizlized and implanted, it forms the corpus albicans

Lasts about 28 days
The LH surge:

Stops estorgen synthesis by follicular cells
It initiates meiosis in the oocyte
Triggers release of local factors that increase the swelling of the follicle and weaken the wall
It differentiates the follicular cells into luteal cells

The uterine cycle:

Lasts around 28 days
The uterus is prepared for the possible implantation if fertalized egg, if it doesnt happen the uterus is stripped clean for the next cycle
Myometrium = an outerlayer comprised of smooth muscle
Endometrium = inner lining that is highly vascularized and also has many glands
The 3 phases:

Menstrual phase = Protaglandins constrict the blood supply to the endometrium and causes the myometrium to contract. The endometrial lining is then expelled through the vagina
Proliferation phase = begins when period stops. Ovulation occurs during this phase, the egg leaves the ovary and travels through the oviduct towards the uterus
Secretory phase = Large amounts of prgestoerone and estorgen covert the endometrium into a highly vascularized and glycogen filled tissue to support early embryo.

Hormones in females

Progesterone = causes changed in the uterine lining to preparte for potential implantation if an embryo to establish pregancy
LH = Important in the production of estorgen which is secreted in increasing quantities by the secondary follicles
Estrogen = Exerts a positive feedback action to cause a surge in LH secretions
FSH = Important for stimulatring ealy follicular development and formation of the sefcondary follicle
Inhibin = Inhibit the production of LH and FSH by the pituitary gland

Endometriosis

A disorder in which the endometrium grows outside the uterus
Commonly growth on the ovaries, fallopian tubes and ligaments stabilizing the uterus and ovaries

Menopause

The end of reproductive capacity
The cycle continues until the age of 45-55
Without monthly follicular development, estorgen secretion decreases
This can affect the skeletal and cardiovascular systems
After menopause, osteoclast activity increases which can cause osteoporosis

Section 04: Sexual Intercourse between Males and Females

Sexual intercourse is the delivery of the sperm into the vagina

Males during intercourse

The male sex act involved two components: erection and ejaculation
The erectile tissue of the penis is made up of 3 columns of sponge like spaces (corpora cavernosa
During arousal, the arterioldes that supply these vascular spaces dilate (hard pp)
Thoughts about sex or stimulation f mechanoreceptors in the glans penis cause an erection (spinal reflex)

Inhinuts the sympathetic supply tp the penile arterioles
Activates the parasym;athetic supply to penile arterioles to cause vasodialation via NO-mediated mechanism
Activates the parasympathetic supply to the bubourethral glands to secrete mucus for lubrication

Erectile dysfunction = inability to obtain and maintain an erection rigid enough for sex
Ejaculation is rthe result of a spinal reflex, and mediated by the same tactile and psychological stimuli that cause an erection

Emission = Increased sympathetic activity causes smooth muscle contractions in the prostate. The timing id coordinated so that sperm, prostatic fluid and sminal vesicle fluid is released into the urethra.
Expulsion = The filling of the urethra with semen triggers the activation of skeletal muscles at the base of the penis. The pressure increases and forcibly expels the semen.

Sexual Response Cycle:

Excitement phase: heightened sexual awareness and erection
Plateau phase: more generalized reponses such as increased heart rate, blood pressure, and respiratory rate
Orgasmic phase: ejaculation as well as other physical and emotional responses
Resolution phase: the return of the body to its pre-arousal stage

Female sexual response

Excitement = stimulation of clit activates a spinal reflex that activates the parasympathetic system to dilate through the vagina and external genitalia. Nipples also erect. Secretions from Batholin’s gland serve as a lubricant for sex.
Plateau = uterus raises upwards, lifting the cervix and enlarging the upper portion of the vagina. Breathing, heart rate and blood pressure all increase.
Orgasm = If erotic stimulation continues, the sexual response culminates in orgasm. No female equivalent to ejaculation
Resolution = heart rate, blood pressure and breathing return to normal. Marked by a general sense of well-being, enhanced intimacy and often fatigue.

Section 05: Fertilization, Pregnancy, Parturition, and Lactation

Fertilization

Egg transport to the oviduct

The fimbriae guide the egg into the oviduct and then peristaltic contractions move the egg to the ampulla

Sperm transport to the oviduct

The cervical canal is the first barrier (heavy mucus)
High levels of estrogen cause the mucus to become thin enough for passages
Once in the uterus, myometrial contractions push the sperm into the oviducts

Fertilization

Sperm must penetrate both the corona radiata and the zona pellucida
The first to reachthe egg fuses with it’s membrane, the egg hardens so that no other sperm can penetrate it
Within an hour of fertilization the sperm and nuclei have fused and it is now a zygote

Implantation

The zygote remains in the ampulla for a few days (mitotic division occurs)
Corpus leuteum secretes a lot of progesterone to relax the oviduct and move the zygote to the uterus
The zygote floats around for a bit, then sticks to the side of the uterus

Ectopic pregnancy

A fertilized egg implants itself outside of the main uterine cavity
Most often occurs in the fallopian tubes

The placenta

Used to exchange maternal and fetal blood
4 weeks → embryo is completely embedded in the endometrial tissue (helps the development of the placenta)
8 weeks → Placenta not fully developed but well established
12 weeks → Maternal blood supply to placenta is complete, it has developed all the necessary structures to support the embryo
40 weeks → The placenta continues to grow throughout pregnancy. It functions as the digestive system, respiratory system and the kidneys of the fetus. Nutrient exchange occurs in the placenta.
The placenta is active in secreting hormones

Human Chorionic Gonadotropin = first hormone to be secreted by the placenta. Stimulates and maintains the corpus luteum. The primary source of estrogen and progesterone. This hormone is used to detect pregnancy (preggo test).
Estrogen = placenta takes the DHEA and converts it into estrogen
Progesterone = hormone secretion is proportional to the placenta’s mass. It maintains the cervical mucus plug, stimulates milk glands and suppresses uterine contractions

Parturition (childbirth)

Requires dilation of the cervical canal where the baby will be birthed
During early gestation, estrogen levels are fairly low but progressively increase to prepare both the cervix and uterus for delivery
Oxytocin is a hormone released by the posterior pituitary which helps with uterine contractions
As estrogen levels increase the uterine reponseivness to oxytocin to the point where contractions start (positive feedback cycle)
The pressure of the fetus head on the cervix helps it open and creates even more oxytocin

Lactation

A breast prepared for lactation has a network of ducts that branch ouy from the nipple and get smaller until they terminate in lobules
The lobules are epithelial-lined milk-producing glands
Milk is made in the epithelial cells and secreted into the alveoli
Estrogen → promotes the development of milk-collecting ducts
Progesterone → stimulates the formation of alveolii
Prolactin and hCG → stimulate the synthesis of enzymes necessary for milk production
Suckling = milk production and ejection happen in response to the suckling reflex
Hypothalamus = infant’s suckling of the nipple activates afferent nerve endings to the hypothalamus
Posterior pituitary = release of oxytocin
Oxytocin = responsible for milk ejection
Contrapception of myoepthelial cells surrounding alveoli = milk is forcibly ejected
Prolactin-inhibiting hormone decreases, prolactin-releasing hormone increases
Prolactin = released from the anterior pituitary
Secretion by alveolar epithelial cells = triggers the alvelolat epithelial cels to replace ejected milk

MODULE 3 - Respiratory Physiology

Section 01: Introduction to Respiratory Physiology

External respiration = involves all of the processes that bring oxygen into the body

Ventilation: Aire is moved in and out of the lungs (breathing)
Exchange of O2 and CO2 between Air and blood : diffusion of O2 from the alveoli to the pulmonary capillaries and the movement of CO2 in the opposite direction
Transport of O2 and CO2: transport of O2 to the tissues
Exchange of O2 and Co2 between blood and tissues

Anatomy

Lungs

Upper tract = Nose, nasal cavities, pharynx and larynx

Pharynx - A common tube for breathing and the digestive system
Larynx - Location of vocal chords

Lower tract = Trachea, left and right bronchi, bronchioles and alveoli

Bronchi - each supplies a lung
Bronchioles - some gas exchange can occur
Alveoli - Air sacs where the majority of gas exchange happens

Convective flow = requires energy in the form of muscle contraction to m maintain airflow
Diffusive flow = occurs passively to allow air to flow into the alveoli
Chest wall - Contains the muscles that rae necessary in generating pressures that allow airflow

Muscles of inspiration: the diaphragm and the external intercostal muscles

The diaphragm descends to enlarge the thoracic cavity
Contractuib if the external intercostal muscles elevate the ribs

Muscles of expiration: Internal intercostal muscles and the abdominal muscles

Only recruited when there is an increase in ventilator demand

Pleural space

It covers the lung and the inside wall of the thorax
Allows membranes to rub against each other during breathing

Respiration

The ability of the respiratory muscles to generate the necessary pressure gradient to move air through the airways and to inflate the lungs
The ability of oxygen and carbon dioxide to diffuse across the alveolar-capillary barrier

PressureResistance = Flow (or diffusion)

The pressure gradient is used to overcome the elastance or stiffness of the respiratory system

Section 02: Mechanics of Breathing

Pressures

PB (Atmospheric pressure) = there is not enough difference between the height of the lungs and nose, so we treat it as 0
PA (alveolar pressure) = at the end of inspiration, it’s the same as PB
Ppl (pleural pressure) = negative to atmospheric pressure, cuz the lungs want to collapse yet the chest wall wants to expand
Ptp (transpulmonary pressure) = difference between the alveolar and pleural pressure

Elastin fibres = arranged in a meshwork that enhances their elastic behaviour

When the lung is stretched, this elastic recoil causes the lung to deflate

Surface tension = force exerted by the liquid lining the inside of the alveoli

The liquid layer resists any forces that try to increase its surface area
The surface area of liquid shrinks as much as it possibly can

** IF the surface liquid was water alone, the alveoli would collapse and the force (pressure) required to open them upon inspiration would be much greater.

Pulmonary Surfactant

Complex mixture of lipids and proteins secreted by type II alveolar cells
Help disperse water molecules
It decreases the effort needed for inflation
Reduced the surface tension of smaller alveoli
Small alveoli secrete more surfactant

Alveoli Interdependence

If one alveolus starts to collapse, it is supported by neighbours (they are stretched by the collapsing alveolus
As the neighbouring alveoli recoil, they pull outwards on the collapsing ones
This prevents the alveolus from collapsing

Law of LaPlace

The magnitude of the collapsing pressure is directly proportional to the surface tension and inversely proportional to the radius of the alveoli.

Collapsing pressure (P) = Surface tension (2T)Alveolar radius (r)

Alveolar Pressure

Equations:
Alveolar pressure (PA) -Pleural Pressure (Ppl) = Lung Recoil Pressure (PL)
Lung Recoil Pressure (PL) + Pleural Pressure (Ppl) = Alveolar Pressure (PA)

Inhalation VS Exhalation

The result of changes in pleural and alveolar pressure
Before (onset) inspiration - no flow, because alveolar pressure = atmospheric pressure

There is an increased resistance to flow that the pleural pressure most overcome

During inspiration - a pressure gradient is established
After inspiration - the contraction of inspiratory muscles decreases
Onset expiration starts when the contraction of inspiratory muscles stops

Lung recoil pressure is now greater than pleural pressure
Air flows from the lungs until alveolar pressure equals atmospheric pressure
Activation of expiratory muscle is not necessary for normal expiration due to strong recoil forced

Active exhalation = emptying the lungs faster or more forcefully

Activation of expiratory muscles reduces the end-expiratory lung volume, which increases the tidal volume independent of the inspiratory muscles
To forcefully breathe out, alveolar pressure must be increased by more than is accomplished by decreased excitation of inspiratory muscles of the abdominal wall
As expiratory flow continues, the pressure decreases because of lost energy

Pressure-Volume Relationship

Shows the difference in pressure, volume and lung volume through the cycle of breathing
PL = As lung volume increases, its PL increases from about 0 to 30 at total capacity
PW = The chest wall pressure acts more like a spring, the compressed spring exerts negative pressures, yet at 100% capacity, the chest wall (now a stretched spring) wants to collapse
Prs = Pressure-volume relationship of the respiratory system (we combine PL and PW)

Compliance

The ability of the lung to stretch so at functional residual capacity
The amount of work or pressure needed to either inhale or exhale
Low compliance = more pressure is required to move air in or out

Section 03: Dynamics of Flow

Resistance

The primary determinant of resistance is the radius
Flow rate (Q) = Pr48L

Bronchoconstriction

At rest, parasympathetic activity is dominant and promotes bronchoconstriction
Smooth muscle contraction in the bronchioles occurs because ventilator demand is low
It can also occur under the influence of local chemical control (decreased CO2)
Pathological factors: histamine release, excess mucus, airway collapse, edema of the airway walls, and allergy-induced spasm

Bronchodilation

When not at rest, sympathetic activity is dominant and promotes bronchodilation
Allows maximum flow rates with minimal resistance
Direct innervation = nerve terminals release norepinephrine, which activates Beta2-receptors on the bronchial smooth muscle cells
Indirect innervation = epinephrine released from the adrenal medulla circulates through the pulmonary circulation to the airway smooth muscle

Airway resistance + Diseases

Asthma = Chronic inflammatory disease of the airways that causes difficulty breathing

Symptoms: shortness of breath, chest tightness, coughing or wheezing
The triggers for these impairments are varied but frequently involve repeated exposure to allergens, irritants or infection

The airway walls are thickened due to histamine-induced edema
Thick mucus secretion physically blocks the airways
Airway hyper-responsiveness causes spasms of smooth muscles in smaller airways resulting in constriction

Chronic Obstructive Pulmonary Disease (COPD) = a term used to cover both emphysema and chronic bronchitis

Caused by long-term cigarette smoking

Chronic bronchitis = long-term inflammatory condition of lower airways

Usually caused by chronic exposure yo cigarette smoke, allergens or air pollution
Airways become narrowed due to edema of the airway walls and secretion of a thick mucus

Emphysema = Irreversible condition characterized by the collapse of the smaller airways and breakdown of alveolar tissues.

In choric exposure to cigarette smoke, alveolar macrophages release substances like trypsin as a defensive mechanism
Excess trypsin and other destructive enzymes destroy the lung tissue

Section 04: Lung Volumes

Lung volumes

Spirometer = a device that measures the volume of air breathed in and out
Tidal volume (VT) = the volume of air entering or leaving the lung during a single breath (500ml)
Inspiratory reverse volume (IRV) = the extra volume of air that can be maximally inspired above the resting tidal volume (3000ml)
Inspiratory capacity (IC) = the max volume of air that can be inhaled starting from the end of a normal expiration (3500ml, VT + IRV)
Expiratory reserve volume (ERV) = the max volume of air that can be expelled starting at the end of a typical tidal volume (1000ml)
Residual volume (RV) = the volume of air remaining in the lungs after max expiration (1200ml)
Functional residual capacity (FRC) = the volume of air in the lungs at the end of passive expiration (2200ml, ERV + RV)
Vital capacity (VC) = the max volume of air that can be expelled during a single breath following a max inspiration (4500ml, IRV + VT + ERV)
Total lung capacity (TLC) = the max volume of air the lungs can hold (5700ml, VC + RV)
Forced expiratory volume in some sec (FEV1) = derived from only the 1st sec of expiratory effort (80%)

During pulmonary function testing, it’s more common to use expiratory data than inspiratory data
In a normal person, flow peaks are around 7 L/s, then decrease in a linear fashion

Respiratory dysfunction

Obstructive Lung disease = cannot exhale as much

FEV1 is lower
FRC and RV values are greater and VC is smaller

Restrictive lung disease = low lung volumes

FEV1 is reduced because the lungs are smaller
FVC is normal because there is no obstruction to airflow

Ventilation

Ventilation = the amount of gas breathed in 1 min
Tidal volume (VT) Respiratory Frequency (f) = Minute Ventilation (VE)
In a typical adult person (500 ml), not all of the inspired air will reach the alveoli (only 350ml will, 150 ml will just stay there)
When we exhale, only 350ml of air is expelled and 150ml is in the airways
With each breath you are rebreathing the air of the anatomical dead space
Anatomical dead space = The voleume of the airways that represents the inspired gas that is unavailable for exchange with pulmonary capillary blood

Work of breathing

During normal quiet breathing, the inspiratory muscles overcome the elastic recoil of the lung and airway resistance
Less than 3% of total body energy is expended during quiet breathing
Work of breathing = the energy expended to inhale and exhale a breathing gas
At lower respiratory rates, the tidal volume must increase.

Increasing tidal volume means the inspiratory muscles are working harder, the elastic work of the lung is higher

At high respiratory rates, the tidal volume can decrease

This reduces the elastic work of the lungs
The flow resistive work of the lung increases

Factors that affect the work of breathing

Decreased compliance = tidal volume decreases and the respiratory rate increases
Increased resistance = when more work is required to overcome the increased flow resistance, seen in COPD and asthma
Decreased elastic recoil = when passive expiration alone cannot expel air from the lungs so the expiratory muscles are recruited, as seen in emphysema
Increased demand for ventilation = occurs during exercise when there are increases in both tidal volume and respiratory rate

Section 05: Gas exchange

Gas exchange

Gas exchange = the diffusion of O2 from the alveoli into the blood, and CO2 from the blood to the alveoli
Pressure gradient is based on the partial pressure of the gas in the alveoli and pulmonary artery and the resistance to diffusion.
Partial pressures = the pressure that would be exerted by one of the gases in a mixture of gases, if it occupied the same volume on its own.
Partial pressure in the air: the greater its partial pressure, the more gas will be driven into the liquid
Solubility in liquid: the more soluble a gas is in a liquid, the more will dissolve
Alveolar air does not have the same composition of inspired air.

Because of these gradients, oxygen will move from the alveoli into the blood until the partial pressures are equalized. The same occurs for carbon dioxide leaving the blood.
How gases are exchanged across systemic capillaries are essentially identical to those in pulmonary capillaries
Tissue metabolism creates the driving force for gas exchange

Concentration of dissolved gases

(Oxygen) Blood leaving the lungs has a concentration of 200 mlO2/L
(Oxygen) Blood returning to the lungs has a concentration of 150 mlO2/L
(Carbon Dioxide) Blood leaving the lungs has a concentration of 480 mlCO2/L
(Carbon Dioxide) Blood returning to the lungs has a concentration of 520 mlCO2/L

Factors Affecting Gas Exchange

Surface Area = The greater the surface area, the greater the amount of gas that can be exchanged

At rest, pulmonary capillaries are closed
During exercise, pulmonary capillaries increase in surface area

Capillary Transit Time = the duration of exposure of capillary blood to alveolar gas

During exercise, it only decreases by 0.4 seconds
Not a limitation to gas exchange

Membrane thickness = Increased thickness results in a decrease in gas exchange

Steps of Gas Exchange

Venous blood entering the lungs is low in O2 and high in CO2
Alveolar air is replaced with fresh atmospheric air during each breath
O2 diffuses into the blood and CO2 diffuses into the alveoli until pressure is equal
Blood leaving the lungs is high in O2 and low in CO2
The blood slowly becomes less oxygenated and more abundant in CO2
O2 diffuses from ythe blood to the tissues/cells, the CO2 from the cells are diffused into the blood tissue cells is low in O2 and high in CO2, the cycle repeats

Section 06: Gas Transport in Blood

Blood, Oxygen, and Hemoglobin

Oxygen is poorly soluble in liquids (plasma)
The solution to this problem is hemoglobin
Hemoglobin = iron-bearing protein within red blood cells that can carry oxygen
The hemoglobin/oxygen reaction is fully reversible. Allows Hb to bind to oxygen for transport and then unbind for delivery

Oxygen Dissociation Curve

Oxygen Dissociation Curve = the relationship between PO2 and % Hb saturation
Plateau portion = 60 mmHg to 100 mmHg

Represents the PO2 range found in the pulmonary capillaries where Hb is collecting O
At high altitudes where PO2 of inspired air is reduced
In O2-deprived environments, the plateau phase of the curve ensures that until your arterial PO2 drops below 60, near-normal amounts of O2 can still be transported to tissues.

Steep portion = 0 mmHg to 60 mmHg

Represents the range of PO2 that is found in the systemic capillaries.
Allows for larger amounts of O2 dissociation for small decreases in PO2.
With decreased atmospheric pressure, there is a decrease in alveolar PO2 and a decrease in arterial PO2.

Factors affecting the Dissociation curve:

pH = Enhances the dissociation of oxygen from hemoglobin (Bohr effect)
BPG = Shifts the dissociation curve to the right
CO2 = When there is an increase in PCO2, the oxygen dissociation curve shifts to the right (Haldane effect), leading to more oxygen unloading
Hb and CO = CO compete with O2 for the same binding site on Hb, shifting the curve to the left, requiring larger drops in PO2 to unload O2 into the tissues.

PO2 and Hemoglobin Saturation

Hemoglobin plays a crucial role in permitting the transfer of large quantities of O2 before blood equilibrates with surrounding tissues
No Hb present = the alveolar PO2 and the pulmonary capillary blood PO2 are at equilibrium
Hb partially saturated = by binding some of the dissolved oxygen, Hb favours the net diffusion of more oxygen down its partial pressure gradient from the alveoli to the blood
Hb fully saturated = the alveolar PO2 and the pulmonary capillary blood PO2 are at equilibrium

Carbon Dioxide

Physically dissolved = more CO2 is transported physically dissolved in the plasma

10x more soluble than O2

Bound to Hb = binds to the globin part of the molecule

Hb without O2 has a greater affinity of CO2
The unloading of O2 in the systemic capillaries enhances the uptake of CO2

As bicarbonate = CO2 combines with water to form carbonic acid, which forms with hydrogen, which creates bicarbonate.

As more CO2 enters the red blood cells, bicarbonate and hydrogen ions accumulate
Red blood cells have a bicarbonate-chloride carrier that allows the exchange of ions
Bicarbonate leaves the cells and chloride enters (Hamburger shift)

Reverse Haldane Effect

Occurs when there are increases in arterial PO2
The increased PO2 prevents the Hb from binding CO2
This forces the CO2 to travel back to the lungs wither dissolved in the plasma ir as bicarbonate
Blood acidity may rise

Gas transport abnormalities

Hypoxia = Insufficient oxygen at the cellular level

Hypoxic Hypoxia = low arterial PO2 with inadequate Hb saturation

Caused by either inadequate gas exchange or exposure to high altitude

Anemic Hypoxia = reduced oxygen-carrying capacity of the blood

This can result from a decrease in circulating red blood cells
This can result from decreased Hb within the red blood cells
This can result from CO poisoning
PO2 is always nirmal but the O2 content of arterial blood in decreased

Circulating Hypoxia = occurs when to little oxygenetaed blood is delivered to the tissues

Usually caused by something that blocks the delivery of blood (blockage or spasms)

Histotoxic Hypoxia = O2 delivery to the tissues is completely normal but something within the tissue presents O2 usage

Cyanide positioning can be a cause

Hyperoxia = Characterized by an abnormally high arterial PO2

Can happen to someone breathing supplemental O2
Can cause oxygen toxicity

Hypercapnia = Excess CO2 in the blood caused by hypoventiliation, results in decreased PO2
Hypocapnia = Below normal arteria PCO2 and is caused by hyperventillation

Can be caused by anxiety, fever, aspirin poisonning or even exercise

Section 07: Control of Ventilation

Central Control of Breathing

Lungs rely on external control to changes that alter the matched intake of O2 and release of CO2
Generation of alternating inspiration/expiration rhythm = this occurs in the medullary respiratory centre that sends its output to the respiratory muscles

Dorsal respiratory group neurons firing causes inspiration and cessation causes expiration
Ventral respiratory group neurons are both inspiratory and expiratory

Regulation of the level of respiration to match metabolism = This is controlled by the brain stem under the influence of receptors involved in respiration
Modulation of respiratory activity for other purposes = may be either voluntary as in speech, or involuntary as in cough or sneezing

Mechanical control of respiratory pattern

There are 2 main classes of receptors → Mechanical and chemical
There are mechanical receptors in the lungs, the diaphragm and the chest wall (rib cage)
Pulmonary Receptors = slowly adapting receptors, rapidly adapting receptors and C-fibres

Slowly adapting receptor = Has endings in the airway smooth muscle, responds to changes in lung volume. Their rate of discharge increases as the lungs inflate
Rapidly adapting receptors = Has endings in larger airways' epithelia and responds to mechanical and chemical stimuli. Activation can cause the airway to narrow and mucus production
C-fibres = Has endings close to the pulmonary capillaries and detect increases in pulmonary ulterior pressure and pulmonary edema. Activation causes bronchoconstriction

Rib Cage Receptors = highly innervated with muscle spindles

Their role in respiration is unclear
The spindles detect discrepancies in actual chest wall distention
The intercostal muscles play a role in posture

Diaphragm Receptors = contains very few mechanical receptors

Has small myelinated and unmyelinated afferents that respond to local metabolic conditions

Chemical Contol of Breathing

PO2 and PCO2 of the arterial blood remain remarkably constant
IF metabolism increases, then ventilation also increases. This is achieved by info about the chemical composition of the blood being sent ti the medullary control centre
Arterial PO2 is monitored by peripheral chemoreceptors in the carotid and aortic bodies.
Carotid chemoreceptors respond to changes in O2 content
Aortic chemoreceptors are relatively insensitive to small changes in arterial PO2, until it drops below 60 mmHg (activation causes an increase in ventilation)
CO2 readily crosses rhe blood-brain barrier so any increase in arterial PCO2 will cause an increase in brain extracellular fluid PCO2
As excess PCO2 is exhaled, the reaction reverses to decrease H+ again
H+ does not readily cross the blood-brain barrier
The effects of increasing H+ are so powerful that they can override voluntary inhibition of breathing

Effects of Exercise on Ventilation

During exercise, alveolar ventilation can increase up to 20-fold, and arterial PO2 and PCO2 generally remain normal
Exercise-induced ventilation occurs very fast
Reflexes Originating from Body Movements:

Muscle mechanoreceptors excited during muscle contraction reflexly stimulate the respiratory centre to increase ventilation
Even minor movements can have a large effect on ventilation rates

Epinephrine Release:

The release from the adrenal medulla stimulates ventilation

Increased Body Temp:

Sweating alone can’t counter the heat generated during exercise so body temp rises slightly
Increasing body temp increases ventilation

Impulses from the Cerebral Cortex:

Motor areas of the cerebral cortex simultaneously stimulate the medullary respiratory neurons and activate the motor neurons of the exercising muscles