Systems Phys 2 Exam 3

Distinguish between the two metabolic states

Absorptive State occurs when nutrients are being absorbed from the GI tract (high nutrient availability) right after eating usually

Postabsorptive state occurs when nutrients are no longer being absorbed and the body uses its stored fuels and catabolism of energy stores

What are the major fates of glucose?

It can be used for energy production via glycolysis and ETC

It can be stored as glycogen in the liver and skeletal muscle as an energy reserve

It can be stored in adipose tissue as fats

What is the role of the liver in the absorptive state?

It takes up glucose from the blood and can convert it into triglycerides which get packaged into Very Low Density Lipoproteins (VLDL)

These particles transport fat in the blood

How are VLDL’s processed

They cannot cross capillaries since they are too large so they are broken down by lipase into fatty acids and monoglycerides to enter the adipose tissue

What are the sources of fatty acids for adipose tissue?

1) Fatty acids synthesized from glucose metabolism

2) Fatty acids from VLDL triglyceride breakdown by lipases

3) Fatty acids from chylomicrons (packaged in lacteal of Small intestine)

What are the sources and function of cholesterol?

It comes from our diet or production in the body and is necessary for plasma membrane composition, steroid hormones and for bile salts

What other lipoproteins exist for cholestrol compared to VLDL and Chylomicrons for fat/triglycerides?

For cholesterol it is just Low DL and High DL

LDL delivers cholesterol to tissues while HDL removes cholesterol from tissues

Explain amino acid metabolism in the liver?

Some amino acids are used for protein synthesis, while those who can’t be used for proteins are typically converted into energy

This is done by deamination of an amino group which allows the a.a to enter the krebs cycle

Otherwise excess amino acids are stored as glucose and fat

Since the postabsorptive state is about catabolism while still maintaining blood glucose, what are the different sources of blood glucose in the body?

1) Glycogenolysis - Breakdown of glycogen in glucose (1st defense) → performed first in the liver and then in the muscles

2) Lactate recycling - In low oxygen conditions, muscle glycolysis produces lactate which can be converted into glucose via cori cycle

3) Gluconeogenesis - Creation of glucose from other things like lactate, amino acids mainly occurring in the liver

4) Protein breakdown - amino acids converted into glucose after deamination in the liver

What are the main hormones controlling the metabolic state and where do they come from?

Insulin and Glucagon are both produced by Islets of Langerhans in the panceas while Insulin is produced by Beta cells and Glucagon is produced by alpha cells.

Explain why insulin is the most important hormone for metabolism?

Insulin is high in the absorptive state promoting glucose uptake, but low in the post absorptive state.

It acts as a polypeptide hormone acting on skeletal muscle, adipose and the liver (inserts more glucose transporters in cells)

What are the major effects of insulin on different tissues?

1) Skeletal Muscle - Promotes glucose uptake and glycogen + protein synthesis while downregulating protein breakdown

2) Adipose Tissue - Promotes glucose uptake and triglyceride synthesis while decreasing fat breakdown

3) Liver - Decreases gluconeogensis, glucose release, and ketone production while increasing glycogen and triglyceride synthesis

How is insulin controlled?

It is regulated by plasma glucose, which after eating increases so beta cells increase the production of insulin to promote glucose uptake and storage

How do incretins change insulin production?

Incretins like GLP-1 and GIP amplify insulin secretion before glucose even rises (feedforward)

What is the neural and brain relationship with insulin?

The brain supply of glucose is independent of insulin since brain glucose is necessary regardless of fasting state.

Parasympathetic = increased insulin

Sympathetic = decreased insulin (increase blood glucose during stress)

What are the major actions of glucagon?

Glucagon mainly acts on the liver and stimulates glycogenolysis, gluconeogensis and ketone production to increase blood glucose

How is glucagon controlled?

Also controlled by plasma glucose as low glucose will stimulate alpha cells to produce glucagon

What is the relationship of the 2 major metabolic hormones and the absorptive states?

Low insulin and high glucagon = Post absorptive state

High insulin and low glucagon = Absorptive state

What is the role of cortisol?

Cortisol allows for gluconeogensis and lipolysis(converts triglyceride into glycerol for gluconeogensis and fatty acids for energy)

It also causes more protein breakdown and decreased glucose uptake by tissues (opposes insulin)

Explain the countermeasures of hypoglycemia caused by insulin?

Various other hormones than just glucagon oppose insulin such as epinephrine, cortisol, and even growth hormone which all promote glycogenolysis and gluconeogenesis preventing low blood glucose.

How is blood glucose maintained during exercise?

Decreased insulin and increased glucagon allow for increased blood glucose to help maintain its levels despite consumption by the muscles for energy.

Other methods of energy consumption are fatty acids from lipolysis and muscle glycogen breakdown

How can muscles still take up glucose when insulin is low during exercise?

Contraction of muscle triggers movement of glucose transporters to the membrane AND increased production of new transporters

Where does energy go in the body?

Energy cannot be created or destroyed, but around 60% of metabolic energy becomes heat with the rest being captured in ATP for biological work

What are the different types of biological work?

External work is to move objects outside the body (skeletal muscle)

Internal Work is things like protein synthesis and active transport (most internal work becomes heat eventually)

Formula for total energy expenditure?

Total Energy Expenditure = Internal Heat + External Work + Energy Stored

Metabolic Rate = Total Energy Expenditure / Time

What is the basal metabolic rate?

Metabolic rate measured when a person is at rest and has fasted in post absorptive state (minimum energy to maintain life)

What factors affect the metabolic rate?

Sleep, Aging and Fasting decrease our metabolic rate while exercise growth and stress increase it

How is the metabolic rate hormonally controlled?

Thyroid hormone is the most important determinant of BMR since it increases oxygen consumption and heat production (raises metabolic activity of tissues)

Epinephrine also increases the metabolic rate by inhibiting insulin and promoting glucagon → glycogen and fat breakdown and more ATP production

How does muscle activity affect metabolic rate?

Exercise Associated Thermogenesis (EAT) - Energy expenditure associated with exercise

Non-Exercise Acitivity Thermogenesis (NEAT) - Energy used for all other non exercise movements like standing and walking

When does body weight remain stable?

It is when energy intake = energy expenditure such that all the energy from food is used for work, storage or heat production and none is stored as fat in adipose

Body weight does not = energy content since body weight also depends on water bones and muscle

What is the body weight set point?

The body tends to regulate around a set weight point by either increasing our metabolic rate during over eating or decreasing it during under eating to oppose weight change

What is the role of Leptin?

Leptin tells the brain essentially how much fat is stored since it is released by adipose tissue. Thus it acts on the hypothalamus to decrease food intake and increase our metabolic rate if fat stores are high

How does ghrelin work?

Ghrelin is the hunger hormone and is produced mainly in the stomach.

What is thermoregulation’s purpose?

Heat produced during metabolic reactions must be counteracted by the body in order to maintain a stable internal temperature

How is core temperature maintained?

Heat gain must = heat loss in order to maintain temperature internally.

This is done via 4 mechanisms:

1) Radiation - heat transferred via infrared EM waves

2) Conduction - touching cold metal or other cooler molecules causes heat transfer

3) Convection - Movement of air or water removes warm air from the body which increases conduction

4) Evaporation - Water vaporization via sweat and respiratory water loss

What is the regulating reflex system for temperature?

Thermoreceptors detect core and shell (surface) temperature all over our body which send the signal to the hypothalamus sending its signal to effectors (sweat glands, skin blood vessels etc.)

How do we produce heat when body temperature drops?

Shivering - Rapid skeletal muscle contractions with little external work → most energy released as heat

NonShivering - Mainly occurs in infants which uses brown adipose tissue to produce heat instead of ATP

How is skin blood flow heat loss controlled?

Heat exchange occurs through the skin and the amount of blood flowing through the skin blood vessels determines how much heat leaves the body

Sympathetic activation in cold conditions causes decreased blood flow due to vasoconstriction

In Hot conditions sympathetic activation decreases and vasodilation increases skin blood flow for more heat loss

What is insensible water loss?

This is water not lost due to sweat but via skin diffusion and respiration

There is a certain range of outside temps in which body only loses heat via skin blood flow (thermoneutral zone)

How does humidity affect heat loss?

Humid air prevents sweat from evaporating and since sweat evaporating is the only way to cool the body, humid air feels much worse since the heat becomes less tolerable

What is heat acclimitization?

Repeated exposure to hot environments leads to increased aldosterone production (increased Na+ reabsorption for less salt in sweat) and increased sweat volume along with earlier onset of sweating

What is fever?

Fever is the increased body temperature caused by resetting the body’s set point determined by the hypothalamus usually caused by an infection

What is the role of endogenous pyrogens?

They are released from macrophages during infection and stimulate the hypothalamus to raise it’s temperature set point

Why do chills occur during fever?

Since you changed your set point, your body is now below that set point so the typical things happen as if you are feeling cold, like vasoconstriction and shivering

What is the difference between fever and hyperthermia?

Hyperthermia is when heat production exceeds heat loss while fever is when the entire bodily set point is increased.

In hyperthermia the body tries to cool while during a fever the body initially warms itself up to the new set temp

How does exercise induce hyperthermia?

Muscle activity increases heat production which now exceeds heat loss leading to rising bod temperature (reset via sweating and skin vasodilation)

Why is heatstroke fatal?

It is a complete failure of thermoregulation, so increased temp is not checked on, and just leads to increased metabolism which produces more heat (positive feedback) until the body is too hot to survive.

What is the role of the gonads?

Gonads are the testes in males which produce sperm and testosterone, while they are ovaries in females which produce the egg, estrogen and progesterone

What are the main gonadol hormones?

These are all steroid hormones derived from cholesterol:

Androgens - Testosterone produced in testes

Estrogens - Estradiol produced in ovaries

Progestins - Progesterone produced in ovaries

How does testosterone work?

It is produced primarily in the testes, but is converted into dihydrotestosterone (DHT) when inside target tissues to make it much more potent

Explain the difference between male and female hormones?

Hormones are not sex specific since males produce small amounts of estrogen and females produce small amounts of androgens

What is progesterone?

It is produced in the ovaries during certain parts of the menstrual cycle to act as an intermediate in steroid synthesis

How do steroid hormones work?

They enter a cell → Bind to a INTRAcellular receptor (can diffuse through) → Binds to DNA → alter gene transcription → alters protein synthesis

What are the effects of gonadal steroids?

They lead to primary sexual characteristics which involve the sperm ducts and reproductive tracts but they also lead to secondary characteristics which are not directly needed to reproduction but help differentiate the sexes (hair distribution, breasts, height etc)

What is the Hypothalamus Pituitary Gonadal Axis?

This is a hormonal cascade beginning with the hypothalamus:

Hypothalamus releases Gonadotropin releasing hormone which stimulates the release of FSH and LH by the anterior pituitary (gonadotropins) which act on the Gonads causing sex hormone secretion and production of gametes

GnRH released in pulses to decrease tolerance

Negative feedback since sex hormones inhibit GnRH FSH and LH to inhibit the pathway as it has served its function

What is the special case of positive feedback for sex hormones?

In the middle of the menstrual cycle, high estrogen levels actually stimulate GnRH, FSH and LH release (LH surge leads to ovulation)

What are the components of the male reproductive system and their functions?

Testes - Produce sperm (spermatogenesis) and hormones

Scrotum - Pouch of skin containing testes to keep them at lower body temperature

Seminiferous Tubules - Highly coiled and long tubes where sperm is produced

Epididymis - Long coiled tube to store and mature sperm

Vas Deferens - Transports sperm during ejaculation

Ejaculatory Duct - All vas deferens join forming a single duct

Accesory glands produce seminal fluid which is secreted into the pathway to carry sperm (Semen = sperm + seminal fluid)

• Glands include the seminal vesicles (seminal fluid), prostate gland (fluid) and bulbourethral glands (mucus)

Sperm travels from seminiferous tubules to epididymis to vas deferens to ejaculatory duct and then out thru urethra

Explain Spermatogenesis

1st Stage - Undifferentiated germ cells divide (supply of spermatogonia not depleted)

2nd Stage - Spermatogonia differentiate into primary spermatocytes which undergo the first meiotic division leading into 2 secondary spermatocytes

3rd Stage - Secondary Spermatocytes have 23 chromosomes and 2 chromatids and undergo a second round of meiosis leading to spermatids

4th Stage - Spermatids are haploid cells and undergo STRUCTURAL differentiation (not division)

Spermiogenesis - Spermatids transform into mature sperm called spermatozoa

What are the features of mature sperm?

Head - Contains DNA

Acrosome - Contains enzymes needed for fertilization

Midpiece - Has mitochondria for movement

Tail - Flagellum to propel the sperm

What are sertoli cells?

They are support cells in the seminiferous tubules that support sperm development by nourishing developing sperm, producing inhibin and killing defective sperm

Adjacent Sertoli cells also form tight junctions creating the blood-tester barrier (protects sperm from immune attacks and toxins)

What is the role of Leydig cells?

They are located between seminiferous tubules and produce testosterone

Seminiferous = Sperm

Leydig = Testosterone

All in testes

How is spermatogenesis hormonally controlled?

LH stimulates Leydig cells to produce more testosterone

FSH stimulates sertoli cells to aid in sperm maturation

Testosterone itself also promotes sperm development

Explain the role of the epididymis and vas deferens for sperm motility

In the epididymis fluid is absorbed for sperm to become concentrated and gain functional maturity

Due to lack of fluid in vas deferens now, sperm must travel through a peristalsis like contraction of the tubule

What is the role of testosterone and inhibin?

Testosterone has 2 different effects

1) Local effects on seminiferous tubules to promote spermatogenesis

2) Endocrine effects throughout the body

Inhibin is secreted by Sertoli cells and inhibits FSH secretion (negative feedback)

Where is testosterone not converted to DHT?

Most target cells of testosterone convert it to DHT for it to be more potent, but in the brain it is converted into estradiol to have some estrogen like signaling effects

What is puberty?

Period of growth when the reproductive organs mature and fertility becomes possible.

What are the early signs of puberty?

Adrenal androgens (not testosterone) are released leading to some hair development and height increase

What is the main trigger of puberty?

The Hypothalamus-Pituitary-Gonadal axis that leads to production of testosterone become increasingly active is the main trigger of puberty onset.

What does kisspeptin do?

It is a peptide that stimulate GnRH secretion in the hypothalamus (key regulator in puberty onset)

Describe what happens in one full circle of the female reproductive system

Female system is cyclical rather than continuous like in sperm production in men.

Each cycle results in the maturation of ONE oocyte, a process of ovulation during the mid-cycle, and hormone driven uterine changes.

If no fertilization occurs, than menstruation occurs due to ovarian hormones.

What are the 2 main hormones secreted by the ovaries and what is their purpose?

Estrogen is secreted to build the lining of the uterus

Progesterone is secreted to maintain this lining of the uterus

During menstruation, there is a large drop in estrogen and progesterone causing a shedding of the uterine lining.

What is the functional flow of the organs of the female reproductive system?

Ovaries produce the oocyte

Fallopian Tube ends sweep the oocyte USING FIMBRIAE (cilia) into the Fallopian Tube which acts as the site of fertilization

Uterus is the site of implantation of the fertilized egg and is where the egg begins to develop into an embryo

The cervix → vagina is the passage outside the female body

What are the 2 roles of the ovary?

1) Gamete Production or oogenesis

2) Hormone secretion (estrogen and progesterone)

Describe Oogenesis (gamete production)

Oogonia (analogous to spermatogonia) develop into primary oocytes which then proceed to begin Meiosis I

They then STOP in the middle of meiosis I

This entire process happens before the birth of the child meaning that a female is born with all of the eggs (or primary oocytes) that they will ever have)

Every month, one primary oocyte continues through meiosis I to become a secondary oocyte (and 1 polar body). Then it starts meiosis II BUT AGAIN STOPS until or IF the egg becomes fertilized.

1 primary oocyte → one final ovum/egg

Explain the process of estrogen and inhibin production by Granulos and Theca cells

Theca cells first are stimulated by LH to produce androgens which are passed to nearby Granulosa cells

Granulosa cells are stimulated via FSH to then convert this androgen into estrogen and inhibin via an enzyme. Inhibin inhibits FSH synthesis in the anterior pituitary.

What is the Zona Pellucida?

It is a glycoprotein layer surrounding the egg that stimulates the acrosome reaction of the sperm allowing for fertilization and preventing multi-fertilization called poly spermy

What happens during ovulation?

About midway through the reproductive cycle (day 14) the follicle ruptures and releases the secondary oocyte (midway through meiosis II) with its zona pellucida for support and granulosa cells which supply the oocyte with nutrients.

The egg is not metabolically independent → relies on Granulosa cells.

What is the role of the corpus luteum?

After ovulation and the release of the egg, the follicle turns into the corpus luteum which secretes lots of Progesterone and Inhibin (to prevent maturation of second oocyte)

But if progesterone keeps the lining for more than around 10 days without fertilization, progesterone levels drop (loss of corpus luteum) and menstruation occurs

What are the 2 Ovarian Cycle Phases?

Follicular Phase - Development of the follicle and domination of estrogen as the primary hormone

Luteal Phase - AFTER ovulation occurs, corpus luteum becomes active and progesterone becomes the dominant hormone

Explain the full cycle of the female reproductive system in terms of the hormones

Start of Cycle - Low estrogen and progesterone → low negative feedback meaning increase in FSH + LH by ant pit

Early Follicular Phase - FSH stimulates the follicles which then start to produce estrogen (slight negative feedback of GnRH FSH and LH) → prevents development of too many follicles

Dominant Follicle Selection then occurs as the dom follicle will have more FSH receptors and that one will then gain responsiveness to the LH surge → other follicles die (apoptosis)

Late Follicular Phase - Here there is a major change as estrogen is high → High sustained Estrogen leads to POSITIVE FEEDBACK → LH surge

LH Surge - Causes ovulation and completion of meiosis I of the primary oocytes → follicle ruptures and forms corpus luteum

Luteal Phase - Progesterone dominates in order to maintain uterine lining (negative feedback to prevent secondary ovulation from occuring)

If no pregnancy → corpus luteum dies and progesterone and estrogen lower

What are the 3 Uterine Phases (menstruation)?

1) Menstrual Phase - Decreased estrogen and Progesterone causes breakdown of Endometrium (blood vessel rich membrane) via vasoconstriction of uterine arteries due to prostaglandins (also cause cramps) → tissue death leads to bleeding

2) Proliferate Phase - Estrogen dominates causing the endometrium to regrow and new progesterone receptors are reformed

3) Secretory Phase - Progesterone now dominates causing growth and secretion of glycogen and glycoproteins to thicken the endometrium (ripe environment for implantation of fertilized egg)

Follicular Ovary = Menstrual + Proliferate

Luteal Ovary = Secretory Phase

What happens during female puberty?

Puberty = Activation of Hypothalamic - Pituitary - Gonadal Axis connection

Before puberty there were low levels of all hormones leading to no ovulation or cycles.

Puberty then begins when the hypothalamus secretes more GnRH leading to more FSH and LH which causes follicle development and increased estrogen production

Estrogen initiates the menstrual cycle and is responsible for development of reproductive organs + secondary characteristics

What is an Amenorrhea?

This is the absence of a menstruation

Primary = Never had their first period

Secondary = Loss of period after normal cycles

Secondary is usually caused by pregnancy or menopause in older women

Also if energy levels are low, reproduction cycles will shut down since pregnancy requires high energy

What are the components of the Female Sexual Response?

Arousal Phase = Increased blood flow to reproductive organs due to vasodilation

Orgasm = Rhythmic contractions of sex organs (not required for fertilizatin)

Libido = Sexual Desire influenced by androgens

What is Menopause?

It is the loss of ovarian function

Perimenopause occurs first and it is irregular cycles

Official Menopause is no menstruation for over 12 months

Happens due to depletion of Follicles via apoptosis and the ovaries cannot respond to FSH and LH

What happens during Fertilization?

1) Sperm bind to Zona Pellucida via glycoprotein receptors

2) ACROSOME REACTION = enzymes released from head of sperm which digest through the zona pellucida coat paving a path towards the egg

3) One Sperm penetrates the egg membrane and fusion of gametes occurs

4) Polyspermy blocked via 2 mechanisms: Membrane depolarization and CORTICAL REACTION which hardens Zona Pellucida

5) Fertilization completes as egg finishes meiosis II and Zygote forms

Explain the formation of the blastocyst

During early development, totipotent stem cells divide rapidly. First differentiation of these stem cells include the ones for the embryo and the ones for the placenta (Trophoblast).

The Blastocyst includes these 2 types of cells along with a fluid cavity surrounding them

What happens during implantation?

After ovulation, the zygote now attaches to the endometrium due to the Trophoblast which releases enzymes to burrow into the uterine lining

How is the corpus luteum maintained?

The trophoblast (placenta) secretes hCG which maintains the corpus luteum → keeps progesterone high

What are the key features of the placenta?

The trophoblast develops into the fetal side of the placenta, with the maternal side consisting of endometrium.

Placenta formation prevents mixing of blood and immune reactions

Exchange of gasses, nutrients and wastes still occurs

Umbilical arteries → fetus → placenta

Umbilical veins → placenta → fetus

What happens to hormone levels during pregnancy?

Early Pregnancy means Progesterone levels are high due to hCG secretion from trophoblast maintaining the corpus luteum

After some months this burden shifts to the placenta as corpus luteum dies off

What is the role of Human Placental Lactogen and Relaxin?

Lactogen is a hormone that increases glucose production and fat mobilization such that the breasts are prepared to give nutrients to fetus

Mother essentially gets more diabetic to feed the fetus

Relaxin is a vasodilator that just increases blood flow to the uterus and kidney filtration (why you have to pee more) and helps prepare pelvis for baby delivery

Why do no menstrual cycles happen during pregnancy?

This is because progesterone and estrogen levels are maintained very high by the corpus luteum which means that inhibins are having a strong negative feedback effect on release of GnRH LH and FSH

What are the main functions of the Myeloid cells?

1) Phagocytosis: Neutrophils and Macrophages engulf and destroy pathogens

2) Macrophages: Found throughout the body’s tissues but especially in the skin, respiratory and digestive tract. Main function is to perform phagocytosis, secrete cytokines, and present antigens to helper T cells (different part of immune system)

3) Dendritic Cells: Highly motile cells that perform phagocytosis before moving to the organs of the lymphatic system to initiate immune response (also present antigens)

4) Mast cells: Located in connective tissue and contain histamine (similar to Basophils but those exist in the blood)

What are the main functions of Lymphoid Cells?

1) B cells: Responsible for producing antibodies specific to an antigen (some B cells differentiate into plasma cells to secrete antibodies)

2) Cytotoxic T Cells (CD8): Responsible for killing virus infected and cancer cells (main killing cell)

3) Helper T Cells (CD4): Secrete cytokines which activate Cytotoxic T cells and B cells → leading to antibody production

4) Regulatory T cells: Responsible for suppressing the immune response to prevent an overreaction

Which cells present antigens to T cells?

• Macrophages

• Dendritic Cells

• B cells

What is the role of the immune secretion, cytokines?

They essentially act as a communication system between different types immune cells (T to B cells)

Mostly act auto (same cell) and paracrine (nearby cells) but can sometimes have an endocrine hormone like function that acts systematically.

They are redundant in the sense that one cytokine activates others via a cascade and multiple cytokines do the same function

What are the two types of Interferons (type of cytokine)?

Type 1: Antiviral to make cells resistant to an infection

Type 2: Activate Macrophage and Natural Killer cells

What are the 2 immune cell classes?

Myeloid: Innate (nonspecific immediate defense), responsible for phagocytosis and inflammation

Lymphoid: Adaptive (recognizes specific patterns and antigens), focused on recognition and specificity of the immune response to a infection

Describe the body’s first line of defense

Physical/Mech: Skin prevents pathogen entry and noise hairs + coughing/sneezing remove particles

Chemical: Stuff like stomach acid and lysozymes kill pathogens and bacteria

Mucus: Stickiness traps pathogens while cilia moves the mucus out of the body