Human Physiology Final Exam Review Guide(SARC – Beau M.)

-Chapter 15: The Endocrine System -The endocrine system and nervous system are the major information centers between different cells and tissues of the body. -________________: “President” of the Endocrine System >inferior region contains the Pituitary Gland-________________: “Vice President” of the Endocrine System >has 3 lobes: Anterior, Intermediate, Posterior-________________: “citizens”, includes the Adrenal Gland, Thyroid Gland, Ovaries, Testes

-Mechanisms of Hormone Secretion-Endocrine Hormones: a chemical substance which is produced and secreted by the cells of an Endocrine gland and released into _______________, which carries it to its target cells. Endocrine hormones all require specific receptors on their target cells, without receptors they cannot bind to the target cell, and the cell will not carry out the physiological action that the hormone is signaling for (stimulation or inhibition).

Exocrine Hormone: a chemical substance produced in exocrine cells that is NOT secreted into the circulatory system but instead secreted into interstitial fluid, the surface of tissue, or into a cavity. This includes: -Pancreatic enzymes secreted by: -Saliva secreted by: -Sweat secreted by: -Exocrine hormones are produced in the _______ and secreted out of the gland by ducts (Pancreatic duct, Common Bile duct, Parotid duct, etc.), which open into the cavity/surface of the target organ/tissue. >___________ Hormones: stimulate/inhibit the actions of neighboring target cells. Target cells may or may not be hormone-producing. For example: Somatostatin inhibits Insulin secretion in Pancreatic β-cells. >___________ Hormones: give feedback to their own cell to stimulate/inhibit cellular activity. They bind to their own receptors on their own cell surface. >___________ Hormones: stimulate/inhibit cellular activity inside their own cell without being secreted. For example: Insulin can inhibit its own secretion from pancreatic β-cells.

-Hormone Synthesis-___________ hormones: Are produced the same way as other cellular protein products. Includes GH, Prolactin, and PTH.___________ hormones: Are produced from cleaving off a portion from larger protein precursors. Includes Insulin, ACTH, and Glucagon. ___________ hormones: Are produced by “Organification”, the combination of Iodine and Tyrosine (residues of Thyroglobulin proteins), and the “Coupling” of the different molecules produced by those combinations.___________ hormones: Are produced from a cholesterol precursor molecule.

-Protein Hormones vs Steroid Hormones-Binding Site: -Protein hormones bind to: -Steroid hormones bind to:

Lipophobic vs Lipophilic: -Protein hormones: are -Steroid hormones: are

Hydrophobic vs Hydrophilic: -Protein hormones: are -Steroid hormones: are

Requires a Carrier/Transport molecule in the blood: -Protein hormones: _________ require a carrier, can ________________ in the blood -Steroid hormones: _________ require specific carriers to move through blood to reach their target cell -Thyroid hormones: _________require carriers

Duration of the hormone action on their target cell: -Protein hormones: _________ because they have _______________________ -Steroid hormones: _______ because they ____________________________________ before binding

Precursor: -Protein hormones: ________________ precursor -Steroid hormones: ________________ precursor -Thyroid hormones: ________________ precursor and amino acid: ______________

-Hormone Receptors- -Cell surface receptors -are located on target cell membrane surface -bind _______________ and ______________ hormones -ex: Insulin, Growth Hormone, and Prolactin

-Nuclear receptors (intracellular receptor) -are located inside the target cell at the nucleus -bind _______________ and ______________ hormones -ex: Testosterone, Androgen, Estrogen, Progesterone, Aldosterone, Cortisol, T3, T4, and vitamin D

-Hormone Effects-

______________ Effects: When two or more different hormones have similar functions and effects on their target cell, and work in harmony for a specific outcome. For example: Aldosterone and Norepinephrine both increase blood pressure, and Cortisol and Insulin both regulate blood glucose.______________ Effects: When one hormone gives “permission” for the action of a second hormone. It can also enhance the responsiveness of a target cell to the second hormone, or it can increase the activity of the second hormone. ______________ Effects: When the binding of one hormone inhibits the effects of another. This effect is typically used when designing drugs like synthetic hormones, so they can recognize and bind to natural hormone receptors to block natural hormones from binding there (inhibits a process that may have become pathological). For example: Propranolol is an antagonist for β1 receptors by binding and blocking Norepinephrine from being able to bind.

______________: act like natural hormones and bind to natural hormone receptors. For example: in Hormone Replacement Therapy, Growth Hormone (GH) receptors are bound by synthetic Growth Hormones to treat growth conditions like Dwarfism.

-Four types of Cell Surface Receptors-1 – G-protein coupled receptor (GPCR):-G-protein is an intracellular protein connected to a receptor protein with __________________ domains >The receptor __________-terminal is exposed _________________ >The receptor __________ -terminal is exposed _________________-G-protein has 3 subunits: -when a hormone binds to the receptor, G-protein ____-subunit binds ___________________________ intracellularly for energy (using GTPase) to become activated. α-subunit binds ________________________ when inactive.-G-protein α-subunits can either be ______________________ or _______________________-G-proteins are coupled with other effector molecules that they pass activation signals along to for signal transduction to Second Messengers inside the cell. -Effector & Second Messenger molecules include: -These are some molecules that bind GPCRs: >Catecholamines: Noradrenaline and Adrenaline

>Prostaglandin >ACTH >Glucagon >PTH (parathyroid hormone) >TSH (Thyroid Stimulating Hormone)

2 - Growth factor receptor:-Is a receptor protein with its ____________-terminal exposed extracellularly as a ___________________ -has one ____________________ domain-its __________-terminal is intracellular and acts as a catalytic domain for ____________________ and the activation of its Second Messenger ____________________ when the receptor is bound by a hormone signal.-These receptors bind: -Insulin: decreases blood glucose level by facilitating glucose uptake into cell -Insulin Growth Factor (IGF)

-Epidermal Growth Factor (EGF) >IGF and EGF are hormone cytokines involved in cell proliferation and cell growth

3 - Cytokine receptor -A receptor protein specific for ______________________ binding -has its _________-terminal exposed ______________________ as a binding site-has _______ transmembrane domain-has its ____________-terminal exposed ________________ for effector activation of Second Messengers-When GH binds to the receptor, the association between the now activated receptor’s carboxyl-terminal and the Second Messenger protein _______ leads to conformational changes in the structure of ______ which activates its tyrosine kinase catalytic activity. This allows ______ to activate the next Second Messenger, ______________, which begins the signal transduction pathway towards a cellular reaction.

4 – Ligand-Regulated Transporter (Guanylyl cyclase receptor)-Are protein receptors that _______________ when they bind a ligand (hormones in this case) in order to open as a channel and allow specific ions to flow through.-The ions that flow through are considered ___________________________.-These receptors bind: >______________: a vasodilator, causes an increase in Nitric Oxide Synthase (NOS), which stimulates Guanylyl Cyclase (GC) activity to increase intracellular levels of cGMP (energy) to activate Protein Kinases (PKG) for vasodilation of the penile dorsal vein during erections >ANP ( atrial natriuretic peptide) : a vasodilator that decreases blood pressure mostly during Hypertension using a similar mechanism

-Nuclear receptors--Receptors are specific for Steroid hormones, Vitamin D, Thyroid hormones, Retinoids, Fatty acids, Bile acids-The receptor’s ______-terminal has high amino-acid variation for specific control of target gene transcription-The receptor has a ______-binding domain, and a _________ -terminal that acts as a binding site as well as being able to control transcription.-These receptors control __________________, since they can bind to DNA on the promoters of target genes or to the transcription factors of target genes. -Binding of a signal stimulates an increase or decrease in target gene ______________________ into a protein product meant to be used for some function.

-Steroid and Thyroid hormone mechanisms-Step 1 – Steroid or Thyroid hormones __________________ the target cell membraneStep 2 – hormone binds to the cytoplasmic site on its ___________ receptor proteinStep 3 – Nuclear receptor undergoes conformational changes to expose ______-binding site of the target geneStep 4 – The target gene is transcribed, resulting in an _________ sequence of that target geneStep 5 – The new ________ sequence is ___________ to produce a specific protein product that will satisfy the cellular physiological reaction to the binding of the initial hormone signal

-HYPOTHALAMUS SECRETIONS AND FUNTIONS--The Hypothalamus controls many things including body temperature, sleep, memory, learning, emotional and sexual behavior (associated with the Limbic System), Autonomic Nervous System, and Endocrine System.

1 – CRH (Corticotropin Releasing Hormone): The blood vessel connecting the Hypothalamus and Anterior Pituitary, _____________________________________, releases Releasing Hormone (RH) from Hypothalamic nuclei into the Anterior Pituitary, which contains Trophic cells. ______ is released from Hypothalamus into the HPPS vessel and carried into the Anterior Pituitary, where there are ______________ cells. CRH binds to these cells on their membrane surface (activating ________ as a second messenger inside the cell) and the cells secrete __________________________________, which is then carried by the blood to the Adrenal Cortex (of the Adrenal Gland) in order to bind to Adrenal Cortex cell-surface ____________ receptors (with _______ second messenger) to stimulate secretion of zone-specific hormones.

2 – TRH (Thyrotropin Releasing Hormone): Released through HPPS and binds to surface receptors on ___________ cells in the Anterior Pituitary in order to stimulate the cells to secrete TSH (Thyroid Stimulating Hormone), which enters the blood to stimulate the Thyroid Gland to secrete T3 and T4 hormones. TRH can also stimulate the ____________________ to secrete Prolactin.

3 – GnRH (Gonadotropin Releasing Hormone): stimulates ________________ cells in the Anterior Pituitary to secrete ___________________________ and ______________________. GnRH uses _____ as its second messenger.

4 – GHRH (Growth Hormone Releasing Hormone): secreted by Hypothalamus into Anterior Pituitary to bind to cell-surface ______ receptors on _____________ cells to stimulate the secretion of GH (Growth Hormone). GH is also secreted by the Placenta in pregnant females. Uses ____ and ______ as second messengers.

-Anterior Pituitary Hormones- 1 – TSH (Thyroid Stimulating Hormone) & PL (Prolactin): TRH is secreted by Hypothalamus through HPPS vessels into the Anterior Pituitary and binds to _____________ cell _______ receptor (using ____ as a Second Messenger) to stimulate the cell to secrete TSH & Prolactin: >TSH: binds to the surface of __________ cells in the Thyroid Gland (to a ______ Receptor) and uses _____ as a secondary messenger. Helps control the development of fetal Thyroid Glands (along with the T3 and T4 it stimulates) and helps with the development of the Central Nervous System (including Brain), and bones.

>Prolactin (PL): -in females: develops mammary glands for breastfeeding when pregnant, excess PL can cause infertility because it suppresses other sex hormones such as FSH and LH to inhibit menstruation and ovulation BUT during pregnancy Prolactin this is necessary to avoid spontaneous miscarriage of the fetus. -in males: PL helps control emotional and sexual behavior, but excess can cause infertility because it suppresses other sex hormones -_______________ inhibits release of Prolactin -Uses ________ as a secondary messenger -Hyperprolactinemia is treated with synthetic Dopamine (________________)2 – ACTH (Adrenocorticotropic Hormone): Hypothalamic CRH stimulates ______________ cells to secrete ACTH from the Anterior Pituitary lobe. -ACTH enters the blood to stimulate cells in the Adrenal Cortex, which leads to secretion of:

3 – GH (Growth Hormone): Hypothalamic GHRH uses _______ surface receptors and ______ and ______ second messengers to stimulate Somatotropic cells to secrete Growth Hormone (GH) from the Anterior lobe of the Pituitary gland. GH is also secreted by the Placenta in pregnant females. -Effect of GH (growth hormone): Binds to __________ cell-surface receptor and uses ______ and ________________ as second messengers. GH stimulates cell ______________ (increase in cell number) and cell ________ in child and in fetus (active during embryogenesis, and development of brain, heart, blood vessels, soft tissue). -GH levels increase in pregnancy & in childhood -GH levels decrease after puberty -GH excess during childhood may cause ___________, where the child grows extremely tall, and have an enlarged heart. This is usually treated preventatively with synthetic _________________. -excess GH secretion after puberty or in adults causes Acromegaly (enlarged face, hands, and feet) -GH deficiency can lead to ___________, which is treated with ____________________.

4 – FSH (Follicle Stimulating Hormone) & LH (Luteinizing Hormone): Hypothalamic GnRH stimulates _____________________ to secrete Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH):

-Effect of FSH & LH in females: Receptors in the ________. Controls development of follicle and ovum during first two weeks of menstrual cycle (Follicular Phase), when FSH level __________ to control maturation and development of a follicle. By the Midcycle (day 13, 14, or 15) FSH level decreases & LH level increases for the beginning of Ovulation. LH takes over last steps of maturation of follicle after FSH. LH causes the rupture of follicle cell, elimination of ovum from follicle, and the migration of ovum toward fallopian tube. After ovulation, if there is no sperm there is no pregnancy.

-Effect of FSH & LH in males: FSH has receptors in the ___________, and controls development of sperm from germ cells. LH has receptors in the testicle on _________ cells, where it stimulates Testosterone secretion. Testosterone is important for the development of testicles in male fetus, development of external genitalia in fetus and child, and in the descent of testes from the abdominal cavity to the scrotum in the fetus. >Testosterone controls secondary sex characteristics: muscles, voice, libido

>Testosterone: Controls body temp, increases red blood cell production, controls mood, sleep, appetite, body metabolism >Testosterone deficiency in the fetus leads a failure of testicular descent

-Posterior Pituitary Hormones--The cell bodies of two nuclei, the _______________ and ___________________ nuclei are contained in the Hypothalamus, but their axons project into the Posterior Pituitary lobe. When stimulated, they produce and secrete 2 hormones from their axon terminals: >ADH (Antidiuretic Hormone): (also called Vasopressin) osmoreceptors in large blood vessels are sensitive to blood osmolarity and are stimulated when blood becomes too concentrated (possible dehydration). These osmoreceptors are under the control of two cranial nerves: ________________ and ________________________and they carry information about blood osmolarity to two Hypothalamic nuclei: Supraoptic nuclei and Paraventricular nuclei, which stimulates them to secrete ADH into the Posterior Pituitary when the blood volume is low (dehydrated). ADH is released into the blood and carried to the Renal System, where it binds to the ____________________ surface receptor on the Collecting Tubule of the Nephrons. This stimulates reabsorption of H2O into the Peritubular capillaries to decrease osmotic pressure in the tubules and increase blood volume by diluting the blood. This decreases urination and relieves dehydration. >Oxytocin: -in females: is important for lactation in mammary glands, and in the uterus it has receptors on the myometrial cells of the uterus smooth muscle layer (_______________) to control contractions during labor and childbirth. -in males: is important in the control of ejaculation and vasoconstriction

-Adrenal gland (Cortex)--Adrenal glands (Suprarenal glands) are located on the upper pole of each ___________. -Each gland is 90% outer layer (________________) and 10% inner layer (__________________). -Adrenal Cortex secretion is regulated by ACTH from the Anterior Pituitary-The Adrenal Cortex has 3 layers: Zona _______________, Zona _______________, & Zona _______________ >Androgen: sex hormone seen in males and females (important in females to begin puberty) -sex hormone produced in the ____________________ of the Adrenal Cortex -binds to a Nuclear receptor -crucial hormone in puberty, involved in _________ and ________ hair growth, and _______

>Aldosterone: increase NaCl and H2O reabsorption in Nephron, increases blood pressure & volume -is a “___________________” produced in the ___________________ of the Adrenal Cortex -binds to a Nuclear receptor in cells of the Collecting Tubule of Nephron -involved in the Renin-Angiotensin System (see below) -Increases NaCl, H2O, and HCO3

- reabsorption, increases blood pressure -Increases excretion of H+ and K+ into urine -Activated when blood pressure is low >Cortisol: “stress hormone”, maintains blood glucose, metabolism and appetite

-is a “________________” produced in the _____________________ of the Adrenal Cortex -binds to a Nuclear receptor on target cells -increases metabolic break down of proteins (Proteolysis) and lipids (Lipolysis) -suppresses immune system and inflammation -Stimulates gluconeogenesis and

-More on Aldosterone: >Renin-Angiotensin-Aldosterone System: activates when blood pressure, blood volume or Na+ level is low → stimulates _________ secretion → Renin converts Angiotensin (Ag) into ___________________ → Then _____________________________ secreted from the lungs converts Ag1 into Ag2 (Angiotensin 2) → Ag2 acts as a vasoconstrictor and stimulates the production of Aldosterone from __________________ in the _________________ of the Adrenal Cortex → Aldosterone is carried by the blood to the Nephron and binds to its receptor on the _________________ and _________________ → stimulates Peritubular capillaries to reabsorb _______ and ______, absorb HCO3

-, and excrete ____ and ____ into the urine. In this way Aldosterone increases _________________ and Na+ blood concentration.-Excessive amounts of K+ in the blood (Hyperkalemia) increase Aldosterone secretion, and Aldosterone then increases K+ secretion into the urine to regulate its level in the blood.

-Adrenal gland (Medulla)--Secretes Catecholamines: __________________________ and ______________________________ -Adrenal Medulla is NOT under the control of the Pituitary gland or Hypothalamus. (Neither are Pancreas or Parathyroid) -The Adrenal Medulla is derived from embryonic _____________ tissue (which is neural and gives rise to the CNS and PNS as well)-Noradrenaline & Adrenaline have receptors in the _______ for controlling Gluconeogenesis and Glycogenesis.

-Norepinephrine: is produced by _____________ cells in the Adrenal Medulla, CNS, and in Peripheral Sympathetic nerves. These hormones also act as neurotransmitters. It controls smooth muscles (including the smooth muscles layer around blood vessels and the viscera lining of organs) in the GI, Respiratory System, Sweat glands, and Heart. Heart activity, heart rate, conduction velocity, and contractility are all influenced by Norepineprine as well. -Effects of Norepinephrine depend on the type of receptor it binds to: >___: vasoconstriction, contraction of smooth muscles (including sphincters), blood pressure increases >___: relaxation of smooth muscle, dilation of sphincter, vasodilation >___: increased heart rate, myocardial contractions, and conduction velocity. Propranolol and Atenolol are ______________ (β-blockers). >___: Relaxes bronchi. Albuterol is an __________ for Norepinephrine at this receptor

-Epinephrine: is produced by ____________ cells in the Adrenal Medulla. Controls blood pressure, Controls glucose formation and absorption in liver

-Adrenaline and Noradrenaline Synthesis:-Precursor amino acid ___________ is catalyzed by the enzyme ____________________ to become ____________________________, which is catalyzed by the enzyme _____________________ to become _______________, which is catalyzed by enzyme _______________________ to become Norepinephrine, which can be catalyzed by enzyme ________________________________________ to become Epinephrine

-Thyroid gland--The located alongside the Hyoid bone and the 1st ring of the Trachea in the throat. -Has 2 lobes (Left & Right). -The blood supply to the Thyroid gland is important and brings Iodide (I-), a precursor for hormones (T3 & T4). -Blood from the ___________________ (a branch of the Thyrocervical trunk, which comes from the Subclavian artery) supplies the Inferior lobe of the Thyroid gland. -Blood from the ____________________ (a branch of the External Carotid artery, which comes from the Common Carotid artery) supplies the Superior lobe of the Thyroid gland. -Venous blood drains from the Thyroid gland into the ___________________________ → to the Internal Jugular vein in the neck → to the Brachiocephalic vein → then into the Superior Vena Cava. -Thyroid nerve supply is controlled by the ______________ Nervous System (Parasympathetic & Sympathetic).-The Thyroid gland derives from embryonic _________________ tissue. -Internal Structure: The Thyroid gland has a single layer of ___________, which have receptors for TSH on the basolateral surface of the cells, which faces the bloodstream. Inside the follicular lumen is “colloid” fluid which contains ___________________ (containing ____________ amino acids) which act as a precursor for T3 and T4 production.

-Thyroid Hormones--The thyroid gland produces two hormones: ________________ (T4) and ____________________ (T3)-In the circulatory system, ~99.9% of all T4 and ~99.5% of all T3 in the blood are bound to plasma carrier proteins, most commonly _____________________________, to inhibit Renal excretion into the urine.-When TSH binds to _______ receptors on the basolateral-surface of follicular cells it activates _____________________, then _______ Second Messenger, causing the apical surface of the cell to reabsorb Thyroglobulin to begin synthesis of Thyroid Hormones T3 and T4.-T3 and T4 bind to ____________ receptors in their target cells and are critical in cell differentiation during development, and help in maintaining thermoregulation and metabolic homeostasis in the body.

-Synthesis of Thyroid Hormones-1 – Na+/I- symport pump transports iodide into follicle cells:-After TSH binds to its receptor on the follicle cell membrane, it activates the cells to uptake ___________ and

iodide, which symports into the cell along with sodium. 2 – Iodide Oxidation: Iodide (I-) is catalyzed by Peroxidase enzyme to oxidize into _________, which is now reactive and ready to form the inactive forms of T3 and T4 by the process of “________________”.

3 – Organification combines Iodine molecules with Tyrosine residues from Thyroglobulin:-when __ molecule of Iodine (I2) and __ molecule of Tyrosine combine, they form Monoiodotyrosine (MIT). -when __ molecules of Iodine (I2) and __ molecule of Tyrosine combine, they form Diiodotyrosine (DIT).4 – Coupling makes combinations of MIT and DIT to form T3 and T4:-While MIT and DIT are attached to the Tyrosine residues of Thyroglobulin, two coupling reactions occur:

> >-These reactions are catalyzed by Peroxidase enzyme, and result in the active forms of thyroid hormones.-More T4 than T3 is synthesized in this process, although T3 is more potent and active in bodily mechanisms.-T4 can be modified into T3 at the site of target tissue.

-Thyroid Hormone Physiological function: -T3 and T4 are both active independent of each other but can collaborate in function.-T4 can pass through Placenta membrane and converts to T3 to control the development of the _____, _____, and ____________ in the fetus. >More specifically, T3 is synergistic with ____ and ______________ hormones for fetal bone formation-In adults, Thyroid hormones control memory, learning, body metabolism and temperature, increases O2 consumption in different cells (except in the Brain, Spleen, and gonads), increases glucose absorption from the GI, controls glucose metabolism, gluconeogenesis & glycogenolysis in the Liver, increases Lipolysis and Proteolysis, increases sensitivity in ____ and ____ sympathetic receptors, increase ventilation rate, control heart rate, contractility of myocardium, and blood pressure.

-Parathyroid glands--Glands consist of 4 pea-sized lobes located posterior to the Thyroid Gland-Uses a cell-surface ______ and ______ as a Second Messenger-They are sensitive to Phosphorus and Ca2+ levels in the blood (____ mg/dL is the normal Ca2+ value)-_________ secrete Parathyroid Hormone (PTH), which regulates blood levels of Ca2+ and Phosphorus >If PTH increases one the other will decrease-PTH secretion is controlled by a __________ feedback loop, high levels of Ca2+ will __________ PTH secretion-PTH binds to receptors on bone (________________) to remove Phosphate and Ca2+ from the bone and release it into the Extracellular fluid. This does not directly translate to increased serum levels of Ca2+ because the Phosphate will associate with Ca2+. By inhibiting Phosphate reabsorption in the _________________ of the Nephrons in the Renal System, Phosphates can be excreted into the urine in larger amounts (Phosphaturia), causing Phosphate to dissociate from Ca2+ to replace what was lost, then Ca2+ can enter blood serum to increase Ca2+ levels. -PTH receptors on the __________________ of Nephrons results in Ca2+ reabsorption directly to the blood.-PTH also has receptors on the Epithelial cells of the small intestine and binds to increase Ca2+ absorption from Chyme in the small intestine.-Slight decreases in Mg2+ increase PTH secretion, but deficiencies in Mg2+ inhibit PTH secretion, which can lead

to _____________________ and _____________________.-PTH has receptors in the _______________ of Nephron and binds to convert the inactive form of __________ (_____________________) into its active form (1,25-dihydroxycholecalciferol), which is then absorbed into the Peritubular capillaries. This process can generate ________ for intracellular energy, which is then expelled as waste into the urine.-The vitamin D then travels to the GI to assist with Ca2+ absorption from epithelial cells in the small intestine.-Deficiency of PTH causes a deficiency of vitamin D, which causes a deficiency of Ca2+ and ________________.-_________________________ also causes Osteoporosis since excess PTH removes too much Ca2+ from the bones, weakening them.

-The Importance of Calcium in the Body--Calcium is important for muscular contractions and is seen in large amounts in the mechanism of the ______________________________.-Calcium is used in large amounts in ________________ to regulate contractility of myocardium, and in contractions of the smooth muscle layer of blood vessels, __________________ of the GI tract, and smooth muscle layers of internal organs.-Calcium regulates action potentials of _____________ and ________________ node in the right atrium of the Heart, and we see in ____________, that excess Ca2+ ________ heart rate by stimulating the SA and AV nodes-Calcium (and vitamin D) are important for maintaining bone density and development.

-Pancreas--The Pancreas is located between the second part of the Duodenum and the Spleen. It has both Exocrine and Endocrine function.-The Exocrine portion of the Pancreas has acini (acinar cells) which secrete digestive enzymes: >___________________, __________________, ___________________-The Endocrine portion of the Pancreas, called the _______________________ contains 4 major cell types:α-cells: located in the outer rim of islet, secrete _________________β-cells: located in the central part of the islet, secrete ______________ δ-cells: are found throughout the Pancreas and secrete __________________ and GastrinPP cells: produce less than 1% of Pancreatic polypeptide, which can act as Paracrine hormones (that act like Somatostatin)-________________________ link β-cells to β-cells, α-cells to α-cells, and β-cells to α-cells to facilitate more rapid cell to cell communication.

-Pancreatic Endocrine Hormones--Glucagon (α-cells):-Glucagon secretion depends on blood level of glucose; low levels increase Glucagon secretion which increases blood glucose in response. Glucagon has cell-surface GPCR receptors in the Liver and in Adipose tissue that use Second Messenger _________ to stimulate the production of Glucose from stored Glycogen.-Glucagon is very efficient in small amounts, 1 g/kg of Glucagon elevates blood levels of Glucose by 20 mg/dl within 20 minutes.-Glucagon elevates blood glucose levels by increasing the rate of ___________________ (Glycogen → Glucose) and inhibiting __________________ (Glucose → Glycogen) in the Liver.

-Glucagon also increases blood glucose by increasing ____________________ along with Cortisol. This process utilizes lactic acids, fatty acids, amino acids and glycerol to produce new glucose molecules. ______________ generates glycerol, fatty acids and ketoacids. ____________ generates amino acids from protein degradation, and any unused amino groups are dumped into urea (increasing urea production) for excretion in the urine.

-Somatostatin ( δ-cells) : Down-regulates _____________ and ____________ by inhibiting their secretion, indirectly decreases peristalsis, indirectly decreases secretion and absorption in the GI tract by inhibiting Histamine and Gastrin action on G-cells, therefore inhibiting secretion in Parietal cells. Prolongs digestive window for nutrient assimilation from the small intestine into blood.

-Insulin (β-cells):-Is increased when blood glucose levels are ________ to facilitate cellular uptake of glucose and decrease blood levels to normal (___________ mg/dl)-Insulin has receptors in most types of tissue but most importantly in the: ______, ________, & ____________-target cell uptake of glucose from blood facilitates the production of ATP-Hyperglycemia increases _________ secretion, while Hypoglycemia increases __________ secretion.-Hyperglycemia occurs when blood glucose exceeds 120 mg/dl - Insulin increases and Glucagon decreases-Hypoglycemia occurs when blood glucose drops below 50-60 mg/dl – Insulin decreases an Glucagon increases-When blood glucose is too high: >Insulin stimulates __________________ (Glucose → Glycogen) in the Liver >Insulin inhibits _____________________ (Glycogen → Glucose) and >Insulin decreases ______________________ by increasing levels of ________________________ by promoting _________________________ enzyme activity. >Insulin decreases Lipolysis and increases _____________, which decreases ______________ formation by decreasing the acetyl CoA by-product formed by Lipolysis. >Decreases blood levels of K+ by closing cell membrane K+ channels during Glucose uptake

-Insulin Secretion Mechanism--Increased blood glucose above the normal range stimulates β-cells in the Pancreas to secrete Insulin by the following process: Glucose from the blood enters the β-cell through ________ channels in the membrane, causing some uptake of K+ from the blood followed by the closure of K+ channels. Increased K+ remains inside the cell and depolarizes it to open calcium channels for Ca2+ to enter the cell. As Ca2+ levels increase in the cytoplasm it causes the exocytosis of Insulin secretory vesicles out of the β-cell and into the blood.

-Target Cell uptake of Insulin--Insulin binds to cell-surface receptors and activates the ________ molecule to insert itself into the cell membrane and act as a channel for Glucose transport. This allows Glucose to enter the target cell. Once inside the cell, Glucose is converted into ________________ during _____________ inside the cell, which can then enter the ______________ for ATP production. Energy generation from glucose and O2 is ________________________________.

-Glycogenesis: creation of glycogen from glucose. Glucose->Liver->___________________________-> glucose-1-phosphate->Glycogen. _____________________ enzymes catalyze this process. Glucagon is secreted by Pancreatic alpha-cells and stimulates the Liver to inhibit this process.

-Glycogenolysis: The reverse process, when the body needs more glucose, the Liver breaks down stored Glycogen back into Glucose. Glycogen->_____________________->glucose-6-phosphate->Glucose. Glucagon from Pancreatic alpha-cells stimulates Liver to begin this process.

-Gluconeogenesis: Stimulated by Glucagon and _____________. The formation of glucose from fatty acid, lactic acid, glycerol, and amino acid in the Liver, which is carried to the muscle for use.

-Pineal gland--Is located in posterior region of the 3rd ventricle of the brain and secretes _______________ to control sleep.

-The absence of light stimulates melatonin secretion to induce sleep. -As you age, Pineal glands may atrophy or calcify, causing ___________________. >This can be treated with synthetic melatonin.-Melatonin Synthesis: ________________ precursor is a neurotransmitter that is derived from its precursor, _________________, an amino acid. Pineal cells install _________ functional groups (________________) and -CH3 groups (________________) onto Serotonin to convert it into Melatonin. This process is dependent on the amount of light exposure to the eyes, as abnormal light exposure inhibits this process and may result in sleep issues.

-The effects of Light-Dark exposure: When the retina of the eye is exposed to _____________ amounts of light (like when the sun is setting) it stimulates a signal to activate the _________________ nucleus found in the __________________, which is an organ that regulates many biological processes including sleep and our natural Circadian rhythm. Nerve fibers extend down the spinal cord to transmit the activation signal to the ______________________________, which sends the signal back up the spinal cord along its post-ganglionic nerve fibers to innervate the Pineal Gland to begin hormone synthesis and secretion.

-Prostaglandins--Prostaglandins bind to cell-surface ________ of target cells and use Second Messenger _________-Every cell has prostaglandin secretion, which can stimulate a wide variety of functions, including: >blood vessel >smooth muscle > > -Prostaglandin secretion increases: >During erections, where it vasodilates the dorsal vein in the penis. -Synthetic prostaglandin is used to treat Erectile Dysfunction. >During labor it dilates the cervix of the uterus >During menstruation it can irritate the pelvic cavity and cause pain-Prostaglandin-E2 can irritate the temperature center in the Hypothalamus and cause fever -Forms from the precursor _____________________ which is converted by _____________________ enzyme -Common types of Prostaglandins (PG):-_______: active in Antiplatelet aggregation (inhibits blood clotting) and vasodilation-_______: active in smooth muscle relaxation, vasodilation, and is the causative agent in fevers -_______: active in smooth muscle contractions and vasoconstriction >PGE2 and PGF2α both involved in uterine contractions during childbirth-__________________________: active in platelet aggregation (blood clotting) and vasoconstriction

-Prostaglandin precursor Arachidonic acid can also be oxidized by _____________________ enzyme to form ____________________ inside specialized leukocytes. Leukotrienes are mostly active in __________ reactions to induce bronchial inflammation, bronchoconstriction and vasoconstriction in the Respiratory System. -Leukotrienes and specialized Prostaglandins are usually synthesized at the same time as they act ______________________ in Asthmatic ______________________ reactions.

-Prostaglandin Inhibitors:-Certain drugs can inhibit Cyclooxygenase enzyme from being able to catalyze Prostaglandin synthesis, including _________________________________________ like Aspirin, Ibuprofen, Naproxen, and Indomethacin (preferred for babies with heart conditions)

-Hormones of the Gonads and Placenta--Prolactin: prepares mammary gland for breast feeding-Precursors: for TSH, ACTH & GH secreted by Placenta-Growth factors: secreted by the Placenta, which are important for embryonic cell proliferation and growth-Relaxin: relaxes the Pelvic joints and prepares the pelvic cavity for pregnancy, relaxes cervix for delivery-Testosterone, Progesterone, and small amounts of Estrogen are also secreted by the Placenta-Estrogen- -Is secreted by the gonads once puberty begins, and from ________________ during pregnancy-Estrogen in excess can suppress __________________ and cause infertility in males-Estrogen is important in the development of genitalia in female fetus, for the development of the ovaries and the descent of ovaries from the abdominal cavity and into the pelvic cavity-Estrogen levels increase after menstruation for the regeneration of the Endometrium layer in the uterus.-Estrogen is important for the development of _________________________ including breast development, changes in body shape, and the accumulation of fat for the rounding of the hips and legs. -Estrogen deficiency can cause depression, anxiety, nervousness, and infertility. -Before and during menstruation Estrogen levels decrease and commonly causing feelings of depression. -Depression caused by Estrogen deficiency can occur in menopausal and post-menopausal people due to Estrogen levels decreasing significantly and permanently.-Progesterone--Important for preparing and maintaining the _______________ of the uterus for implanting a fertilized ovum.

-Secretion is controlled by ______________ that develop into the Corpus Luteum in the ovary, during the ______ trimester of Pregnancy. -In the ________ & _______ trimester, the control of Progesterone secretion is taken over by the placenta. -Progesterone deficiency can cause ________________________________________. -Testosterone--LH stimulation of the _____________ in testicles induces Testosterone secretion-High levels of Testosterone can __________ LH secretion via ___________ feedback-A male sex hormone important in the development of testicles in the male fetus, and the descent of testicles from the abdominal cavity and into the scrotum during intrauterine life. -Controls the development and growth of genitalia after birth as well. -Dihydrotestosterone is another sex hormone complementary to Testosterone-Testosterone is important in the development and maintenance of Secondary Sex Characteristics during and after puberty, including muscle development, voice changes and increased libido -Controls production of sperm after puberty. -Testosterone deficiency can cause infertility and depression, since it controls mood to an extent (though emotions are also under the control of serotonin and dopamine neurotransmitters and the Limbic System) -Important for fluid absorption into the blood, in this way it has a hand in regulating blood volume

-Testosterone can stimulate an increase in red blood cell production-Ovaries secrete small amounts of Testosterone since it is molecularly similar to Estrogen and can be converted into Estrogen via Aromatase enzyme. Adipose tissue can increase Aromatase levels, so obese males with Testosterone deficiencies may be infertile due to Aromatase catalyzed conversion into Estrogen.

-Chapter 16: The Reproductive System--Spermatogenesis: the production of mature sperm from germ cells, which is regulated by ____. During pregnancy the embryo is connected to its yolk sac, which produces ____ germ cells that migrate to the gonads (testes in males). In Spermatogenesis, the fetal germ cells are converted into _________________, which stay dormant within seminiferous tubules in the testes until puberty. During puberty the Spermatogonia (type B) undergo ___________________ and growth to become diploid ______________________, which each undergo their first ______________________ to become 2 ___________ Secondary Spermatocytes, which then undergo a second Meiotic division to become 4 haploid _________, which eventually enter ______________ to mature into 4 ____________ (sperm).

>FSH (Follicle Stimulating Hormone) in males: FSH has receptors on some cells in the testes, and controls maturation of sperm and Spermatogenesis from germ cells. When the rate of sperm production is too ______, Sertoli cells secrete _________ to prevent FSH from sending feedback to the Anterior Pituitary (for more FSH), in this way it inhibits further FSH secretion. -FSH uses ________surface receptors and _______ as a second messenger

>LH (Luteinizing Hormone) in males: LH has receptors on specific testicular cells called ____________. LH binding to these receptors stimulates secretion of Testosterone (used in reproductive regulation & puberty) -Oogenesis- -Oogenesis is controlled by FSH and LH, which are both controlled by GnRH.-The development of mature ________ from germ cells. During embryonic development, germ cells _____ migrate to the primitive gonads of the fetus (the ovaries), during ________ of pregnancy. Then the germ cells are converted into _________, which begin Mitotic cell division to proliferate (as opposed to sperm which begin Mitosis during puberty). After proliferation the Oogonia grow and develop into _______________, collecting an outer single layer of connective tissue that later becomes a follicle. The Primary Oocyte begins its first Meiotic division during fetal life but does NOT _______________. Female newborns are therefore born with a limited number of Primary Oocytes “arrested” in ____________. The Primary Oocyte stays dormant due to follicular cell secretions of _____________________________ until puberty, where it then continues to enlarge, and the single layer of connective tissue cells around it develops into cuboidal epithelial cells to form a protective __________________. Further maturation of the follicle into a Secondary Follicle results in ___________________________. During puberty, once a follicle begins this maturation process, the Primary Oocyte inside grows and completes its first Meiotic cell division, becoming a ____________________, where it stays “arrested” until _____________. Upon ovulation a single Secondary Oocyte (sometimes 2 or more) will begin _____________ but will NOT complete this second Meiotic division unless __________________ occurs.

-If fertilization occurs then the second Meiotic division completes, and the Secondary Oocyte becomes a fertilized oocyte (also called a Zygote, or mature ovum).-If fertilization does NOT occur, then _________________ follows ovulation, and the Secondary Oocyte is shed along with the Endometrial lining of the uterus.-Typically, one follicle containing one Primary Oocyte matures per monthly ovulation cycle.

-Birth control: can cause a reduction in Oocyte maturation, although by the age of 50-55 there is a complete reduction in Primary Oocytes which causes the onset of ___________________, where infertility is permanent. Contraceptives can increase blood pressure and may cause hypertension, acne, weight gain, emotional changes, and decreased or inhibited menstruation. Contraceptive pills typically consist of synthetic Estrogen and ________________, which suppresses ________ to inhibit ovulation and the menstrual cycle by mimicking the hormone levels present during pregnancy. This false pregnancy state keeps the ovary from maturing follicles and oocytes for fertilization, since in a real pregnancy this would cause a miscarriage.

-FSH (Follicle Stimulating Hormone) & LH (Luteinizing Hormone) in females: see menstruation & ovulation

-Male Fertility- -Depends on anatomic structure of sperm, the number of sperm, hormones, content of semen, and the anatomy of reproductive organs. Any change or deficiency from the norm can cause infertility. The __________ and ____________ release factors that provide nutrients to sperm into the semen (seminal fluid).-At least ___% of all sperm in ejaculate is unable to fertilize an oocyte due to structural abnormalities or immobility.-The average volume of seminal fluid in ejaculate is _____mL, which contains about 100 million sperm per mL of semen.

-Mature Sperm Structure- -Sperm structure is important for the fertilization of the ovum. The head contains the _______, which holds __ paternal chromosomes, ___ of which are somatic and __ sex-determining chromosome (either X or Y). The head is covered in a membrane called the _________, which contains the enzymes Acrosin, Prostaglandin, and ACE (Angiotensin Converting Enzyme). By releasing these enzymes, the head can digest outer layers of the ovum and penetrate it for fertilization. The paternal nucleus fuses to the maternal nucleus in the ovum and the egg is fertilized, becoming a ________, which contains ___chromosomes, ___ are somatic and 2 are sex chromosomes (XX or XY). The ______ arm of chromosome Y contains a gene that codes or the development of testicles in the fetus. The neck of the sperm contains ___________ which produce ATP to fuel motility of the sperm’s tail. Sperm begin to move faster once they reach the female reproductive tract and reach the Fallopian tube and Ampulla above the ovary to find and attempt to fertilize the ovum.-Sperm alone is not enough for fertilization, so semen (ejaculate fluid) not only contains sperm but some factors as well to facilitate fertilization: __________, _____________, ________, and ________-These factors provide energy for the sperm or help to accelerate their motility.-Abnormally shaped sperm cannot perforate the ovum-______________: an inability to produce normal amounts of sperm; can be due to a hormonal issue, FSH deficiency, Testosterone deficiency, or excess in Estrogen.

-The Male Reproductive System--The Endocrine system receives signals from the _________ and _______ to control the reproductive system. ________ from the Hypothalamus stimulates Anterior Pituitary Gonadotropic cells to secrete ____ and ____. FSH controls Spermatogenesis while LH controls the secretion of ________________ from Leydig cells.

-Sex determination in the male embryo:-Sertoli cells in the male fetus secrete _____________________. The Mesoderm layer of the embryo has tubes called _________________ which contain the gonad in the abdominal cavity before they descend. Parallel to them are the _______________________, which help to develop female reproductive organs (uterus, fallopian tubes, and vagina). The Anti-Müllerian Hormone from Sertoli cells ______________ Paramesonephric ducts from forming female reproductive structures. -A deficiency of fetal _____________________ leads to intersexuality, resulting in male genitalia and a uterus. Intersexuality can also be caused by a genetic disorder (Klinefelter’s Syndrome, XXY), a hormonal disorder (increased Estrogen), or by a conversion of sex hormones induced by fat tissue in obese patients. Fat tissue is full of the enzyme __________, which can catalyze the conversion of Testosterone into Estrogen, decreasing the Testosterone levels in obese males and leading to infertility.

-Erection, Emission, and Ejaculation- -Emissions consist of seminal fluid and sperm circulation, controlled by the Sympathetic Nervous System. -Ejaculation is controlled by both Parasympathetic and Sympathetic nervous systems. Ejaculate fluid consists of secretions from the _________ and ______________, which provides important nutrients and components to the sperm to facilitate ____________________ and increase the possibility of successful fertilization:

>____________, _____, _____, _______________, _________, _________

-Erection is controlled by __________________ vasodilation innervated by ___________ neurotransmitter, which stimulates ________ production to increase blood flow in the _____________ of ________________ tissue in the penis.

Ejaculate Pathway: In the testicles, sperm is contained in the ________________________ → Epididymis → ____________ → Seminal vesicle adds seminal fluid to sperm → _______________ → Prostate → __________

-The testes- -Seminiferous Tubules: contain sperm germ cells at different stages of maturation and make up _________% of volume of the testicle.-Sertoli cells: line the inner wall of __________________ and help regulate Spermatogenesis via Inhibin secretion to regulate ________ levels. These cells _________ divide-Leydig cells: secrete Testosterone as a response to LH secretion. The highest level of Testosterone secretion occurs during ______________.

-Female Fertility--The Menstrual Cycle: goes through 3 phases over 28 days.-1 st Phase ( ________________ ): First 2 weeks of the cycle, FSH levels increase to mature a follicle in the ovary-2 nd Phase (Luteal Phase): FSH decreases and LH increases during the midcycle (days 13-15), and Ovulation begins about _______ hours following the increase in LH. The follicle develops an avascular spot (without blood supply) called the ________, where the follicle ruptures to release the ________________. The remnants of the follicle convert into ______________, which secretes _____________ and __________ to help maintain and prepare the Endometrium of the uterus for the possible implantation of a fertilized egg. The Secondary Oocyte, covered in two layers, the ______________ and ______________, wait in the Ampulla of fallopian tubes for possible fertilization. -the Zona Pellucida is a protective layer around the ____________ that consists of ______________ material-the Corona Radiata is a protective layer around the ______________ that consists of ______________-3 rd Phase (Secretory Phase) : If no fertilization occurs then Estrogen levels drop, and menstruation occurs to shed the prepared layer of Endometrium and the unfertilized Secondary Oocyte. The Corpus Luteum degrades over ____________ following ovulation, becoming scar tissue called the _____________. Lasts 5-7 days. After menstruation, Estrogen levels increase again for the regeneration of the Endometrium and the development of another ovum.

-Ovulation: Occurs on days ______ of the menstrual cycle and is under the control of LH. If any sperm are present during these days, the ovum has a much higher chance of being fertilized. If fertilization occurs the Corpus Luteum grows into the __________________________ and increases Progesterone secretions. These secretions are under the control of _____________________________, which stimulates the Corpus Luteum to maintain specific levels of Progesterone secretion during the first trimester while the Placenta develops.-After the first week of pregnancy implantation of the ovum into the endometrium of the uterus occurs, and the formation of the primitive placenta begins. Placenta secretes _______ and maintains the Corpus Luteum during the first trimester. Corpus Luteum secretes Progesterone during the first trimester and then

degenerates at the end of the first trimester, so the Placenta takes over Progesterone production for the rest of the pregnancy. -Progesterone deficiency in pregnant females can cause _________________________________. -If there is no sperm present during ovulation or no fertilization occurs after day 15, the Corpus Luteum degenerates into scar tissue called the _______________. LH and Estrogen levels then decrease, and the unfertilized ovum and endometrial tissue layer are shed over the course of 5-7 days during menstruation.-After menstruation FSH and Estrogen levels increase again to start the process over.

-The Female Reproductive System: The uterus has a fundus and body, the wall has 3 layers: ____________, _____________, and Endometrium. The Endometrium is full of ______________. There are some ligaments supporting the structures and holding them in suspension within the pelvic bowl. For example: the ovarian ligament allows the ovary to be suspended above the uterus but still be directly attached to it (keeps ovary in place so it doesn’t get tangled with the fallopian tube). The fallopian tube covers the ovary with extensions called Fimbriae. The __________ is the lower opening of the uterus into the vagina.

-Fertilization--Normally takes places within the Ampulla of the uterine tubes during or after ovulation. During the Luteal (mid-cycle) phase of menstruation, the properties of the mucus layer of the cervix change to increase production of mucus that is thinner and watery. Cervix mucosal changes support sperm entry into the uterus and protects sperm from degradation by acidic vaginal secretions. Once the sperm reaches the Secondary Oocyte it must penetrate through the ______________ layer around the Zona Pellucida of the Oocyte. Then, using the degradative enzymes _______________ and ____________ stored beneath the ____________ layer of the sperm head, the sperm can degrade and penetrate the _______________ layer around the Secondary Oocyte. Once the sperm contacts the Secondary Oocyte, their plasma membranes fuse, which induces completion of _____________ in the Oocyte to become the _________________ (23 chromosomes, 22 somatic and 1 X sex chromosome) and the formation of the _________________ (23 chromosomes, 22 somatic and 1 sex chromosome, X or Y). Their nuclear envelopes degrade, allowing their chromosomes to condense together and prepare for ______________ as a single-cell_____________ with 46 chromosomes, 24 somatic and 2 sex chromosomes (XX or XY).

-Pregnancy- -Pregnancies typically take ______ weeks, or 266-280 days from the date of fertilization, to produce offspring.-After fertilization (penetration of sperm head into ovum via release of digestive enzymes that digest 2 layers of the ovum (the zona pellucida and corona radiata)) the paternal and maternal nuclei fuse to form a Zygote.-A missed period is a typical indicator of possible pregnancy, then blood or urine analysis can be done to detect the presence of _______________________________ as the chemical marker confirming pregnancy. -After fertilization, mitotic cell division occurs and the zygote doubles in cell number after each division, going from 1 cell->2 cells->4 cells->8 cells->16 cells, etc. -By day 5 the Zygote has already been implanted into the Endometrium and has proliferated into a _________, which secretes _______ to stimulate Progesterone secretion from the _______________, which then maintains the Endometrial lining so it can continue nourishing the Blastocyst until the ___________ develops. -As cell proliferation continues during the first 2 weeks of pregnancy the Blastocyst changes and forms 2 distinct layers, the _____________________ and the ____________________.

-The Trophoblast becomes the ___________________.-The Embryoblast develops into the embryo at weeks 3-4, then becomes the fetus at weeks 8-9.-During week 3 the Embryoblast develops 3 distinct layers: >___________: becomes CNS, PNS, Epidermis, lens, oracle (external ear), ganglion >___________: becomes dermis, connective tissue, blood, muscle, bone, reproductive organs, kidneys >___________: becomes the GI tract (except for oral cavity, anus and Endocrine glands)-After the 3rd week, the differentiation of stem cells (mother cells) for internal organ development occurs and they undergo cell proliferation for the development of those organs. -The first trimester (3 months) is important because the development of the CNS, PNS, Cardiovascular System and primitive forms of internal organs occurs during this time.-During the first 8 weeks the developing organism is called an _____________-From the 9th week of development until birth the organism is called a ___________-Pregnancy can be divided into 3 trimesters (3 months each): >during the 1st trimester the ________________ controls Progesterone secretion >during the 2nd and 3rd trimester the ___________ controls Progesterone secretion -The 1st Trimester is important for proper development and cell differentiation, so the patient’s diet, habits and non-strenuous activities should be healthy and consistent to support development.

-Labor and Parturition- -The duration of the pregnancy and childbirth is under the control of specific hormones.-____________ causes uterine contractions and the dilation of the cervix to allow the fetus to move into the vaginal canal.-Prostaglandins control labor and delivery: >Prostaglandin-F2α (PGF2A): >Prostaglandin-E2 (PGE2):

-hCG (human Chorionic Gonadotropin):-hCG binds to cell-surface _________ receptors on follicle cells and uses ________ as a Second Messenger.-hCG controls the follicle cells in the _____________ after fertilization to control the secretion of _________________, which helps to maintain and prepare the Endometrium layer of the uterus for implantation of the fertilized egg. hCG regulation of Progesterone is important during pregnancy, as a decrease can lead to _________________________________.