Human Physiology pt 1

What are the 4 general categories of specialized cells? Give a general description for each

1. epithelial cells

   • found at surface of body or hollow organ

   • specialized to secrete or absorb ions/organic molecules

2. connective tissue cells

   • form extracellular elements

   • connect, anchor, and support body structures

3. neurons

   • highly specialized cells for rapid communication

   • initiate, integrate, and conduct electrical signals

4. muscle cells

   • electrically excitable

   • key feature is that they can change their shape based on actin and myosin filaments that generate force and movement

What are tissues, organs, and organ systems?

• tissues = collections of cells that carry out related functions

• organs = collections of multiple tissue types that carry out related functions

• organ systems = collections of multiple organs that work together

What are the 10 physiological organ systems in the body?

1. integumentary system

   • skin

   • one of 2 barriers between you and outside world

   • forms a protective boundary that separates the body’s internal environment and external environment

2. digestive system

   • the other barrier between you and outside world; tube that takes outside world through the body essentially

   • takes up nutrients and water and eliminates wastes

3. reproductive system

   • produces eggs or sperm

4. immune system

   • provides defense against foreign invaders

5. endocrine system

   • coordinates body function through synthesis and release of regulatory molecules

   • one of two communication systems in the body

6. nervous system

   • the other communication system in body

   • coordinates body function through electrical signals and release of regulatory molecules

7. circulatory system

   • transports material between all parts of the body

8. respiratory system

   • exchanges O and CO2

9. musculoskeletal system

   • provides support and is responsible for movement

10. urinary system

    • maintains water and solutes in internal environment

    • waste removal

Explain how the outside world affects the cell turnover rate in the integumentary and digestive systems?

• integumentary and digestive systems are the 2 main protective barriers between internal and external environments 

• their cells are so abused by the outside world that they need to keep turning over the cells 

• they keep shedding and creating new cells at a relatively fast rate because of their contact with the outside world

Explain cellular differentiation

• cellular differentiation is a process that happens during development

• a single cell proliferates and those cells become specialized into the 4 functional groups

What is one important way in which cells regulate their own activity?

By maintaining differences in fluid composition across the cell membrane

What is intracellular fluid and what is extracellular fluid?

• intracellular fluid = fluid inside cells

  • distinct from ECF

• extracellular fluid = ECF

  • made of plasma and interstitial fluid

    • interstitial fluid = fluid directly in contact with outside of cells

    • plasma = fluid in blood; flowing around in cardiovascular system

  • serves as buffer zone bw cells and outside environment

What is the interstitium?

The space containing interstitial fluid 

What percent of body weight is water? What percentages are intracellular, plasma, and interstitial volumes?

• 60% of TOTAL body weight is water

• 2/3 of body FLUID is intracellular fluid

• of the remaining 1/3:

  • 20-25% is plasma

  • and remaining 75-80% is interstitial fluid

• another way to think about it is this:

  • 67% of ALL body FLUID is intracellular

  • 26% of ALL body FLUID is interstitial

  • 7% of ALL body FLUID is plasma

How does the ECF serve as a buffer zone bw cells? How is it for red and white blood cells?

• essentially all cells except for RBC and WBC are surrounded by interstitial fluid and the plasma from their nearest blood capillary also does buffering/exchange of materials

• however since RBC and WBC are already in the blood, they aren’t surrounded in interstitial fluid they only have the plasma

• when the ECF composition varies outside its normal range of values, the body has compensatory mechanisms that bring it back to the normal state

  • that is how the intracellular state is controlled/maintained

Compare the composition of intracellular fluid and extracellular fluid

• ICF = higher in protein and potassium (K+)

• ECF = lower in protein but higher in Na+

Compare the compositions of interstitial fluid and plasma

• both are quite similar but plasma has a much higher concentration of protein

  • think bc it has RBC, WBC, and cellular fragments

Why is there a greater difference in composition between ECF and ICF, compared to the difference between interstitial fluid and plasma?

• there is the cell membrane between the ECF and ICF keeping them separate and deciding what passes between them

• there is no such barrier between the interstitial fluid and plasma (blood capillaries are very leaky so they freely allow fluid to pass from one compartment to the other)

What is homeostasis? What is the term for when it is normal and what is the term for when it is not?

• homeostasis = relatively stable condition of internal environment that results from regulatory system actions

• physiology = when homeostasis is normal

• pathophysiology = when homeostasis is not normal

What is dynamic constancy? Give an example

• levels of a certain physiological variable change over short periods of time (dramatically) but over a long period of time they remain relatively constant

• ex)

  • blood sugar remains relatively constant throughout day but then spikes after a meal but then goes back to set point

What is a reflex?

• a specific INVOLUNTARY, unpremeditated, unlearned, built-in response to a particular stimulus

What is a reflex arc? What are the 7 parts of it?

1. stimulus = DETECTABLE change in internal/external environment

   • a change in a physiological parameter

2. receptor = detects stimulus

3. afferent pathway = takes signal from receptor to integrating center

4. integrating center = compares signal to set point and decides what to do next

   • can receive signals from many receptors at a time

5. efferent pathway = takes signal from integrating center to effector

6. effector = muscle or gland that carries out response

7. response = brings back environment to set point (in negative reflex arc at least)

REMEMBER: A comes before E in alphabet → afferent BEFORE efferent

• note actual body parts/organs/glands/etc are bolded; others are more so processes or pathways, etc

What is a negative feedback arc and what is a positive feedback arc?

• negative arc = response acts to counter the stimulus and bring it back to set point → HOMEOSTATIC

• positive arc = response reinforces stimulus and brings further away from set point → NOT HOMEOSTATIC

What is an example of a positive feedback arc/loop?

• childbirth 

  • basically, when a woman is in labor, the baby pushes on cervical stretch receptors which causes a signal to go to brain and indicate that labor has started, to which the brain produces more oxytocin. the oxytocin travels through blood down to uterine lining and causes more contractions, which leads to baby pushing against cervical stretch receptors even more (reinforcement of stimulus)

• in terms of a reflex arc:

  • stimulus: uterus drops and baby’s head pushes on cervical stretch receptors

  • receptor: the cervical stretch receptors

  • afferent pathway takes signal to brain

  • integrating center: hypothalamus → sends efferent pathway

  • efferent pathway → oxytocin, which gets circulated throughout body by vascular system and reaches the effector

  • effector organ = uterine lining

  • response = more contractions and pushing

What are 2 ways in which cells communicate short distance and 2 ways in which they communicate long distance?

1. if target is close:

   1. paracrine = signal diffuses to nearby cells

   2. autocrine = cell sends signal to itself but externally

2. if target is distant:

   1. endocrine = signal travels by blood circulation

   2. neuronal = signal transmitted by nervous system

What are two advantages of intracellular signaling pathways?

1. can amplify a signal → make small signal into big response in cell

2. can allow for tight regulation of pathway → cells can integrate multiple signals

What are 4 potential responses/effects a signaling pathway can cause in a cell?

1. immediate change in metabolism in the cell

   • ex) increased glycogen breakdown when a liver cell detects epinephrine

2. immediate change in electrical charge across plasma membrane 

   • source of action potentials

3. immediate change in regulation of cytoskeletal proteins 

   • affects cellular motility

4. change in transcription → takes more time

What is signal transduction?

• any process by which a cell converts one kind of signal to another

• can take millisecond to a few seconds

• signaling cascade → signal is amplified bc of increasing number of enzymes and second messengers, etc, with every step of the chain

  • can also lead to diversification of outcomes within cell bc of multiple second messengers

What is a second messenger? Give 2 examples

• a molecule (that is not a protein or peptide) that relays signals to target molecules in the cytosol and/or nucleus

• often times, serves to amplify signal

• ex) cyclic nucleotides

  • cyclic AMP → derived from ATP

  • cyclic GMP → derived from GTP

• ex) Ca²⁺

What are the 2 types of extracellular signal molecules? What are the examples we learned for each subcategory?

1. with intracellular receptors

   1. small/hydrophobic enough to cross plasma membrane by self

   2. examples:

      1. Nitric oxide (NO) → gasses can also be signaling molecules

      2. Cortisol → steroid molecules have intracellular receptors bc they are hydrophobic (derived from cholesterol)

2. with extracellular receptors

   1. too big/hydrophilic to cross membrane

   2. 3 types of hydrophilic cell signaling receptors:

      1. G-protein linked receptors

      2. ion-channel linked receptors

      3. enzyme linked receptors

Explain how nitric oxide (NO) works as a signaling molecule?

1. a nerve innervating an endothelial cell of the lumen of a blood vessel has a signal that causes it to release acetylcholine

2. the acetylcholine binds to the receptor of an endothelial cell of the lumen of a blood vessel, which opens gate for Ca²⁺ to enter cell

3. increased Ca²⁺ levels in cell, causes activation of NO synthase, which is the enzyme that breaks down arginine (amino acid) into NO

4. NO is a nonpolar gas molecule, which diffuses rapidly and acts as a paracrine signal to nearby smooth muscle cells of the blood vessel

5. NO enters smooth muscle cells, and activates the guanylyl cyclase, which is the enzyme that converts GTP to cGMP (cyclic GMP)

6. increased cGMP levels leads to dilation of smooth muscle cells by perturbing the cytoskeletal machinery→ causes blood vessel to dilate

   1. only happens in arteries and veins, not in capillaries bc capillaries have no smooth muscle cells

Explain how Viagra works

• Phosphodiesterase (PDE) are the enzymes that break down the cGMP and allow the smooth muscle cells to contract again, so pharmaceutical companies wanted to create a drug that would inhibit PDE so the smooth muscle cells could stay dilated for longer

  • another way this is phrased is that PDE is inhibited so NO signal is prolonged, but Viagra doesn’t actually affect the NO signal pathway by any way it just inhibits PDE so the cGMP isn’t broken down for a longer time

• original plan was to do this as a way to counteract hypertension → PDE inhibited would allow arteries to remain dilated and lower BP

• Pfizer made Viagra for this purpose, but found there are multiple types of PDE in the body, and the one that Viagra inhibited is found only in the male reproductive organ

• Viagra inhibits that specific PDE and counteracts erectile dysfunction by allowing smooth muscle to remain dilated for longer

How do steroid hormones work as signaling molecules? Give 4 examples

• all steroid hormones are derived from cholesterol and have the nonpolar ring structures allowing them to pass through plasma membrane easily

• the receptors for many of these steroid hormones are transcription factors

• process:

  • steroid hormones pass through plasma membrane and bind to transcription factor receptors

  • the steroid receptor complex then moves into nucleus and binds to regulatory region of the target gene and either activates or inhibits transcription of that gene

• ex) cortisol, estradiol, testosterone, and thyroid hormones

Where are hydrophilic cell signaling receptors found in a cell? What are the 3 types of hydrophilic cell signaling receptors?

• found on cell-surface (extracellular side of plasma membrane)

• 3 types

  1. G-protein linked receptors

  2. Ion-channel linked receptors

  3. Enzyme linked receptors

What are G-protein linked receptors?

• largest family of cell-surface receptors

• many types of G-protein receptors → specific to ligand

• all have trimeric G-proteins with y, a, B subunits and GDP attached to the a subunit during inactive state

• different effector proteins as well

What is the general process for all G-protein linked receptors?

1. hydrophilic ligand binds to extracellular side of receptor and causes conformational change to receptor on the cytoplasmic side

2. this change causes receptor to bind with G-protein, which causes GDP to be exchanged with GTP which activates the G-protein

3. once activated, the G-protein splits into By and a subunits that can both interact with target proteins in plasma membrane, but we are usually primarily interested in what the a subunit is doing → go and activate effector proteins

4. upon activating the effector protein, the a subunit replaces GTP with GDP and that shuts down the protein → the trimeric G-protein reunite

What effector protein do all G_s coupled protein receptors interact with?

adenylate cyclase

Explain the G_s protein linked receptor pathway

1. signal stimulus binds to the extracellular side of receptor and activates it

2. the activated receptor then activates the trimeric G_s protein

3. the a subunit of the G_s protein goes to adenylyl cyclase and activates it, which deactivates the G_s 

4. when adenylyl cyclase is activated, it catalyzes formation of cyclic AMP (cAMP)

5. cAMP is a 2nd messenger, which goes and activates Protein Kinase A (PKA)

   1. Phosphodiesterase quickly degrades cAMP

6. PKA moves into the nucleus and phosphorylates specific gene regulatory proteins

   1. PKA can also phosphorylate proteins in cytosol

7. when phosphorylated they go and stimulate the transcription of a whole set of target genes

Explain G_Q protein linked receptor pathway

1. ligand binds to extracellular end of receptor which causes intracellular part to bind to G_Q trimeric protein and activate it, causing a subunit to go and activate Phospholipase C (PLC)

2. the activated PLC cleaves PIP₂ into two different second messengers: IP₃ and DAG 

3. IP₃ binds to a ligand gated ion channel on the smooth ER, which opens a gate to allow Ca²⁺ to leave smooth ER

4. DAG goes to Protein Kinase C (PKC) and removes the inhibitory protein attached to it

   1. DAG is hydrophobic so it remains embedded in the intracellular side of the membrane

5. the Ca²⁺ from IP₃ subpathway also goes to PKC and helps it go do other stuff

6. basically DAG and IP₃ together maximize what PKC does

What does the G_i protein linked receptor pathway do?

• it inhibits adenylyl cyclase, in turn inhibiting production of cAMP, inhibiting activation of PKA, and inhibiting activation of gene regulatory proteins

What does G_t protein linked receptor pathway do?

• stimulates cGMP phosphodiesterase production

What degrades cAMP? Why is fast cAMP degradation necessary? What happens if cAMP is not degraded?

• Phosphodiesterase (PDE) degrades cAMP

• it is important to shut down cAMP quickly to maintain sensitivity of the cell to the extracellular signal molecules

Give an example of a natural phosphodiesterase inhibitor and explain how it works

• Caffeine is a natural inhibitor of PDE that breaks down cAMP

• it allows cAMP to continue staying in the cell, causing PKA to continue being activated

• in neuronal cells, the PKA continuing being activated leads to improved synaptic transmission and increased neuronal activity → which is why caffeine is a stimulant 

What are the two ways in which G protein pathways are regulated? (at least the ones we studied)

• the G protein a subunit is self-regulating in the sense that it turns off (replaces GTP with GDP) after activating effector protein

• Phosphodiesterase breaks down the cyclic nucleotides (cAMP or cGMP) to preserve sensitivity of cell receptor to signal

Explain how ion channel-linked receptors work

1. a ligand binds to ion channel protein gate on receptor on extracellular side 

2. this causes a conformational change in the shape of the gate, making it go from closed to open

3. ions (Na+, K+, Ca2+, Cl-, etc) can be let out or in depending on concentration gradient

How do ion channel-linked receptors convert signals?

• they convert a chemical signal (in the form of a hydrophilic ligand) into an electrical signal because ions bring a charge with them whether they are leaving or entering the cell, and therefore cause a change in voltage across the plasma membrane of that cell

• this is especially important in the nervous system

How do enzyme linked receptors work? Give the name of an example

• ligand binds to receptor, causes conformational change in the enzyme, triggering activity

• ex) receptor tyrosine kinases (RTK)

What are receptor tyrosine kinases (RTKs)? Give a specific example

• basically RTKs cause assembly of an intracellular signaling complex on the intracellular tail of the receptor (from trans-autophosphorylation after dimerization of receptors) 

• specific example we studied was the Epidermal Growth Factor receptor pathway → note even tho pathway name is EGF the main enzyme is the RTK

Explain how the epidermal growth factor receptor pathway works

1. 1 epidermal growth factor (EGF) binds to extracellular end of 1 epidermal growth factor receptor (EGFR) 

2. this causes dimerization of the EGFR 

   1. basically another EGF must bind to another EGFR and that causes two of them to bind to each other (dimerize)

3. this dimerization causes enzymatic activity that causes trans-autophosphorylation basically all the tyrosine residues on the EGFRs get autophosphorylated

4. the phosphorylated tyrosine residues activate downstream scaffolding cytoplasmic proteins

   1. the tyrosine on the EGFR are called receptor tyrosine kinase (RTK)

   2. scaffolding proteins are aka adaptor proteins

5. these proteins build a bridge between the (RTK) and the Ras protein, activating it

   1. unactivated, the Ras protein has a GDP but upon activation it gets a GTP (Ras GDP → Ras GTP)

   2. the Ras protein is bound to plasma membrane on cytoplasmic side by a lipid tail

6. when activated, Ras protein activates a phosphorylation cascade

   1. phosphorylates MAP-kinase-kinase-kinase. which phosphorylates MAP-kinase-kinase, which phosphorylates MAP-kinase, which phosphorylates several other target proteins

   2. these other target proteins can affect cell metabolic activities or activate transcription factors etc.

7. eventually causes cell growth in case of EGF

How similar are all growth factor receptor pathways?

• they have different signaling ligands and different ligand-specific receptors, but the main process is the same

• the pathways all activate the Ras-GTP

• once Ras-GTP is activated it will cause proliferation of the cell

What is the connection between the Ras gene and cancer?

• ~30% of human cancers involve mutations of the Ras gene that cause it to be constitutively activated

  • basically a mutation of the gene causes Ras proteins to always be bound to GTP (turned on) therefore constantly stimulating cell proliferation

  • uncontrolled cell proliferation is cancer

• Ras protein is a monomeric GTP protein which dephosphorylates the GTP to GDP and turns itself off under normal conditions

Why do drugs have side effects?

• signaling pathways are highly interconnected

• a drug is made to affect one pathway but may have unintended impacts on the effects of other pathways too which causes side effects

What is the endocrine system? Also, give four examples of organs you don’t expect to be a part of the endocrine system but are

• one of the two major communication systems in the body

• made of glands and hormone secreting cells

• includes glands exclusive to endocrine system but also other organs (such as heart, kidneys, liver, and stomach) that you don’t expect to be part of the endocrine system but they are bc they produce hormones

What are main differences between the two major communication systems of the body?

• nervous system is very fast and directly sends signal to targeted spot it wants to, however, endocrine system is much slower and sends signal throughout body through the vascular system but only cells with correct receptors elicit a response

• this is also why endocrine system signals are longer lasting than nervous system signals

What is the difference between a neurohormone and a neurotransmitter?

• neurotransmitter = neuronal chemical signal released at the synapse by a neuron

• neurohormone = neuronal chemical signal released directly into bloodstream by a neuron/neurosecretory cell

Briefly go over what it means if a single endocrine gland is secreting multiple hormones and give an example

In general, single cell types in glands secrete only one hormone. This means, multiple hormone secreting glands have different types of endocrine cells producing and secreting different hormones.

ex) pancreas

Explain pancreas as a multiple hormone secreting endocrine gland. What are the 3 main hormones it produces and how does its structure allow that?

• Hormones:

  • insulin = lowers blood glucose levels

  • glucagon = increases blood glucose levels

  • somatostatin = inhibits secretion of pancreatic hormones

• Islets of Langerhans = endocrine areas of the pancreas in which there are alpha, beta, and delta cells

  • alpha → glucagon

  • beta → insulin

  • delta → somatostatin 

What is the difference between exocrine and endocrine glands? Give example with pancreas

• exocrine = gland that secretes into a duct from where secretion either leads out to lumen of organ or from where they exit the body

  • ex) part of pancreas (called acinar cells) producing and secreting digestive enzymes → goes from pancreas to intestines 

• endocrine = gland that has no ducts and secretes into interstitial fluid which diffuses into bloodstream

  • ex) part of pancreas (islets of Langerhans) producing and secreting insulin, glucagon, and somatostatin

What are the 3 major chemical classes of endocrine hormones? Give brief description of each

1. amine hormones

   • derived from the amino acid tyrosine

   • made by thyroid gland, adrenal medulla, and hypothalamus

2. peptides and proteins

   • largest class of endocrine hormones → makes up most endocrine hormones

   • produced in tissues all over the body

3. steroids

   • lipids with ring-like structures

   • primarily produced by the adrenal cortex, gonads, and placenta during pregnancy

What are 4 examples of amine hormones? How are they produced?

• 4 examples:

  • 1. thyroid hormones (T3 and T4) → produced in thyroid gland

  • catecholamines → produced in adrenal medulla

    • 2. epinephrine (aka adrenaline)

    • 3. norepinephrine (aka noradrenaline)

    • 4. dopamine → produced in hypothalamus

• they are produced by thyroid gland, adrenal medulla, and hypothalamus

• they are all derived from tyrosine, which is an amino acid

  • which hormone that tyrosine gets converted to in that secretory cell, depends on the enzymes present within that cell 

What are the thyroid hormones?

The thyroid hormones are T3 and T4 and they are amine hormones derived from tyrosine and iodinated 

Why is iodine so important in our diets?

• iodine is essential to make the T3 and T4 (thyroid hormones) functional

• thyroid hormones are essential in metabolic processes, and if they are not iodinated properly, they will not work

  • if T3 and T4 are messed up, then person is lethargic and does not grow properly 

• if the body has insufficient iodine for extended time, it can form a goiter which is proliferation of thyroid cells in an attempt to make more T3 and T4 

• which is why salt is iodized to make sure ppl are getting enough iodine

What are catecholamines?

• amine hormones with the catechol groups

• dopamines, epinephrine, norepinephrine

What does iodine do to thyroid hormones that makes them different from catecholamines?

• the iodination allows thyroid hormones to pass through plasma membrane more easily → thus they can have intracellular receptors

• however, catecholamines cannot pass easily through plasma membrane so they need extracellular receptors

What are peptides and proteins? Gvie 2 examples

• the largest class of endocrine hormones

• made not just by exclusively endocrine system hormones

• examples

  • insulin

  • glucagon

• they have extracellular receptors because they are hydrophilic

What are insulin and glucagon? How do those pathways work?

• insulin and glucagon are produced and secreted by the beta and alpha cells of the pancreas, respectively

• the beta and alpha cells act as both receptor and integrating center for blood glucose levels

  • they monitor blood glucose levels

  • if too high (above 110) → release insulin → goes to liver or muscle cells to get them to take up glucose and convert to glycogen

  • if too low → release glucagon → goes to liver to release stored glucose

• in this way, insulin and glucagon act as efferent signals

How are peptide hormones made? Give the example of insulin

process:

1. preprohormones are large and inactive polypeptide chains encoded by the mRNA

   1. contains signal sequence, one or more copies of the hormone, and additional peptide fragments

2. the signal sequence takes preprohormone to the rough ER, where the signal sequence is cleaved off, making it an inactive prohormone

3. the prohormone travels to Golgi apparatus, where it is packaged into secretory vesicles

4. within the vesicles, prohormone is cleaved into the final hormone and the inactive parts

Example of insulin:

1. preproinsulin goes to rough ER, where the signal sequence is cleaved off, making it proinsulin

2. the proinsulin goes to Golgi apparatus where it is packaged into vesicles

3. the enzymes cut the proinsulin into insulin and C-peptides

4. the vesicles store the insulin and C-peptides until ready to be released via exocytosis

How is insulin measured in body, usually by diabetic patients?

• C-peptide levels are measured because insulin as pretty short half-life, but C-peptide does not → it can be used as a marker of insulin secretion

What are steroid hormones? Give 4 examples with a brief description of each

• steroid hormones are lipid hormones derived from cholesterol 

• examples

  • cortisol 

    • aka stress hormone

    • glucocorticoid

    • secreted from adrenal cortex

    • regulates metabolism during stress

  • aldosterone

    • mineralocorticoid

    • promotes Na⁺and H₂O reabsorption 

  • testosterone - sex hormone

  • estradiol - sex hormone

How long before release are steroid hormones synthesized?

• steroid hormones are released as soon as they are synthesized because they are lipids → they can pass through the plasma bilayer so there’s no way to hold them back and wait till release

How are steroid hormones synthesized?

1. an anterior pituitary gland hormone binds to cell surface receptor

2. intercellular end of receptor activates trimeric G_s protein

3. G_s protein a subunit goes and activates adenylyl cyclase

4. activated adenylyl cyclase produces cAMP, which activates PKA

5. activated PKA phosphorylates many proteins including cholesterol esterase

6. activated cholesterol esterase releases free cholesterol from liquid droplet (from LDL) that exists in the cell

7. the free cholesterol is transported to the mitochondria where it is processed in many steps and shuttled between the smooth ER and the mitochondria

8. once formed, the steroid hormone diffuses out of the parent cell and travels to target cell (sometimes with help of carrier protein) and diffuses into target cell

How do carrier proteins help certain hormones? Give some examples

• they help transport steroid hormones and thyroid hormones through the blood to get to their target cell because they are both hydrophobic so they don’t like being in the blood

• ex)

  • corticosteroid-binding globulin → helps cortisol

  • albumin → general protein 

Explain the parts of the adrenal gland and what hormones they produce

• 2 adrenal glands (one on top of each kidney but doesn’t really impact kidney filtration function)

• capillary beds go all the way in to ensure hormones can be transported easily

• 2 main parts:

  • adrenal medulla

    • inside part

    • ¼ of mass

    • secretes catecholamines (epinephrine and norepinephrine)

      • secretes 4 times more epinephrine than norepinephrine

      • involved in fight or flight response

  • adrenal cortex

    • outside of medulla

    • ¾ of mass

    • has 3 layers from closest to medulla to furthest out:

      • Zona reticularis → sex hormones

      • Zona fasciculata → glucocorticoids

      • Zona glomerulosa → aldosterone

stupid memorization trick: meri raat faltu gayi

What are the two factors upon which a hormone’s plasma concentration depends?

1. rate of secretion by endocrine gland

2. rate of removal (clearance)

   1. happens either by excretion or by metabolic transformation

What are the 3 possible ways that a hormone can be removed (cleared)?

1. metabolized or excreted by kidneys and liver

2. metabolized by target cell by way of endocytosis of hormone-receptor complex

3. enzymes in blood 

What are the 4 ways in which hormones can interact with one another in a cell?

1. Permissiveness

   1. hormone B can only exert its full effect when hormone A is present 

   2. one possible mechanism is that this happens because hormone A upregulates the expression of receptors for hormone B

   3. ex) epinephrine can release large amounts of fatty acids from adipose tissue but only in the presence of thyroid hormones bc thyroid hormones stimulate the synthesis of B-adrenergic receptors for epinephrine in adipose tissue

2. Additive

   1. when hormones are combined, their combined effects are added together (measuring same factor ex. blood glucose)

3. Synergistic

   1. when hormones are combined, their combined physiological effect is far greater than additive 

4. Antagonistic  

   1. opposite effect

What are the 3 types of inputs that control hormone secretion in endocrine cells? Explain all 3 in the example of insulin secretion from pancreatic B cells.

1. changes in plasma concentrations of ions or organic nutrients

   • ex) increase in blood glucose concentration can trigger release of insulin

2. neurotransmitters released from neurons ending on the endocrine cell

   • ex) stretch receptor in digestive tract, send afferent signal to CNS, which sends efferent signal to pancreas to release insulin

3. another hormone acting on the endocrine cell

   • ex) blood glucose also releases Glucagon-like peptide-1 (GLP-1) from endocrine cells in small intestine

   • GLP-1 is another hormone that promotes insulin secretion from pancreas

often times cells are receiving simultaneous opposing inputs and the rate of hormone secretion reflects the integration of all of these inputs

ex) insulin secretion from pancreatic B cells is regulated by all 3

What are the 2 main categories of disease in endocrine systems? What are the 4 total endocrine disease types within those 2 categories? Give examples

1. disease from abnormal hormonal secretion

   1. hyposecretion = too little hormone

   2. hypersecretion = too much hormone

2. disease from abnormal responsiveness of target cells

   1. hyporesponsiveness = reduced responsiveness

   2. hyperresponsiveness = increased responsiveness

Example:

• Type 1 diabetes mellitus → hyposecretion of insulin

  • patient has reduced number of active pancreatic B cells so not enough insulin is produced

• Type 2 diabetes mellitus → hyporesponsiveness

  • patient has reduced cellular sensitivity to insulin, so not enough responsiveness

What is the most important control area for homeostatic regulation of the internal environment?

the hypothalamus

What is the pituitary gland?

• two glands with different embryological origins that fused during development

• not considered part of the brain → sits in protected pocket of bone, connected to the hypothalamus (which is part of the brain) by a thin stalk called the infundibulum or pituitary stalk

• together the hypothalamus and pituitary gland regulate essentially every part of the body

What are the 2 parts of the pituitary gland? Describe both of them

1. anterior pituitary gland 

   1. anterior = closer to front of body

   2. the anterior pituitary is a true endocrine gland of epithelial origin

2. posterior pituitary gland

   1. not a true gland but rather just an extension of the hypothalamus → no endocrine cell bodies found here

      1. the hypothalamus sends its axons down

   2. secretes neurohormones synthesized in the hypothalamus

      1. oxytocin → milk ejection and childbirth

      2. vasopressin → water regulation

Label all of the parts of this diagram

1. hypothalamus

2. supraoptic nuclei

3. paraventricular nuclei

4. infundibulum

5. posterior pituitary

6. anterior pituitary

7. sphenoid bone

What do nuclei refer to in the central nervous system? What are the two nuclei in the posterior pituitary and what do they do?

• nuclei = cluster of nerve cell bodies in the central nervous system

• the two nuclei in the posterior pituitary are neurosecretory endocrine cells - even tho they look like neurons

  • they both extend axons to posterior pituitary and synthesize the neurohormones: Vasopressin and Oxytocin

  • end of axons terminate in interstitial fluid - not into a synapse and that is why they are not neurons

    • Supraoptic nuclei → just above the optic nerve 

    • Paraventricular nuclei

Describe the two posterior pituitary neurohormones

• Oxytocin and vasopressin

• both are small peptide neurohormones made of 9 amino acids each

• Oxytocin:

  • involved in 2 reflexes:

    • ejection of milk in response to stimulation of nipples during nursing

    • stimulation of contractions of uterine smooth muscle cells in response to stretch receptors being activated in the cervix during birth

• Vasopressin

  • aka antidiuretic hormone (ADH) 

  • acts on the kidneys to regulate water balance in body

What is the process of neurohormones being secreted from posterior pituitary gland?

1. neurohormone (oxytocin or vasopressin) is made and packaged in cell body of neuron (supraoptic nuclei or paraventricular nuclei)

2. vesicles transport it down axons

   1. in the infundibulum

3. vesicles containing the neurohormone are stored in axon terminals were they wait for a release signal

   1. axon terminals are in the posterior pituitary gland itself

4. the signal - in the form of an action potential - passes down neuron and releases neurohormones into blood

What is the structure of the anterior pituitary gland? How do neurohormones get from hypothalamus to anterior pituitary gland?

• several hypothalamic nuclei send axons from hypothalamus to median eminence → these nuclei are what primarily regulate the anterior pituitary

  • median eminence = where hypothalamic axon terminals end

• those neurosecretory cells release neurohormones into interstitial fluid then to capillary bed in the median eminence 

• from the capillary bed, portal vessels take neurohormones to all over body, but primarily they take them from median eminence to anterior pituitary, where they leak into interstitial fluid again and get to endocrine cells in the anterior pituitary

What regulates the anterior pituitary gland endocrine cells?

• Hypophysiotropic hormones

  • aka hypothalamic inhibiting/releasing hormones

• some non-hypothalamic hormones also influence the anterior pituitary gland - involved in some feedback inhibition

What is the structure of the anterior pituitary? What is the name of the circulatory region through which neurohormones from the hypothalamus reach the anterior pituitary gland?

• hypothalamic neurons/neurosecretory cells (bc they secrete into capillaries not synapses) synthesize hypophysiotropic hormones in cell bodies and extend axons down to median eminence 

• here the neurosecretory cells release their neurohormones into capillaries of the hypothalamic-hypophyseal portal system

• portal vessels carry hormones directly to anterior pituitary endocrine cells

• from their the endocrine cells release their hormones to second set of capillaries that distribute them to rest of body

What is the 3 hormone sequence through which hypophysiotropic hormones act?

1. Stimulus

2. Hypothalamus → Increase in Hormone 1 secretion

3. increase in Hormone 1 plasma concentration in hypothalamo-pituitary portal vessels (aka hypothalamic-hypophyseal portal system)

4. Anterior pituitary → increase in Hormone 2 secretion

5. Increase in Hormone 2 plasma concentration

6. Third endocrine gland → Increase in Hormone 3 secretion

7. Increase in Hormone 3 plasma concentration

8. Target cells of Hormone 3 → response to Hormone 3

What is the 3 hormone sequence for producing insulin-like growth factor in the liver?

1. Hypothalamus releases GHRH into portal vessels

2. GHRH stimulates anterior pituitary to produce GH

3. GH goes through vascular system to reach the liver, which then produces IGFs (insulin-like growth factors)

4. IGFs go to bone and soft tissue to stimulate growth

What are the 6 hypophysiotropic hormones and what tropic hormones do they regulate?

• FSH and LH

  • 1. GnRH = gonadotropin releasing hormone

    • stimulates release of FSH and LH (gonadotropins)

• ACTH

  • 2. CRH = corticotropin releasing hormone

    • stimulates release of ACTH (corticotropin)

• TSH

  • 3. TRH = thyrotropin-releasing hormone

    • stimulates release of TSH (thyrotropin)

• Prolactin

  • 4. DA = dopamine 

    • inhibits release of Prolactin; prolactin is produced only in absence of dopamine, there is no stimulatory hormone

• Growth Hormone - under dual control

  • 5. GHRH = Growth Hormone Releasing Hormone

    • stimulates release of GH

  • 6. SS = Somatostatin

    • inhibits release of GW

What are the 6 peptide hormones the anterior pituitary secretes? Give a brief description of them

• Tropic hormones = hormones that ONLY stimulate other endocrine glands

  1. FSH = Follicle-Stimulating Hormone

     • gonadotropic

  2. LH = Luteinizing Hormone

     • gonadotropic

  3. ACTH = Adrenocorticotropic Hormone

     • tells adrenal cortex to make and secrete cortisol

  4. TSH = Thyroid Stimulating Hormone

     • tells thyroid gland to make and secrete T3 and T4

• hormones that stimulate another body part DIRECTLY

  1. Prolactin

     • milk producing hormones goes to mammary glands

  2. i → ignore; just to help with memorization

  3. GH = Growth Hormone

     • tells liver to make and secrete the growth promoting hormone (which is an insulin-like growth factor)

How is ACTH synthesized in the anterior pituitary from POMC protein?

• POMC = pro-opiomelanocortin

  • precursor protein to ACTH, synthesized in Golgi apparatus of endocrine cells in the anterior pituitary gland

• in post-translational processing, POMC gets cut into:

  • ACTH

  • y-lipotropin (alpha lipotropin)

  • B-endorphin (beta endorphin) → endogenous opioid that helps block pain

• after acting as a hormone, ACTH can get further processed in non-pituitary tissues:

  • a-MSH 

    • stimulates melanin synthesis, immune response, and decreases food ingestion/intake

Where are hypophysiotropic hormones produced and where are tropic hormones produced?

• hypophysiotropic → produced in hypothalamus, pass through median eminence, and pass via the portal vessels to get to the anterior pituitary

• tropic → produced in anterior pituitary

Explain how negative feedback is used to control the hypothalamo-pituitary system and the two loops through which this can be done

• one hormone out of the 3-hormone pathway will go back and switch off the pathway at some point

• can be done in two ways:

  • short-loop: when hormone goes to switch off the one before

    • ex) pituitary hormone feeds back to switch off hypothalamic hormone secretion

    • ex) hormone 3 feeds back to pituitary gland to switch off hormone secretion

  • long-loop: when last hormone goes to switch off hypothalamus

    • ex) hormone 3 goes to pituitary to switch off hormone 2 production and to hypothalamus to switch off pathway

Explain the milk ejection reflex in terms of prolactin and oxytocin

• prolactin

  • anterior pituitary hormone

  • stimulates milk PRODUCTION

• oxytocin

  • posterior pituitary hormone

  • involved in control of milk EJECTION

What is cortisol?

• steroid hormone secreted from adrenal cortex

• stress hormone

• plays direct role in mediation of chronic stress

What is stress as used in biology?

• any change in the environment that changes or threatens to change an existing optimal state

• most stresses activate homeostatic reactions at the molecular, cellular, or systemic level

What is the control pathway for cortisol secretion?

• hypothalamic-pituitary-adrenal (HPA) pathway

• 1) corticotropin-releasing hormone (CRH) is secreted by the hypothalamus into the hypothalamic=hypophyseal portal system

  • this secretion is stimulated by circadian rhythm or by stress

• 2) CRH stimulates release of adrenocorticotropic hormone (ACTH) from anterior pituitary gland

  • ACTH aka corticotropin

  • from anterior pituitary it passes into interstitial fluid and then into the capillaries/vascular system all through simple diffusion

• 3) ACTH goes to adrenal cortex (zona fasciculata) to promote synthesis and release of cortisol

• 4) cortisol acts as negative feedback signal and inhibits ACTH and CRH secretion

  • cortisol can inhibit ACTH and CRH

  • ACTH can inhibit CRH and stimulate cortisol

What is the most important metabolic effect of cortisol in non-stress conditions?

Protection against hypoglycemia

• when blood glucose drops, pancreas secretes glucagon

  • glucagon promotes gluconeogenesis and glycogen breakdown

• in the absence of cortisol, glucagon cannot respond adequately to a hypoglycemic challenge

• cortisol has permissive effect on glucagon and catecholamine activity

What does cortisol do in non-stress conditions and how?

• cortisol has permissive effect on glucagon and catecholamine activity

  • protects liver against hypoglycemia

    • when blood glucose levels drop, pancreas secretes glucagon to bring it back up through gluconeogenesis and glycogen, but glucagon can’t do that adequately without the presence of cortisol

  • helps arterioles maintain normal blood pressure

    • has permissive action on the reactivity of catecholamines by smooth muscle cells that surround arterioles → cortisol basically increases vascular smooth muscle responsiveness and promotes vasoconstriction

    • basal levels of cortisol help maintain normal blood pressure

What has happened in experiments when adrenal glands have been removed?

the subjects have died when exposed to any significant environmental stress

What impact does cortisol have on the immune system? How does it do this?

• Cortisol suppresses immune system

  • cortisol prevents cytokine release and antibody production by WBC

    • cytokine signals white blood cells to activate and proliferate

  • cortisol inhibits inflammatory response by decreasing leukocyte mobility and migration

    • leukocytes are WBC, so very important for immune system

What are pharmaceutical applications of cortisol?

• because cortisol inhibits inflammatory response by decreasing leukocyte mobility and migration it has been used as an anti-inflammatory drug

• can be used to treat bee stings, pollen allergies or even to prevent the rejection of transplanted organs

What do cortisol pathologies usually result from? What are the 2 main types? What is an uncommon cause?

• cortisol pathologies result from too much or too little cortisol

• 1) hypocortisolism

  • cortisol deficiency

• 2) hypercortisolism

  • cortisol excess

  • aka Cushing’s syndrome

Abnormal tissue responsiveness is an uncommon cause of adrenal steroid disorders