Exam 1 Content Flashcards
4 Basic Tissue Types:
-epithelial
-muscle
-connective
-nervous
_ Tissue covers most internal and external surfaces of the body.
Epithelial Tissue
The epithelial tissue connects to the _ membrane AKA _ matrix
basement membrane, extracellular matrix
4 functions of epithelial tissue:
-protection
-secretion
-absorption
-excretion
What does the extracellular matrix of epithelial tissue do?
separates epithelial cells from connective tissue; smaller membrane surrounding many cells (opposite of connective tissue)
Are all epithelial cells uniform?
no, differ by location/function
ex) some are smooth, some have villi etc
What is the overall purpose of connective tissue
framework on which epithelial tissue clusters form organs
4 functions of connective tissue:
-binding
-support
-anchoring for organs
-storage site for excess nutrients
What is extracellular matrix of connective tissue made of?
ground substances and fibers
What are the properties of the extracellular matrix of connective tissues?
abundant matrix surrounding just a few cells, opposite of epithelial tissue
How connective tissue is classified:
consistency of ground substance and type of organization of its fibers within
-ex) loose vs dense
5 classifications of connective tissue
-cartilage
-bone
-vascular connective tissue
-adipose tissue
-blood
Where is cartilage found, what is its purpose
long bone, nose, trachea, larynx etc
-flexibility and support
Purpose of bone:
-support
-protection
-muscle attachment
Where is vascular connective tissue found and what is its purpose?
blood vessels
-transports O2, CO2, immune response and clotting factors
Where is adipose tissue found, what is its purpose?
deepest layers of skin, around heart and kidneys,
-padding of joints, paracrine hormones, support, protection, heat conservation, energy source
What kind of connective tissue is blood?
-liquid connective tissue
Organization of body
-cells
-tissue
-organs
-organ systems
-organism
Tissue regulation: autocrine
signals itself/ regulates itself
Tissue Regulation: paracrine
targets adjacent cells
Ex) N2O
Negative feedback function:
-promotes stability and resists/opposes change; can be increase or decrease in something to bring balance
-ex) what sweat glands do with high body temp; heart rate and BP responding to each other (baroreceptors)
Feedback control: Sensor refers to:
regulator, input, or afferent; senses change in system
ex) nerve cells sensing something, anxiety, high glucose
Feedback control: Control refers to the:
control center, regulatory system; guides/directs the responding change
ex) CNS/ brain
Feedback control: Effector refers to:
output, motor pathway, efferent; acts out the responding change
ex) sweat glands, kidneys, heart
Feed Forward function:
tries to prevent negative feedback change, anticipatory
ex) test anxiety
Positive Feedback function:
not as common and often temporary, promotes change in ONE direction for specific cause, causes instability
ex) increasing cx until childbirth; coagulation cascade (altho the clot itself is a negative feedback to stop bleed)
Pathology happens when _ feedback fails.
negative
Muscle tissue is made of _ which are highly contractile
MYOCYTES
3 types of muscle tissue
-smooth
-cardiac
-skeletal
Purpose of skeletal muscle
movement
Purpose of cardiac muscle
contraction
Purpose of smooth muscle and where is it found?
propulsion of material
-GI tract, uterus, bladder, vessels
Purpose of nervous system:
communication
-delivers signals from outside brain and SC
Nervous system is made of:
neurons and synapses
Homeostasis fails because of (2 items)
-failure to compensate
-failure to recognize need to compensate
Fluid compartments (2 type)
ECF ~33%
ICF ~67%
ECF is made of (2 items)
-ISF(interstitial fluid) ~26%
-plasma ~7%
Most water in body is found in:
ICF
When the body fluid compartment is dehydrated, water is pulled first from:
plasma (ECF)
What are neurons:
basic building blocks of nervous system, send and receive electric impulses across synapses
What are synapses:
gaps between neurons; impulses pass between neuron-neuron gaps or neuron-muscle gaps when NTs are relaeased
Anatomy of neuron:
-cell body
-single axon (long, conduct impulse away from neuron)
-one or more dendrites (long, conduct impulses to neuron)
Disruption of homeostasis=
disease or pathology
Homeostatic trade off refers to:
less crucial functions can be traded off so that vital functions can continue
-ex) blood being pulled from extremities to organs when BP low, anemic, etc
Rough ER function:
protein synthesis (ribosomes, proteins)
Smooth ER function:
lipid synthesis (phospholipids, cholesterol)
Golgi Apparatus function:
stores ER vesicles from rough ER and processes/modifies them into substances and sorts them out (like UPS of cell)
Mitochondria function:
powerhouse, makes ATP
Nucleus function:
control center, sends messages thru cell and contains DNA
Lysosome function:
garbage disposal, contains digestive enzymes
PATHOPHYSIOLOGY: Tay-Sach’s syndrome
Ribosome funciton:
assembles proteins on it
Peroxisome function:
oxidizes substances like alcohol and hydrogen peroxide
-self replicates and contains oxidase
Organic Molecule: carbohydrate (subunit, function)
subunit: glucose
polysacch>disacch>monosacch
-important in immune reaction and cell-cell attachments
Organic Molecule: Lipids (3 subunits)
-triglycerides
-phospholipids
-sterols (steroids)
Plasma Membrane is made of
phospholipid bilayer
Tail of phospholipid bilayer:
hyprophobic
Head of phospholipid bilayer:
hydrophillic
Steroids are made of:
cholesterol
How does cholesterol affect the cell membrane:
increases membrane flexibility and stability
Organic Molecules: Proteins (3 subunits)
-amino acids
2 types of proteins:
integral and peripheral
Integral protein
permanently attached to biological membrane
-channels, pores, carriers, enzymes
Peripheral protein:
enzymes, intercellular signal mediators
Organic Molecule: Nucleic acid (subunit):
subunits: nucleotide
-make up DNA/RNA
Chromatin:
less condensed DNA;
proteins and histones
What general reaction creates energy in the cell?
ATP hydrolysis
Steps of ATP creation:
-CATABOLISM of carbs into glucose, protein into amino acids, and fat into fatty acids
-glucose, AA, and FA are processed into Acetyl CoA
-Acetyl CoA react with O2 to yeild ATP
What makes energy ATP or ATP hydrolysis?
-ATP hydrolysis because ATP is broken down into ADP when H2O is added
Are fuel metabolism reactions reversible?
most are reversible
Anaerobic metabolism:
glucose undergoes glycolysis to make 2 ATP without using O2
Where does glycolysis occur?
cytoplasm
Aerobic metabolism:
metabolism with respiration of O2, occurs in mitochondria and yields 38 ATP
Glucose is stored as _ and excess becomes _.
glycogen, fat
Which is used as energy source first, glycogen or fat?
glycogen
What happens to fat in anaerobic metabolism?
glycerol is metabolized via glycolysis to make 2 ATP
What happens to fat in aerobic metabolism?
FA produce 38 ATP with respiration of O2
How are proteins metabolized for fuel?
broken down into amino acids and are used in Kreb’s cycle
Where does transcription happen?
inside nucleus
Process of DNA transcription:
-RNA polymerase binds with promoter at start of gene
-ends when RNA polymerase reaches terminating sequence
Which enzyme is used in DNA transcription?
RNA polymerase
What does DNA transcription yeild?
DNA ->mRNA
Where in the gene are promotors located?
beginning of gene sequence
What is microRNA and its function
-regulates gene expression, can suppress transLATION process
Where does translation(protein synthesis) happen?
inside cytoplasm
What does transcription produce?
proteins
-mRNA
What is the process of translation?
-mRNA in cytoplasm attaches to ribosome
-ribosome bonds between AA on tRNA making protein chain
-protein chain grows until ribosome reaches end point
Proteins are made of:
AA linked together by PEPTIDE bonds
Enzyme required for DNA/cell replication:
RNA polymerase
**(is this a typo?)Which phase is RNA polymerase used in?
Interphase - S phase
Uses of ATP (3 items)
-membrane transport
-synthesis of chemical compounds
-mechanical movement
Cilia
hairlike projections extending from plasma membrane used for locomotion
Oncogenes:
genes that are cancerous
Genome:
all the DNA in one cell of an organism; humans are 99% same in coding regions
Proteome:
full range of proteins made by the genome;
-10K proteins per cell or 15% of total gene products
miRNA
RNA interference molecule that targets specific mRNAs
Causes of gene mutation:
-ionizing radiation (xray, CT scans)
-chemicals
-physical irritants
-hereditary
Proto-oncogenes:
normal genes that stimulate normal cell growth/division but become cancerous after mutation
Anti-oncogenes
tumor suppressor genes
Impact of genomics/genetics on pathophysiology:
nature vs nuture; study genes to see how they influence diseases
How does cancer kill people?
competes with rest of body for nutrients and takes them all resulting in death, uncontrolled cell growth/division
What is a gene?
section of DNA that codes for a polypeptide
DNA replication occurs in:
the nucleus
What is Down’s Syndrome?
Trisomy 21, autosomal aneuploidy;
3 chromosomes on 21st chromosome instead of 2 pair normally
Example of pathological autosomal aneuploidy?
Downs syndrome/ Trisomy 21
Autosome:
any chromosome that ISN’T a sex chromosome
Sex Chromosome:
X or Y, determines sex
Does X-linked Recessive inheritance affect boys or girls more?
boys; only have 1 X chromosome
Can a father give his son a X-linked recessive inheritance?
No, they can only give the Y chromosome
If a father has X-linked recessive trait will his daughter automatically receive it?
yes, there is only one (bad) X chromosome to give
Example of X-linked Recessive Trait?
Duchene’s Muscular Dystrophy-damages muscle cells from ages 3-5yo; most common and most severe :(
Which genes are impaired for Type 1 DM?
insulin genes
Which genes are impaired for Type 2 DM?
PPAR-y and glucokinase genes
Which genes are impairs for breast cancer?
BRCA2 (chromosome 13) and BRCA1 (chromosome 17)
Is breast cancer recessive or dominant?
Autosomal DOMINANT
If someone has a mutated gene will it always be expressed?
No, depends on environmental factors as well
What is epigenetics?
the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself; it is reversible
What is DNA methylation?
addition of methyl groups (-CH3) to certain positions on the nitrogenous bases on the nucleotide; causes deacetylation and SILENCES DNA
What does DNA methylation do?
methyl group attaches to DNA encoding a gene -SILENCES DNA expression
What is acetylation of histones?
attaching acetyl group to a histone component of lysines on nucleosomes causing GREATER DNA expression (unwinds which makes it easier to express)
What is deacetylation of histones?
chemical alteration of a histone that results in SILENCED expression (coils which makes it harder to express)
How does a proto-oncogene become an oncogene?
-tumor suppressor gene is hypermethylated and deacetylation occurs
- this causes oncogene to be hypomethylated and acetylation occurs
What is genomic imprinting?
The silencing of a gene that is ‘stamped’ with an imprint during gamete production
What can readily enter the phospholipid bilayer?
-Water (thru PORES on hydrophobic membrane)
-urea
-lipids and lipid-solubles
-CO2 and O2
-non-polar molecules
What CANNOT readily enter the phospholipid bilayer?
-ions (Cl-, K+, Na+)
-glucose
-amino acids
-large molecules
-polar molecules (except water)
What does the ECF contain more of:
-Na+
-Ca++
-Cl-
-HCO3-
-glucose
-PO2
(pH is HIGHER)
What does the ICF contain more of:
-K+
-Mg++
-Phosphates
-SO4–
-AAs
-Lipids
-PCO2
-Proteins
(pH is LOWER)
What is protein conformation?
Protein changes shape when binding with a messenger protein
Why is DNA wrapped around histones?
Negatively charged sugar-phosphate backbone wraps around positively charged histones
What happens when your diet is protein deficient?
Your body cannot produce proteins; it uses the amino acids from your diet
What is the process (general) of creating a protein (beginning from codons)?
Codon > Anti Codon > Amino Acid > Protein
In general, what is replication and what is transcription?
Replication - Unwinding DNA, making a duplicate cell (more DNA)
Transcription - Unwinding DNA, making proteins (RNA)
What is the process of genes becoming proteins (starting from pre-mRNA)?
-in nucleus pre-mRNA is formed
-introns are removed and extrons are expressed creating mRNA
-mRNA moves to the cytoplasm where it attaches to a ribosome and tRNA begins the translation process
What is expressed, and what is removed in a protein?
Introns removed, extrons expressed
What is a karyotype?
the number and visual appearance of the chromosomes in the cell nuclei of an organism or species.
What is a gamete?
a mature haploid male or female germ cell that is able to unite with another of the opposite sex in sexual reproduction forming a zygote
What is meiosis?
cell division that makes 4 daughter cells each with half the number of chromosomes of the parent cell, producing gametes
What is a euploid?
‘Good polidy’ - i.e. the normal amount of chromosomes for a species
E.g. Humans have 46
What is polyploidy? What is the survival rate?
condition in which an organism has extra PAIRS of chromosomes; 0%
What is aneuploidy? What is a common cause?
the presence of an abnormal number of chromosomes in a cell; non-disjunction
What is monosomy?
missing a chromosome
What is Turner’s Syndrome?
A chromosomal disorder in which a female is born with only one X chromosome; 45 total chromosomes
Example of monosomy:
Turner’s syndrome (only one X chromosome in females) 45 total chromosomes
What is Kleinfelter’s?
Individuals will have at least 1Y and 2X’s, but can have more than 2X’s, can also have extra Y’s.
e.g. XXXY, XXYY
Example of aneuploidy?
Kleinfelter’s ,Down’s Syndrome
What are some causes of abnormal chromosome structure?
Deletion
Duplication
Inversion
Translocation
Chromosome Breakage
What increases risk for genetic disorders?
Family link - the closer the relative the higher the risk
Also depends on the proband region of the gene
What is a chromatid?
one half of a duplicated chromosome
What is a chromosome?
A coiled up piece of DNA that has genes that code for traits.
What is hypermethylation in DNAs?
silences DNA!
What is hypomethylation in DNA?
expressed DNA
What is HDAC(histone deacetylase inhibitor) inhibition? What does it do?
prevents the process of deacetylation, thereby increasing acetylation which promotes expression
What are siRNAs and what is their function?
small double stranded pieces of RNA; block translation or degrade mRNA
What happens when genomic imprinting goes wrong?
Prader-Willi / Angelman Syndrome
What are the two transport proteins?
Channels & Carriers
What is the main property of carrier proteins?
Conformational (can change shape)
What is passive transport?
The movement of materials across the cell membrane without using cellular energy
What is active transport?
the movement of ions or molecules across a cell membrane into a region of higher concentration, assisted by enzymes and requiring energy
What is simple diffusion? What does it utilize?
when molecules spread from an area of high to an area of low concentration; uses ion channels-no ATP
What is facilitated diffusion?
Movement of specific molecules across cell membranes through protein channels
What does facilitated diffusion utilize?
protein channels via carrier proteins, no ATP use
What limits facilitated diffusion?
VMax, i.e. when all carrier proteins are occupied
What does active transport utilize:
carrier proteins assisted by enzymes and requiring ATP
What are the two types of active transport? How do they differ?
Primary & Secondary
Primary - Uses ATP to activate carrier protein
Secondary - Indirectly uses ATP e.g. glucose entering as sodium enters (sodium most leave using the K/Na+ pump which utilizes ATP)
What is the process of action potential?
- Resting state of ~ -70mV
- Threshold of activation is reached (~ -50mV)
- Action potential occurs (sodium influx, cell becomes slightly positive due to it ~ +30mV)
- Depolarization (Because the inside of the cell and outside of the cell are both positive, polarity is lost)
- Repolarization (K+/Na+ pump activates to force Na+ out and and bring K+ in at a ratio of 2K to 3Na, resulting in a net negative charge within the cell)
What is secondary active transport?
the use of the electrochemical gradient of one molecule to move a second molecule
e.g. using Na+ to move glucose
What is an ungated ion channel?
A channel that determines transport based on size, shape, and charge of the ion
What is a gated ion channel?
Gates that must reach certain voltage, or must be activated with the correct chemical before opening
What is saturation with regards to facilitated diffusion?
When all gates or proteins are being utilized, thus reaching maximum capacity. It limits how much can be diffused at once via facilitated diffusion.
What is osmosis?
diffusion of water across a selectively permeable membrane, from low solute to high solute
What must be present for osmosis to occur?
Osmotically active solutes
How to calculate osmolality?
Take the chemical substance, separate it by ion and multiply by # of moles.
E.g. 2 moles NaCl –> Na + Cl
2 moles of Na + 2 moles of Cl = 4 osmoles
What is tonicity?
The # of non-permeable solute in a solution; relative concentration of electrolytes on either side of the cell membrane that are NONpermeable
What is hypertonic, hypotonic, isotonic?
Hypertonic –> more non-permeable solutes
Hypotonic –> less non-permeable solutes
Isotonic –> same #
What is membrane potential?
a voltage or electrical charge across the plasma membrane
What is a symporter?
an integral carrier protein that transports 2 positive charged molecules in the same direction
What is an antiporter?
an integral carrier protein that transports multiple solutes in opposite direction
How do cardiac glycosides/digoxin work?
Inhibit Na/K ATPase which leads to indirect inhibition of Na/Ca exchange
-Na not pumped out of cell so there’s not enough Na outside of the cell to be exchanged in for Ca out
-MORE CA IN CELL causes increased Ca means INCREASED cardiac contractility
What does osmotically active mean?
It means a solute is non-permeable;
if a solute is permeable osmosis would not occur
What is molarity?
Amount of solute in 1L solution (volume)
What is molality?
Amount of solute per 1 kg (weight)
What is osmolarity?
Amount of osmoles per 1L of solution (volume)
What is an osmole?
the number of particles into which a solute dissociates in solution
e.g. NaCl breaks into Na+ Cl-
What is osmolality?
Amount of osmoles per 1 kg of solution (weight)
What is osmotic pressure?
The amount of pressure required to stop the osmotic flow of water
What is a major determinant in osmotic pressure?
The concentration (and weight) of the solutes
A cell in a hypertonic solution will:
shrink
A cell in a hypotonic solution will:
burst/swell
A cell in an isotonic solution will:
stay the same
Osmolality of plasma:
mOsm/L
Osmolality of a cell:
~ 275-299 mOsm/L
What are leak channels?
Always open! But they are not open to all ions. They are very specific per ion.
Why is potassium a major determinant in resting cell charge?
Leak channels allow it to pass through easily
Nerst Equation:
E ion= 61/Zlog ([concentration out]/ [concentration in])
RMP voltage:
-70mV
Voltage of K+ in Nerst Equation:
-94mV
Voltage of Na+ in Nerst Equation:
+61mV
What is the Goldman-Hodgkin-Katz equation?
An equation that states that the resting membrane potential is the closest to equilibrium potential of the ion that has the highest permeability
How does hyperkalemia affect RMP?
More K+ outside, cell becomes more negative inside (due to reduced leaking of K) –> less excitable
What is excitability?
how easy it is to start an action potential
increases with positive charge
What is threshold?
the minimum voltage needed to start an action potential
What is depolarization?
the inside of the membrane becomes less negative (more positive) due to influx of Na+ ions into cell
What is repolarization?
return to resting potential; Na+ gates close and K+ gates open
What is hyperpolarization?
Hyperpolarization refers to a state where the potential across the membrane is more negative than the resting potential
What does it mean when action potential is an all or none event?
if the threshold is achieved the action potential is conducted the entire length of the neuron, if not, nothing happens
Why is myelin important?
-It speeds up signal conduction in the nerve fiber.
-It is formed to assist in the regeneration of damaged fibers.
-It insulates the nerve fiber.
What is an absolute refractory period?
Time from the opening of the Na+ activation gates until the closing of inactivation gates. Prevents the neuron from generating an action potential. Ensures that each action potential is separate. Enforces one way transmission of nerve impulses.
What is a relative refractory period?
The interval following the absolute refractory period when sodium gates are closed, potassium gates are open, repolarization is occuring. The threshold level is elevated, allowing STRONG stimuli to increase the frequency of action potential events.
What forms the myelin sheath?
Schwann Cells, found in PNS, not CNS
What is a Node of Ranvier?
nodes that interrupt the sheath every 1-3mm allowing for jumping of signals (faster signals)
Why can’t CNS regenerate?
No Schwann Cells, no regen. only found in PNS
What is an excitatory synapse?
a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell
Makes inside cell positive
What is an inhibitory synapse?
synapse at which a neurotransmitter causes the receiving cell to stop firing
Makes inside cell negative
What is a graded potential?
Strength of stimulus determines response, greatest impact at point of stimulus, multiple potentials can build on each other for a sum effect
What is a subthreshold potential charge?
A graded charge that exhibits summation, but does not achieve action potential
What is excitatory postsynaptic potential (EPSP)?
any voltage change TOWARDS the direction of threshold that makes a neuron more likely to fire
What is Inhibitory Postsynaptic Potential (IPSP)?
graded hyperpolarization of postsynaptic membrane farther from AP threshold-less likely to fire
-does this by OPENING Cl- channels allowing hyperpolarization
What is an inhibitory ligand?
Molecules that inhibit action potential depending on which channels they open
What is an excitatory ligand?
molecules that increase action potential depending on which channel they open
How does an action potential happen?
- Cell is resting with -70 mV RMV
- Threshold is reached (e.g. -55 mV)
- Sodium channels open and influx of sodium ions occur –> move towards positive charge inside the cell (Depolarization)
- The positive charge inside the cell causes K+ gates to open, thus making the cell more negative as K+ ions leave (repolarization)
- Hyperpolarization occurs as the channels return to their resting state (-90 mV)
- RMV is achieved again (-70 mV)
What is action potential?
the change in electrical potential associated with the passage of an impulse along the membrane of a muscle cell or nerve cell.
What is propagation of AP?
When an action potential is passed from one portion of an excitable membrane to other directions until the entire membrane is excited
What is an oligodendrocyte?
a cell that has cytoplasmic extensions that can surround multiple axons compared to just one (found in CNS)
How does diameter affect transmission rate of an AP?
Larger diameter, faster transmission
How does myelination affect the current of a neuronal cell?
Contains it inside and speeds up transmission
What are the two types of graded action potential?
EPSP
IPSP
How does botulin toxin affect AP?
Prevents release of ACh from presynaptic terminals
How do curariform drugs affect action potential?
Blocks nicotinic ACh channels by competing for receptor sites, reduces end-plate potential
How does nicotine mimic ACh?
Not destroyed by AChE
What does neostigmine do?
Prolongs the effects of ACh by inhibiting enzymes
Where is ACh secreted?
Motor neurons that innervate skeletal muscle
Where is ACh synthesized?
Presynaptic terminal, made from acetyl CoA and choline with the enzyme choline acetyltransferase
Neuronal action potential vs ventricular action potential
Ventricular AP is longer than neuronal
Neuronal depolarization is caused by sodium channels
Ventricular AP utilizes many channels (Na+, Ca++, others)
What are myofibrils?
bundles of thick and thin myofilaments that run the length of a fiber
What are thick filaments?
myosin, myosin heads
What are thin filaments?
actin, troponin and tropomyosin
Where do actin attach?
Z-discs
What is a sarcomere?
portion of myofibril from z-disc to z-disc
What is the sarcolemma?
muscle cell membrane
What are the bands of the sarcomere?
H band, I band, Z band, A band, M band (HIZAM)
A band dark or light? Does it move during contraction?
dark, no
I band dark or light? Does it move during contraction?
light, yes
What is titin?
elastic protein, keeps thick and thin filaments aligned (passive stretching/tension) to Z-disc allowing for elastic recoil of muscle fibers
What is an antagonist muscle?
a muscle that relaxes during joint movement
What is tropomyosin?
It is a long, fibrous protein that winds around the actin polymer, blocking all the myosin-binding sites.
What is troponin?
a regulatory protein that moves tropomyosin aside & exposes myosin binding sites when Ca+ is released during muscle contraction
What is F actin?
Filamentous actin, made up of two strands of G-actin (globular) monomers
ADP is bound to each G-actin site
Titin protein provides what for skeletal muscle?
passive stretch
What is in the I-band?
actin filaments
What is in the H-zone?
myosin only
What is in the M line?
middle sarcomere (contains myosin)
What is in the A bands?
Connection of actin and myosin filaments (cross-bridge)
What is in the Z-disc?
It is protein (different than actin or myosin) that holds the thin filament in place
What is the sarcoplasmic reticulum?
the endoplasmic reticulum of a muscle cell
Surrounds myofibrils, located in the sarcoplasm
Regulates Ca++ (storage, uptake, release)
Rapidly contracting muscles have extensive SRs
What two things need to happen in order for myosin to be ready for movement?
Ca++ to allow actin sites to be uncovered and bound to
ATP to “cock” the head and prepare to be bound to a new site
What are the stages of the walk-along theory?
Myosin heads attach to the actin and tilt, which pulls the actin filaments. This happens repeatedly to cause muscle contraction.
- Before contraction, ATP binds to myosin head
- ATPase on the myosin head breaks down ATP into ADP which allows the myosin head to extend
- Ca++ ions bind with troponin to expose actin sites
- Myosin head binds to actin
- Power stroke occurs as myosin tilts towards the arm of the crossbridge (contraction)
- Tilting causes the ADP + Pi to be released, new ATP attaches to myosin allowing it to release itself from actin
- Process starts over
How can we measure active tension?
Passive tension
+ Total tension
Where is optimum length of sarcomere for contraction?
2.2mm
Maximum contraction is gained at that point
Is muscle contraction concentric?
yes
What isotonic contraction?
-Contraction with a change in length but no change in tension
-Begins when internal tension builds builds to where it overcomes resistance
-Muscle shortens, moves the load, and maintains same tension from then on
Can isotonic contraction become isometric?
yes
What is isometric contraction?
-Contraction without a change in length
-Isometric contraction of antagonistic muscles at a single joint is important in maintaining joint stability at rest
-Keeps body from sinking into a heap to the floor
How does muscle contraction occur?
Sliding filament mechanism
When is muscle contraction maximized?
When it is at optimum overlap of thin and thick filaments (at rest)
Cardiac muscle operates at lengths below optimal length? T/F
true
What are some attributes of Type II skeletal muscle/white muscle?
Larger
Faster
Glycolysis for ATP (short/quick process)
Few capillaries, few myoglobin, has more glycolic enzymes for glycolysis
extensive SR, innervated by larger nerve fibers
What are some attributes of Type I skeletal muscle/ red muscle?
smaller
Shorter
Oxidative phosphorylation for ATP (long process)
Lots of capillaries –> lots of myoglobin
Endurance but a bit slower
innervated by smaller muscle fibers
What is a motor unit?
A motor neuron and all of the muscle fibers it innervates
Can a motor neuron innervate more than one muscle fiber?
yes
Can a muscle fiber be innervated by more than one motor neuron?
no
What is the role of Vmax ATPase in speed of contraction?
High Vmax - Fast shortening
Low Vmax - Slow shortening
Can one type of muscle fiber become the other type?
yes
What are the three phases of muscle contraction?
latent, contraction, relaxation
What is tetany?
Non-stop muscle contractions without rest
What is myoglobin?
A protein that holds a reserve supply of oxygen in muscle cells
What is tetanic contraction?
APs are continuisly activated to hold mucle contraction, does not happen in cardiac APs
What is hypertrophy of muscle?
Increase in muscle mass
More actin and myosin
Muscle growth from heavy training it increase diameter of muscle fibers, number of myofibrils and mitochondria and glycogen reserves
physiologic - muscle growth with exercise
compensatory - enlargement of remaining organ tissue once a portion has been excised
pathologic - results from disease conditions and can be compensatory (e.g. heart disease)
What is force summation?
Increased contractility due to additive effects of a single fiber contracting
What is multiple fiber summation?
increasing the number of motor units contracting simultaneously, thereby increasing contractility
What is frequency summation?
addition of multiple simple twitches before the muscle has an opportunity to fully relax (tetany)
What causes tone in muscles?
Constant state of partial tension
What increases tone in muscles?
regular exercise!!
What are flaccid muscles?
Muscles without tone, caused by atrophy and destroyed nerve connections
What is muscle hyperplasia?
Muscle growth due to an increase in number of muscle fibers/cells NOT abnormally
Compensatory - Organs regenerating
Hormonal - estrogen dependent organs like the uterus and breast e.g. after pregnancy endometrium grows and thickens to prepare for reception of ovum
Pathologic - Endometrial hyperplasia that results in excessive bleeding (too much growth)
What is atrophy of muscle?
Decrease in total muscle mass
Less contractile proteins
Less maximum velocity
Less maximum force
Loss of fibers
physiologic - thymus cells shrink in early childhood
pathologic - brain cells shrink with age and stress
How does atrophy with fiber loss occur? What happens to the lost fibers?
Happens with disuse of 1-2 years
Very difficult to replace lost fibers
what is the process of muscle contraction?
- AP from motor neuron to skeletal muscle releases ACh into the synapse between the motor neuron and skeletal muscle (NMJ)
- ACh vesicle released
- ACh binds to receptor on sarcolemma causing Na+ influx, generating an AP
- AP travels through T-Tubules allowing Ca++ channels to open and release into the cytoplasm
- Ca++ combines to troponin to activate the actin-myosin binding sites and crossbridges between actin and myosin
- ATP is hydrolyzed to provide energy for myosin heads
- Flexion brings actin closer to the middle of the sarcomere, shortening and contraction occurs
- Another ATP is used to pump Ca++ back into the SR to start relaxation
Where is the NMJ?
Motor end plate
How do muscle hypertrophy and hyperplasia affect tension?
Increased force, no change to maximum velocity or shortening
What terminates the muscle contraction?
The release of acetylcholine stops and an enzyme produced at the axon terminal destroys any of the remaining acetylcholine (AChE)
How does Botox effect muscle contraction?
Decreases ACh release
How do curariform drugs affect muscle contraction?
Competitive antagonist to ACh
What is myasthenia gravis?
An autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigue.
Neostigmine is the tx
Antibodies attack nicotinic ACh receptors at post synaptic NMJ
What is Lambert-Eaton syndrome?
antibodies attack presynaptic voltage gated Ca++ channels at NMJ
impairs release of Ach
Tx Neostigmine
What enzyme can be found on myosin heads?
ATPase - helps break down ATP
What is troponin C?
binds calcium
What is sliding filament theory?
During contraction actin is pulled inward so that its ends overlaps myosin’s ends. At the same time the actin filament pulls the Z-discs inwards causing muscle contraction. Myosin “slides” along the actin.
What drugs stimulate ACh?
nicotine
What drugs inactivate AChE?
neostigmine
What drugs inhibits transmission of ACh at the NMJ?
Curariform drugs
Why does rigor mortis occur?
- Ca++ leaks out of cell
- Ca++ binds to troponin
- Tropomyosin moves and myosin/actin bind
- Heads get stuck @ 45 degrees b/c there’s no ATP to release heads
- Muscles are stuck in contraction
What are DHP receptors?
These are voltage-gated Ca2+ receptors in the T-tubules of skeletal muscle cells. They allow Ca2+ into the cell after being depolarized. DHP receptors link up with ryanodine receptors of the SR and induce massive releases of Ca2+ from the SR.
What are ryanodine receptors?
Calcium release channels that are opened under the influence of activated dihydropyridine receptors on the T tubules. leads to release of Ca2+ from the SR and induction of muscle contraction.
How does malignant hyperthermia occur?
-Mutation in the ryanodine receptor in skeletal muscle may result in MH susceptibility
-Exposure to a triggering agent (all volatile anesthetics and succinylcholine) results in uncontrolled release of calcium
What is the pathway of cardiac muscle contraction?
- AP by the pacemaker cells in SA/AV nodes conducted to cardiomyocytes
- Calcium channels activated by AP –> influx of Ca++ causing a plateau of depolarization
- Ca++ binds to troponin which moves troponin away from actin binding sites
- Myosin binds to actin and pulls it towards the center of the sarcomere (contraction)
- Ca++ removed by SR and relaxation begins
Smooth muscle characteristics
Mononucleate (no striations)
“Latch state” allows it to contract for days
Can be myogenic (spontaneously activated)
What are the two smooth muscle groups?
Multi-unit
Single-unit (unitary)
What are the characteristics of a multi-unit muscle group?
Each fiber can contract independently from the others, control exerted by nerve signals
E.g. Eye muscles
What are the characteristics of a unitary smooth muscle group?
Mass of hundred-thousand muscle fibers that connect together as one unit
E.g. Viscera, syncytial
Smooth muscle contraction process
instead of troponin, smooth muscle uses calmodulin
- Ca++ inside the cell increases due to calcium channels opening and SR releasing Ca++
- Ca++ binds to calmodulin
- Ca++-Calmodulin complex joins and activates myosin light chain kinase (MLCK), a phosphorylating enzyme
- The Ca-Calodulin-MLCK complex phosphorylates the myosin light chain (MLC)
- The MLC (part of the myosin head) is energized and the head binds to actin and power strokes
- Another ATP comes and releases the myosin for relaxation
Skeletal muscle vs other muscles, what’s unique?
Ca++ binds to troponin which results in a conformational change of tropomysoin, allowing for binding of actin sites by myosin –> contraction
Calcium from SR only, Na++ comes from ECF
Cardiac muscle vs other muscles, what’s unique?
Ca++ binds to troponin-C, which results in troponin-C moving away from the actin, allowing for binding of actin sites by myosin –> contraction
Calcium from SR and ECF
Smooth muscle vs other muscles, what’s unique?
Ca++ binds to calmodulin which joins and activates MLCK. Ca++Calmodulin-MLCK phosphorylates myosin light chain (MLC), myosin attaches to actin and contracts
Calcium comes from SR and ECF
What is necrosis?
sum of cellular changes after local cell death and the process of cellular autodigestion, inflammatory changes
What is apoptosis?
Active process of cellular self-destruction called programmed cell death in both normal and pathologic tissue changes
Does apoptosis involve inflammation?
no
What is apoptosis type 1?
Cell death (caspases)
What is apoptosis type II?
mitochondria dependent apoptosis
Cell injury due to hypoxia
Lack of sufficient oxygen; commonly caused by ischemia, anoxia, results in decreased mitochondria phosphorylation –> lack of ATP –> Na+/K+ pump stops, build up of ions, cell swells and bursts
What happens when the cell membrane is damaged?
Ca++ influx, swells (is reversible by O2 at this stage)
–> continued influx results in activation of enzyme systems –> further damages the membranes
What is reperfusion injury?
tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen, damaged via the creation of free radicals
Is reperfusion injury reversible?
no
How does alcohol injure cells?
Creates folate deficiency, gastritis, FAS, alcohol induced disease (fatty liver, cirrhosis, hepatitis)
What are the two signals associated with hypertrophy?
Stretch and trophic (growth)
What is metaplasia?
The reversible replacement of one mature cell by another type of mature cell. Example: changes in the cells of the lungs of people who smoke
What is dysplasia?
Disordered cellular growth
Proliferation of precancerous cells
Often arises from longstanding pathologic hyperplasia or metaplasia
DYSPLASIA IS REVERSIBLE (with alleviation of inciting stress)
If stress persists –> dysplasia progresses to carcinoma (IRREVERSIIBLE)
What is a cell more permeable to K+ or Na+?
K+ due to leakage channels
