Homeostasis, Cells Flashcards

1
Q

Homeostasis

A

-Conditions within the body, the internal environment, that are maintained at near constant conditions
-WALTER CANNON
-The internal environment refers to everything under our skin, which is about 35 trillion cells
-The body has sensors and feedback mechanisms to maintain homeostasis
Ex: Maintaining body temp of 37C. Shivering or sweating

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2
Q

Anesthesia & Homeostasis

A

-Anesthesia takes your feedback mechanisms and takes them completely offline
Ex: Paralyzing in the cold OR, body can no longer shiver to bring core temperature up

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3
Q

What do cells need to maintain homeostasis?
Forms of input and output

A

-Cells need reasonably constant conditions and a supply of energy;
-Input for energy is oxygen, food such as sugar, fats
-Output is energy (work, heat, potential energy) and waste products such as;
-CO2: byproduct of metabolism
-H+: Protons formed during a chemical rxn
-urea (not useful, body needs to get rid of it as it’s being produced)
and H2O, solid waste

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4
Q

Homeostasis Examples: Kidneys

A

-Responsible for maintaining BP at a normal level
-Responsible for the majority of our ECF buffering abilities
-Generate buffers and make sure that our buffer levels are w/in normal constraints in the body

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5
Q

Homeostasis Examples: GI

A

-Replaces nutrients in the blood as they’re being used or consumed by cells

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6
Q

Homeostasis Examples: Lungs, Heart

A

-Lungs: Helps regulate our blood gasses
-Heart: Essentially two pumps separated by a wall (septum)
- L & R heart pump are responsible for making sure that we get a decent amount of gas exchange happening w/in the lungs and that we peripheral cardiovascular system is supplied with the proper nutrients

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7
Q

Homeostasis: Peripheral Vascular Beds

A

-Blood flows into tissue through the arteries and into the arterials.
-The fluid being brought in by the CV system has the opportunity to deliver nutrients that the cells are going to be using, and removes wasteful byproducts via the venous system.
-The amount of blood that flows through a tissue is determined by the metabolic demand of that tissue

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8
Q

Homeostasis: Peripheral Vascular Beds, Arterial Side

A
  • If the cells are really active, the composition of the ECF changes. Because the cell is pulling in oxygen and nutrients, there will be a deficiency in the ECF
    • This change is picked up by sensors w/in the CV system–> increased blood flow to that area to bring levels back to normal
      -This process is very tightly controlled and delivers only enough to meet tissue needs **
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9
Q

Homeostasis: Peripheral Vascular Beds, Venous Side

A

-Because blood flow increases on the arterial end, it should also increase on the venous end to help remove wasteful byproducts at a faster rate because of the increased metabolic demand

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10
Q

Negative Feedback Mechanisms

A

-Major control system w/in the body. Almost all systems are managed via negative feedback
-Positive or negative changes are detected by a sensor somewhere out in the periphery and the body counteracts/opposes that change
-Change is always opposite or negative to the initial change

Ex: pH or CO2 levels are changing. The body responds to correct the change occurring. The sensor detects the change, feeds that information back to the “controller,” and the controller acts to correct the problem

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11
Q

Negative Feedback Example; BP change

A

-BP goes from 100mmHg to 50mmHg. Sensors in periphery send information back to the CNS, the CNS acts to bring the BP up by squeezing your blood vessels or making the heart pump harder.
-CNS increases sympathetic outflow (increased circulating norepinephrine)
-CNS decreases parasympathetic outflow
-Circulating compounds such as vasopressin (ADH) increase
-Atrial natriuretic peptide levels decreased
-This is a negative response to the original stimulus. We are counteracting it
Remember: Negative feedback works the same way a thermostat in a house does

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12
Q

Negative Feedback Example: CO2 Levels

A

-CO2 levels rising in the blood stream
–> brainstem senses–> ventilation increases

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13
Q

Positive Feedback Loop

A

-Stimuli in the body/outside the body causes some type of change
-The body responds by amplifying this change
-Good for some things
-Can be bad, potentially terrible, for other things
-Vicious cycles can happen with pathologic positive feedback loops (typically avoided w/ physiologic positive feedback loops)
-There are checkpoints in place that turn off the physiologic positive feedback loop

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14
Q

Physiologic Positive Feedback Loop Example; Oxytocin during L&D

A

-Uterus contracts–> pushes the fetus towards the cervix–> cevix stretches out after being exposed to pressure from the fetus
-In response to the cervical stretch, oxytocin is released from the brain. It acts on smooth muscle in the uterus and causes more contractions–> pushes fetus more–> cervix stretches more–> more oxytocin released
-Birth of the child is the “check point” that shuts this feedback loop off. Oxytocin levels decrease, contractions stop

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15
Q

Physiologic Positive Feedback Loop; Blood clotting

A

-Blood vessel is injured (scalpel in the OR?)–>it bleeds–> coagulation factors are liberated when the endothelial cells are damaged and those factors influence platelet plug formation
-In platelet plug formation & coagulation cascade activation, coagulation & platelet plug formation speeds up as more time passes
-Under normal circumstances, this continues until the bleeding stops
-The coagulation factors will either get covered up, put back into the cell, run out, and all of this signals for the coagulation to stop
-The checkpoint here should be that the bleeding has stopped. If coagulation didn’t stop, the blood vessel would become occluded

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16
Q

Pathologic Positive Feedback: Severe Hemorrhage

A

-We lose a significant amount of blood
–> BP is decreased–> coronary blood flow is reduced
-If our coronary blood flow is reduced while our BP is low, our heart is trying to correct the problem but coronary perfusion is insufficient to keep up with the metabolic demands of the heart –> cardiac output drops–> BP is reduced even more–> If allowed to progress unchecked, death with probably occur
Positive feedback loop that has run completely out of control

-We can typically handle a 20% blood loss if otherwise healthy. The pumping effectiveness of the heart is initially reduced and cardiac output is decreased; however, cardiac output should be back to normal w/in a few hours
-Blood vessels are going to squeeze, the heart is going to try and pump harder, and there will be massive fluid shifts that rearrange volume w/in the body (fluid shifted into cardiovascular system from out spaces)
-40% blood loss will likely result in death

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17
Q

Pathologic Positive Feedback: Sepsis/Necrosis

A

-Sepsis –> widespread infection –>cells in the body are dying at a rate faster than they can the body can manage
–> toxic, metabolic byproducts, potassium w/in dying cells are released into the internal environment surrounding the neighboring cells–> neighboring cells begin to die

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18
Q

Pathologic Positive Feedback: Severe Acidosis/CNS Effects

A

-Severe acidosis–> CNS is affected–> respiratory drive is reduced–> perpetuates the acidosis making us more acidotic

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19
Q

Pathologic Positive Feedback: Kidneys

A

-Each kidney has ~ a million nephrons
-As we age (45yrs +), nephrons begin to die and the remaining nephrons have to carry a larger load–> the larger the load placed on the remaining nephrons, the more likely those nephrons are to die
-The older we get, the faster this process happens–> some degree of renal failure

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20
Q

Cells: Basic Functional Unit

A

-Smallest living unit
-Specialized for specific tasks (skin cells, lung cells for gas exchange)
-Usually capable of replication
~35 trillion human cells per body, 25trillion of those being RBCs
-Cells are capable of sustaining their own lives because of everything that is contained w/in them (enzymatic machinery to create ATP –> energy for cell)

Groups of cells that are like-minded–> Tissues–> Organs–>Body

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21
Q

Cells; Replication

A

-Typically capable of replicating themselves
-If unable to replicate themselves, there is typically a progenitor cell nearby that can perform that task
-RBC’s cannot replicate themselves; however, there are progenitor stem cells within the bone marrow that are capable of producing RBCs
-Lifespan is ~90-120days
-RBCs do not have a nucleus or genetic material to create copies of themselves

-Neurons do not replicate very fast or very often

-Heart cells replicate at a very, very slow speed and low rate

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22
Q

Cells; Basic Borders/Internal Elements

A

-Internal contents of the cell typically dictates it’s function
-Cell Wall/Membrane is a phospholipid bilayer. This provides a large barrier because of the orientation of the cell wall. The fatty, oily middle layer is an obstacle
-The phosphate head is a charged region of the cell wall; charged compounds typically behave well in water.
-Lipid tails (uncharged) do not behave well in water. Fatty acid chain

-Cytoplasm: Fluid within the cell. The chemistry of the cytoplasm is very important; this is where the chemical reactions occur

-Nucleus: Barrier or protected internal environment that keeps our DNA/Genetic information packed up & secure from things like viruses and bacteria

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23
Q

Cells: Nuclear Compartments

A

-Nuclear Envelopment/membrane: A double phospholipid bilayer. Almost an entire cell wall creating a barrier between what’s inside and the cytoplasm of the cell

-The body does allow some things to come into contact w/ our DNA through pores within the nuclear membrane
Ex: Steroids- Can affect gene transcription to turn on stress response proteins

If the wrong things come into contact with our genetic information, terrible things such as cancer can happen

-DNA/Genes float inside of the nucleus and can be turned on and off to help the cell accomplish different tasks

-Endoplasmic reticulum: An extension of the nuclear wall and a storage place. Fats and proteins are produced here, calcium is stored here
Ex: Muscle cells need Ca+ to function

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24
Q

Cells: Protein & Fat Production

A

-As genes are read or turned on, they are encoded for protein or lipids. These instructions are then carried to various places where they can be turned into lipids and proteins

-Granular/Rough Endoplasmic Reticulum: Where proteins are synthesized. The rough ER is covered in ribosomes–> they take the genetic instructions from our DNA (transcription) –> RNA is formed
–> RNA spliced –> Transported out of the nucleus to ribosomes for translation–>Proteins are packaged into vesicles–> transported through cytoplasm to the Golgi apparatus
-95% of proteins are manufactured in the rough ER. The rest happens freely in cytoplasm

-Smooth Endoplasmic Reticulum: No ribosomes present; where lipids are created. Lipids are needed for our cells to survive

-Golgi apparatus: Used for post-translational processing; sometimes proteins need to be modified, folded differently, or altered in some way. Proteins are then packed into vesicles and are ready for use

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25
Q

Cells: Vesicles

A

-Transport vesicles transport proteins within the cell
-Active proteins or peptides are transported out of the cell by secretory vesicles (ADH or oxytocin)
-Secretory vesicles can move to the cell wall, fuse with the cell wall, and then dump their contents immediately outside the cell wall

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26
Q

Cell Wall: Proteins

A

-Proteins are able to position themselves in the cell wall and permit passage of charged compounds across the cell wall
Ex: Ion channel, Ion pump
-Proteins are made up of strings of AA

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27
Q

Genetic Translation (Proteins)

A

-RNA will contain nucleotides in a certain sequence dictating which amino acids get attached to each other
Ex of AA: Alanine, cysteine, histidine, Phenylalanine, serine, proline
-Ribosome will grab these AA from the cytoplasm, attach to other AA to form protein chain
-As the chain is formed, it typically folds, but is transferred to the Golgi for further manipulation to provide some sort of function
Ex: A protein in the cell wall w/ a large pore in it allowing K+ ions through

28
Q

Cell Components: In Detail
Organelles, Enzymes

A

-Organelles: Transport vesicles, secretory vesicles, mitochondria, Golgi, ER
-lysosomes: digestion, use very acidic environment to destroy old protein, pull AA apart and put them back into cytosol for reuse
-peroxisomes: Known for degrading toxins by using oxidative reactions

-Enzymes: Catalyzes a chemical reaction. Typically a protein. End in “ASE”
Ex: ATP-ase, enzyme that pumps K+ and Na+ by metabolizing energy compounds. ATP-ase in muscle produces force for the muscle to contract

29
Q

Cell Components: In Detail
Structural Components, Sugars, Fats

A

-Internal support to give the cell shape/structure; filaments, proteins

-Sugars: Float around in cytoplasm used for energy; pulled out of cytoplasm and used to generate ATP (glycolysis, anaerobic metabolism)
-Proteins can have sugars attached to them; used for structure,
-Sugars outside of the cell can attach cells to each other, or can be used at human “ID tags” for immune function
-Sugar is sticky
-External sugar is negatively charged and can repel negatively charged proteins (ex: Kidney uses these to ensure we don’t filter as much protein)

Glyco: Sugar group attached to something (glycolipid, glycoprotein)
Carboxy: Starch
Ex: Carboxyhemoglobin, sugars stuck to Hgb, makes it less efficient

-Fats: lipid soluble compounds (cholesterol), Arachidonic acid
-Fats typically live in the cell wall because of the lipid layer
-Fats are uncharged

30
Q

Cell Components: In Detail
Proteins

A

-Numerous types of protein in the cell; structural, functional (transport across cell membrane), enzymes
-Depending on what types of protein are expressed inside the cell, dictates what that cell’s job is
-Not every cell will be able to produce every signaling compound or secretory compound. The specialized role of a cell is dictated by what genes are expressed and that is determined by what proteins are found within the cell

31
Q

Cell Components: In Detail
Motility structures, Genetic material, Membrane Components

A

-Motility Structures:
-Flagella; Can move cells around their environment
-Cilia; Moves objects around them. Small projections that come out of the cell and move fluid, mucous in a wave-like manner

-Genetic Material: DNA –> RNA,
-Mitochondria; We have ~20 different sets of mitochondrial DNA. We inherit mitochondrial DNA from our mother.
-Majority of genetic material is found in nucleus

-Membrane components: Things that live in the cell wall that have some sort of function (turning the cell on and off)
Vast majority of drugs dictate what happens at the cell wall

32
Q

Cell Components: Water

A

-70-80% of cells are water (except fats)

-Chemistry of the water & the dissolved compounds are VERY important to the body and dictates how a drug will work important for anesthesia

-Hydrophilic compounds: Behave in water, charged (electrolyte)

-Hydrophobic compounds: Do not like water, uncharged (fats)

–Acid/base balance, electrolytes, proton concentration, energy compounds. Need near constant conditions to function normally

33
Q

Cell: Water
Soluble vs Insoluble

A

Soluble/Hydrophillic:
-Ions (electrolytes)
-Some proteins
-Carbs (charged)
-Some gasses (CO2)
-Buffers

Insoluble/Hydrophobic:
-Cholesterol
-Lipids
-Steroid hormones
-Certain drugs; need to be given w/ a carrier compound to help it travel through CV system if hydrophobic
-Some gasses (nitrous)

34
Q

Body Fluid Compartments & Barriers

A

H2O is 60% of your TBW (total body weight)

ICF is 2/3rds
ECF is 1/3rd
Plasma is 1/4th-1/5th of the ECF
Interstitial Fluid is ECF-Plasma

-At rest and under normal conditions, ECF and ICF are kept fairly constant, in a steady state
- Ion & Glucose concentration vary markedly between ECF & ICF
-We do not want equilibrium here, can be detrimental
-This steady state contributes to homeostasis

-Capillary membrane: Provides a barrier between the CV system and the interstitial fluid. Fairly permeable membrane allowing small charged ions (electrolytes) across
exception is w/in the brain, tight membrane there)
Tight enough to keep plasma proteins from crossing

-Cell membrane: Very tight, fairly impermeable membrane. Doesn’t let anything across without some form of regulation

35
Q

Ions & Electrolytes
Na++, K+, Ca++, Mg++, Cl-, HCO3-, Phosphate

A

Na+:
ECF; 140/142 mOsm/L, ICF; 1/10th
Primary cation in the ECF

K+
ECF: 4meq/L, ICF: 30x the ECF
When cells are unhealthy, K+ can leave the cells affecting neighboring cells

Ca++
Virtually “0” Ca++ found w/in the cell. Much higher concentration outside the cell.
Ca++ is used as a signal for the cell to turn on/off. Ex: Neurotransmitter hits the cell, Ca++ turns it on. Ca++ causes muscle cells to contract. Ca++ turns a cell on by opening the ca++ channel, allowing it to briefly come into the cell to turn it on

Mg++
Higher in the ICF than in the ECF
Used as a cofactor for chemical reactions w/in the cell

Cl-
Primary anion in ECF; therefore, higher in the ECF than ICF.
Follows distribution of Na+

HCO3-
Secondary anion in ECF; therefore, higher in the ECF than ICF
Buffer managed by the kidney to balance acid/base

Phosphates: HPO=, H2PO4-
-Higher concentration in the ICF
-Important intracellular buffer
-Can be attached or detached from proteins to regulate activity level by turning on/off (phosphorylation, dephosphorylation)
-Energy storage system; ATP = adenosine + 3 phosphates. As we consume ATP we pull phosphates off

36
Q

Ions & Electrolytes
Amino Acids, Creatine, Lactate, ATP, Glucose, Proteins

A

Amino Acids:
Higher in ICF, AA are put together inside the cell to form protein
Proteins are also broken down into AA inside the cell

Creatine:
-Found inside skeletal muscle (majority)
-High energy storage compound

Phosphocreatine:
-Creatine that is phosphorylated w/in the skeletal muscle cells ( takes energy to do this)
-Skeletal muscle contracts, pulls phosphate off the creatine (gives us short term energy)
-Depleted very quickly

Lactate:
Byproduct of metabolism from w/in the cell
Higher concentration ICF

ATP:
-Only found inside cells. Never allowed out of the cell; however, adenosine alone can be found outside of the cell.
-Adenosine is pretty small, leaves the cell, increases blood flow in an area with high metabolic demand

Glucose:
Higher concentration in the ECF. Not produced inside the cell. Cells are reliant upon glucose being delivered to them

Proteins:
Higher in ICF, produced here
5x higher in plasma vs. interstitial fluid

37
Q

Osmolarity & Osmotic Pressure

A

Osmolarity:
-Typically consistent between ECF & ICF
-Total Osmo: ~300
How many of these dissolved compounds are there in a fluid sample?

-Corrected/Biologic Osmo: 280-283mOsm/L. (2x Na+)
In reality, not all of these ions will be freely dissociating at once (dissolved in water). There are differently charged ions floating around, and when they get close together they do not act as individual ions and are not dissolved.
That’s where the correction comes in

-Ions do not travel freely across cell membrane. Proteins do not travel freely across the capillary membrane.

-Water can move freely back and forth; therefore, if one compartment has a higher osmolarity–> water can move quickly and freely to correct/stabilize it

The osmolarity of these dissolved solutions can generate an enormous amount of pressure, ~5,440mmHg

Incredibly important to keep osmolarity in range so we’re not exerting that much force on someone’s brain

38
Q

Membrane cholesterol

A

-Cholesterol lives in the cell wall
-Considered a precursor compound
-Easily accessible if cell needs cholesterol to create a hormone or signaling compound

-Rigid & flat composition at 37C.
-High cholesterol increases the rigidity and stiffness of our blood vessels–> this is a bad thing
-Can become more “fluid” at a lower temperature (think; butter, ice cream)

39
Q

Cholesterol Synthesis

A

Two Sources:

-Endogenous: 80%
-Exogenous: 20%
Diet can only do so much when reducing cholesterol; Statins (HMG CoA-Reductase)

Acetyl-CoA & Acetoacetyl-CoA are compounds used to create cholesterol (and ATP!)

40
Q

Cholesterol: Metabolites

A

1) Sex Hormones

   -E2: Estradiol
   -T: Testosterone
   -Progesterone
   -Androstenedrione: T precursor, baseball players were using ~20 years ago
 -Cortisol
 -Aldosterone

Our adrenal glands are the source of these hormones, so it should follow that our adrenal glands utilize a lot of cholesterol
Aldosterone & Cortisol receptors look very similar to each other, so if you do not have enough Cortisol around; those receptors can utilize Aldosterone in it’s place

41
Q

Cell Membrane: Important Precursors

A

Specialized Phospholipids in the cell wall:

-Arachidonic Acid (AA)
-Phosphatidyl-inositol (PI)
-Phosphatidly-serine (Cytosolic)
-Phosphatidyl-ethanolamine (PE)
-Phosphatidly-choline (PCh)

These phosphatidyl compounds play some role in the production of surfactant (surface tension of lungs)

-PI: Used in smooth muscle to regulate contraction. PI is liberated from the cell wall, enzymes work on it–> IP3 (Inositol triphosphate) makes smooth contract

-PCh: Storage molecule that’s useful for signal transduction. Stores choline to later assemble acetylcholine

-PE: Nothing special

-Cytosolic: Usually an immune marker. In cells that are healthy, serine is located only inside of the cell wall
-If our immune system sees serine that is outward facing, it destroys the cell.
-Occasionally, just by random movement of particles, phosphatidylserine will flip outwards.
-We have an enzyme, “Flipase,” that flips it inward again
-Because flipase is moving the serine into an orientation that it doesn’t want to naturally go into, this requires energy (needs a good supply of ATP).
-If we have an unhealthy cell, on the verge of dying, it starts to run out of ATP. More serines will flip outward –> flipase does not have the required energy to change orientation
–>immune system will destroy

Energy deficiency mediated dysfunctional flipase; an example of this is when you have a large ischemic area of the brain, it’s been that way for ~20mins because it hasn’t been getting normal blood flow. We do not want the immune system going in there and destroying that area of the brain before we can open those blood vessels up

-Sphingomyelin: A fatty compound that the body uses to construct myelin

42
Q

Arachidonic Acid (AA)

Pathway 1: Prostaglandin Formation

A

-A long, long fatty tail that can be saturated or unsaturated in some areas
-Prostaglandins & Leukotrienes are so distinct from AA that they have no issue being in the cell water

1) AA–> Cox 1 & Cox 2 catalyzes two chemical reactions in which AA is turned into —-> PGG2 (precurser compound)—-> PGH2 —> Prostaglandin E2 Synthase–> several prostaglandin pathways: PGE2, PGI2, PGF 2 alpha, PGD2, TXA2

-Cyclooxygenase 1 & 2 are enzymes that are responsible for prostaglandin & TXA2 production. Reducing these enzymes should reduce the amount of prostaglandins that we see in the body.
-Prostaglandins usually increase pain signals throughout the body
-TXA2- Thromboxine A2 is an important part of the coagulation cascade. Mediates injured vessel healing. It helps us control bleeding by initiating vasospasm, reducing blood flow through the area and allowing the repair to take root

-Cox 1 is pretty widespread. More specific to TXA2 production
-Cox 2 is a more inducible form. Typically the isoform that is turned on when things are painful/bad. Cox 2 is also involved in keeping the kidneys healthy, helping the heart make corrections after ischemia
Vyox; Drug ~20yrs ago that was super cox 2 selective, caused some pretty bad problems

Cox 1 inhibitors- Less pain control, but tend to have issues associated with bleeding (TXA2 inhibition) ASA, Nsaids

Cox 2 inhibitors are more effective for pain (Naproxen)

Tylenol is unique because it is specific for targeting neurons in the body (Cox1 & 2 inhibitor)

43
Q

Pathway 2: Leukotriene Formation

Pathway 3: HETE/EETS

A

Leukotriene Pathway

Involved in immune-mediated inflammation. Typically a bad process in the body, lungs swell up and mucus glands are all goofy

Singulair- Leukotriene receptor antagonist.
Drugs currently on the market are Leukotriene receptor antagonists; however, would not be surprising if drugs come out targeting the lipoxygenase enzyme in the future

AA–> 5-LO (lipoxygenase)–> 5HPETE
–> 5HETE OR LTA4–> LTC4, LTD4, LTE4

HETES/EETS

Large, fatty compounds that are short-lived. Involved in acute renal failure. Mediators in some very bad disease processes.
These drugs are extraordinarily hard to deal with, they are unstable, do not live a long time it water, hide in the cell wall

44
Q

Cell Membrane: Simple Diffusion

A

Simple Diffusion: The process of something moving across the cell wall without needing help. There is no binding or releasing. Dictated by a concentration gradient (gas) or if an electrolyte, the electrochemical gradient.

-Dissolved gas needs no assistance crossing the cell membrane. Gasses are small, usually lipid soluble, and can move in and out of the cell quickly.
Ex: O2, CO2 move in and out of the cell without any assistance

-Channel Protein: Provide a conduit that’s either going to be specific to an electrolyte or specific to a charge. No binding or releasing. These electrolyte channels also allow water through; can be difficult to regulate water
Ex: Na+, Cl- Channels

-Aquaporines (AQP): Channels that some cells have to easily allow H2O back and forth. An area of the body that needs to regulate its water permeability is probably going to have relatively few ion channels, or control water permeability through AQP channels in the cell wall

45
Q

Cell Membrane: Primary Active Transport

A

Active Transport: Pumps that require energy. Moving something against its electrochemical gradient, or needing to move something across the cell membrane quickly both require energy. All pumps are ATPase in nature

Primary Active Transport:
Na+, K+, ATPase pump*
-An enzyme that metabolizes ATP. The ATP is pulled from the inside of the cell.
The enzyme takes one ATP, degrades it to ADP by pulling one phosphate off.
The energy that is liberated when the phosphate comes off moves five ions against their electrochemical gradient;
3 Na+ out of the cell, 2 K+ into the cell

There’s a lot of work being done here, and this system has evolved to be very efficient. The Na+, K+ pump is what sets up almost all electrical gradients. Most other gradients are all somehow linked to this pump.
All excitable cells will have a Na+,K+, ATPase pump. Even in cells where they don’t do work other than sending messages, the metabolism & energy requirements to maintain this pump are 60-70% of the cells energy.

This is the single most energy requiring process that happens within the body, provided we’re not running a marathon or anything crazy like that

Ca++ Pump:
Ca++ flows into the cell to turn it on, Ca++ pump pushes Ca++ back out of the cell against its gradient (10,000:1 concentration)

Simple Acid Pump/Proton Pump:
In acid producing cells in our stomach. pH of gastric contents can go as low as 1. The way the pH gets that low is by our stomach cells secreting acid. The pump takes protons from inside the cell, pumps them outside of the cell, thus acidifying the environment inside the stomach

46
Q

Cell Membrane: Secondary Active Transport

A

Requires energy & a functional cell, but does not directly rely on ATP

NCX: Na+, Ca++ Exchanger/Transport:
Used for bulk removal of Ca++ when the Ca++ pump cannot keep up. It moves one Ca++ outside the cell in exchange for moving three Na+ inside the cell.
The energy that this pump relies on is the Na+ electrochemical gradient, setup by the Na+, K+ ATPase pump

SGLT/Na+Glucose Transporter:
-Allows glucose to move into the cell with Na+. Speeds up the process of getting glucose into the cell
-Not found in cells all over the body. Found in the kidney because we want to reabsorb glucose after it’s filtered so that it’s not lost in the urine

47
Q

Cell Membrane: Facilitated Diffusion

A

Facilitated Diffusion:
-Usually involves binding, undergoing a conformational change, and releasing on the opposite side of the cell, but does not require ATP.
-Capable of moving compounds in either direction, the direction in which the compounds move depend on the electrochemical gradient
-The speed at which this process happens depends on how many transporters are on the cell wall, and also the electrochemical gradient. Can only move so fast, Vmax = maximum speed at which conformation can happen

Glut Transporter:
Glucose binds to the transporter/receptor–> conformational change–> glucose is transferred inside the cell
No energy requirement
How 95% of our glucose transport is done. Glucose is pretty large, so having a glucose channel wouldn’t work without other ions sneaking through

Glut-4 Transporter: Insulin dependent. Insulin attracts more glut-transporters to the cell wall, allowing more glucose to move into the cell and increasing the rate at which glucose is moving into the cell. In skeletal muscle and fat

Glut-1 Transporter: Non insulin dependent. Transports glucose into RBC’s for energy

48
Q

Osmolality vs Osmolarity

A

-Osmolality: Quantity of solute/ 1 Kg (L) of H2O
More accurate, impractical

-Osmolarity: Quantity of solute/ 1L soln
What we’ll be using this for A&P

Only about 1% difference between the two

49
Q

Osmotic Pressure

A

-In order to have osmosis, must have semi-permeable membrane
-U shaped test tube filled with H2O, separated by semi-permeable membrane
-Adding solute to one side of the test tube makes that side “more salty” meaning increased osmolarity, decreased H2O concentration
-Water will move down it’s concentration gradient (high to low) to correct it’s concentration difference

Test tube example; L side has more solute- As water diffuses to the left side, the osmotic pressure of the solution is being offset by the weight of the water

1mOsm/ 19.3 mmHg in 1L

1mOsm of solution can push a column of Hg up by 19.3mm

All measurements like this are done at sea level

50
Q

Things that affect diffusion rate across cell wall

A

-The larger the difference in concentration, (inside cell vs outside cell) the faster the diffusion rate
-Lipid Solubility (Higher solubility, higher diffusion rate)
-Size of the particle
-Size of the pores in cell wall
-# of pores available
-Heat (Higher temp, faster diffusion)
-Physical pressure (ex: BP at the level of the capillary)
-Electrochemical gradient

51
Q

Na+, K+, ATPase, Cell Osmolarity & Diuresis, Where does the Na+ come from?

A

-Which each cycle of the pump, we are losing 1 (+) charge, causing the inside of the cell to be more negative than the outside
-This pump cleans out excess Na+, pushing extra H2O out with it because water follows salt (cell diuretic effect)
-If this pump were to shut down, we would see intracellular edema, very hard to treat, very bad. Will not be pitting edema
-Na+ is allowed back into the cell via our secondary active transport processes (Na+Ca+Exchanger)
-The process of moving Ca+ out of the cell IS LINKED to Na+ coming into the cell
-Leaky Na+ channels
-Na+ comes into the cell during action potential

52
Q

Resting Membrane Potential (Vrm) (What contributes to our Vrm)

A
  • At rest, excitable cells (almost every cell in the body) are electronegative compared to conditions outside of the cell (-mV)
    -When the cell is activated, it is briefly positively charged
    -Voltage refers to a potential difference between two places

-At rest, the cell is typically MORE permeable to K+ than Na+
pNa «< pK, 1:10

-Proteins contribute to the negative intracellular charge and Vrm. AAs are typically negatively charged. Many proteins are aligned along the inner cell wall (cytosolic face) causing a difference in polarity across the cell wall.

-Na+K+ATPase pump plays a major role in resting membrane potential; with each cycle of the pump we are losing one + charge

-K+ Leak Channels: The concentration gradient is typically 30:1; K+ wants to continuously flow out of the cell down its concentration gradient, thus making the cell more negative (losing ++ charges)

-Na+ Leak Channels: concentration gradient is 10:1

53
Q

Membrane potential; Do we need constant current?

A

Our membrane potential remains where it is because of the potential for current.
Open pathways (Na+, K+ leak channels) give our membrane the potential for current

54
Q

Normal Membrane Threshold; Factors that shift our membrane potential & threshold

A

-Under normal conditions, the most negative our membrane potential can be is ~ -91mV and the most positive it can be is ~ +61mV.

-The cell is more permeable to K+, making the Vrm closer to the equilibrium potential for K+.

-Normal Vrm is ~ -80mV

-Differences in the electrolyte concentration ratios or differences in our ion levels will determine the nernst potential for each ion.

Ex: K+ level of 8, rather than 4. That changes our concentration gradient from 30:1 to 15:1. K+ is not nearly as motivated to leave the cell. Nernst Potential for K+ shifts from -91mV to ~ -70mV (the lower limit of our membrane potential has now shifted), meaning our Vrm will be even higher than that -70mV.
The cell cannot get back to its regular Vrm, and this impacts electrical activity substantially (especially the heart)

-K+ of 12 almost always = some kind of vfib. Nernst potential here is -61mV
-What would happen if our Cl- was too high? The concentration gradient would increase, causing Cl- to flow into the cell faster making the cell more (-). This will usually cause the cell to be more difficult to excite

Cells need to rest normally, or their function is going to be abnormal

55
Q

Nernst Potential

A

Nernst Potential = Equilibrium Potential

-Tells us what the charge of a cell would be if it were to allow one ion to move across the cell wall down its concentration gradient (remember, cells are more permeable to K+ at rest)

Equilibrium potential also tells us at what point that specific ion will STOP moving down its concentration gradient.
Ex: K+ will no longer flow out of the cell when the cell is as -91mV

-The overall charge of the cell is dictated by the ions it is permeable to
Use the nernst equation to determine the equilibrium potential for both Na+ and K+, add the two together and that gives us our Vrm

Why does this matter?

Ex: Potassium; changing our K+ concentration affects this formula; meaning, our underlying membrane potential changes for all excitable cells

56
Q

Goldman Equation (GHK)

A

-Similar to the Nernst equation except that it takes multiple ions into account.
-Not an equation we will ever have to use

57
Q

Action Potential

A

-When the cell needs to be activated, it is briefly, suddenly very permeable to Na+ making the membrane potential more positive (~ +35mV) –> generating an action potential

-We do not ever reach the equilibrium potential for Na+ during an action potential because that would require all of our K+ channels to be closed

58
Q

Cell Polarization

A

A difference in electrical charge between the inside and outside of the cell.
At rest, cells are polarized (-mV @ Vrm)

59
Q

Depolarization

A

-To become LESS polar, more positively charged
-Stimulated or turned on
-Na+ Channels open early during action potential–> inactivate very quickly

60
Q

Repolarization

A

-The return to normal, resting polarity (Vrm)
-Dependant upon additional K+ channels open to allow K+ to flow out of the cell faster.

The number of K+ channels that open will depend on how quickly the cell needs to return to Vrm in order to generate an additional action potential.

-Extra K+ channels do not close until after Vrm is back to ~ -80mV. Channels are slow to close, resulting in hyperpolarization

61
Q

Hyperpolarization

A

-To become MORE polar, more negatively charged.
It is inhibited, more difficult to excite.
-Can also happen after an action potential, during repolarization

62
Q

Action Potential in the Heart

A

-There is a plateau phase after depolarization where the action potential is sustained to allow the heart to pump

63
Q

Voltage Gated Na+ Channels

A

-Any drug that ends in “-caine” affects the Na+ channels
-These channels are “fast,” are only open for a few miliseconds if that
-Are highly selective for Na+, have a selectivity filter in the middle of the channel
-Have two gates;
M-gate is the activation gate on the ECF side
H-gate is the inactivation gate on the ICF side

-Under resting conditions, the M-gate is closed and the H-gate is open
-During activation, the M-gate opens. Na+ has a clear path into the cell
-Inactivation happens immediately. M-gate opens faster than the H-gate closes, so both gates are open for a very short amount of time
-The M-gate needs to close FIRST, and the H-gate needs to open again in that order for the gate to “reset.” If the H-Gate opens first, it will allow more Na+ to flood into the cell
-The resetting of these channels is entirely dependent on repolarization. If we do not have normal repolarization, our gates cannot open and close

64
Q

Voltage Gated K+ Channels

A

-Slow channels
-One gate on the ICF side
-Gate is closed at rest
-K+ channel opens slowly at around +35mV
-Closes when the cell gets to Vrm, but they are slow, resulting in hyperpolarization

65
Q

Driving Force

A

-The cell’s motivation to enter the cell.
Depends on three things:
1. Electrochemical gradient
2. Charge of the ions
3. Charge inside the cell

Under normal circumstances at rest, Ca++ has the greatest driving force. Na+ is second. K+ has the least driving force