Download 1 NORMAL and ABNORMAL CELLULAR FUNCTION Lois E

NORMAL and ABNORMAL CELLULAR FUNCTION
Lois E Brenneman, MSN, ANP, FNP, C
INTRODUCTION
- Structural and functional unit of body
- Building blocks for tissue, organs, organ systems
- Functions of cells
- Obtain O2 and nutrients
- Metabolize nutrients
- Eliminate CO2
- Synthesize proteins, other biomolecules
- Respond to changes in environment
- Regulate movement between external and internal cellular environments
- Replicate
- Agents which harm cells disrupt basic survival
- Cells have specialized functions (in addition to basic functions
- Kidney cells maintain fluid and electrolyte balance
- Myocardial cells: contraction
- Processes which control of cellular components
- Regulation of availability of cellular components (gene expression)
- Altering rate at which cellular components carry out physiologic functions
CYTOPLASM and CELL ORGANELLES
- Cell organelles
- Cytosol: fluid medium (mostly water with some electrolytes, proteins, CHO)
- Intracellular fluid (ICF): all fluid inside cell
- Cytosol and nucleoplasm (fluid inside nucleus)
- Chemical composition of organelles differs from cytosol
- Electrolyte balance differs from extracellular fluid
- Proteins:
- Structural strength, form
- Muscle contractility
- Transport agents
- Enzymes, hormones
- Lipids: small portion most cells
- Combine with proteins to keep cell membrane soluble in water
- CHO - small portion of cell - used to form ATP
- ATP- high energy phosphate compound required by cells to function *
* Contraction, secretion, conduction, transport, etc.
- Membrane bound compartments with specific functions
- Plasma membrane also considered organelle
- Nucleus is largest organelle
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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Mitochondria: Inner membrane forms
transverse folds called cristae where
enzymes needed for final step in ATP
production
The Cell: Shows nucleus,
cytoplasm and organelles
ORGANELLES
1. Mitochondria
- Site of ATP synthesis
- Double membrane - inner membrane folded into cristae
- ATP formed from enzyme reactions on cristae
- Highly active cells have high energy requirement (skeletal muscle)
- More active cells have more mitochondria
- Mitochondria can replicate - contain DNA`
CLINICAL EXAMPLES
Cyanide kills by interfering with final step in Krebs cycle It interferes with oxidative
phosphorylation and resulting in inability to form ATP
2. Endoplasmic reticulum
- Tubular, sac-like interconnected channels - cisternae
- Net-like structure with membranes continuous with nuclear membrane
- Surface covered with RNA granules which synthesize protein
- Granules called ribosomes
- Granular ER - contains ribosomes - production of cellular proteins
- Smooth ER: no ribosomes - production of nonproteins
Fat-soluble triglycerides, fatty acids, steroids, phospholipids
- Functions to provide surface for chemical reactions
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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3. Free ribosomes
- Not bound to ER
- Linked together in chain called
polyribosome - varying lengths
- Synthesize protein molecules - most
for use within cell
Endoplasmic Reticulum: 3-D view of
endoplasmic reticulum (ER) with attached
ribosomal RNA and smooth endoplasmic
reticulum - ER serves as surface for chemical
reactions. Ribosomes serve as site of protein
molecule synthesis
CLINICAL EXAMPLES
Many antibiotics operate by interfering with the ribosomes of certain bacteria hence
the bacteria cannot synthesize necessary proteins and die. Antibiotic resistance often
develops as the bacteria synthesize “ways around” this ribosomal issue.
4. Golgi complex
- Golgi complex or Golgi apparatus
- Concentric flattened sacs with membranes
- Sometimes connected to ER or even a part of it
- Membrane-bound vesicles in close approximation
- Packaged chemicals for exocytosis
- Active in various secretory cells e.g. pancreatic acinar
- Role in secretion via vacuole formation for exocytosis
- Other functions:
- Produce polysaccharides
- Chemical modification - activate enzymes
- Store synthesize molecules
- Produce lysosomes
Golgi Complex:
Concentric flattened
sacs with
membranes
sometimes
connected to ER;
Functions to
package chemicals
for exocytosis;
active in secretory
cells. Produce
lysosomes
Hormone Synthesis and Secretion: Hormone
synthesized by ribosomes attached to endoplasm
reticulum (ER). Moves from rough ER to Golgi
complex where it is stored as secretory granules.
Granules stored within cytoplasm until released
from cell in response to appropriate signal
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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5. Lysosomes
- Membrane bound, spherical - contain digestive enzymes
- Intracellular digestion
- Hydrolytic enzymes: proteins, nucleic acids, CHO, lipids
- Endocytosis - lysosomal enzymes digest contents
- Digest worn-out/damaged cell components via autophagy
- Autolysis: cell death releases lysosomes which self-destruct cell
- Phagocytosis: lysosome process
- Granulocytes: WBCs: lysosomes numerous - gives granular appearance
- Remove dead/injured tissue in inflammatory process
Lysosomes: The process of
autophagy and heterophagy,
showing primary and secondary
lysosomes, residual bodies,
extrusion of residual body contents
from cell, and lipofuscin-containing
residual body
CLINICAL EXAMPLESBy products of W BC death in a septic knee can destroy cartilage as d ead W BC liberate
lysoso m es. A cco rdingly septic k nee s m ust be dra ined (asp irated) q 24 hou rs.
Abscess destroys good tissue as W BCs/phagocytes - attracted to the area to fight the
infection - die and liberate lysosomes which destroy other tissue (besides the bacteria)
6. Peroxisomes
- Contain oxidative enzymes which form H202 (peroxide)
- Peroxide detoxifies harmful substances esp in liver/kidney
CLINICAL EXAMPLES
Peroxide is very toxic to many organisms esp anaerobic organisms which is why cellular
liberating peroxide would be effective in fighting infection. Dentists sometimes
recomm end peroxide rinses or peroxide toothpaste (M entad ent) to control anaerobic
bacteria which are resp onsible for tooth plaque and gingiv itis. Unfortun ate ly peroxide
also destroys good tissue which is why it stings on wounds and also why we now
discourage its use on decu biti
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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7. Cytoskeleton
- Network of proteins providing for cellular shape and/or movem ent
- M icrofilamen ts and microtubules
- Microfilam ents : rod-like stru cture s of a ctin an d m usc le filam ents
Occ ur in both m uscle and non-m uscle cells
- Microtubules- non-membranous cylindrical organelles contain tub ulin
- Functions
Structural support
Inte rnal conduit for m ovem ent m ate rials within cells
Provide for locomotion e.g. cilia
Cytoskeleton: The microfilaments
associate with the inner surface of the
cell and aid in cell motility. The
microtubules form the cytoskeleton
and maintain position of the
organelles
8. Centrosomes and centrioles
Centromere: dense area of cytoplasm within nucleus
Centriole: two hollow cylindrical structures within centrosome
Function in non -dividing : organize microtubules
Function in dividing cells: form spindle apparatu s for m itos is
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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PLASMA AND INTRACELLULAR MEMBRANES
A. Introduction
- Surrounds cells; sep arate s intracellular-extrace llular com partm ents
- Organelles have mem branes
- Primary role is to regu late pa ssa ge b etwe en c om partm ents
- Role in cellular com m unication - selective b arriers
- Composition
Lipid bilayer: double layer of lipid molecules - polarity
Phospholipids, glycolipids, cholesterol
Amphipathic phospholipid m olecules - polar end and nonpolar end
Polar end points toward interior of cell - hyd rop hillic
Nonp olar buried in interior of mem brane - hyd rop ho bic
Polarity allows m em brane to act as ba rrier - restricting loss and e ntry
Mem brane exists in fluid sta te at body temp
Structure is dynam ic - fluid mosaic m od el of m em brane structure
Protein bound to eac h layer and within layers
Anchored in or on lipid bilayer - forms structural component
Proteins may have other structures attached to them
CH O attache d outer surface - glycoproteins
CHO attached to polar region - glycolipids
Proteins also function to transport/ex change m ate rials - trans port
Proteins function as enzymes
Cell Membrane:
Hydrophillic (polar) heads
and hydrophobic (fatty
acid) tails. Note positions
of the integral and
peripheral proteins in
relation to interior and
exterior of cell as well as
the pores through which
various substances pass
CLINICAL EXAMPLE: Certain drugs which are said to be lipophilic can penetrate the cell
membrane better than other drugs in the same class hence have better tissue levels and
sometimes better efficacy. Certain ACE-inhibitor agents used to control hypertension are more
lipophilic then others in the class and have increased tissue penetration with a long half-life
(permitting once day dosing). Similarly older antihistamines (Benadryl -diphenhydramine)
cross the blood-brain barrier causing sedation while newer - 2 ND generation antihistamines do not cross the blood brain barrier and have little or no sedation (Claritin - loratadine)
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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B. Functions of membrane components
Lipid bilayer gives membrane its physical characteristics
- Forms structure of membrane
- Barrier (hydrophobic interior) to water-soluble substances: ICF - ECF
- Gives membrane its fluidity
Proteins give membrane its biologic features
- “Gated channels” protein ion channels - ion passage
- Protein channels across lipid bilayer
- Channels permit passage of water-soluble substances
- Ions are example of water-soluble substance
- Channels are specific to ion; vary in number kind or type pending cell
- Some channels are regulated - “open” or “closed” to specific ions
- “Carrier molecules” - transport materials unable to transverse on their own
- Bind with specific molecules - hormones or neurotransmitter
- Orchestrate signal transmission to interior of cell
- Catalyze biochemical reactions
- ATP synthesis - energy production in mitochondria
- Cellular structure - specialized membrane junctions
CLINICAL EXAMPLES
An entire class of antihypertensive drugs - calcium channel blockers - is based on the
effects these molecules have on the calcium ion pores within the cell membrane. The
issue is further complicated by so called fast-channel and slow channels
Glucose requires protein molecules to “carry” the molecule across the cell membrane
e.g. from the intestine where it is absorbed
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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MEMBRANE TRANSPORT
- Passive movement: diffusion, osmosis, filtration, carrier-mediated facilitated diffusion
- Active: energy driven carrier-mediated transport; endocytosis, exocytosis
A. Diffusion - movement of a substance
- Net movement of a substance from higher concentration to lower
- Movement down a concentration gradient
- Diffusion equilibrium: substance equally distributed between 2 compartments
- No movement if substances equally distributed between two regions
- Rate of movement - rate function of concentration gradient
- Amount of substance; kinetic movement, size of membrane pores
- Other factors: ability to dissolve in lipids; electrical charge
- Plasma membrane presents barrier
1. Dissolve in fluid structure of plasma membrane and pass through
2. Pass through pores (channels formed by proteins)
Na+, K+, Ca++, chloride, bicarbonate, water
- Example: movement of O2 molecules; CO2, N2, steroids, fat-soluble vitamins
Diffusion: Particles
move from areas of
higher concentration
to areas of lower
concentration so as to
become equally
distributed across
membrane
Osmosis
osmotically active
particles induce the
flow of water across
membrane
CLINICAL EXAMPLES
Ethyl alcohol (ETOH) readily diffuses across cell membranes and rapidly enters all
body compartments accounting for the fact that it can affect a wide variety of body
systems and functions. Oxygen and carbon dioxide readily diffuses across the cell
membrane even in avascular areas such as the cornea or synovial joints
B. Osmosis - movement of water
- Net diffusion of water through selectively permeable membrane
- Membrane separates two aqueous solutions with different solute concentrations
- Membrane is impermeable to one or more of the solutes
- If concentration on non-diffusable solute is greater on one side then net diffusion of
water occurs (osmosis) through membrane toward area of higher solute concentration
- Movement occurs until concentrations solute/solvent equal on both sides
- Water molecules move from area of greater concentration to lower concentration
- Pressure is created on membrane
- Osmotic pressure - pressure created on membrane during water movement
Magnitude of pressure is function of number of solute particles
Greater the number of non-diffusible solute particles; greater is the pressure
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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CLINICAL EXAMPLES
Clinical examples: brain swelling and use of osmotically active compounds like
mannitol to pull water out of brain tissue and into blood
Edema and anasarca when proteins is low - fluid flows out of blood vessels and into
surrounding tissue
Magnesium citrate is used as laxative because it osmotically pulls water into the colon
causing loose stool. Similarly diabetic has polyuria because the osmotically active
glucose pulls water into vessels which in turn are filtered by kidney into the urine
- Isotonic
- Fluids containing osmotically active particles in the same concentration as
plasma (example sodium chloride 0.9%)
- RBCs neither string nor swell in isotonic solutions
- Water volume of cell remains constant - neither shrinks nor swells
- Cells shrink in hypertonic solutions - water diffuse out of cells
Higher concentration of osmotically active particles
- Cells swell (burst) in hypotonic solutions - water diffuses into cells
Lower concentration of osmotically active particles
CLINICAL EXAMPLES
Drowning in salt vs fresh water is readily apparent on autopsy due to (among other
things) the effect of the hypertonic (sea water) presenting with shrunken lung cells vs
hypotonic (fresh water) presenting with swollen lung cells. Normal saline (0.9%)
causes neither shrinking nor swelling of erythrocytes or other body cells hence it is
widely used in clinical therapy. There are select circumstances where hypertonic or
hypotonic solutions would be used clinically but for the most part we tend to use isotonic
solutions in clinical practice.
C. Filtration
- Substances move across membrane due to pressure differences
- Move from areas of greater pressure to lower pressure
- Example: Renal formulation of glomerular filtrate
Large particles remain in capillaries due to size and impermeability of basement
membrane
CLINICAL EXAMPLE
INFLAMMATION: Intercapillary fluid pressure - capillary filtration pressure forces water through pores
and into interstitial spaces. Capillary filtration is a function of the arterial pressure, venous pressure and
also the effects of gravity. Edema (swelling) which occurs when inflammation results histamine release
which, in turn, causes dilation of precapillary sphincters and arterioles in the affected area.
DVT: Venous thrombosis obstructs venous flow thereby producing increased venous and
capillary pressures. Normally, the lower pressures would facilitate movement of fluid into the
capillaries where it is pushed back to the heart to be re-circulated. In this case the increased
venous pressure results in an outward flow (flow from capillaries into tissue) hence the
associated swelling to the affected area. Typically DVTs present with swelling, redness and
pain.
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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D. Carrier-mediated transport systems
Certain molecules need carrier to travel down gradient
- Molecule is too large to pass unaided
- Molecule is not lipid soluble hence needs carrier
Examples: glucose, amino acids, inorganic ions (Na+, Cl-, K)
Some require energy (active) some require no energy in put (facilitate diffusion)
Specificity - specific for a particular solute
Example: glucose transport system will not transport other molecules (aa)
Saturation: maximum rate (transport maximum) at which solute can be transported
System is saturated if more solute is present
Saturated system transports at maximum rate; can’t handle additional solute
Below saturation level rate is proportional (linear) to solute concentration
Higher the solute faster the rate of transport
Competition
Same carrier system transports two different molecules
Rate of transport for each will diminish by presence of other
Solutes compete for carrier; some of each transported at maximum rate
Energy Dependency
Many carrier systems require energy
Metabolic inhibitors (interfere with energy-producing reaction) stop transport
Speed
Substances transported by mediated transport usually more rapid than simple
diffusion
1. Facilitated diffusion
Carrier protein - facilitates movement of molecule which otherwise can’t diffuse
- Energy not required because movement is down the gradient
- Subject to protein-binding
- System is saturable
- Subject to competition
-
Example: glucose across membranes of RBCs, muscle, adipose
- Molecule is too large to pass unaided; not lipid-soluble
- Combines with carrier - conformational changes
Insulin increases number of transport proteins
Insulin also increases rate of glucose metabolism
Facilitated Diffusion: carrier system
required to move molecules across
gradient. Moves down gradient thus
no energy requirement
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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CLINICAL EXAMPLE
Glucose in urine (glycosuria) of diabetic. Excess blood glucose saturates carrier system
in kidney which normally re-absorbs all of the glucose presented. Kidney cannot keep
up and glucose “spills” into urine. Glycosuria creates osmotic gradient which in turn
increases water content of urine and results in polyuria
Certain drugs - aspirin for one - are carrier mediated. Blood levels (and toxicity) are
directly related to increased dosing (linear) to a point then toxicity sharply rises (nonlinear) with small increases in dosing after the point when carriers become saturated.
- tinnitus, GI toxicity
2. Active transport
- Carrier-mediated process against concentration gradients
- Energy (ATP) is required because movement is against gradient
- Reverses the effects of diffusion
- Always requires energy; reverses diffusion
- All body cells capable of active transport
- Depends on energy derived from metabolism
- Two classes depending on how system derives energy
Active Transport: selected
molecules transported across
membrane against gradient
thus require using energy driven
ATP pump
a. Primary active transport systems
- Same protein which binds is also capable of hydrolyzing ATP
- Uses energy released to move against gradient
FOUR PUMPS
- Sodium-potassium adenosine triphosphatase (Na+,K -ATPase)*
- Calcium ATPase (maintains lower conc Ca++ in cytoplasm)
- Hydrogen ion ATPase (energy transduction; acid-base balance)
- Hydrogen-potassium ATPase (acid-secreting cells stomach, kidney)
* Na+,K -ATPase pump is important for cell volume regulation
- Prevents accumulation of Na+ ions in cell
- Water follows Na+ (osmosis); pump prevents H20 influx
- Accumulation of Na+ in ICF causes osmosis of H20 into cell
- Pumping Na+ out counteracts tendency of water to enter cell
CLINICAL EXAMPLE: hypoxia causes decreased/ceased cellular metabolism (no ATP is
generated) hence pump does not operate. Na+ is not removed from cell and water
follows resulting in cellular swelling
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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b. Secondary active transport systems
- Many organic molecules transported via this method
- Uses ion gradient created by primary active transport as energy source
- Concept is similar to kinetic energy of a dam
Water is allowed to build; when dammed-up water is released, the
energy released can be harnessed for other purposes
- Ions allowed to flow down gradient create energy
- Energy so created used to drive another reaction against the gradient
- Energy is stored in ion gradient - can be used in 2 ways
- Phosphorylate ADP to ATP for purposes of energy storage
- Coupled to the pumping of another solute molecule
- Most common ion used is sodium - sodium binds to transport protein
- Result is change in affinity of binding site for transported solute
- Allosteric modulation
- Binding of ligand to a protein
- Changing conformation of protein
- Sodium moves down gradient - transported substance moves against
gradient
Cotransport or symport - both molecules move in same
direction
Counter-transport - molecules move in opposite directions
through common carrier mechanism
CLINICAL EXAMPLE:
There is a coupled ratio of glucose-sodium in a 1:1 molar ratio in the intestine via a
sodium-glucose cotransporter. This discovery (early 1960s) led to the formulation of
oral rehydration solutions for the treatment of diarrhea particularly for infants/children.
The glucose in these oral rehydration solutions acts through a sodium-coupled
transport mechanism to promote fluid absorption in the small intestine even during
diarrheal episodes. Accordingly the glucose-sodium solutions reduce (potentially
dangerous) fluid loss from diarrhea. Gatoraide and Pedialyte are mildly sweet and salty
at the same time.
E. Endocytosis and exocytosis
Endocytosis: process of bringing particles into cell and
releasing into interior
Exocytosis: process releasing secretions to exterior of cell
Pinocytosis:
Exocytosis: membrane engulfs particle forming vacuole
transporting it inside cell. Exocytosis: membrane surrounds
particles within cell forming vacuole which subsequently
transports contents across membrane and releases them into
extracellular fluid
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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Endocytosis: bringing in protein an other substance through cell wall invagination
Pinocytosis - movement in of water or ECF adhering to cell membrane
Phagocytosis: ingestion of particulate material or macromolecule (commonly
refers to engulfment of bacteria)
Receptor-mediated endocytosis
Movement of substances through cell-surface receptors that stimulate
endocytotic process
Cell membranes have cell-surface receptors
Substances - ligands - bind selectively - taken into cell
Example LDL which provide cholesterol for membrane synthesis
LDL = low-density lipoprotein
Exocytosis - reverse pinocytosis - active release of products into ECF
- Secretion granules formed by Golgi apparatus
- Formed granules move to inner surface of membrane causing outpouching
- Outpouching ruptures and releases contents
- Secretory process necessary for digestion, glandular secretion,
neurotransmission
Endocytosis: Membrane engulfs
particles forming vacuole which is
taken into the cell
Exocytosis: Particles engulfed
within vacuoles then expelled
from cell through membrane
CLINICAL EXAMPLE
Monocytes (type of WBC) and macrophages (tissue monocytes) are large cells which
function to engulf bacterial and viral organisms (phagocytosis). Killer lymphocytes also
function in this manner. While some WBCs “die in combat” e.g. neutrophils (type of
granulocyte) generally die at the site of infection releasing microbe-toxic substances in
the process, monocytes very often survive the phagocytotic process. Subsequently,
they may expel the remains of the organism(s) so destroyed (exocytosis)
Low density lipoprotein (LDL) is a necessary molecule to facilitate cholesterol import
into the cell for membrane synthesis. Too much LDL however (very endemic in cultured
societies) results in hyperlipidemia and the associated sequelae of atherosclerotic
cardiovascular and cerebrovascular disease
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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F. Epithelial transport
Molecules cross epithelial cells via one of two routes
Paracellular pathway: molecules pass through extracellular spaces
Transcellular pathway (more common) - pass through cell
Molecule must cross both basal and luminal pathways
May involve active and passive processes
Epithelial Structure:
Arrangement of epithelial cells
in relation to underlying tissues
and blood supply. Epithelial
tissue has no blood supply of its
own relying instead on vessels
in underlying connective tissue
for nutrients (N) and elimination
of wastes (w)
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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ELECTRICAL PROPERTIES OF CELLS
Membrane potentials
- Differences in electrical potential across membrane
- Characteristic of all living cells
- Exists due to unequal ion distribution on either side of membrane
- Factors maintaining unequal distribution
- Differences in membrane permeability to various ions
- Active transport systems
- Membrane with potential said to be polarized
- Inside of cell is more negative than outside
Cell Membrane Potential: negative charge along cell
membrane. Electrical potential is negative on the
inside of cell membrane relative to the outside
Cells are “excitable” when they can generate action potential (AP)
Can generate impulses along their membrane
Impulses so generated transmit signals along membrane
Resting membrane potential normally -70 to -85 mV from inside to outside
Small excess of negative ions in the intracellular fluid (ICF)
Small excess of positive ions in the extracellular fluid (ECF)
Opposite charges attracted to one another
- membrane separates them
Graph of Action Potential
Potassium (K+) higher concentration
in intracellular fluid
Sodium (Na+) higher concentration in
extracellular fluid
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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Potassium and sodium ions are the major determinants of resting membrane potential
Membrane at rest is more permeable to potassium than sodium
More potassium leaks out of cell
50-70 times more potassium channels than sodium channels
Potassium moves down concentration gradient
Some of positively charged K+ ions move into cell due to electrical gradient
Equilibrium potential: occurs when electrical and concentration gradient are equal
- Value is function of concentration gradient of ion across membrane
- Larger the concentration gradient, the greater equilibrium potential
Equilibrium potential value varies with cell type
Average cell : K+ = -90 mV; Na+ = +60mV
Nerve cell: -70 mV
Some positively charged Na+ ions are leaking into cell making it slightly
more positive than usual potassium equilibrium potential
Nerve cell excitability
- Neither K+ nor Na+ are at equilibrium so flow of ions continues
- Resting membrane potential is closer to potassium equilibrium potential
- Gradients maintained via Na+, K+ -ATPase
- Pumps Na+ - which has leaked into cell - back out of cell
- Pumps K+ - which has leaked out of cell - back into cell
- Pump is unequal resulting in a net charge across membrane
Pumps 3 Na+ ion out for every 2 K+ ions in
Results net movement of charge across membrane creating potential
Accounts for name “electrogenic pump”
- Transient changes in membrane permeability to ions
- Alter voltage across membrane
- Major mechanism by which cells can communicate
CLINICAL EXAMPLE excess potassium (K+) given IV can stop the heart - mimicking an MI due to its effect to decrease membrane reactivity. Done intentionally, it may not be readily
apparent and has, at times, become a forensic issue where “foul-play” is suspected. Similarly,
during open heart surgery, the heart is bathed in a potassium solution - the so-called
cardioplegic - to stop the heart. The solution is then flushed away with normal saline after
surgery is completed to allowing the heart to resume beating.
Cell excitability - changing or altering electrical potential across cell membrane
- Nerve and muscle cells are considered excitable
- Can change membrane potential
- Effect an action or response
- Return to resting state
- Excitable cells rapidly change resting potential in response to stimulus
- Graded potential - local potentials that vary in amplitude - conducted decrementally
- Action potential: rapid reversal of polarity in electrically excitable cells
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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A. Action potentials
Effect responses in target cells mainly skeletal muscle and next neuron
After AP cell returns to normal resting state - re-establishes resting membrane potential
Process occurs in wave which spreads down neuron
- Entire membrane does not depolarize at once
- Results in propagation of a nerve impulse
Nerve impulse is wave of depolarization followed by wave of repolarization
Depolarization-repolarization travels along nerve away from point of stimulation
Once generated - impulse conducted in identical manner without change
No change in magnitude or velocity
Stimuli (individual or collective) which fail to generate AP produce no nerve impulse
Response of nerve to stimuli is per all-or-none law (maximal or zero)
Nerves don’t generate weak or strong impulses as a function of stimuli intensity
At axon terminal- AP activates voltage-sensitive Ca++ ion channels
Located in presynaptic membrane
Ca++ ions diffuse into cell
Ca++ diffusion stimulates vesicles containing neurotransmitters
- Vesicles fuse with membrane and release contents into synapse
- Neurotransmitters diffuse across synapse
Neurotransmitters cross synapse - bind to postsynaptic neuron receptors
Ultimately trigger response on target cell (tissue)
Refractory period: minimum amt of time after AP before cell can be restimulated
Length of refractory period determines conduction frequency
- Maximum number of impulses which can be conducted per second
- Fibers with shorter refractory periods have higher conduction frequency
- Fibers with longer refractory periods have lower conduction frequencies
Nerve fibers conduct impulses at higher frequency than myocardial fibers
Neuron
Showing cell body, axon
and dendrite
Synapse:
Shows rupture of vesicles with diffusion of
neurotransmitter across synapse to another
neuron (left) and to neuromuscular
endplate (right)
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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CLINICAL EXAMPLE:
The SA node of the heart is called the pacemaker. This is because it is the first area to
depolarize and initiate and action potential which spreads throughout the heart via the normal
conduction pathway (SA node to AV node to bundles etc.). The end result is atrial and
ventricular contraction when the action potential spreads to the respective muscle fibers which
then depolarized and contract. Similarly, the SA node it has the shortest refractory period hence
it is the first area capable of depolarizing again Occasionally arrhythmias occur when there is
a portion of the heart (outside of the AV node) - spontaneous pacemakers - which
spontaneously depolarizes and aberrantly takes over the role of the pacemaker.
Calcium ions decrease membrane permeability to sodium and vice versa. With insufficient
calcium (hypocalcemia), permeability to sodium increases and membrane excitability increases
which results in spontaneous muscle movement known as low-calcium tetany
Local anesthetics (procaine, lidocaine, cocaine, etc.) operate via decreasing membrane
permeability to sodium and preventing an action potential from occurring
STAGES OF ACTION POTENTIAL
1. Adequate positive stimulus to neuron causes rapid and marked change in membrane
potential (MP)
- Sodium permeability increases
- Na+ enters faster than it can be pumped out
2. Membrane potential less negative as more Na+ passes through
- Potential is reduced to critical value called threshold
- Gated Na+ channel open at -45 mV - rapid infusion of Na
- Membrane is more permeable to Na+ than K
- Na+ equilibrium - inside of membrane becomes more positive
3. Depolarization Positively charged Na+ reverses polarity of membrane potential ->
AP
- AP when inside of cell becomes positive to outside of cell
- Increase in membrane permeability is transient (less 1 msec)
- Inactivation gates of sodium channel begin to close
4. At peak of AP K channels open thus increasing permeability to K+ ions
- Increase in K+ diffusion out begins - it accelerates movement of Na+
- Causes inside of membrane to become positive
- K+ leaves cell for same reasons Na+ entered
- Favorable electrical and chemical gradient
- Increased membrane permeability
5. Diffusion of Na+ inhibited by decrease in K+ permeability
- Net loss of K+ from inside causes MP return to zero then become positive
- Reestablishment of resting membrane potential
- More K+ leaves cell than is actually required to restore resting MP
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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6. Hyperpolarization: inside of membrane briefly more negative than normal resting
state
- Sodium-potassium pump returns normal membrane resting potential
- Pump exchanges internal Na+ for external K+
- Restores normal internal/external ratios of the ions
7. Repolarization - activities which restore resting membrane potential
CELLULAR ENERGY METABOLISM
- Sum of all biochemical reactions - anabolic (building) and catabolic (breaking down)
- Many reactions require energy - would not occur spontaneously
- ATP is major cellular energy unit - required for many functions - adenosine triphosphate
- Nucleic acid derivative containing high energy phosphate bonds
- Release energy when bonds are broken
- All cells generate ATP from catabolism of energy (fuel) sources
- Energy generated as ATP is transferred to cellular functions
- Energy is released during breakdown of ATP to ADP (adenosine diphosphate)
- ATP production via three metabolic pathways - glycolysis, Krebs cycle, oxidative
phosphorylation
A. Glycolysis
- Breakdown of glucose (hexose) into two 3-carbon pyruvate
molecules
- Lactic acid is byproduct - diffuses out into tissue and plasma
- Enzymes for the breakdown in cytoplasm - requires 10 enzymes
- CHO are only fuel molecules involved
(only carbohydrates can be used)
- Generates 4 molecules ATP for each glucose but 2 used in process - net of 2 ATP
- Anaerobic system - inefficient but can keep cell viable for short periods
- Forms less than 5% of ATP needed
- Occurs during intense muscular exertion where O2 demand exceeds supply
- Produces oxygen debt requires deep breathing afterwards to restore debt
- Process of restoring called recovery oxygen consumptions (minutes to hours)
- Lactic acid in muscle reconverted to glucose or pyruvic acid in presence of oxygen
- Lactic acid leaving cell during exercise travels to liver and changed to C02 and
glycogen
ATP - adenosine
triphosphate
Storage form of cellular
energy. Energy released
from hydrolysis of highenergy bonds fuels cell
metabolism
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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CLINICAL EXAMPLE
On vigorous exercise (or not-so-vigorous if one is
“out-of-shape”) the person begins to feel muscle
pain as the lactic acid accumulates. Eventually
pain increases to a point where exercise must stop.
With conditioning, more and more exercise can be
performed prior to pain making further movement
intolerable. Figure skaters, for example, will report
leg muscles aching as they near the conclusion of
their programs. When experiencing lactic-acid
induced pain, they are then less able to perform the
more demanding athletic feats as compared to
earlier in the program prior to the build-up. They
frequently schedule “rest periods” between jumps
where they simply glide around the ice. Skaters
(and other athletes) are observed to be breathing
heavily at the end of their performances (often
while seated and waiting for their scores) as they
repay the oxygen debt during so called recovery
oxygen consumption. Similarly, deep knee
bending or holding prolonged muscle positions
in ballet exercises will often cause the muscle
quivering as lactic acid levels build.
Cell Metabolism
Glycolysis: anaerobic process which is less efficient (2
ATP). Uses glucose as energy source and generates
lactic acid as a byproduct
Krebs Cycle: first step in aerobic metabolism - uses
CHO, lipids or proteins as energy source - End products
enter oxidative phosphorylation to form ATP
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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Krebs cycle
- First step in aerobic metabolism
- Also known as citric acid cycle
- Aerobic process - requires oxygen
- Several products can be used as fuel (carbohydrates, lipids, proteins)
- Required enzymes located in mitochondrial matrix
- Acetyl coenzyme A (acetyl CoA) is major substrate (from pyruvate)
- Pyruvate (from glycolysis) is major fuel molecule as converted to Acetyl CoA
- Pyruvate is converted to acetyl CoA in mitochondria
- Lipids and proteins also form acetyl CoA which enters cycle
- Acetyl CoA from lipid and protein metabolism also enters
- Amino acids are capable of entering at certain points (can thus be used as fuel)
- First step is combination of 2 acetyl groups with 4 carbons forming citrate
- Eight sequential steps follow - each cycle produces the following end products
- 2 molecules of CO2
- 4 coenzymes formed from transfer of 4 pairs of H+ atoms
Flavin adenine nucleotide (FAD) to form 1 FADH2
Nicotinamide adenine dinucleotide (NAD) to form 3 NADH
- 1 Guanosine triphosphate (GTP ) from phosphorylation of guanosine
diphosphate (GDP)
- Transfer of H+ ions to coenzymes represents transfer of energy
- These transferred H+ ions subsequently used in oxidative phosphorylation
- End products of Krebs cycle used in oxidative phosphorylation to form ATP
Oxidative Phosphorylation: Last step in aerobic metabolism
- Uses H+ electrons to transfer energy via reduced
coenzymes formed in glycolysis and krebs - Results in energy
release and formation of 38 molecules of ATP in combination
with Krebs
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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C. Oxidative phosphorylation
- Last step in aerobic metabolism
- Synthesis of ATP from ADP
- Uses energy released when molecular O2 combines with H+ to form water
- Enzymes located in inner mitochondrial membrane
- Uses hydrogen atom (H+) electrons to transfer energy
- Transfers of H+ is via the reduced coenzymes formed from glycolysis and Krebs
- H+ electrons transferred to series of metal-containing enzyme complexes
- Metal-containing enzyme complexes known as electron transport chain (ETC)
- Molecular oxygen is the final acceptor molecule in the chain
- As electrons flow through complex, series of energy transfer occurs
- Each protein complex in ETC has greater affinity for electrons than previous protein
- Electrons flow from higher to lower energy states - thus energy is released
- Energy so released is used to pump H+ across mitochondrial membrane
- Pumped into intermembrane space
- Sets up an ion gradient
- Flow of ions back down electrochemical gradient provides energy
- Energy so provided used for oxidative phosphorylation of ATP
- Chemiosmotic model
- Protons pass through enzyme protein channel known as ATP synthetase
- Energy released as protons diffuse across membrane
- Released energy from ATP synthetase use to phosphorylate ADP to ATP
- ATP output is 38 molecules for Krebs-oxidative phosphorylation
- 3 ATP for each NADH - 2 ATP for each FADH2
- Aerobic process much more efficient than anaerobic pathways
CLINICAL EXAMPLES
ATP DEFICIENCY: A variety of relatively rare diseases - collectively known as oxidative
phosphorylation diseases - present with muscle weakness and multi-organ system
dysfunction. All of these diseases are related to an inability of the mitochondria to produce
adequate amounts of ATP. List is quite extensive and comprises mostly rare or little-known
diseases, however, some of the more well known diseases on this list include Frederick’s ataxia,
pigmentary retinopathies, certain sequelae of diabetes, and neuropathy syndromes.
DIABETIC KETOACIDOSIS:
The Krebs cycle uses pyruvate (from glycolysis) as the major fuel
molecule from which the end products (CO2, FADH2, NADH, GTP) are produced. These end
products are subsequently acted upon via oxidative phosphorylation to produce 38 molecules
of ATP for energy. Lipids and proteins can also be used as an fuel source although in the
normal, non-diabetic individual, they are used to a much lesser extent as compared to pyruvate
(from glucose). Due to the diabetic’s insulin deficiency, glucose is not available as a fuel
source resulting in excess breakdown of adipose stores which, in turn, result in increased
levels of free fatty acids. These free fatty acids are oxidized within the liver via acetyl CoA
producing ketone bodies (acetoacetic acid and beta-hydroxybutyric acid). Oxidation is
accelerated by glucagon. The ketone bodies so formed exceeds the rate at which they can be
utilized by muscle and other tissue. Accordingly, ketonemia and ketonuria develop.
Dehydration will further compromise urinary excretion of ketones resulting in increased plasma
hydrogen ion (H+) and systemic metabolic ketoacidosis. Ketogenic amino acid from protein
catabolism further increases the ketotic state. Infections commonly precipitate ketoacidosis
in the diabetic because the stress of the infection increases insulin requirements
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
22
THE NUCLEUS AND REGULATION OF GENE EXPRESSION
- Nucleus: large membranous organelle - frequently centrally located within cell
- Large quantities deoxyribonucleic acid (DNA) which forms genes
- Genes control synthesis of proteins which, in turn, controls cellular function
- Nuclear envelope separates nucleus from cytoplasm - large membranous envelope
- Two distinct membranes (in contrast to plasma membrane)
- Fused together periodically to form circular pores
Materials pass in and out of nucleus via pores
Pores 10X larger than plasma membrane pores
Proteins pass through pores with relative ease
- Ions-water move easily between nucleus and cytoplasm
- Nucleolus - collection of dense fibers and granules within nucleus
Most visible when cell is not in mitosis
Primarily RNA and proteins
Granules are precursors of ribosomes (sites of protein synthesis)
- Chromatin: long molecules of DNA in association with protein
Non-visible with light microscope except during mitosis
Coil and condense during mitosis into chromosomes
- Chromosomes - X-shaped structures (condensed chromatic during mitosis)
22 pairs of autosomes - different in size and shape from each other
1 pair sex chromosome - XX or XY
A. Genes
Entire cellular activity controlled via genes
Linear sequence of nucleotides on DNA
Code for production of a single protein
Sequence divided into units of 3 nucleotides - each called codon (triplet)
Exact sequence of codon codes for single amino acid
Nucleotide bases: guanine, thymine, cytosine, adenine
Genes determines specific code that transcribed as RNA
Gene is located on one of the two DNA strands - master strand template (pattern)
Template for messenger RNA (mRNA) synthesis
Transfer RNA (tRNA) or ribosomal RNA - formed from template on other parts DNA
Genetic code (to ribosomes) allows formation of several thousand proteins
Essential to function of organism
Most proteins contain 100 to 1,000 amino acids
DNA Double Helix:
Showing sugarphosphate-sugar
backbone supporting
the paired four bases
where cytosine pairs
with guanine and
adenine pairs with
thymine
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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CLINICAL EXAMPLE
Substitution of a single amino acid glutamic aid is replaced with valine resulting in the synthesis
of an abnormal globulin chain causing the formation of hemoglobin (HbS) which results in
sickle cell anemia. Whether the person has relatively asymptomatic sickle-cell trait or the
actual disease, sickle cell anemia, depends on whether the individual is heterozygous (one
abnormal gene and one normal gene) or homozygous (two abnormal genes) for the abnormal
trait. Chromosomes are paired structures, made up of individual genes. Individuals inherit one
chromosome (with its associated genes) from each parent . Variety of genetic combinations
(and associated disease states) are possible depending on the genetic makeup of the parents
B. RNA and protein synthesis
Almost all chemical reactions are enzyme dependent
All enzymes are proteins - synthesis is controlled by nuclear DNA
Cellular activity regulated directly or indirectly by DNA
DNA contains blue prints for other proteins - hormones, structural proteins
DNA visualized as twisted ladder - double helix model
RNA formed from DNA template and travels outside nucleus
DNA-Directed Control of Cellular
Activity - Synthesis of Cellular Proteins.
Messenger RNA carries the transcribed
message which directs protein synthesis
from the nucleus to the cytoplasm. Transfer
RNA selects the appropriate amino acids
and carries them to ribosomal RNA where
assembly of proteins takes place
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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1. Transcription:
Synthesis of RNA from DNA (in the nucleus)
DNA partially unwinds
One strand acts as template on which mRNA is synthesized
Other strand is noncoding
DNA coding is carried via series of triplets (bases)
Code is transferred to RNA via complementary pairing bases
Only part of gene is transcribed
Non-transcribed portions important for regulation of transcription
RNA leaves DNA, leaves nucleus and forms template for protein assembly
2. Translation
Translation (protein assembly) occurs in ribosomes (in cytoplasm)
mRNA leaves by way of pores in nuclear envelope enters cytoplasm
mRNA becomes associated with ribosomes - organelles which synthesize proteins
Correct amino acids are joined in proper sequence to form a protein molecule
Assembly process is called translation
Once mRNA is associated with the ribosome, peptide (protein) synthesis rapidly occurs
DNA Double Helix and
Transcription of Messenger
RNA (mRNA).
Top panel: sequence of four
bases (adenine, cytosine,
guanine, thymine), which
determines specificity of genetic
information. The bases face
inward from sugar -phosphate
backbone and form pairs
(dashed lines) with
complementary bases on the
opposite strand.
Bottom panel: transcription
creates a complementary mRNA
copy from one of the DNA
strands in the double helix
CLINICAL EXAMPLE: Occasionally, a patient has an idiopathic reaction to a drug which is
usually safely prescribed for most patients. Such idiopathic reactions are unpredictable and not
dose-related. As an example, most people were able to troglitazone (Rezulin) - drug designed
for Type II diabetes - without problems. Rarely, however, some patients experienced fatal liver
toxicity; the drug was eventually withdrawn from the market. Human (animal) biochemistry is
made up of thousands of enzyme reactions, leaving the potential for genetic variation in the form
of spontaneous or inherited mutations. Many of these enzyme variations (mutations) are not
clinically significant. However, the potential exists for clinical consequences where a particular
drug interacts negatively with a here-to-fore unnoticed (clinically insignificant) enzyme variation.
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
25
CELLULAR REPRODUCTION
- Mitosis - means of cellular reproduction; most cells can reproduce
- Adult: new cells replace old, worn, damaged cells
- Control - rigid control allows for replacement of only needed cells
- Turnover is billions of cells per day
- Specific controls produce the correct quantity of cells
- Diminished stimulation or specific inhibition controls stops process
- Neoplasia occurs when control process does not function
CLINICAL EXAMPLE:
RBCs reproduce at levels to maintain normal hemoglobin and hematocrit thereby prevented the
individual from polycythemia (excess RBCs manifest by a high hemoglobin). Erythropoietin is
a compound normally secreted by the kidney which functions to stimulate RBC production to
maintain normal levels. Formulated as a drug, it is used to treat patients with anemia often
secondary to renal or HIV disease. Athletes have been known to illicitly inject erythropoietin
in an effort to stimulate RBC production in an effort to enhance sports performance via an
increased oxygen-carrying capacity. The drug, a natural compound, is otherwise undetectable
except that the athlete will have an abnormally high hematocrit simulating polycythemia. While
a COPD patient would be expected to have polycythemia, an athlete would not normally present
in this manner. Many sports associations disqualify athletes whose hematocrit is above 50%.
This problem has presented in the Tour de France bicycle race as well as in the 2002 Winter
Olympics wherein several athletes where disqualified.
Regeneration of cells
Regenerative capacity: ability of cells to reproduce
Labile cells: regenerate frequently - life-span measured in hours or days
Leukocytes
Epithelial cells
Stable cells: reproduce only under special circumstances - life-span years or even lifetime
Osteocytes (bone), parenchymal cells (liver), glandular cells
Mitotic figures rare but abundant after injury (liver can regenerate readily)
Permanent cells - live for entire life of organism
Nerve cells (neurons lose ability to reproduce after 6 months)
Most muscle cells eg cardiac muscle does not regenerate - forms scar after MI
Reproduction of cells
The cell cycle
Begins when cell is created from division of its parent cell
Ends when cell divides forming two daughter cells
Replication: chromosomes duplicate themselves in anticipation of mitosis
Mitosis: process by which cell divides forming 2 identical daughter cells
Meiosis: specialized form of reproduction which occurs only in gametes
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
all rights reserved - www.npceu.com
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STAGES OF CELL CYCLE
G1 stage
Time interval after cell formation which precedes replication of DNA
S stage - time during which DNA replication occurs
G2 stage - time interval after DNA replication; before beginning of M stage
M stage - time period when cell division occurs
Go stage - time interval during which no reproduction occurs
Cells not destined for early reproduction can be arrested at Go stage
Stable cells can be stimulated to go from Go to G1 to replace lost cells
STAGES OF CELL CYCLE
G1 Stage - time interval after cell formation which precedes
replication of DNA
S Stage - time during which DNA replication occurs
G2 Stage - time interval after DNA replication; before
beginning of M stage
M Stage - time period when cell division occurs
Go Stage - time interval during which no reproduction occurs
•
Cells not destined for early reproduction
can be arrested at Go stage
•
Stable cells can be stimulated to go from
Go to G1 to replace lost cells
Replication
Replication occurs during the S stage of interphase
DNA strands uncoil and form template
Each daughter cell inherits one new strand and one parent strand
Chromatids: two identical double-stranded DNA molecule
MITOSIS: reproduction processes for non-gamete cells
- Process where cell splits into two daughter cells
- Each cell has identical chromosomes to original
- All cells except gametes (sperm/egg cells) divide in this fashion
- Enables organism to grow while cell size remains small
- Example: reproduction of blood cells in the bone marrow
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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PHASES OF MITOSIS
Prophase - chromatin condenses into two distinct chromosomes
Paired chromatids joined at centromere
Nuclear membrane/nucleolus disappear
Centrioles migrate to opposite poles; spindle fibers forms between them
Metaphase
Chromosomes align in plane along spindle midway between poles
Plane called equatorial plane
Equal pull from two poles
Anaphase
Centromere division
Newly divided chromosome move to opposite poles of spindle
V-shaped chromosomes pulled through cytoplasm by spindle
Telophase
Two sets of daughter chromosomes gather at opposite poles
New nuclear envelope forms around each set
Chromosomes gradually unravel and disperse
Spindles disappear; centrioles remain, nucleolus reappears
Cleft or cleavage forms in plasma membrane
Cytoplasm divides equally during anaphase-telophase - cytokinesis
Furrow deepens - cell splits
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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MEIOSIS
Reduction division - special nuclear division which forms gametes
Ova: 1 ovum and 3 polar bodies from each parent call
Sperm: 4 sperm formed from parent cell
2 stage process resulting in 4 cells
Produces daughter cells with ½ number of chromosomes as parent cell
Enables cells to reproduce sexually
Sexual reproduction creates organisms which are unique
•
Asexual reproduction (mitosis) produces organisms which are identical
with the parent cell
•
Sexual reproduction results in production of new organism which is
unique and contains genetic material from each of 2 parents
Subsequent union of gametes form zygote which develops into new organism
PHASES OF MEIOSIS
Gametogenesis
Meiosis 1 - Number of cells is doubled; chromosom e
number unchanged
- Results in ½ num ber of chrom osom es per cell
- Prophase 1, metaphase 1, anaphase 1,
telophase1
M eiosis 2 - Division is similar to mitosis
- The number of chromosom es does not get
reduced
- Prophase 2, metaphase 2, anaphase 2,
telophase 2
Oogenesis results in 1
ovum and 3 polar bodies
after meiosis
Spermatogenesis where
meiotic division results in 4
spermatozoa from primary
spermatocyte cells
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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PHASES OF MEIOSIS
MEIOSIS I
Prophase I
- Events similar to those which occur during prophase I of mitosis
- Chromosomes coil up; nuclear membrane disintegrates
- Centrosomes move apart
- Synapsis of homologous chromosomes produce tetrads (bivalents)
- Crossing over: process whereby two chromosomes exchange fragments
Likely to occur at several different points
Results in chromosomes which are mixtures of original two chromosomes
- Chiasmata (sing chiasma) areas where crossing over has occurred
Hold chromosomes together until they separate during anaphase
Chromosomes partially separate during late prophase
- Kinetochore forms on each chromosome instead of on each chromatid in mitosis
- Spindle fibers: attach to chromosomes and begin to move them to center of cell
Crossing Over
Occurs between homologous
chromosomes at several different points.
Results in mixtures of the original two
chromosomes. Chiasmata: areas where
crossing over has occurred (remain
attached until anaphase). Crossing over
and independent assortment promotes
variation in gametes. Results in gametes
with some genes from each of the two
parents - Accounts for why various children
from same parents are unique
Metaphase I
- Bivalents (tetrads) become aligned in center of cell - attached to spindle fibers
- Independent assortment: random arrangement of pairs of chromosomes
- Various alignment possibilities of chromosomes inherited from each parent
- Random arrangement contributes to variability among gametes
Anaphase I - homologous chromosomes separate
Telophase I - Nuclear envelope reforms and nucleoli reappear (stage absent in some species)
Interkinesis
Interkinesis is similar to interphase except that DNA synthesis does not occur
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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MEIOSIS II - Similar to mitosis
Prophase II - similar to prophase of mitosis
Metaphase II - similar to metaphase of mitosis
Anaphase II - similar to anaphase of mitosis
Telophase II - similar to telophase of mitosis
CLINICAL EXAMPLE
Meiosis accounts for variation of the individual which in turn accounts for adaptation and
ultimate survival of the species. Offspring of sexual reproduction are unique individuals
having characteristics of each parent. Various combinations of genes (expressed and
recessive) from each parent in addition to random mutations accounts for disease resistence,
biologic differences which impact on the survival of any species. As an example, certain people
who have been repeatedly exposed to the HIV virus have never seroconverted because these
individuals genetically lack the binding site needed for the virus to enter the cell. Another
example involves tolerance to measles which had evolved over centuries in Europeans who had
long been exposed to this disease. Measles was not typically lethal for this group of people who
normally recovered uneventfully from a childhood episode. By contrast, the native Hawaiian
Islanders - a group never previously exposed to measles - were wiped out in huge numbers
during the 1800s when they contracted this disease from European missionaries and colonizers
who traveled to the Islands. Finally, one of the concerns regarding possible cloning of livestock
or other animals is the lack of genetic variation would leave large numbers of individuals
vulnerable to new diseases. In contrast to animals, most plants can reproduce both asexually
(via rooting shoots, cuttings, etc) or sexually (via planting seeds). In the former case - the plant
grown from a cutting - is identical (cloned) to the parent plant. In the latter case - the plant
grown from seed - will likely show some degree of variation (color, disease resistence, type of
fruit, etc.).
© 2003 Lois E. Brenneman, MSN, CS, ANP, FNP
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31