Week 1 Flashcards
what is the extracellular environment
includes all constituents of the body located outside of the cells. Cells receive nourishment from and release waste into the extracellular environment. Cells interact with each other via chemical regulators secreted into extracellular environment
What are primary cilia
non-motile cilia are on every type of cell except blood cells. They have important functions in communication, signal transduction, and cell growth control. They can have huge effects on growth and development, kidney disease, obesity, wound healing, and cancer
what are some ciliopathies
Diseases cause by dysfunction of cilia include polycystic kidney disease, congenital heart disease, mitral valve prolapse, retinal degeneration.
Describe the water content of the body
67% of total body water is WITHIN cells. 33% is extracellular. About 20% of the extracellular fluid is in blood plasma and the remaining 80% is the interstitial fluid in tissues
describe the interstitial fluid (where is it)
it is contained in the gel-like extracellular matrix. Molecules must pass through the interstitial fluid to get between blood and body cells
What composes the extracellular matrix and what does each component do
collagen, elastin, and gel-like ground substance (contains glycoproteins and proteoglycans with high content of water bound molecules)
collagen and elastin provide structural strength to the connective tissues (Collagen IV contributes to the basement membrane)
glycoproteins and proteoglycans form bonds with carbohydrates on membrane of cells making a basement membrane which weds the epithelium to its connective tissues
What are integrins
a class of glycoproteins that extend from the cytoskeleton in a cell through its plasma membrane and into the extracellular matrix. Serve to provide adhesion, polarity, signaling, and motility
“Integrate” the two compartments
why is it called the plasma membrane?
because the extracellular fluid is either blood plasma or derived from it. The membrane separates extracellular from intracellular
explain how the plasma membrane is selectively permeable
It only allows some molecules to penetrate the membrane because it has a large non polar region so only non polar molecules can pass. Generally proteins, nucleic acids, and other large polar molecules are not permeable. But certain ions or small non polar molecules are permeable
This is relevant to PHARMACOLOGY
categories of transport through the plasma membrane
Carrier-mediated transport includes facilitated diffusion and active transport
Non-carrier-mediated transport includes simple diffusion, simple diffusion through channel proteins, and aquaporin channels
Can also categorize by PASSIVE and ACTIVE transport. Passive moves with concentration gradient and uses no energy. Active moves agains gradient and requires energy (PUMPS!)
difference between carrier and channel proteins
carrier proteins are membrane proteins that change their configuration (3D structure) in some way to ferry a molecule or ion across the membrane
channel proteins are membrane proteins with structures that provide selective channels for the movement of specific ions or water molecules across the membrane
what are the components of an aqueous solution
solvent: liquid doing the dissolving (usually water)
solute: molecule being dissolved (like salt, sugar, etc)
What is Brownian Motion
the visible manifestation of random electromotion of a solution. The molecules of a solution are in a constant state of random motion as a result of their thermal energy
This is the driving force for diffusion!
define diffusion
If there is a concentration difference or concentration gradient between two regions of a solution, random motion (Brownian motion) tends to eliminate the concentration difference as the molecule become more diffuses spread out
define NET diffusion
as a result of random molecular motion, molecules in the part of the solution with a higher concentration will enter the area of lower concentration. There is motion in both directions, but more move in the high to low direction so there is a NET MOVEMENT from the region of higher concentration to lower until the difference no longer exists
when does net diffusion occur?
whenever there is a concentration difference across a membrane AND that membrane is permeable to the diffusing substance
what molecules can pass through the plasma membrane easily and why?
PM has a thick non polar core, so non polar molecules can easily pass through it. This includes oxygen gas and steroid hormones. Small, uncharged, polar molecules such as CO2 and H2O can also pass through.
explain the distribution of O2 and CO2 concentrations inside and outside cells
Oxygen concentration is high in the extracellular fluid because oxygen is carried from lungs to tissues in blood. During cell respiration (metabolism, ETC) oxygen is constantly being depleted and made into water, so intracellular oxygen is low.
Carbon dioxide is higher inside the cell. Cells produce CO2 during cell respiration (metabolism, CAC) so intracellular CO2 is constantly being produced.
This contributes to Gas Exchange
how does water diffuse through the membrane
water can diffuse through membrane to a limited degree because of the small size and lack of net charge. However, most membranes have greatly aided water passage through AQUAPORIN water channels.
define osmosis
Net diffusion of water molecules (the solvent instead of solute) across membrane
define ion channels
transmembrane proteins that provide passage for impermeable charged inorganic ions (Na+ and K+ for example). They are relatively selective. Some are always open and many are gated so they can open or close
What determines the rate of diffusion (4 things)
- The magnitude of the concentration difference across the membrane
- the permeability of the membrane to the substance
- the temperature of the solution
- the surface area of the membrane
Can you explain why all of these things contribute to diffusion rate? Page 008
what are microvilli
tiny fingerlike projections in the epithelial membranes in the small intestine which aid in increasing cell surface area and therefore increasing rapid diffusion of digestion products across membranes
2 criteria for osmosis to occur
- There must be a difference in the concentration of a solute on the two sides of a selectively permeable membrane
- The membrane must be relatively impermeable to the solute
define osmotically active
solutes that cannot freely pass through the membrane can promote the osmotic movement of water are osmotically active. Basically if they cause osmosis
when are aquaporins present? what organ as special importance in aquaporin regulation
some cells always have aquaporins present while others have those channels inserted into the membrane in response to regulatory molecules. This regulation is especially important to the KIDNEYS which are the major organs regulating total body water balance
IMPORTANT: aquaporins do not open and close, they are inserted and removed!
explain osmotic pressure
The pressure needed to stop osmosis. E.g. in plant cells, the cell walls provide a rigid box that will prevent further expansion. Animal cells don’t have this and will LYSE (burst) if placed in pure water
the greater the solute concentration of a solution, the greater its osmotic pressure. Measures the force required to stop osmosis, so measures how strongly a solution draws water by osmosis
explain molarity and molality
molarity is a measure of mol/liter so when making a solution you add the weight of 1 mol to a total volume of 1 liter. This means you DO NOT KNOW the exact ratio of solute to water because you don’t know how much water exactly is added
molality is a measure of mol/kg water so you would add the weight of 1 mol to 1 kg of water. Now you know the EXACT ratio of solute to solvent because you know how much water is added!
what is osmolality
the TOTAL MOLALITY of a solution. Depends on ratio of solute to solvent, NOT chemical nature of solute molecules. Add the molality of everything in the solution together for osmolality.
NOTE: for electrolytes like NaCl, they will ionize in water and dissociate. So if a solution is 1 molal NaCl it ends up being 2 osmolal because the Na and Cl ionize
how to measure osmolality
freezing point depression occurs because the freezing point of a solution is affected by total concentration. So by seeing how much freezing point is changed from 0 C, we know the osmolality!
Through this we know that plasma is 0.3 Osm or 300 milliosmolal (mOsm)
describe 2 common isosmotic solutions
5% dextrose or D5W: 0.3 m glucose solution is 0.3 Osm. made by 5 g of glucose per 100 ml.
physiologic saline or normal saline: 0.15 m NaCl solution is 0.3 Osm. made by 0.85 g of NaCl per 100 ml. (NOTE: 0.9 g NaCl is commonly used but 0.85 is the exact number!)
describe tonicity
Tonicity is the effect of a solution on the osmotic movement of water.
Isotonic: no net movement of water occurs, both solutions have the same osmolality
Hypotonic: water moves into cells because solution has a lower total concentration of solutes than plasma. Cells may burst (hemolysis or cytolysis)
Hypertonic: water moves out of cells because solution has higher total concentration of solutes than plasma. Cells shrink (crenation)
describe some of the mechanisms that prevent extracellular fluid osmolality from changing more than 1 - 3% in response to Dehydration
Dehydration increases plasma osmolality and the increases osmotic pressure stimulates osmoreceptors (neurons located by hypothalamus) to shrink and increase nerve impulses, causing thirst and water drinking!
Dehydrated person will also excrete less urine because the osmoreceptors trigger hypothalamus which also triggers posterior pituitary to release antidiuretic hormone (ADH) or vasopressin into blood. antidiuretic hormone acts on kidneys to promote high water retention and less urine excretion.
describe the osmotic effect of eating salts and not eating salts and the pathways that are triggered
Eat salty food: increases plasma osmolality but is not dehydrated (not low blood volume), so antidiuretic hormone is released and person drinks more, urinates less to restore correct osmolality. Result is blood volume high and blood pressure high.
Salt deprivation: lowered plasma osmolality so less osmoreceptor and antidiuretic hormone stimulation. More water excreted in urine to restore proper plasma concentration but at a lower blood volume and low blood pressure, can be fatal!
common characteristics of carrier proteins (and enzymes)
- Specificity: only interact with specific molecules
- Competition: if two molecules are transported by same carrier, rate of transport is lower when they are present together
- Saturation: as concentration of a transported molecule increases, so does rate of transport, but only up to a TRANSPORT MAXIMUM (Tm)
How is glucose transported from blood across plasma membrane
by facilitated diffusion which is passive and powered by the thermal energy of the diffusing molecule (Brownian motion) down a concentration gradient. Uses a carrier.
- glucose binds to a specific site in its carrier protein
- this binding causes a conformation (shape ) change in this carrier that brings the glucose to the cytoplasmic side of the membrane
- Glucose is released into the cell (to the side of lower concentration)
Types of glucose carriers
GLUT1: central nervous system and is increased under certain conditions
GLUT2: pancreatic beta cells and hepatocytes of liver
GLUT3: major glucose transporter in neurons
GLUT4: adipose tissue and skeletal muscles. Insertion of GLUT4 carriers into plasma membrane of adipocytes and skeletal muscle fibers is regulated by exercise and insulin (important for health/diabetes)
(these two maybe less important to memorize)
GLUT5: small intestine sugar absorption
SGLUT1: small intestine/kidneys
when is glucose transported against its gradient
in the epithelial cells of the kidney tubules and small intestine glucose is transported against gradient by a secondary active transporter that moves Na+ with its gradient
how are fatty acids transported
through carriers similar to GLUT carriers. The uptake of fatty acids likewise increases with exercise and insulin (like GLUT4)
define active transport
movement of molecules and ions agains their concentration gradients from lower to higher concentrations. requires energy obtained from ATP (Primary) or coupling with favorable second molecule gradient (Secondary)
PUMPS or ATPase enzymes refer to primary active transport carriers
describe the Ca2+ pump
a Primary Active transporter (pump, ATPase enzyme) located on plasma membrane of all cells and in membrane of ER of striated muscle cells. Removes Ca2+ from cytoplasm by pumping into extracellular fluid or ER. creates high concentration outside cell ( and in ER). so when ion channels open, calcium rapidly diffuses into cytoplasm. Rise of calcium signals diverse processes, like neurotransmitters and muscle contraction.
describe the sodium potassium pump
A primary active transporter (pump, ATPase enzyme) in all body cells. 3 Na+ ions in cytoplasm move partway into pump and bind, activates ATPase to hydrolyze ATP and block both exits. ADP released, producing shape change that opens passage for the Na+ ions to enter extracellular fluid. 2 K+ ions in extracellular fluid bind and Pi is released, allowing pump to return to initial state and release K+ inside cytoplasm.
Summary: pump transports 3 Na+ out of cell for every 2 K+ transported inside cytoplasm (both against gradient)
why do cells spend so much energy maintaining the steep Na+ and K+ gradient? 3 reasons
- Na+ gradient used to provide energy for coupled transport of other molecules
- both gradients are used to produce electrochemical impulses needed for nerve and heart muscles
- extrusion of Na+ is osmotically important. if intracellular Na+ is too high, water flows inside cell and damages it
explain hypokalemic periodic paralysis
a mutation in the calcium channels screws up calcium ion flow. This causes there to be low extracellular potassium ion concentration (hypokalemia) and so the muscle cells repolarize more quickly, so calcium conductance can’t be sustained if it even occurs. The threshold for muscle contraction is hard to reach and maintain. Increasing extracellular potassium concentration would help
describe secondary active transport or coupled transport
the energy needed for the uphill movement of a molecule or ion is obtained from the downhill transport of Na+ into the cell. ATP is only INDIRECTLY required (to maintain the Na+ gradient)
cotransport or symport: molecules move in same direction into cell
counter transport or anti port: molecules move in opposite direction (Na+ into and other out of)
describe cotransport of Na+ and glucose into intestine or kidney cells
Sodium Coupled Glucose Transporters (SGLTs)
downhill movement of Na+ into the cell furnishes energy for uphill movement of glucose into cell. carrier has conformation change that transports molecules
SGLT1 is in small intestine and moves 2 Na+ for every 1 glucose
SGLT2 is in kidney and moves 1 Na+ for every 1 glucose
describe the sodium calcium exchanger / Na+ - Ca2+ exchanger / NCX
a counter transport of uphill movement of Ca+ out of cell with downhill movement of Na+ into cell. no direct use of ATP, but needs ATP to maintain Na+ gradient.
NOTE: this exchanger can work in REVERSE depending on the concentration gradients
how does Digitalis or Digoxin (from foxglove) work?
the drug induces stronger contractions of the heart. It binds to and inactivates Na+/K+ ATPase pumps in the heart cells. Na+ accumulates inside the cell. This increases the REVERSE direction activity of the Na+ Ca2+ exchanger so Na+ pumps out and Ca2+ pumps in. As intracellular Ca2+ increases, a stronger contraction is possible in the heart cells! improves blood flow and reduces congestion in heart/lungs
how does cyanide affect active transport
Cyanide interferes with the electron transport chain and halts ATP production. After primary pumps stop working (they have no ATP to hydrolyze) the concentration gradient for Na+ decreases. Transport of glucose from the intestinal lumen into the epithelial cells (as well as other secondary transports) declines.
define exocytosis and endocytosis
exocytosis: fusion of a membrane bound vesicle that contains large cellular products with the plasma membrane so the products are released into the extracellular space
endocytosis: same thing but in reverse. vesicles from extracellular space fuse with plasma membrane and bring vesicle into cell. (cholesterol example)
together, these provide BULK TRANSPORT
define exocytosis and endocytosis
exocytosis: fusion of a membrane bound vesicle that contains large cellular products with the plasma membrane so the products are released into the extracellular space
endocytosis: same thing but in reverse. vesicles from extracellular space fuse with plasma membrane and release materials into cell. (cholesterol example)
3 factors that contribute to the unequal Na+ K+ gradient
- the Na+ / K+ pump moves 3 sodium out and 2 potassium in
- fixed anions inside cell attract positively charged cations from extracellular fluid
- the plasma membrane is more permeable to K+ than any other cation so accumulates inside the cell (towards anions) the most
what are the potassium concentrations? Net result on cell charge?
Potassium intracellular 150 mEq/L and extracellular 5 mEq/L
Inside of cell is negative and outside is positive, called the potential difference or membrane potential
the extent to which an ion contributes to the potential difference across the membrane (membrane potential) depends on:
- its concentration gradient
- its membrane permeability
K+ is the most permeable so membrane potential is primarily determined by K+
what is the resting membrane potential (-70 mV) determined by
many ions contribute to the resting membrane potential including K+, Na+, Ca+, and Cl- and the extent to which they contribute is determined by their concentration differences and membrane permeabilities. Changing either of those two factors will change the resting membrane potential.
K+ is the most permeable ion and so changes in its concentration have the greatest effect on membrane potential
what would be the effect of inhibiting Na+ channels? specifically in relation to membrane potential and impulses
inhibiting Na+ channels would prevent action potentials (when increased permeability to Na+ drives membrane potential to a positive value) and so would stop neurons from firing and no pain would be felt.
describe the role of the Na+ / K+ pump on membrane resting potential
sodium and potassium concentrations are not a equilibrium, but they are kept constant due to the constant expenditure of energy in active transport by the pump. The pump counters leaks and maintains membrane potential. it also has a net effect of increasing the negative charge inside the cell (3 out, only 2 in) which adds 3 mV to the membrane potential
how can cell signals travel directly from one cell to another and example of cells that use this signaling system
through gap junctions which are tiny links between the cytoplasms of two cells made by proteins called connexins. allows signals to travel by diffusion
Present in smooth muscle and cardiac muscle (allows for all cells in the heart to contract together)
three categories of cell signaling
paracrine: local signal to same organ. cells secrete regulatory molecules that diffuse to nearby targets with receptors
autocrine: regulatory molecules act on the same cells that released them
synaptic: refers to neurons. axon innervates its target organ through a functional connection (synapse) between axon ending and target cell
endocrine: cells of endocrine glands secrete chemical regulators called hormones into extracellular fluid. effects the whole body, but only cells with receptors for signal.
explain oral rehydration therapy
drink a solution with equal amounts Na+ and glucose to promote the cotransport of sodium and glucose into intestine. Helps with rehydrating cholera patients who have excessive loss of sodium and water
explain how diabetes messes with osmolality and the effects of that
high blood sugar (HYPERGLYCEMIA) caused by diabetes means high plasma osmolality and osmotic pressure, this causes osmoreceptors to signal hypothalamus and thirst. there is also more glucose in the urine (GLYCOSURIA) caused by the high blood sugar exceeding glucose carriers maximum so glucose remains in the urine. This increases osmosis of water into urine and loss of water.
what are matrix metalloproteinases and what diseases are they related to
Matrix metalloproteinases break down extracellular matrix proteins. If they are over active they can allow for tumor cells to easily metastasize and migrate through the body. TIMPs (tissue inhibitors of metalloproteinases) inhibit MMPs to prevent this
explain dialysis treatments
If kidneys fail to filter out waste molecules of blood we can manually remove them by a dialysis bag which has a semipermeable membrane and a dialysate solution that will draw the molecules out of the person into the bag. Can be done outside the body with bags or inside the person (PERITONEAL dialysis)
what causes cystic fibrosis
A defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTCR) causes abnormal NaCl and water movement across epithelial membranes
what causes Edema
low blood plasma proteins that cause there to be too much water accumulating in interstitial fluid (tissues). Normally blood plasma proteins are osmotically active and draw water out into blood stream. Liver disease interferes with producing Albumin, the primary blood plasma protein, and causes edema
treatment can therefore be to provide blood plasma proteins such as in a Mannitol intravenous solution.
what is the effect of a diuretic drug
cause increased urination and so increase plasma osmolality (?)
effect of hypoglycemia
hypoglycemia is very low blood sugar. Causes decreased glucose in tissues and so no energy, leads to unconsciousness and death
what is sexual reproduction
when genes from two individuals are combined in random and novel ways with each new generation. This offers the further advantage of introducing great variability into a population
review reproduction terminology: germ cells, gametes, gonads, meiosis, fertilization, zygote, mitosis
germs cells or gametes include the sperm and ova
gonads include testes and ovaries, where gametes are formed
meiosis is reduction division and is the process by which the gonads form gametes
fertilization is the fusion of sperm and ovum cells
zygote is the fertilized egg with the full 46 chromosomes
mitosis is duplication division and contributes to growth of the zygote into an adult
describe chromosome numbers throughout the process of reproduction
The germ cells (gametes) have half the normal number of chromosomes (23) and are haploid. They then fuse during sexual reproduction and have the normal 46 chromosomes, 23 from mom and 23 from dad in homologous pairs. This is called diploid. All cells besides the gametes are diploid
autosomal vs sex chromosomes
The first 22 pairs of chromosomes are autosomal. They are homologous pairs with similar gene content. They can recombine
The final pair are the sex chromosomes X and Y. They are not homologous and don’t contain similar genes. Males have XY and females have XX. In the testes, X and Y can’t recombine except for at the tips of the X.
explain X linked genes
Because X and Y don’t really recombine, there are a large number of genes which are restricted to the solitary X chromosome in males. These are X linked genes. Many of them can be responsible for diseases which are more common in males than in females because the genes responsible (recessive genes) don’t have an additional copy to overwrite
describe testes specific genes and their origin
Genes on the Y chromosome from X-transposed sequences. Most are found to be located in huge palindromes, which enable the Y chromosome to have gene conversions where defects in one region of the palindrome can be corrected by a corresponding region (substitutes crossing over)
what determines the sex of a zygote
The fertilizing SPERM. The chromosomes are randomly divided during meiosis and the creation of the gametes, but in a female only X chromosomes are available to end up in the ova (egg). In males, either the X or Y chromosome can end up in the sperm. So sperm determines the sex of the zygote
explain the importance of X chromosome inactivation
Each diploid cell in a woman’s body has two X chromosomes, but only one is fully active. The result is expression of only one allele of X chromosome genes. Which X chromosome is inactivated is completely random, so a woman’s cells are a mosaic
what are Barr Bodies
The inactive X chromosome in a woman’s cells forms a clump of heterochromatin which can be seen as a dark spot (Barr body). This is seen in cheek cells. It’s also seen as a drumstick appendage in the nucleus of some neutrophils
Provides a microscopic test for chromosomal sex of a person!
describe formation of testes and ovaries
Gonads of males and females look the same for the first 40 days or so of development. This is a “primordial germ cell” with potential to become either testes or ovaries. The hypothetical substance that promotes conversion to testis is called Testis Determining Factor (TDF) encoded by the Sex-Determining Region Y (SRY) gene on the short arm of the Y chromosome. Otherwise, female is the default formation during development.
Are males always XY? And females XX?
Some rare cases of XX males occur when one of the X chromosomes contains a segment of the Y chromosome
Similarly, XY females occur when they are missing the same portion of the Y chromosome.
This portion of the Y chromosome is the Sex Determining Region Y (SRY) gene.
