Unit 1: cell biology, homeostasis, electrolytes Flashcards
Describe homeostasis
the maintenance of nearly constant conditions in the internal environment (ECF)
- Walter Cannon (1929)
“what goes in = what comes out” in a steady state; name examples of what “goes in” to a cell and what “comes out” of a cell to maintain homeostasis.
in: nutrients
out: energy and waste products
waste products can be: CO2, H+, solid waste, H2O, urea, and heat
explain how peripheral circulatory beds maintain homeostasis
they deliver only enough to meet tissue needs
increased metabolism > leads to a response in the CV system > increases blood flow to tissues/organs to meet O2 requirements
through arterioles, blood brings nutrients into the capillary bed, where O2 is exchanged to cells, and the venules bring blood back to the heart but also help to remove byproducts from blood
explain how the following organs maintain homeostasis:
2 hearts
lungs
GI system
kidneys
liver
peripheral vascular beds
L & R heart:
peripheral CV nutrients
O2 circulation to pulm system
lungs: regulate our O2 exchange/blood gas
GI system: replaces nutrients in the blood as they’re being consumed
kidneys: ECF buffering systems (pH)
liver: eliminates wastes/toxins through biliary system
peripheral vascular beds: moves around nutrients
What are 4 different ways the body uses a negative feedback loop to correct a drop in MAP
- increases sympathetic outflow
- decreases parasympathetic outflow
- increases vasopressin and ADH
- decreases ANP
all of these negative feedback systems will counteract the drop in MAP to bring the MAP back up
ANP - atrial natriuretic peptide - a hormone that helps regulate blood pressure by vasodilating vessels in response to atrial stretch due to hypervolemia
This feedback system is the most used in the body.
Negative Feedback System
List the steps for how negative feedback loops help the body maintain homeostasis?
- change/disturbance of homeostasis occurs
- regulatory mechanisms kick in
- body reacts to oppose/counteract the change
ex) increased CO2 leads to increased ventilation to decrease CO2
Explain how a Positive Feedback System responds to changes caused by select stimuli
positive feedback AMPLIFIES the changes
can be good or bad
bad = vicious cycles (pathologic positive feedback loops)
what 2 safety net features prevent physiologic positive feedback loops from progressing into vicious cycles
- checkpoints
- safety valves
explain how active labor is a physiologic positive feedback system
- labor causes the uterus to contract to push the fetus towards the cervix
- cervical stretch (change) causes a release of oxytocin into the bloodstream
- oxytocin causes the smooth muscle of the uterus to contract (amplified via the stretch of cervix)
- loop continues until it hits a “checkpoint” which, in this case, is birth
explain how the clotting cascade/platelet plug formation is a physiologic positive feedback loop
- injury to endothelial wall of a blood vessel occurs (change)
- clotting cascade initiates
- TXA2 (thromboxane 2; a potent platelet activator) initiates platelet aggregation to plug up vessel wall opening – amplification
- continues until reaches checkpoint (controlled bleeding)
name 6 pathologic positive feedback loops
sepsis/necrosis
severe acidosis
peripheral acidotic conditions
atherosclerotic plaque clotting
diabetic renal inflammation/hyperfiltration
severe hemorrhage
describe how sepsis/necrosis is a pathologic positive feedback loop
cellular death increased > wastes/toxins infiltrate neighboring healthy cells > increased cellular death
describe how severe acidosis is a positive feedback loop and what type of positive feedback loop is it?
in severe acidosis, pH is lowered, which decreases your respiratory drive, which further exacerbates CO2 retention and therefore continues to exacerbate acidotic state
pathologic positive feedback loop
describe how diabetic renal inflammation/hyperfiltration is a pathologic positive feedback loop
nephrons die off with aging > which in turn causes healthier nephrons to work harder > healthy nephrons age faster > increased nephron death
describe how severe hemorrhage is a pathologic positive feedback loop
decreased MAP d/t hypovolemia > decreased coronary blood flow > decreased CO > further decreases your MAP
compare and contrast compensated shock versus decompensated shock and how negative and positive feedback loops are integrated
in COMPENSATED shock, a negative feedback loop works well; compensatory mechanisms (fluid shifts) will help the body return to homeostasis
in severe hemorrhage (DECOMPENSATED shock), positive feedback leads to death: hypovolemia > decreased MAP > decreased coronary flow; less blood circulating > decreased CO > cellular death
too much blood loss too fast means that the negative feedback compensatory mechanisms will be outweighed by the positive feedback loop
describe the relationship between anesthesia and homeostasis
anesthetics can alter systems’ physiology (control systems usually in place go “offline” when anesthetics are administered)
also, changes in physiologic systems can alter anesthetic drug responses
cells are usually capable of replication; give 2 examples of some cells that have trouble with replication
neurons
cardiac cells
the cellular membrane contains a hydrophobic tail and a hydrophilic head; this is called a…
phospholipid bilayer
these types of compounds can pass easily through the phospholipid bilayer
charged compounds
the cytoplasm is 70-85% of this material
H2O
describe what the nucleus of a cell does
barrier to keep DNA packed, secured away from pathogens
the contents inside of a nucleus include the following:
nuclear membrane/nuclear envelope
nucleolus
nucleoplasm
chromatin material (DNA)
outside of a nucleus:
selective pores
endoplasmic reticulum
cytosol/cytoplasm
the nucleus has very selective pores to let specific material pass into and out of the nuclear membrane; name two of these materials.
steroids
RNA
which structure is an extension of the nuclear wall and produces fats, proteins, and calcium?
endoplasmic reticulum
differentiate granular (rough) ER vs smooth ER
granular (rough) ER: responsible for protein synthesis; transports proteins to be sent to golgi apparatus to be modified
smooth ER: no ribosomes are present; responsible for lipid production
describe the process of protein formation
- DNA transcription
- RNA transcribed and spliced
- mRNA leaves nucleus to cytosol
- ribosomal translation of mRNA into amino acids
- amino acids packaged and brought to rough ER (95% of protein synth occurs here) & sent to be modified at the golgi apparatus for post-translational processing
- proteins are sent to their specific sites to carry out their specific functions such as cell structure and cell enzymes (Na/K ATPase)
what is the role of the golgi apparatus
packaging/condensing proteins and post-translational processing; proteins are modified and sent out of the cell via secretory vessicles
describe what mitochondria do
mitochondria are the “powerhouse” of the cell; ATP production factory
describe the difference between lysosomes and peroxisomes
lysosomes:
use acidic conditions to digest/recycle cell content/proteins
peroxisomes:
use oxidative stress to destroy/process toxins in the cells; can also destroy proteins – mostly degrade toxins
what is unique about the nucleus in terms of barrier and protection?
the nucleus has a double phospholipid bilayer with highly selective pores on the nuclear membrane allowing only a few material to pass through into the nucleoplasm
how do water soluble materials get from one side of the cell wall to the other?
proteins – strings of amino acid structures; allows passage of charged molecules (such as potassium) through the selectivity filter of the pores in the cell wall
where do most proteins get made and what percentage is this?
where do the remaining % of proteins get made?
95% proteins made in R.E.R
5% in cytosol (most do not get packaged here)
why is it important for the chemistry of the water inside of a cell to be balanced?
homeostasis; acid/base balance
proton concentration
electrolyte concentration
give a few examples of some organelles
ex) peroxisomes
ex) mitochondria
ex) lysosomes
ex) golgi apparatus
ex) endoplasmic reticulum
not nucleus; it’s a membrane to protect genetic material
what is an enzyme?
typically are proteins that catalyze (speed up) a chemical reaction
ends in suffix “-ase”
ex) ATPase
describe what a sugar molecules role would be on a cellular wall
- identification (self vs non-self) (immune system)
- cell anchoring (to each other); “sticky”/adherence
- repelling negatively charged proteins (kidneys do this to prevent filtering out too many proteins)
filaments/proteins provide what function for a cell?
cellular structure; “skeleton”
describe how atherosclerotic plaque clotting is a pathologic positive feedback loop
plaque inside of a blood vessel > activated enzymes (clotting factors) act on other enzymes within clot itself > these enzymes act on unactivated enzymes in adjacent blood to accumulate more blood clotting > leading to infarct
decribe fats (lipids)
primarily found in cell wall (phosphlipid bilayer)
non-charged; found in oily substrates
ex)
lipid soluble compounds (cholesterol)
arachidonic acid (used to generate signaling compounds)
name 2 cell components responsible for motility structure
flagella – moves cell itself
cilia – moves other cellular components (ex. mucus)
describe genetic material in detail
most of our genetic material is found in the nucleus (DNA)
humans also inherit mitochondrial DNA from their mother; at least 20 different sets
describe secretory granules in detail
secretory granules/vesicles, found in specialized cells, empty other cellular material into environment around it
relate membrane components to anesthetic drugs
vast majority of anesthesia drugs dictate function at cell wall/membrane
describe ICF compartment calculations
inTRAcellular fluid
2/3 of TBW (in L)
ex) 70 kg male
42L = TBW
(2/3) x 42L = 28L ICF
describe ECF compartment calculations
extracellular fluid – fluid found outside the cells/in between cells
divides into two categories: plasma and ISF
ECF = 1/3 of TBW
ex) 70 kg male
TBW = 42L
(1/3) x 42L = 14 L ECF
describe plasma compartment calculations
plasma - found in entire CV system that doesn’t include the volume of any blood cells in the CV system
1/4-1/5 of ECF = plasma
ex) 70kg male, 42L TBW
ECF = 14L
so (1/5) x 14L = 2.8
or (1/4) x 14L = 3.5
therefore: 2.8-3.5 L = plasma
describe ISF compartment calculations
ISF - interstitial fluid (fluid found outside the CV system, that is not plasma “left over fluid”)
3/4 or 4/5 of ECF
ex) 70kg male, 42L TBW
ECF = 14L
so (4/5) x 14L = 11.2 L
or (3/4) x 14L = 10.5 L
therefore, ISF = 10.5 - 11.2L
- ISF can fluid shift to make up for volume loss in hemorrhage *
explain why a “steady state” is much different than equilibrium; what does “steady state” mean?
if the sodium concentration was in a state of equilibrium in the body (inside and outside the cell), our cells could not function properly; instead, they are in a “steady state” meaning sodium’s concentrations are tightly regulated in their respective compartments in and out of a cell
ex) external body temp vs internal body temp – if we were at an equilibrium state with our body temp, our organs and cells also would not be able to function
equilibrium = “equal”
differentiate capillary membrane vs cell membrane in terms of cellular body fluid compartments
capillary membrane: + separates plasma from ISF (separates CV system from interstitium)
+ fairly permeable; more porous than cell wall
+ tight enough to prevent plasma proteins from leaking out of CV system
cellular membrane/cell wall:
+ separates ICF from ECF
+ does not let charged compounds across membrane unless there is a channel/pump protein to let pass
TBW = ?
0.6 x body mass in kg
ex) 0.6 x 70kg = 42L TBW
2/3 of TBW = ?
ICF (intracellular fluid)
1/3 of TBW = ?
ECF (extracellular fluid)
1/4 or 1/5 of ECF = ?
plasma
3/4 or 4/5 of ECF = ?
ISF (interstitial fluid)
standard healthy body mass = ?
70 kg
standard, healthy TBW = ?
42 L
standard, healthy ICF = ?
28 L
standard, healthy ECF = ?
14 L
standard, healthy plasma = ?
3 L
standard, healthy ISF = ?
11L
ECF [Na+]
140 - 142 mOsm/L H2O
2 x [ECF Na+] = corrected osmolar activity in mOsm/L
ex) 140 (x2) = 280 mOsm/L
ICF [Na+]
14 mOsm/L H2O
1/10 of ECF [Na+]
ex) 140 = ECF [Na+]
(1/10) x 140 = 14 mOsm/L H2O
Na+
predominant ECF cation
[Na+] ECF > [Na+] ICF
ECF [K+]
4 mOsm/L H2O
ICF [K+]
120 or 140 mOsm/L H2O
30 x ECF [K+] = ICF [K+]
ex) ECF [K+] = 4
30 x 4 = 120 mOsm/L H2O
K+
important for heart function
[K+] ICF > [K+] ECF
Ca2+
a signaling electrolyte
(toggles on/off cell functions)
ex) neuromuscular cells
“0” [Ca2+] in ICF
10,000 : 1 – ECF : ICF ratio
Mg2+
important in chemical reactions; a cofactor for chem rxns required inside cell
ICF > ECF Mg2+
Cl-
primary anion ECF
ECF > ICF
HCO3-
managed by kidneys
primary ECF buffer
ECF > ICF
HPO4/H2PO4-
(phosphate)
additional ICF buffer
phosphates can be attached/detached from proteins to regulate activity levels (de/phosphorylation)
energy storage system (ATP) – energy is released when phosphate groups are “pulled off” adenosine
ICF > ECF
Amino acids
linked to form proteins
liberated from protein breakdown
amino acids are being used inside cells
ICF > ECF
Creatine
ATP storage (dephosphorylation)
found in skeletal muscle
short term energy reserve - gets burned through quickly
creatine + phosphate group (phosphocreatine); skeletal muscles can get energy by dephosphorylating phosphocreatine
ICF > ECF
Lactate
byproduct of metabolism inside of cell
ICF > ECF
ATP
formed inside of cells; used inside of cells
0 in ECF < ICF
adenosine alone can be found outside of the cell (after the breakdown of ATP) – used to increase blood flow (vasodilation)
glucose
comes from outside of the cell; turned into energy storage compound or for short term ATP
ECF > ICF (0)
glucose gets turned and burned very quickly inside of the cell, which is why essentially it is “0” intracellulary
Protein
(osmolarity chart)
made in the cells and used in the cells
+cell wall proteins
+enzyme
ICF > ECF
major ECF protein is albumin > liver makes plasma proteins and is just placed there, hence why it’s in the ECF
Urea
byproduct of metabolism
equal in [ ] in and out of the cell
Total mOsm/L (osmolarity)
300 (ECF and ICF)
how many dissolved compounds in a fluid sample
corrected osmolar activity (mOsm/L)
280-282 mOsm/L
corrected because ions can be close enough (ex - NaCl) but won’t freely dissociate from one another (Na, Cl); therefore, the biological osmolarity is lower than the predicted osmolarity of solution
2x ECF [Na+] = corrected osmolar activity
ex) 2 x 140 = 280
total osmotic pressure at 37 degrees C (mmHg)
plasma 5443 mmHg
ISF 5423 mmHg
ICF 5423 mmHg
pressure produced from dissolved compounds
cell membrane components
phospholipids
glycolipids
cholesterol
precursor molecules
proteins
glycoproteins
glycocalyx
describe phospholipids
primarily in the cell wall
amphipathic (charged, phosphate hydrophilic head; uncharged, hydrophobic, lipid tail – mostly carbons and hydrogens)
hydrophilic head: polar group + phosphate + glycerol > all are charged
hydrophobic tail: fatty acid chains
C-C-C bonds (fatty acid tails)
C=C bonds (glycerol portion)
on phosphate head will sometimes be a polar group (another compound that the cell needs) ex) cholesterol
describe cholesterol
“planar (flat), rigid” molecule
mostly lipid soluble (except charged -OH group)
the polar group can be changed into something useful for the cell
@ 37 degrees C = cholesterol is RIGID and less fluid
ex) atherosclerosis = tight, rigid arteries d/t cholesterol
@ temps <37 degrees C, cholesterol is less rigid and more fluid (“ice cream”)
used to make sex hormones (estradiol/testosterone)
different compounds of cholesterol will have different effects; cholesterol changes with different enzymes
hydrophilic
“water loving”
ex) charged ions such as Na+, K+, and Cl-
hydrophobic
“water-fearing”
ex) uncharged molecules such as oils/fats
____ % to ____ % of ICF is water
70-85
name 6 things that are soluble in water
ions (electrolytes)
SOME proteins (partially soluble)
carbohydrates (ex. glucose, bc it’s charged)
SOME gasses: CO2
buffers (HCO3-)
SOME drugs
name 5 things that are insoluble in water
cholesterol (lipid)
steroid hormones
lipids
drugs (that need a carrier protein to cross membranes)
SOME gasses: nitrous
between CO2 and nitrous, which gas is soluble in water?
CO2 - soluble
nitrous – insoluble
what is a glycolipid
glucose attached to lipids
glycocalyx
glycoproteins + glycolipids
the sum of cell external sugar structures sometimes used for identification
ex) when patient has uncontrolled diabetes, glycocalyx will look abnormal and immune system will recognize this
precursor molecules of cell membrane
used for synthesizing other structures that the cell needs; usually found in the cell membrane
explain how water corrects imbalances through the various cell compartments
water has no problem moving in between compartments (capillary wall, cell wall, ICF/ECF) to help correct any changes in total osmolarity
what percentage of cholesterol is exogenous vs endogenous?
80% in the body
20% taken in outside of the body (diet)
if you have a high serum cholesterol problem, why would diet alone not be good enough to lower it?
20% of cholesterol in the body is exogenous; therefore, the other 80% the body would have to “figure out how” to lower it itself.
could be Rx-ed STATINS to help lower cholesterol
what is Acetyl-CoA
a byproduct of glucose + oxygen from ATP synthesis; a sugary compound used to make cholesterol
name 6 cholesterol derivatives
estradiol
testosterone
progesterone
androstenedione
(all of these are sex hormones/precursor to sex hormones)
cortisol
aldosterone
(both of these are regulated by adrenal glands)
why can some cholesterol derivatives have “cross reactivity”
all cholesterol derivatives have similar structures
what do phosphatidyl- compounds do?
play a role in the assembly of surfactant in the lungs (speficically -ethanolamine, -choline, and -inositol)
signal transduction processes inside the cell
phosphatidylinositol (PI)
used in smooth muscle to regulate contraction
phosphatidylcholine (PCh)
stored and used for ACh assembly
Phosphatidylserine (cytosolic)
an immune marker
in healthy cells, phosphatidylserine should be INWARD facing
if immune system sees phosphatidylserine facing OUTWARDS/out of the cell wall, immune system destroys it
phosphatidylserine is regulated by FLIPPASE (it flips the phosphatidylserine’s orientation)
ATP is required for flippase to work
in an UNHEALTHY cell, flippase will not be able to function (no ATP), and phosphatidylserine will accumulate on cell wall, and immune system will kill the cell
sphingomyelin
a fatty compound used to make myelin in the nervous system
arachidonic acid
a parent compound; a long fatty acid chain found in the cell wall
what are the 3 main arachidonic acid metabolism pathways?
PGG2 (prostaglandin pathway)
LTA4 (leukotriene pathway)
EET/20-HETE
list out the prostaglandin pathway
- arachadonic acid uses COX1 and COX2 enzymes to produce PGG2
- PGG2 > PGH2 (by COX1/COX2 enzymes)
- PGE2/PGI2/PGF2alpha/PGD2/TXA2 (synthesized by specialized enzymes to make their respective prostaglandins; ex – PGH2 + PGE2 synthase = PGE2)
differentiate the cylcooxygenase enzymes
COX1
+present throughout body
COX2
+more inducible isoform
+turned on in response to pain/something “bad” is happening
+also involved in kidney maintenance as well as cardiac repair s/p infarct/ischemia
COX 2 inhibitor examples
ASA (although more COX1 specific)
Naproxen
Tylenol
NSAIDs (can be COX1 specific too)
explain how giving a COX2 inhibitor to an elderly patient with RA might be harmful
RA > chronic pain > sedentary patient might now feel “great” and will try to do things they normally don’t do (run a marathon) and could end up in CV events (cox-2 helps with renal/heart health)
ex) vioxx was a COX-2 inhibitor to relieve RA pain, however, chronic use has shown an increase in CV/stroke events in these patients
COX 1 inhibitor example
ASA (will inhibit the TXA2 pathway)
NSAIDS (can also be COX2 specific)
list the leukotriene pathway
- arachidonic acid synthesizes leukotrienes by lipoxygenase enzymes (arachidonic acid + 5-LO = 5-HPETE)
- 5-HPETE > LTA4
- LTA4 turns into LTB4 or LTC4/LTD4/LTE4 leukotrienes
what do leukotrienes do
important in immune mediated inflammation
what is an example of a drug that inhibits leukotrienes
singulair (leukotriene antagonist)
+helpful in blocking inflammatory response caused by asthma/allergies
list the EET/20-HETE pathway
- arachidonic acid + cytochrome P450 enzyme = EET/20-HETE
explain what EET/20-HETE does
involved in acute renal failure disease process as well as inflammatory disease pathways
unstable/difficult to manipulate and are found primarily in the cell wall/don’t live a long time in water
explain what TXA2 does
TXA2 mediates endothelial injury by squeezing injured vessel to control bleeding (vasospasm)
leukotrienes and prostaglandins are different than EET/20-HETE in that they can be found in _____
water.
prostaglandins and leukotrienes do not have to hang out in the cell wall because their structure isn’t as similar to arachidonic acid as EET and 20-HETE.
cell membrane proteins can function as ______ and _____.
enzymes
receptors (ex. GPCRs)
differentiate simple diffusion versus facilitated diffusion
simple:
+molecules need no help crossing the membrane (except for specific ion channel proteins)
+no binding, confirmational change, or releasing of molecules happening
+movement is dictated by a concentration gradient (usually from [high] to [low])
facilitated:
+movement across [ ] gradient
+binds molecules, a confirmation change occurs, and then releases molecules
both ways of diffusion do NOT require ATP
what compounds can cross the membrane via SIMPLE diffusion?
dissolved gasses
small, charged compounds (Na+, K+)
H2O
give an example of a facilitated diffusion tranporter
glut-4
explain how electrolytes use chemical and electrical gradients to move across a membrane
chemical gradient: moves from areas of high concentration to low concentration
electrical gradient:
ex) if the inside of the cell is low in [Na+] and electrically more negatively charged, the sodium will move across the membrane towards the negatively charged area (since Na+ is positively charged)
explain what active transport is
in order for compounds to move across the cell membrane, ENERGY is required
how is primary active transport different than secondary active transport?
primary active transport directly uses ATP
ex) Na+/K+/ATPase pump directly uses ATP to pump 3 sodium OUT of the cell & 2 K+ INTO the cell (both ions are against their own concentration gradient)
secondary active transport pulls the energy from an electrochemical gradient (i.e. Na+ pump) to bring another molecule in/out of the cell
ex) NCX (sodium/calcium exchanger)
give examples of which pumps are PRIMARY active transporters
Na+/K+/ATPase
Ca2+ pump
Proton pump
give examples of which pumps are SECONDARY active transporters
NCX
SGLT
give an example of a facilitated diffusion pump
GLUT-4
& GLUT-1
give examples of simple diffusion pumps
ion specific (Na+, Cl-)
aquaporins
osmolarity vs osmolality
osmolarity: quantity/1L of SOLUTION
+easier to quantify
+solution = solutes + whatever else is in your bloodstream
osmolality: quantity/1 kg of H2O
+impractical – you can’t draw blood and JUST get “H2O” in your sample
osmotic pressure calculation
= total osmolarity x 19.3
blood volume calculation
plasma vol x (1-HCT)
another way to calculate corrected osmolarity
total osmolarity x dissociation constant
ex) 300 x (0.93)
