Fall I Summary Project

TABLE OF CONTENTS:
BLOCK I: CORE CONCEPTS

CHAPTER 1: MOLECULAR BIOLOGY

CHAPTER 2: CELL BIOLOGY
CHAPTER 3: GENETICS
CHAPTER 4: GENERAL HISTOLOGY
CHAPTER 5: MUSCLE
CHAPTER 6: NERVOUS SYSTEM
CHAPTER 7: INTRO TO EMBRYOLOGY
CHAPTER 8: ANATOMY & RADIOLOGY OF EXTREMITIES
BLOCK 2: CARDIAC, RESPIRATORY, RENAL

CHAPTER 9: ANATOMY, EMBRYOLOGY, & RADIOLOGY OF THORAX

CHAPTER 10: CARDIAC CYCLE
CHAPTER 11: EKG
CHAPTER 12: VASCULAR MICROANATOMY AND BIOPHYSICS
CHAPTER 13: BLOOD & HEMOSTASIS
CHAPTER 14: RESPIRATORY HISTOLOGY
CHAPTER 15: RESPIRATORY PHYSIOLOGY
CHAPTER 16: RENAL EMBRYOLOGY & RADIOLOGY
CHAPTER 17: RENAL HISTOLOGY
CHAPTER 18: RENAL PHYSIOLOGY
BLOCK 3: GI, METABOLISM, NUTRITION, ENDOCRINE, REPRODUCTION

CHAPTER 19: ANATOMY & EMBRYOLOGY OF GI TRACT

CHAPTER 20: GI HISTOLOGY
CHAPTER 21: GI PHYSIOLOGY
CHAPTER 22: METABOLISM
CHAPTER 23: NUTRITION
CHAPTER 24: ENDOCRINE HISTOLOGY
CHAPTER 25: ANATOMY & EMBRYOLOGY OF REPRODUCTION
CHAPTER 26: MALE REPRODUCTION
CHAPTER 27: FEMALE REPRODUCTION
CHAPTER 28: INTEGRATIVE SEMESTER TOPICS

SChapter One - Molecular Biology

BLOCK I CORE CONCEPTS
THREAD: BIOCHEMISTRY & GENETICS
CONTRIBUTORS: ALEX SWEENEY, ELIZABETH MCQUITTY & ZAINA AL-MOHTASEB

TABLE OF CONTENTS:
GENE I
GENE II
GENE III
GENE IV
GENE V
GENE VI
PROTEIN TAXONOMY
PROTEIN II
PROTEIN III
PROTEIN IV
PROTEIN V
PROTEIN VI

RAM REDDY
RAM REDDY
RAM REDDY
RAM REDDY
RAM REDDY
RAM REDDY
MIKE SCHMID
MIKE SCHMID
MIKE SCHMID
MIKE SCHMID
MIKE SCHMID
MIKE SCHMID

GENE I
-

DNA synthesis (semi-conservative replication) RNA synthesis

(transcription 5-3 with leading and lagging strand) protein
synthesis (translation)
C:G base pairs are harder to break because they are connected by 3 H-bonds.
A:T pairs have 2 H-bondsusually promoter regions/origins of replication
are AT rich so that less energy is required to start replication.
GC rich regions have a high melting temperature compared to AT rich
regions
DNA synthesis requires template, primer with 3-OH, building blocks (5
dNTPs), energy (p-p bonds), and DNA polymerase.
1. Mg and buffer also reqd. if done in a test tube.
2. 2 replication forks in prokaryotic replication (circular DNA).
3. DNA polymerase makes few mistakes due to 3-5 exonuclease activity
a) Other polymerases: taq polymerase (heat stable, non-proof
reading DNA dependent DNA polymerase), reverse transcriptase
(RNA dependant DNA polymerase), telomerase (RNA dependant
DNA polymerase)
i.
Telomerase: prevents telomere shortening. Cancer
cells become immortal due to telomerase activity. It
uses its own RNA template to elongate DNA
4. Topoisomerase I relieves strain due to supercoiling (gyrase in bacteria
and Topo II in circular DNA)

DNA is packaged into condensed chromatin (inactive genes) or extended

chromatin (active genes)

DNA is found in a:
1) B form (Biological form right handed, 10bp/turn)
2) A form (right handed, 11bp/turn, ssDNA,
DNA:RNA and RNA:RNA)
3) Z form (left handed 12bp/turn, active chromatin)

-DNA repair can be achieved by endo and exo-nucleases

- methylation is commonly used to distinguish the parent strands
-

DNA can also be repaired by ligation of broken strands and using the second
chromosome as a template.
P53 prevents cell replication before DNA repair has occurred. Cells
deficient in P53 can become cancerous.

GENE II
- siRNAs are used as a defense mechanism in lower eukaryotes and plants
- -Dicer cleaves 21 NT long dsRNA from foreign RNA.
- -siRNA is amplified and spread
- -RISC pairs siRNA with viral mRNA for clevage
- -Host DNA is protected by methylation
- -For more info on siRNA, go to www.fuzzymittens.com/ms1 , click on the
link for core concepts, and find the iRNA ppt. in the cell bio folder
- Plasmid cloning vectors
- -Plasmid contains origin of replication, antibiotic resistance gene and
polylinker region (site where polylinker DNA insertion occurs).
- -New DNA, with sticky ends, is annealed to plasmid.
- -Amplification occurs with antibiotic (the plasmid should be resistant) as the
selection marker.
- -You can prepare a genomic library in a plasmid vector.
- Lambda phage cloning vectors and yeast artificial chromosomes
- Both of these accommodate larger pieces of DNA.
- Hybridization or antibody usage helps you to identify the specific DNA insert.
- Genomic libraries vs. cDNA libraries vs. cDNA expression libraries:
- Genomic libraries have introns, promoters, non-transcribed spacer DNA, etc.
- cDNA contains only sequences complementary to post-modification mRNA
(ready to be translated into protein)
- cDNA expression libraries are composed of cDNAs with the requisite DNA
sequences for expression in an artificial system
- DNA inserted into a cloning vector is isolated by using complimentary endonucleases

GENE III
2 ways to produce DNA probes:
1. Separate DNA strands and add radioactive dNTPs
2. Use a polynucleotide kinase to transfer radioactive phosphate to the 5 end of DNA.
DNA sequencing
1. Chemical method (Maxam-Gilbert):
4 tubes used (A, C, G, T)
Use a chemical that will attach to the designated nucleotide and break the strand
Result: a bunch of different sized strands that are sequenced
DNA footprinting also uses chemicals to determine where specific proteins bind
2. Enzymatic method (Sangers dideoxy)
Make 4 different vials (same as above) and include specific dideoxy,
chain terminating nucleotides in each vial.
Result: same as chemical.
Anti-viral drugs (AZT) can work by this same dideoxy method
3. Automated sequencing
Uses fluorescent tags on dideoxy nucleotides.
The stability of a DNA hybrid is directly proportional to its base pair matching. More
perfect hybrids are more stable, so you can separate less perfect hybrids with high
temperature and NaCl concentration.
Blots (Southern uses DNA, Northern uses RNA, and Western uses proteins)
Electrophoresis to separate different size fragments
Heat applied to denature and separate all fragments (i.e. dsDNA ssDNA)
Radioactive probe (complimentary to target sequence) added to the filter and
hybridization occurs.
The sample is exposed to film so that you can identify hybrids.
Restriction fragment length polymorphism is used to detect mutations in gene sequences. It
involves cleavage of an isolated DNA fragment and identification of the digested pieces.
1. Southern blotting used
2. useful for prenatal screening, sickle cell detection and phenylketonuria
PCR polymerase chain reaction is used to make copies of genetic info.
1. Heat to separate strands
2. Add primers to hybridize and add dNTPs
3. Heat and use Taq polymerase to transcribe
4. Repeat
Variable numbers of tandem repeats (VNTR). Unique sequences outside of the coding regions
of DNA are amplified for identification purposes

GENE IV
Transcription (5-3)
Synthesis of RNA from DNA templates.
Enzyme RNA polymerase
Helicase and topo I are needed for accurate transcription
Promoters, enhancers, repressors and insulators are all used to regulate
Most regulation occurs at the level of initiation. Regulation can be negative or
positive.
Prokaryotes have no nucleus so transcription and translation are coupled. 1
strand of Prokaryotic mRNA produces multiple proteins (polycistronic).
Eukaryotic transcription and translation occur in nucleus and cytosol,
respectively. Eukaryotic mRNA is monocystronic.
All genes are present in every cell, but differential expression causes functional
variation.
Methylation on promoters causes inactivation
Acetylation on histones causes activation
Both demethylation of promoters and acetylation of histones are necessary to
activate gene transcription
Steroids hormones alter gene expression (look at Block 3: Endocrine)
Eukaryotic mRNA processing
Eukaryotic mRNA is capped (5) and polyadenalted (3). These modifications
enable the mRNA to exit the nucleus.
Introns (70% of gene) are removed. Alternate and trans-splicing can give you
many mRNAs.
7 subunits of snRNA come together to make snRNP which identifies the
splicing site.

GENE V
Overall: Translation and Translation Control
I.
Translation = synthesis of proteins.
a. mRNA to protein: need mRNA, ribosomes, tRNAs, amino acids,
several protein factors, energy (ATP, GTP)
b. tRNAs have 2 functions: 1. bind correct AA @ 3 end; 2. bind triplet
codon on mRNA using anti-codon segment.
c. Wobble hypothesis: 3rd position in anti-codon pairs loosely, so imperfect
pairing occurs.
d. Eukaryotic vs bacterial ribosomes: Es are bigger!
e. Positioning ribosome correctly on the mRNA: in bacteria, 16S segment
binds 3 end of mRNA; in eukaryotes, ribosome starts at 5cap and
scans for start codon (AUG)
i. Sometimes start at IRES = internal ribosome entry site.
f. Initiation: initiation factors aid small ribosomal subunit, with initiator
tRNA bound (always Met for AUG site), to find start codon; then large
ribosome subunit binds, then next tRNA; now AA can be transferred and
translation begins.
g. Elongation: each new AA residue gets transferred to growing chain.
(believed to be catalyzed by rRNA: a rare ribozyme action).
h. Termination: Release factors are like tRNA but without an AA attached:
when RF binds to ribosome, protein is released.
i. Polysomes lots of ribosomes translating single mRNA at once; on RER
surface (secretory proteins) or in cytosol (soluble proteins).
II.
Post-translation: proteins are folded as they come out of ribosome (see cell
biology lectures) and proteins undergo post-translational modifications (see
biochem lectures).
III.
mRNA stability and Translational Control
a. mutations:
i. silent at protein level, no difference
ii. missense protein still translated but with an AA substituted.
iii. nonsense non-functional protein or truncated (mutation causes
premature stop codon).
iv. Addition/deletion add or delete single nucleotide
v. Frame-shift generally results from addition or deletion.
b. Stability:
i. 5cap: 5-5 linkage: protects mRNA
ii. UTRs UnTranslated Regions at 5 or 3 end of mRNA confer
stability and places for regulatory proteins to bind.
Eg: transferrin (5UTR) and its receptor (3UTR): aconitase (itself
inhibited by Fe molecules) binds both UTR regions, so in low Fe,
inhibits TR translation and stabilizes receptor mRNA to bring Fe
into cell. Converse in Fe overload: TR translated and receptor
mRNA degrades..

-RNA viruses evolve quickly and don't have vaccines

-Need promoter and SD sequence to make recombinant protein in
plasmid
-

GENE VI

Overall: Biotechnology
I.
Recombinant proteins: (example: insulin)
a. Use plasmid to clone insulin gene into bacteria. Cell culture makes
insulin; once purified is perfect replacement therapy.
b. Can get recombinant proteins in milk; expression of recombinant genes
limited to mammary glands. Resolves some problems of making human
genes work in prokaryotes. These proteins get purified from the milk.
c. Recomb proteins in use today: TPA (tissue plasminogen activator), blood
clotting factors, interleukins, enzymes for research, safer vaccines.
II.
Use of transgenic mice in research
a. Humans and mice have similar genes and similar development.
b. Options: gene replacement, gene knock-out, gene addition.
c. Accomplish by growing mouse stem cells in culture, altering DNA, then
introducing stem cells into early embryo; breed 2nd generation to get purebreds.
III.
Genetic therapy
a. ADA (adenosine deaminase) deficiency causes SCID (severe combined
high adensoine levels lead to
immune deficiency). Tx: take stem cells or Tcells from pt, add the ADA
high dATP which inhibits
synthesis of other 3 nucleotides
gene, then reintroduce patients cells into system.
b. Portions of HIV genome used as very effective vector. (used for ADA)
Viruses successful at incorporating into genome randomly or at LTRs
(long tandem repeat segments).
c. Cloning sequence using viral vector: LTR Enhancer promoter
gene cDNA poly(A) signal LTR. (use promoter appropriate to target
tissue).
IV.
Tailor-made anti-cancer drugs:
a. Example is GLEEVAC: treats chronic myeloid leukemia. Disease
caused by abnormal chromosome translocation resulting in a fusion kinase
present only in cancer cells. GLEEVAC is tailor-made to inhibit this
activity. Patient takes pill once a day until all blood cells should have
turned over and all cells with mutation have died. Pt then cancer-free.
V.
Oncogene discovery from cDNA library. Can note cell populations with
over-growth phenotype. Led to discovery of Ras oncogene.
VI.
siRNAs
a. The low-down: siRNAs are small interference RNAs. In plants, double
stranded RNA is chopped by an RNase (dicer) into fragments 23nts long.
After dicer cuts the double stranded
RNA, RNA fragments can anneal to the These mark other incoming RNA that is complementary so that dicer can
RISC (RNA induced silencing complex) cut them as well. RNA dep RNA polymerase makes more of these short
which is made of miRNA. RISC will
fragments to function in future defense. Humans have dicer (but not the
then recognize other bad RNA
RNA-dep RNA polymerase). Research is ongoing to use dicer to chop up
sequences and chop them up
viral or cancer mRNAs in human disease.

- Sanger's dideoxy nucleotide method for determining DNA sequence.

Southern hybridization
- Isolate DNA
- Cut with restriction enzymes that give different fragments
- Smear on agarose gel
- Transfer to filter that binds DNA
- Denature DNA
- Add appropriate probe to detect fragment of interest

- VNTRs can be used to DNA fingerprint

- Restriction fragment length polymorphism (RFLP)- useful for determining single
nucleotide changes in critical genes. Will give fragments of different length if
mutation is present (such as for beta globin gene)

PROTEIN TAXONOMY
Overall: Protein Structure
I.
Amino Acid structure
a. All AAs are chiral with a side chain (giving specific AA), an amino group
(NH2), a carboxy group (COO-) and an H. (exception is glcine with 2
Hs).
carbon
side chain

R-CH-CO2NH3+

carboxyl group

amino group

II.

III.
IV.

V.

b. Learn your amino acids theyre in your syllabus. (note that categories
such as non-polar vs. polar, aliphatic, aromatic, uncharged polar and
charged polar actually matter and are worth learning also).
Acid-Base behavior of AAs
a. The charged AAs are acids and bases; usually they are on the surface of a
protein and form salt-bridges with each other.
b. Acid proton donor; base proton acceptor.
c. Henderson-Hasselbach: relates the pKa of a buffer and the ratio of acid
and base present to the resulting pH of the solution.
pH = pKa + log ([A-]/[HA])
d. Titration curves: pKa = mid-point along the flat segment of these
curves: at this point, half of the molar amount of titrated group is
hydrogenated, half is de-hydrogenated. Work any problems from there,
depending on where you start (pH) and whether youre adding acid or
base.

The peptide bond

a. Peptide bond is planar; rotation only around alph-Carbon and side chain
elements.
Primary structure
a. Each protein: unique number and sequence of amino acids coded from
DNA to RNA to protein.
b. Sequence conservation: percent identity across species.
Interactions of side chains contributing to protein structure.
water structure, hydrophobic interactions, Hbonds, electrostatic
interactions, van der Waals interactions, molecular interaction.

PROTEIN II
Overall: More Protein Structure.
I.
Key concepts:
a. Interactions between sidechains that are far apart in sequence cause
protein to fold into compact shape.
b. Inferior of protein typically hydrophobic, compact with few holes.
c. Exterior typically hydrophilic and charged residues typ on surface.
d. Majority of N-H and C=O are involved in hydrogen bonds which
conver secondary structure.
e. Specialized functional regions may form catalytic sites.
II.
Secondary structure: - when sequence folds in regular, repeated fashion.
a. Helix structures, sheets, turns, random structure.
III.
Super-secondary structure - Recognized sequences of known secondary
structures.
a. helix-turn-helix, beta-meander, beta-alph-beta structure.
IV.
Tertiary structure
a. 3-D structure of single protein molecule; brings together different parts of
primary and secondary structure.
V.
Quaternary structure - describes assembly of multiple enzyme subunits.
a. Hydrophobic interactions important; also, charge and H bond interactions.
b. Association of multiple subunits allows regulation of activity, info
transmission (allostery and cooperativity), and creation of multiple
assemblies using multiple subunit types.
VI.
Protein stability
a. Proteins only marginally stable; this confers flexibility for enzyme
activity.
VII. Protein folding (key to Cystic Fibrosis and other diseases)
a. Mechanism directing protein folding not known.
b. Unfolded proteins will collapse then refold from compact structure.
c. Not all proteins refold spontaneously.
d. Molecular chaperones (bind unfolded proteins to prevent mis-folding)
and Foldases (in ER; forms disulfide bonds) aid process.
VIII. Post-translational Modifications:
a. Disulfide bonds (2 Cys residues) stabilize structure (eg: insulin has 3)
b. Phosphorylation (Ser, Thr, Tyr) think metabolism control mechanisms
c. Hydroxylation
d. Glycosylation alters stability, signal recognition
e. Carboxylation (like Acetyl CoA Carboxylase)
f. Fatty acylation/prenylation increases hydrophobicity of protein
g. Proteolysis all zymogens
Protonation/deprotonation changes in pH cause this

PROTEIN III & IV

HEMOGLOBIN:
Has heme group bound by hydrophobic interactions, and iron as Fe2+, which binds
oxygen.
2 2 tetramer.
Positive cooperativity in binding causes greater steepness about the P50 point;
successive oxygens are easier to add. This increases the amount of oxygen bound in the
lungs and the amount delivered in the tissues.
The Bohr effect: decrease pH, decrease Oxygen binding to hemoglobin; Hemoglobin gives up
oxygen more readily at low pH; saturation curve shifts to the right because it is less oxygen
bound/saturated even at the same PO2.
H+ takes the place of oxygen; hemoglobin is a proton carrier between the lungs and the
tissues, important buffer.
CO2 also binds deoxyhemoglobin in tissues and is carried to lungs.
BPG binds deoxy Hb and inhibits Oxygen binding in presence of BPG. Fetal HB doesnt
bind BPG as well. Therefore, higher oxygen affinity than adult Hb.
BPG is an intermediate in glycolysis, which indicates working tissue in need of oxygen
for oxidative phosphorylation after glycolysis.

pH 7.4

pH 7.0

Lower pH releases oxygen

Higher oxygen releases protons

MYOGLOBIN:
Monomer, similar to one of Hbs subunits
Shows saturation behavior at Oxygen binding site; increases linearly to p50, then begins
to level off.
Releases oxygen at lower pO2 than Hb; takes oxygen to very starved tissues, ex.
Red/type I muscle.
Enzyme kinetics:
Enzymes are catalysts to reach equilibrium faster.
Very specific-few substrates
Active site equals binding domain plus catalytic domain.

Enzymes are controlled by amount of enzyme, posttranslational modification, and

quantity of substrates and products.
Isozymes are different proteins from different genes that catalyze same reactions, often in
different tissues.
CPK found after heart attack (cardiac cells die or after muscle trauma); CPK-BB-brain
and lungs. MB-heart MM-skeletal muscle (different isozymes can tell you which tissue
has the problem).
At low substrate concentrations:
Velocity of enzyme reactivity is directly proportional to [S], then becomes limited by the
concentration of the enzyme.
Km=[S] at Vmax= Michaelis constant, perenzyme, sort of an indicator of enzymes
affinity for its subsrate.
Michaelis-Menten:
V=Vmax [S]/Km+[S] (Usually expressed in umol/minute of substrate consumed)
V or Vmax/[E] = specific activity of enzyme.
V varies the most in the range where [S] is less than Km; therefore most enzymes in the
body have Km close to physiological [S], so their activity can be finely regulated by
changing [S].
Lineweaver-Burk double reciprocal plot:
Y intercept = 1/Vmax
Slope = Km/Vmax
Inhibition by products or product analogs gives reversible inhibition. Bind to active site/occupy
it.

Competitive inhibitor: effector binds E. Can be fought off by increasing [S] and thus Vmax
does not change. Changes slope, Km/Vmax, by increasing [S] required to reach Km. (Either
substrate or inhibitor binds)

Non-competitive inhibitor: effector binds E and ES; cant be fought off by increasing [S] because
inhibitors and substrates bind to different sites. Changes slope and intercept.
Allostery: change enzyme function by changing enzyme shape
Cooperativity: allostery via substrate; + or
Produces sigmoidal kinetics, see hemoglobin.

Phosphofructokinase: an example of
allostery.

Term

Expt'l hallmark

Cooperativity

"s-shaped curve" (n>1) Allostery (using

substrate)

Comp. Inh.

High [S] can overcome 1. S and I Bind at [I] "destroys" f'n

enzyme
it (1/vmax same)
same site
2. allostery

Non-comp. Inh. High [S] cannot

overcome it

Structural cause 'zif

[S] "creates" new f'n
enz.

S and I bind at
different sites

Allosteric act.

Enzyme "works better" Allostery (using

esp at low [S]
activator)

Activator "converts"
enz to f'n form

Allosteric inh.

Enzyme "works
Allostery (as in 2.) "Bohr effect" or BPG
worse" esp at low [S]

PROTEIN V & VI
Catalysts by enzymes:
Specificity constant: efficiency of enzyme finding and converting substrate.
Specificity constant = Vmax/Km
Lock and key: specificity (the substrate fits specifically into the active site).
Induced fit: binding substrate changes shape of enzyme and brings catalytic site into the
right geometry for activity.
Enzymes lower activation energy required for transition state. ( Gact) (dont change
overall equilibrium)

Catalysis mechanisms:
1. Organization of substrates spatially:

2.
3.
4.
5.

Solvation effects/microenvironment excluding water

Covalent catalysis/alternative mechanism
Coenzymes/vitamins:
Alternative (non-AA) side groups like aldehydes, ketones, metals, oxidizing and
reducing agents.
6. Acid base catalysis

Rational Drug Design:

The old way:
Accident
Screening
The new way:
Isolate target enzyme or receptor first
Screen compounds for binding inhibitors and denerage lead compound
Determine lead compounds structure and a synthetic strategy for compound.
Optimize structure (ex combining bits for greater inhibitor efficiency to make a
multisubstrate analog).
Penicillin:
Old way: Inhibited cell wall crosslinking but was susceptible to B lactatmase
New way: Cephalosporins are inhibited but not susceptible to B lactamase.
Substrate analogs: resemble substrates, 5 reactions.
HIV blocked by dideoxy base which is incorporated into DNA and prevents further
polymerization.
Ex. AZT, DDI, DDC. These work because they dont inhibit mammalian DNA
polymerase, only RNA reverse transcriptase action.

AZT (azidothymidine), DDI (dideoxyinosine)

and DDC (dideoxycytidine)

Multisubstrate analogs: More efficient. Cancer blocked by PALA, which inhibits

pyramidine biosynthesis for DNA replication.
Transition state analogs: Very specific, very tight binding to enzymes. AIDS protease
that activates viral preprotein protease inhibitors.
De novo design:
Get 3D structures (positive charge and hydrophobicity info) of target.
Use computer to screen known compounds, synthesize molecule.

Chapter Two Cell Biology

BLOCK 1 CORE CONCEPTS
THREAD: CELL BIOLOGY/HISTOLOGY
CONTRIBUTORS: LAURA HANSON, MICHAEL STEWART, LAURA GARCIA, SAGARI
PONNURU, ADVA BUZI & ROBERT DOMINGO

TABLE OF CONTENTS:
CELL MEMBRANES I
CELL MEMBRANES II
CELL MEMBRANES III

JEANETTE KUNZ
JEANETTE KUNZ
JEANETTE KUNZ

CYTOSKELETON
JUNCTIONAL COMPLEXES

DAVID ROWLEY
DAVID ROWLEY

CELL ORGANELLES I
CELL ORGANELLES II
CELL ORGANELLES III
CELL ORGANELLES IV
CELL ORGANELLES V

RICHARD SIFERS
RICHARD SIFERS
RICHARD SIFERS
RICHARD SIFERS
RICHARD SIFERS

CELL SIGNALING I
CELL SIGNALING II
CELL SIGNALING III
CELL SIGNALING IV
CELL MOTILITY

ERIC KLANN
ERIC KLANN
ERIC KLANN
ERIC KLANN
DAVID ROWLEY

CELL MEMBRANES I: STRUCTURE AND FUNCTION

PHOSPHOLIPIDS: BASIC STRUCTURE
-most common kind is phosphoglyceride (aka
glycerophospholipid)
-is glycerol backbone + 2 fatty acids +
[phosphate + head group]

WHY PHOSPHOLIPIDS ARE SUITABLE AS MAJOR COMPONENTS OF MEMBS

-amphipathic so in solution polar region is in contact with water, and non-polar region is away from water.
-shape allows them to form monolayers, micelles, and bilayers
-lateral fluidity
HOW MEMBRANE FLUIDITY IS
INFLUENCED
1. Longer acyl tail of fatty acids=
increased Van der Waals interactions=
higher Tm
2. More unsaturation= kinks that are
harder to pack together= lower Tm
3. Cholesterol= bulky structure hard to
pack and hard to move fast= wider
range Tm
DIFFERENT TYPES OF MEMBRANE PROTEINS
Peripheral: Soluble proteins that associate with head groups of membrane or other proteins.
Electrostatic interactions that are easily dissociated with high salt or change in pH
Integral: Insoluble proteins that penetrate or traverse the membrane.
Removed with detergents. May be single or multi pass (sequences of hydrophobic helices).
Lipid-Anchored: Proteins with covalently attached lipid anchor in the bilayer
May be fatty acid or isoprenoid on the inner leaflet, or GPI on the outer
FUNCTIONS OF MEMBRANE PROTEINS
1. Communication across membranes
2. Cell-cell and cell-matrix adhesion
3. Cell-cell recognition
4. Transport of compounds across membranes
FACTORS AFFECTING PASSIVE DIFFUSION
Membranes are differentially permeable and allow 1. Small nonpolar, 2. Hydrophobic, 3. Small polar
uncharged molecules to pass through.
1. Flux is proportional to concentration difference across the membrane
2. Lipid solubility: partition coefficient= [concentration in bilayer]/[concentration in aq. soln.]
3. Membrane thickness and surface area (constant in animals)
4. Temp- higher temp= higher velocity of molecules
5. Size- bigger=slower
Rate of passive diffusion is described by Ficks Law: J=-P(Co-Ci) (doesnt apply to charged molecules)
WATER FLUX BY OSMOSIS REGULATES TONICITY
Ingested water will distribute between extracellular and intracellular compartments. Water will flow from
lower solute concentration to higher until the osmotic pressures on both sides of the membrane are equal.
Donnan Effect: If a cell contains concentrated amounts of large molecules, water will tend to flow into the
cell and change the volume. Water can flow across membranes through the membranes or by

facilitated diffusion through water pores. The large molecules cant pass, but Na+ and K+ ions can, so
cells regulate their volume by pumping ions in the direction that will reduce osmotic pressure.

CELL MEMBRANES II: TRANSPORT

FACILITATED DIFFUSION VS. ACTIVE TRANSPORT
Facilitated Diffusion (Passive transport)
Active Transport
Requires channelssimultaneously
open to both sides; or carriers
Moves molecules UP conc. Grad.
(permeases)bind
release
Energy utilized
No energy utilized
Saturable
Saturable
Specific
Selective
Used to generate a membrane potential
Multi-pass with hydrophilic residues
Uniport or Co-transport (sym or anti)
towards the channels

PRIMARY ACTIVE TRANSPORT

Uses the energy of ATP hydrolysis to make conformational change that transports the molecule through.
#1 example: Na+/K+ ATPase
Pumps Na and K up their concentration
gradients: 3 Na out for every 2 K in
and every 1 ATP (antiport)
No ATP means Na and K gradients are
lost (Ouabain, a steroid like drug,
blocks the pump specifically and the
gradients are lost)
Electrogenic (voltage gradient=stored
energy)
Regulate osmotic balance, cell volume,
and resting potential

SECONDARY ACTIVE TRANSPORT

Uses energy to establish a concentration gradient, then uses that gradient to transport other molecules up
their concentration gradient.
#1 Example: Na+/Glucose cotransporter
First step is Na/K pump
Na+ gradient from step one is driving force to transport glucose into the cell
ATP is indirectly used
Gut epithelial cells use this
Na+ goes down its conc grad into the cell, and glucose goes up

MANY DISEASES ARE CAUSED BY TRANSPORT SYSTEM MALFUNCTION

1. Multi-drug resistance: ABC transporters that have highly conserved ATP binding domains, and
are normally found in the liver, kidney, and intestine, and function to remove toxins. MDR gene
is over expressed in certain cancers, and the ABC pumps pump out chemotherapeutic agents,
causing drug resistance.
2. Cystic Fibrosis: ATP and cAMP sensitive Cl- channel becomes insensitive to cAMP. Cl- flux is
disturbed in epithelia (eg lung).
3. Dropsy= Congestive Heart Failure: increasing intracellular Na+ will also increase Ca2+ levels
which will increase force of contraction. Treatments will block or decrease the Na/K ATPase.
Exs of drugs- Ouabain, Digitalis, Digoxin

CELL MEMBRANES III: ION CHANNELS

ION CHANNELS CAN SELECTIVELY ALTER MEMBRANE PERMEABILITY
Non-gated channels are always open and are important in maintaining resting membrane potential. Gated
channels are either open or closed in response to specific electrical, mechanical, or chemical signals. Ions
flow rapidly when the channel is open (passive transport). Gated ion channels are categorized according to
the kind of signal they respond to. The channels have specific amino acids that interact with the ions in
solution and determine which ions will pass (this is called the selectivity filter). Specificity isnt explained
by ion size or charge alone.
BASIC TYPES OF ION CHANNELS AND HOW THEY ARE GATED
1. Ligand-gated: non-covalent, reversible binding of a specific ligand will directly or indirectly
cause conf. Change in the channel. Ligands can be NTs that bind the extracellular face, or can be
second messengers or enzymes that act on the cytoplasmic face of the channel (by binding or
changing phosphorylation state). Ligand-gated channels allow rapid communication.
2. Voltage-gated channels: change in memb potential causes movement of charged regions of the
channel and opens or closes the channel. These channels propogate electrical impulses in nerve
and muscle.
3. Mechanosensitive channels: stretching or deformation of PM induces a change in the shape of the
channel and closes or opens it.
IONIC BASIS OF MEMBRANE POTENTIAL AND ROLES OF ION CHANNELS
Resting membrane potential = the difference in the ionic composition of the cytosol vs the surrounding
fluid. (separation of charge=membrane potential).
Interior Na=15 K=150 Cl=10 large anions=65
Exterior Na=150 K=5
Cl=110 large anions=.2
Ion channels allow the selective movement of the ions above (not the large anions) down their conc grads
creating a difference in electrical potential between the inside and outside of the cell. Extent of the
electrochemical gradient determines the direction and extent of net charge movement.
Resting potential depends mainly on K+ leak channels (passive movement) and the K+ gradient
MEMBRANE POTENTIAL VS. NERNST POTENTIAL VS. ACTION POTENTIAL
Membrane potential= separation of charge/voltage difference b/w the inside and outside of the cell
Nernst potential= equilibrium potential for any conc grad of a particular ion across a membrane, and is
predicted by the Nernst Equation

Action potential= the membrane potential changes that occur during nerve impulse propogation

CYTOSKELETON
Cytoskeleton:
Microtubules
(MT)

Location
Cytoplasm,
cilia, flagella

Microfilaments
(actin filaments)

Present in
every eukaryotic cell

Intermediate
Filament:

Cell Type:

Keratin
Vimentin
Desmin
Glial Fibrillary
Acidic ProteinsGFAP
Neurofilament

Structure
& tubulin subunit
polymerizes to a helical MTs
(13 units/turn) soda-straw
structure. GTP cap at (+) end
grows faster than (-) end.
MTOC- microtubule
organizing center directs
polymerization. MAPsmicrotubule associated proteins
stabilize MTs by cross-linking
them into bundles
Globular subunits (G- actin
monomer) organize into a
double stranded helix (F-actin
polymer). Actively
depolymerized and
polymerized in non- muscle
tissue. + end grows; - end
disassembles; termed
treadmilling. Capping actin w/
ATP stabilizes the polymer

Function
Mitotic spindle: Roadway
for motors; + end attaches
Chromosomes; - at centriole.
Kinesin (- to +) Dynein (+ to -)
Axon/Dendrites:
Roadway for motor proteins to
carry cargo
Cilia/Flagella: 9 +2
arrangement of MTs, Dynein on
A tubule pushes B causing
bending
Muscle: forms
paracrystalline array with myosin
for contraction
Cell cortex beneath
membrane in most cells: aid
endocytosis, exocytosis, and cell
migration
Cytoplasmic streamingassociated with some organelle
movement
Cytokinesis: associated
with myosin in mitotic cells
Actin, like MTs, provide
force and motion via motor
proteins leading to contraction!

Helical monomer wraps around another to form a coiled-coil dimer.

Two coiled-coils unite to form a staggered tetramer. Staggered
tetramers can unite. Then 8 staggered tetramers twist into an
intermediate filament.
Epithelium
Both Keratinized and Nonkeratinized
epithelium
Mesinchymal Fibroblasts, chondrocytes, macrophages,
cells
endothelial cells, vascular smooth muscle
Contractile
Striated & smooth muscle (except vascular
cells
smooth muscle)
Glial cells
Astrocytes
Neurons

Nerve cell body processes

Antimitotic Drugs
Vinblastine: depolymerizes formed MTs, binds subunits of MTs and
prevents polymerization by aggregating bound units into a paracrystalline
array
Taxol: accelerates formation of MTs and stabilizes them thus depleting
the available tubulin for mitotic division
Cochicine: colchicines-tubulin complex binds to growing (+) end of MT
and stops MT growth.

Diameter
24nm

5-7nm

10-12nm

JUNCTIONAL COMPLEXES
Gap Junction

Tight junction (Zonula

Occludens)

Desmosome (Macula
Adherens)

Hemidesomosome

Adherent Junction

Focal Contacts

Structure:
6 connexins create a connexon
which is a pore connecting
adjacent cells (2nm diameter)
multi-protein complex btwn
cells that binds directly to the
integral occludin proteins and to
the cytoplasmic actin
cytoskeleton
2 Disk shaped Cadherin
transmembrane structures
matched between cells.
Attachment Plaque (12 proteins)
located on cytosolic side where
intermediate filaments insert.
Ca2+ necessary.
1 Disk shaped integrin
transmembrane structure that
binds to the basal lamina (laminin
and collagen type IV).
Intermediate filaments attach to
cytosolic side.
Junctional complex with
Cadherin trans-membrane
protein. Inserts into the
cytoplasmic actin of the
Terminal web
Junctional complex between cell
and basal lamina. Integrin is the
transmembrane protein. Actin is
the cytoplasmic anchor

Function:
Allow ions and
molecules up to 1500 D
flow down a gradient.
Ca2+ blocks gap
junctions stopping flow
Forms a seal around
the cell which prevents
flow of materials
between epithelial cells
(paracellular leakage)
Provide firm adhesion
between cells

Bind the cell to the

basal lamina

Encircles one cell and

provides adhesion to
neighbor.
Bind the cell to the
basal lamina & ECM.
Important for the
motility of cells like
fibroblasts. Not present
in epithelial cells.

Facts to Know:
Desmosomes and hemidesmosomes attach to intermediate filaments like
keratin, vimentin, or desmin; Tight junctions, adherent junctions, and focal
contacts attach to actin.
Desmosomes and adherent junctions use cadherins; hemidesmosomes and
focal contacts use integrins.

CELL ORGANELLES I. THE NUCLEUS.

Heterochromatin-highly condensed / Euchromatin-less condensed (transcriptionally
active)
Chromatin=complex of DNA, histones, and nonhistone proteins in eukaryotic cells.
the material of which chromosomes are made.
Histones = one of a group of small abundant proteins rich in positively-charges amino
acids that form the nucleosome with the DNA of eukaryotes
Basic Unit of DNA packing is a Nucleosome:
o consists of the core histones (H2A, H2B, H3, and H4), the linker histone (H1),
and DNA
Making ribosomes:
o Requires nuclear transport in two directions: (1) to bring ribosomal proteins to
nucleolus (2) to export newly assembled ribosomal subunits
o A lot of cellular machinery is devoted to making ribosomes
The nuclear pore complex mediates membrane permeablility
o All movement of
Nuclear
macromolecules between the
Import
NLS importin
nucleus and cytoplasm occurs
through these structures.
Because of its large size, the
NPC allows free diffusion of
macromolecules up to (45-60
kDa)
o
Signals mediate transport
After import,
importin recycles
<<Nuclear localization
back to cytoplasm
for another round
Sequence>> & <<Nuclear
importin
NLS
of import.
Export Sequence>>
In cytoplasm, importin binds import cargo, carries it through
o
These targeting signals on
the nuclear pore complex, and dissociates (releasing cargo)
nuclear cargo are recognized
in the nuclear interior.
by soluble receptor/carriers called karyopherins (nuclear carriers). <<Import
karyopherins = importins>> <<export karyopherins= exportins>>
o Over 20 karyopherins exist in human genome. Each receptor recognizes a
different type of targeting signal.
o mRNA export: very tight relationship between the splicing and processing of a
newly transcribed mRNA and its export
If one inhibits splicing, then export is inhibited also.
In general mRNA export remains poorly understood because of
complicated link between mRNA maturation and export
Relevance to disease: HIV Virus Life Cycle
o Some HIV viral proteins contain NLSs. This allows viral nucleoprotein
complexes to be actively imported into the nucleus of non-dividing cells.
o Export of viral mRNA also uses host machinery.
o Many viruses enter the nullius to gain access to the DNA replication machinery.
The host machinery is used for the viral DNA to integrate into the genome.

CELL ORGANELLES II: THE ENDOPLASMIC RETICULUM

The rough endoplasmic reticulum: where proteins enter the secretory pathway
All ribosomes are equal. The translated
mRNA determines the free vs. membrane
bound state. <<Proteins contain targeting
sequences or zip codes that mediate
sorting to the correct internal organelle>>
o Signal Sequence ER (Mediates
translocation of nascent secretory
and membrane proteins into the ER,
the first compartment of the
secretory pathway)
o Signal sequences are stretches of 20
Three-dimensional reconstruction of a region of the smooth
hydrophobic amino acids (# of AA
and rough ER in a liver cell.
required for a polypeptide to span a
Alberts Fig. 12-38
lipid bilayer)
Covalent modifications assist protein folding (conformational maturation) and stabilize
native structure
o Asparagine-linked glycosylation
o Disulfide bonds (do not form in cytoplasm because of the reduing atmosphere
(glutathione).
o Some membrane proteins lose their transmembrane domain and gain a GPI
anchor
Final modification-protein folds (aided by chaperones of the ER lumen) <<Correct
folding, and release form chaperones, is necessary for exit from the ERFIRST HALF
OF THE CHECKPOINT>>
Fxns for the smooth ER
o Abundant in liver cells, because it contains some of the membrane-bound
enzymes used to degrade certain hormones and to neutralize noxious substances
such as alcohol and barbiturates
o When large amounts of certain compounds, such as the drug Phenobarbital enter
the system, the smooth ER in the liver doubles in surface area in a couple of
days. (This change reflects rapid synthesis of detoxification enzymes, and the
need for more membrane in which to place them.)
o Synthesis nearly all of the major classes of lipids, including phospholipids and
cholesterol, required of r the production of new cell membranes.
o Most cellular lipids are synthesized on smooth ER. They reach the other
membranes in the cell by one of three ways
Vesicles bud off and move along cytoskeletal elements by motor proteins
to other membranes with which they fuse
Diffuse to the rough ER which is continuous with the smooth Er
By transfer of proteins (to take lipids to organelles like mitochondria that
dont receive vesicular traffic from the ER
Smooth ER is common in cless engaged in steroid synthesis and lipid metalbolism
because it contains some of the membrane bound enzymes required for these processes.

CELL ORGANELLES III: GOLGI & LYSOSOMES

Whether to release an ER-situated protein to the Golgi complex represents a crucial prosttranslational checkpoint.
The efficiency of protein clearance, underlies many loss-of-fxn and gain-of-toxic-fxn
disorders
o Cystic Fibrosis: Most common fatal genetic disease in the US today (1/3300 live
births)
o Repeated chest infections result in progressive loss of lung fxn, the major cause of
premature death.
o The most common mutation leading to cystic fibrosis results from deletion of Phe
508 in CFTR.
o The mutant protein slightly misfolds, is trapped in the ER, and then degraded.
o The mutation does not appear to affect the ability of the CFTR protein to transport
ions, indication that the mutant protein would probably fxn if delivered to the plasma
membrane/
o Alpha 1-antitrypsin deficiency: A genetic disease responsible for chronic obstructive
lung emphysema
o Also responsible for liver cirrhosis and is one of the most common genetic causes of
childhood liver transplantation.
o Both disorders are causes by mutations in the alpha 1-antitrypsin protein,
Accumulation (in hepatocytes) of the undegraded mutant protein can lead to cirrhosis
(gain-of-toxic-fxn disorder). Its hindered secretion is responsible for the lung disease
(loss-of-fxn disorder).
Misfolded ER-situated proteins are dislocated into cytoplasm for degradation by proteosomes
(prolonged duration of non-native structure = degradation).
Protein sorting signals specify: (1) ER retention (of native proteins) <<KDEL = retention
signal>> (2) Golgi retention signal (different signals for cis, medial, & trans Golgi) (3)
Signals for diverting secretory proteins to regulated secretory vesicles
Unless signals specify ER-retention, correctly folded proteins are delivered to the Golgi
complex by default.
Golgi consists of flatted membrane-bound cisternae and resemble a stack of plates.
The tetanus toxin (protease) cleaves receptors used for the movement of synaptic vesicles in
inhibitory neurons (blocks secretion of inhibitory NT = convulsive contractions of skeletal
muscle lockjaw).
Lysosomes.
Membrane bound organelle, acid pH (special coating on interior), degrades proteins, lipids,
carbohydrates, DNA, RNA
The modifications of attached sugars divert most newly synthesized acid hydrolases out of the
secretory pathway, and into lysosomes. (Mannose 6-phosphate (M6P) is a signal that targets
newly synthesized proteins to lysosomes)
Lysosomal storage diseases: when a cell lacks one of the hydrolytic enzymes, lysosomes
accumulate material that is normally destroyed
o Tay-sachs disease is especially prevalent among Jews, particularly among those of
Eastern European origin (1/30 reported chance)
o Affected infants appear nml at birth (manifest relentless motor & mental
deterioration & increasing dementia at 6 mths)
death at 2-3 yrs
o Results from an absence of hexoamionidase A (breaks down glycolipids)
o Histological examination shows neurons ballooned with cytoplasmic vacuoles
(distended lysosomes filled with glycolipid) >> progressive destruction of neurons

CELL ORGANELLES IV: MITOCHONDRIA AND PEROXISOMES

Mitochondria = generates cellular energy
Signal sequence for
mitochondrial import
Translocator of Outer Membrane
(cytochrome oxidase)
Chaperones are required both
in the cytosol and inside the
mitochondria to achieve
protein import
# and placement of sorting
signals dictates site of protein
residence
Translocator of Inner Membrane
When mitochondria fail, less
energy (ATP) is generated
with the cell and cell death
OXA complex mediates insertion into
innermembrane.
follows.
Damage is most notable in the following organs/tissues brain, heart, liver,
skeletal muscle, kidney and endocrine system
Peroxisomes fxns = oxidation of fatty acids and other lipids, oxidation of purines,
amino acids, hydroxyl acids, and other metabolites, biosynthesis of cholesterol,
bile, acids, ether based lipids, contain large amounts of catalase which can convert
excess hydrogen peroxide into water
Peroxisomal protein import (soluble matrix proteins only): 2 import signals (PTS1
and PTS2) [no detected targeting signal on some peroxisomal proteins = unknown
mechansism]
Peroxisomal proteins are detected in vesicles that bud from the ER, and are
claimed to represent immature peroxisomes
Multiple human diseases have been linked to peroxisomal disorders
o Zellwegers syndrome (inherited genetic disease): general defect in
importing proteins into peroxisomesexhibits empty
peroxisomesindividuals die son after birth
Peroxisomal pathway is not completely understood
o No chaperones exist in the peroxisomal matrix
Mitochondrial translocation machinery

CELL ORGANELLES V: ENDOCYTOSIS

o Protein trafficking from the plasma membrane
o Phagocytosis cell eating (large particles) i.e antibody activated phagocytosis
o Endocytosis (a) pinocytosis cell drinking (b) Receptor mediated (active
uptake of external & plasma membrane proteins)
o Transcytosis (one side of cell to other)
o Endocytosis: at the cell surface clathrin-coated pits and vesicles cycle between
soluble (disassembled) and membrane-associated states. (adaptin proteins bind
both clathrin, and the cytoplasmic tails of certain receptors clustering those
receptors in coated pits.
o Caveolae-another type of vesicle that buds from the plasma membrane that
clusters GPI-linked membrane proteins
o Transcytosis: In polarized cells, tight junction complexes are responsible for
preventing the diffusion of membrane proteins between apical and basolateral
surfaces limiting transcytosis to select substances.
o Transcytosis is utilized for the uptake of maternal antibodies by nursing
infants
o Autophagy: protein trafficking distinct from plasma membrane that leads to
lysosomal degradation.
o General strategy used by cells to destroy their own organelles
o Active in hepatocytes, but especially during period of amino acid
starvation
o The engulfing membrane may originate from ER or Golgi
o Very little is known about the mechanics
o also used in the destruction of proteins accumulating in the cytosol
(aggressomes) that failed to be degraded by proteasomes (**potential
modifier of the several gain-of-toxic-fxn diseases)

CELL SIGNALING I
Three basic categories of signaling molecules
Category
Produced by
Released
Action
Examples

Endocrine
islets or glands
into blood
diffusely
throughout body
Hormones

Time

Slow acting

Paracrine
many types of cells
not in the blood
locally at nearby target cells
Growth factors, prostaglandins, FA
derivatives
Fast acting

Chemical neurotransmitters
neurons
After action potential
Locally at nearby neurons,
gland, or muscle cells
Fast acting

Endocrine

Paracrine

Three different categories:

1. steroid (i.e. androgens, estrogens,
glucocorticoids, mineralcorticoids, vit D)
-small derivatives of cholesterol
-hydrophobic so when in blood must be
carried by carrier proteins
-lipid soluble/ not water soluble
-receptors are intracellular / bind the steroid
and DNA
2. proteinaceous (proteins and polypeptides)
-hydrophillic and water soluble
-receptors on cell surface
3. amino acid related (i.e. epinephrine)
-receptors on cell surface and have
extracellular domain that bind hormone
Neurosecretory cells in the hypothalamus couple the
control of the nervous system to the endocrine
system
1. Stimulating parvicellular neurons results in release
of releasing and inhibiting factors from the
hypothalamus that affects the secretions of the
pituitary.
2. Magnocellular neurons extend axons to the
posterior pituitary and release oxytocin and
vasopression directly into circulation.

Growth factors:
-small polypeptides with receptors on cell surface of target cell
Functions:
1. Mitogenic: stimulate cell proliferation
2. trophic: stimulate cell survival and growth
3. chemoattractant: gradient of the factors will illicit cells to follow
4. pleiotropic: multiple effects
Nerve growth factor:
If there are too many neurons for the amount of target cells around, NGF
will not be released by those cells and certain neurons will die resulting
in a match in the number of neurons and cells.
Histamine:
-Example of a paracrine signaling molecule that is not a polypeptide.
-IgE leads to histamine release (degranulation of mast cells); histamine
is a vasodilator
Eicosanoids
-oxygenated bioactive derivatives of 20-carbon polyunsaturated fatty
acids
-diffuse across cell membrane and bind to surface receptors on nearby
cells
-an example is prostaglandins which when released from a damaged cell
bind to nociceptors (sensory nerve endings which relay pain to the
CNS), they do this by reducing depolarization necessary for an action
potential
Nitric Oxide (NO)
-gas which can be extracellular messenged (diffuses across membrane)
-vasodilator by relaxing smooth muscle of blood vessel wall (binds to
guanylyl cyclase which converts GTP to cyclic GMP)
Nitroglycerine is converted to NO in the body

Autocrine: cell responds to its own signaling molecules

Example: Activation of T-helper cells
1. Antigen bound to surface of Antigen Presenting cell binds to receptor on helper T cell
2. T Helper cell stimulates APC cell to secrete IL 1
3. IL 1 binds to receptor on T-helper cell which activate synthesis and secretion of IL 2 and
expression of IL 2 receptors on its membrane
4. IL 2 binds to receptors and stimulates proliferation of same cell that secretes it

CELL SIGNALING II
Types of synaptic transmission:
1.
2.

Electrical: ions travel through gap junctions (i.e. cardiac muscle and smooth muscle)
Chemical: transmission between neurons (within the synapse)

Connections between neurons:

Criteria for true neurotransmitter:

1.
2.
3.
4.
5.
6.

(a) Axodendritic
(b) Axosomatic
(c) Axoaxonic
Not pictured: axosecretory (onto
capillary) and neuromuscular (onto
muscle)

Steps Involved in Synaptic Transmission

7.

1.
2.
3.
4.

found in presynaptic neuron

enzymes required for its synthesis are found in the
neuron
stimulation of presynaptic neuron leads to NT in the
cleft
applying NT to postsynaptic neuron gives same result
as stim of presynaptic neuron
way to terminate the neuron must exist
drugs that block synthesis of NT or its reaction should
block the effects of stimulation
drugs that block the degradation or reuptake of the NT
must prolong the action of the NT

action potential
drives down the axon
Ca2+ channels open
and Ca2+ enters the
presynaptic terminal
vessels fuse with
presynaptic
membrane
NT is released and
will have its effect on
postsynaptic neuron

Ionotropic receptor binding of the NT will

allow passage of cations or anions
Na+ channel: inflow of Na+ ions will cause
postsynaptic cell to become positive or excited
Cl- channel: inflow of Cl- ions will cause
postsynaptic cell to become negative or inhibited

Postsynaptic potentials:
(EPSP = excitatory postsynaptic potential / IPSP =
excitatory postsynaptic potential)
1. influx of Na+ - EPSP
2. influx of Cl- - IPSP
3. efflux of K+ - IPSP
4. influx of Ca2+ - EPSP
Amplitude of these is relatively small and degrade
across distance
Spatial summation: summation from several sources
Temporal summation: summation of potentials that
follow each other in time

Metabotropic receptor do not contain the ion

channel
Take longer to affect ion channels
-G protein will be result in modulation of an ion
channel that is close or far
-Na+ and Cl- channels are the same as above; K+
channels will cause an outflow of K+ and the cell
will become negative or inhibited

Removal of NT: either degraded in the cleft or reuptaken into the presynaptic neuron via pumps
Other NT info:

Other receptors:

1.
2.
3.
4.

Autoreceptors: receptors on neurons are activated by

the NT that are released from themselves (usually
feedback inhibition)
Presynaptic: receptors located on axon terminals and
activated by NT from another neuron (usually
decrease release or synthesis of NT)

NT and receptor must match for result

NT is synthesized from precursor molecules
NT is packaged into vesicles
Leaks of NT from vesicle is degraded

CELL SIGNALING III

Types of Receptors:
1) Steroid hormone receptor, composed of:
1. COOH-terminus domain contains hormone binding site
2. NH2-terminus domain involved in activation of transcription
3. middle-domain contains DNA binding site
*in inactive form, Hsp90 is bound to DNA binding site when steroid hormone binds, Hsp90 dissociates
and the complex can bind to specific DNA sequences
2) Adhesion molecules
- activate cells through cell-cell or cell-matrix interactions; involves signal transduction cascades
3) Ion channel-linked receptors (Ex. Nicotinic Ach receptor, GABA, AMPA, and NMDA)
- binding of NT causes an allosteric change in the receptor (channel) channel opens to allow ion flow
Nicotinic Ach: in neuromuscular jxn.; if Ach is bound for too long, channel will close
(desensitization)
AMPA: permeable to Na and K; NMDA: permeable to Na, K, and Calcium also
Glutamate binds to the AMPA receptor (ligand gated) Na comes in depolarization NMDA
(ligand and voltage-gated) channel opens
GABA: GABA is the major inhibitory NT in CNS; receptor type A= ionotropic, type B=
metabotrophic
Other substances that affect GABA receptor (only when GABA is bound also!):
1. Barbiturates increase duration of channel opening
2. Benzodiazepines increase frequency of channel opening
3. Ethanol
4) G-protein-coupled receptors (7 transmembrane -helices with G-protein , and gamma subunits)
**slow response but good for signal amplification (1 NT can affect many channels)
subunit is most important binds GTP to carry out its function, hydrolyses GTP to GDP to turn off
signal
5) Catalytic receptors (Ex. Receptor Tyrosine Kinase)
Ligand binds conformational change in receptor autophosphorylation
phosphorylate something else

now tyrosine kinase can

Protein Kinase (catalyze transfer of phosphate from ATP to substrate protein)

have regulatory and catalytic regions
catalytic region has binding site for ATP; substrate has consensus sequence (signals kinase to
phosphorylate)
regulatory domain often contains pseudosubstrate sequence (binds and inhibits catalytic domain)
Protein Phosphatase (dephosphorylate proteins)
not as specific as kinases; do not have consensus sequence; can be inactivated by corresponding
kinase to amplify phosphorylation
Intracellular signaling Proteins:
1. adaptor molecules
2. anchoring proteins

bring 2 signaling molecules next to each other to facilitate the reaction

help accomplish specificity

Concept of Divergence vs. Convergence

one NT could have multiple effects (divergence) OR several NTs could have the
same end effect (convergence)
this means that there is a very complex circuitry of signaling

drugs can have wanted effects on one cell, but unwanted effects on another cell

CELL SIGNALING IV
Calcium as a 2nd messenger:
- increases in [Ca] can cause dramatic changes within a cell
- normally, [Ca] is low inside the cell (due to calcium pumps, which require ATP)
- [Ca] can increase via: 1. activation of NMDA receptor 2. release from intracellular stores via
activation of G-protein signaling cascade (involves Phospholipase C)
Calmodulin (the principal Ca binding protein)
- binding of Ca results in conformational change activates CamKII (calmodulin dependent
protein kinase II)
Diacylglycerol (DAG)
- activates Protein Kinase C

Overall Pathway:
signal molecule G-protein receptor activates PLC PIP2 hydrolyzed to produce IP3 (which
opens Ca channels on ER to increase [Ca]i) and DAG (which activates Protein Kinase C)

Role of Calcium in NT release:

Action potential arrives at pre-synaptic terminal voltage-gated Ca channels open Ca enters cell
mobilizes vesicles for docking and release
a) Synapsin binds vesicles to the cytoskeleton
CamKII phosphorylates synapsin to release the vesicle from the cytoskeleton
b) Synaptotagmin docks vesicles at the active zone
Calcium has a direct effect on synaptotagmin, resulting in vesicle fusion & NT release

Ca

**Ca channels are located very close to where synaptic vesicles need to be released, so NT release happens
very quickly (200s after Ca channel activation)
** [Ca]i can be altered by pre-synaptic inhibition (cell becomes more neg; inhibit Ca influx) or by presynaptic facilitation (depolarization increases Ca influx). Ca means signal transmission.

Calcium in Memory Formation (in Hippocampus)

Long Term Potentiation (LTP) = cellular event that is thought to contribute to memory formation
depends on activation of NMDA receptor (NMDA channel opens in response to
glutamate binding AND strong depolarization of the post-synaptic cell)
NMDA channel opens
tyrosine kinase, etc)

Calcium influx

activation of numerous kinases (including PKC, CamKII,

Early phase LTP

Can result from:
1. more AMPA receptors on post-synaptic membrane
2. phosphorylation of receptors so that channel stays open for longer
3. more NT release
4. structural changes

Late phase LTP

* includes changes in gene expression
Ca/calmodulin adenylyl cyclase cAMP cAMP kinase CREB-1 affects gene expression
synthesis of effectors/ regulators that are responsible for long-term changes (i.e. creation of new synapses!)

CELL MOTILITY
requires signaling, reorganizing of cell adhesion systems, and alterations in
cytoskeleton
Signaling: chemotactic gradient
Reorganization: cell polarity changes, lamellipodium extension of migrating
cellscytoplasm, breaks in attachments to ECM
Neutrophil Cell Motility
1. Chemotactic gradient signal neutrophil to reorganize
2. Neutrophil reorganization: triggered by surface receptors
- polarization of cell organelles
- Lamellipodia actin filaments polymerized at cell edge to reach; serves as
an extension
3. new membrane mass inserted at leading edge of lamellipodia
4. chemotactic receptors steer cell
ex. F-MLP and f-met cause neutrophil to move towards these signals
Diapedesis: passage of cell between endothelial cells into underlying connective tissue
Margination: ex. Neutrophil attachment to inner vessel wall by binding selectin
binding increases increases calcium cascades inside endothelium
Neutrophils integrins bind ICAMS to increase adhesion so can slow down to enter space
between endothelial cells
Movement across cell wall:
Focal adhesion sites where integrins of neutrophil bind to vessel wall
Thrombin and histaminereleased to increase permeability of endothelium
Act through CD31 that alters the cytoskeleton of the endothelial cells
Regulatory Mechanisms:
inside-out signaling change of conformation of integrins by phosphorylation
that decreases binding
Receptor alterations:change in number of receptors, change receptor conformation
Leukocyte Deficiency Disorder:
- rare autosomal disorder
- neutrophils not have adhesion molecules to follow chemotactic gradient to
infection
Type 1 LAD: cells not bind ICAM 1 on endothelial cells ecause cytoskeletal proteins not
active diapedesis not occur
Type II LAD: neutrophils do not express ligands for E or P selectins on endothelial cells
defect in cell rolling along vessel walls

Chapter Three Genetics

BLOCK 1 CORE CONCEPTS
THREAD: BIOCHEMISTRY & GENETICS
CONTRIBUTORS: ANN MARSHBURN, MEGHA PATEL, THERESA WILLIS & ANNIE WEYAND

TABLE OF CONTENTS:
MITOSIS
MEIOSIS
INTRO TO MEDICAL GENETICS
MEDICAL GENETICS II
MEDICAL GENETICS III
MEDICAL GENETICS IV
CYTOGENETICS I
CYTOGENETICS II

CARLOS BACINO
CARLOS BACINO
LORRAINE POTOCKI
LORRAINE POTOCKI
LORRAINE POTOCKI
LORRAINE POTOCKI
CARLOS BACINO
CARLOS BACINO

MITOSIS
Interphase
G1 machinery of cell prepares for division
S synthesis stage; DNA replication
G2 pre-mitosis; centrioles replicate
Mitosis
Prophase
Microtubule spindle forms
Chromatin condenses
Nuclear envelop disappears
Prometaphase
Chromosomes begin to migrate
MTs begin to contact kinetochores
Metaphase
Sister chromatids align at
metaphasic plate
Force on kinetochores from each
pole is equal and opposite
Anaphase
Sister chromatids separate
Chromosomes migrate to opposite
poles
Telophase
Nuclear envelop reassembles
Cytoplasmic MTs reassemble
Cytokinesis
Actin & myosin filaments make a
contractile ring around cell
Division occurs equidistant from
MT asters
Contractile ring disappears after
mitosis

CDK1 kinase
Protein that
signals mitosis
to begin
3 Classes of Microtubules
1. astral: form an aster around centrosomes
2. kinetochore: attaches to and directs chromosome
3. spindle: overlap at metaphasic plate to form a skeleton

cut2 and PDS1

Proteins that, when
degraded, signal
anaphase to begin

Anaphase Lag
An abnormal separation of
sister chromatids resulting in
abnormal # of chromosomes in
daughters

MEIOSIS
MEIOSIS: process of cell division in the maturation of sex cells
Summary: replication of DNA (diploid with 2 chromatids per chromosome, or 2n and 4c), recombination (or crossing over) between
homologues, followed by 2 divisions
Result: generation of haploid gametes genetically distinct from each other and from the original parent cell
Meiosis I: reduction division
Result: The number of chromosomes (and DNA content) are reduced to 1n, 2c
Sources of genetic diversity
1. genetic recombination, or crossing over, occurs during prophase I period and results in the actual physical exchange of portions of
chromosomes between maternally and paternally derived chromosomes of a homologous pair
2. independent assortment: resulting gamete has varying ratio of maternal and paternally- derived chromosomes; 2n different types of gametes
could be formed (where n is the haploid number of chromosomes)
Stages of Prophase in Meiosis I:
Leptotene: Chromosomes become visible
Zygotene: chromosome pairs with homolog into a synaptonemal complex
Pachytene: crossing over occurs
Diplotene: The homologues repel; joined only at the chiasmata.
Diakinesis: last stage of prophase I; crossing over has completed, nuclear envelope has completely disintegrated by this stage, centromeres
attach to spindle fibers, chromosomes condensed
Dictyotene: only in female meiosis; oocytes are frozen until puberty. Meiosis will be completed in the female only after fertilization with
sperm.
Meiosis II
Result: No DNA replication and DNA is reduced to 1n, 1c
OOGENESIS: process of egg formation
Result: mature ovum + 3 polar bodies
Steps:
1. Primary oocyte is frozen in Meiosis I until stimulated for ovulation in puberty
2. Completion of Meiosis I forms secondary oocyte + 1st polar body
3. Secondary oocyte immediately begins Meiosis II and freezes at metaphase II by cytostatic factor
4. Meiosis II completes upon fertilization to form mature ovum + polar body
Purpose of the asymmetric divisions: preserve the nutrient-rich cytoplasm necessary to sustain the egg until implantation into the uterus
SPERMATOGENESIS: process of spermatozoa formation
Result: 4 functional haploid spermatids which later (inside the seminiferous tubules) differentiate to produce highly motile sperm.
Differences from oogenesis: even divisions, meiosis begins at onset of puberty, process is continuous and never freezes
*greater number of cell divisions of the male germline before the gamete formation leads to higher mutation rate in males than in females.
FERTILIZATION
1. Capacitation: process that makes sperm capable of fusing to an egg; occurs as sperm migrate through the female reproductive tract
2. Binding of the sperm to the zona pellucida: induces the sperm to release digestive enzymes that enable the sperm to bore its way through; the
plasma membranes of the sperm and egg then fuse, and the sperm nucleus enters the egg cytoplasm
3. Digestive enzymes: modify the glycoprotein network of the zona pellucida so additional sperm are no longer able to bind to the egg
NONDISJUNCTION: Failure of a pair of homologues fail to separate (disjoin)
-In meiosis I, one daughter cell will have two of the chromosomes and the other will have none (2:0 segregation)
-In meiosis II, at fertilization (if the other gamete is normal), the conceptus ends up trisomic or monosomic.
-Trisomy 21, 18, 13 most common
-Frequency of trisomies increases with advancing maternal age

INTRODUCTION TO MEDICAL GENETICS

Selected Single Gene Disorders:
1. Achondroplasia (ACH) - most common type of dwarfism.
Autosomal Dominant, 1:26,000-40,000 births
Traits include average-sized trunk, short arms and legs, lumbar lordosis, normal
life span and intelligence.
Problems include compression of spinal cord and airway obstruction, apnea, and
hydrocephalus.
Gene: 2 mutations on FGFR3 in >99% of ACH patients
2. Cystic Fibrosis (CF) - most common Autosomal Recessive disease in Caucasians.
(1:25 are carriers of 1 copy of the gene)
Autosomal Recessive, 1:2,500 births
Most common fatal genetic disease in US today.
Problems include thick, sticky mucus that clogs lungs, infections, obstruction of
pancreas.
Gene: CFTR (Na, Cl transporter), hundreds of mutations in this gene that lead to
the disease
3. Sickle Cell Disease (SC) - most common inherited blood disorder in the US
Autosomal Recessive, 1:500 African Americans have the disease, 1:12 are
carriers
Disorder of hemoglobin resulting in anemia, sickling crisis, risk of infection and
organ damage.
Gene-Beta Hemoglobin, mutation causes structurally abnormal Hb, called HbS.
(Substitution of valine for glutamic acid)
4. Breast Cancer - 2nd major cause of cancer death in American women.
Genes - BRCA1 on chromosome 17 and BRCA2 on Chromosome 13
Mutations on these 2 genes leads to increased risk of developing breast and/or
ovarian cancer.
These genes are thought to participate in repair of radiation-induced breaks in
DNA strands and the mutations are thought to disable the mechanism.
Treatment includes careful monitoring and possibly drug or surgical therapies.

GENETICS II, III & IV

Autosomal Dominant

Features of Transmission
Single allele is sufficient
Vertical transmission patterns, with
male-to-male transmission possible
Number of affected males and females
in population will be roughly equal
Affected children born to non-affected
parents may be explained by
o differences in penetrance
o variability of expression
o new mutation in either the
germ line or in somatic cells of
the embryo
o gonadal mosaicism.

Representative Syndromes
Achondroplasia
o Characterized by short stature, averagesized trunk, short arms and legs, and a
slightly enlarged head with a prominent
forehead.
o 100% penetrance at birth
o 80-90% are new mutations
o Caused by mutation in the FGFR3 gene.
Marfan Syndrome
o Characterized by tall, thin body habitus,
long fingers, extensible joints, aortic root
dilation, floppy heart valves, and dislocated
ocular lenses
o 50% are new mutations
o Caused by mutation in the fibrillin gene.
Huntington Disease
o Characterized by abnormal body movement
(chorea), loss of cognitive skills, and
psychiatric disturbances.
o Disease is progressive and fatal.
o Example of age-dependant penetrance.
Affected individuals are normal through the
first several decades of life, but disease
shows 100% penetrance by age 65.
Neurofibromatosis Type 1
o Characterized by tumor growth along
peripheral nerves, patches of brown
pigment on the skin, bone deformities, and
learning disabilities
o 50% caused by new mutations
o Wide variability of expression

Autosomal Recessive
X-Linked Dominant

Two mutant alleles required, so both

parents of affected child are
considered obligate carriers
Horizontal pattern of affected
individuals, often with unaffected
parents
New mutations are very rare
Number of affected males roughly
equals number of affected females
Consanguinity increases risk
Majority of inborn errors of
metabolism are AR conditions

Cystic Fibrosis
o Characterized by chronic infections,
progressive lung damage and loss of
functional lung tissue, failure to produce
adequate pancreatic digestive enzymes, and
progressive loss of pancreatic function
o Most common AR condition in Caucasian
population
o Caused by mutation in CFTR gene.
Tay-Sachs disease
Gaucher disease
Hereditary Hemochromatosis
B-thalassemia
Phenylketonuria
Sickle Cell

No male-to-male transmission
Generally more severe in hemizygous
males than in heterozygous females
One X-chromosome in each somatic
cell in a female undergoes random
inactivation, causing females to be
functional mosaics
In some disorders, inheritance of the
mutant gene causes prenatal lethality
in hemizygous males
A new mutation can give rise to
observable phenotype in both males
and females

Incontinentia Pigmenti
X-Linked Hypophospatemic Rickets

X-Linked Recessive
Mitochondrial
Multifactorial

No male-to-male transmission
Almost all affected individuals are
male
Females are obligate carriers if they
bear more than one affected offspring,
bear one affected offspring and have a
male relatives with the same condition,
or are the offspring of an affected male
New mutations only give rise to
observable phenotypes in the male

Duchenne and Becker Muscular Dystrophies

o Caused by mutations in the dystrophin gene
o Duchenne is considerably more severe
o Characterized by ongoing muscle cell
degeneration, which leads to elevated levels
of CPK
Fragile X Syndrome
o Most common inherited cause of mental
retardation
o In families with fragile X syndrome, males
in later generations are more likely to be
affected -- anticipation
Hemophilia A

Very wide variety in expression

Exclusively maternal inheritance

LHON
MELAS
MERRF
NARP
Keams-Sayre Syndrome

Refers to genetic traits or disorders

determined by combinations of
multiple genes and their interactions
with the environment and other factors
such as DNA methylation
Although these disorders are obviously
familial, there is no distinct pattern of
inheritance within a single family

Neural tube defects

Isolated cleft lip or cleft palate
Pyloric stenosis
Congenital heart defects
Coronary heart disease
Insulin dependent diabetes
Schizophrenia
Autism

CYTOGENETICS I
Overview:
Chromosomal abnormalities are more common than generally thought. They are present
in over 50% of 1st trimester abortions and 7-10% of all clinically recognized pregnancies.
These abnormalities are either constitutional (arise before/at conception) or acquired (in
somatic cells after conception or birth). They are thought to play a key role in cancers.
Mature human cells contain 23 pairs of homologous chromosomes, 22 pairs of autosomes
and one pair of sex chromosomes.
-Chromatin: condensed packaging of DNA seen in nuclei at interphase.
-30,000-40,000 genes in humans, or about 3,000-4,000 genes per chromosome.
Features of Chromosomes:
Metaphase - chromosomes formed by 2 identical sister chromatids connected at a
centromere.
Dark and light bands obtained by G banding with trypsin

2 arms, p is the short arm, q is the long arm.

Metacentric - 2 arms same length
Submetacentric - one arm distinctly shorter
Acrocentric - very short p arms with specialized structure called a stalk. (stalks assoc.
during interphase, called Nucleolar Organizing Regions.
Satellites - distal to stalk, portions of highly repetitive DNA, no known coding sequence.
Telomeres - telomeres are tandemly repetitive telomeric units that cap the ends of
chromosomes. They play an essential role in the pairing of homologous chromosomes in
prophase of meiosis. TTAGGn=telomere sequence
Examples of karyotype shorthand:
46, XX Normal female
Trisomy 21 most common abnormality.
45, X Turner Syndrome
There are chromosomal abnormalities in 50% of stillbirths
47, XXY Klinefelter syndrome
47, XX, +21 Female with trisomy 21
46, XY, del(5p15.2) male with deletion on short arm of one chromosome 5 15.2 refers to bands and subbands
Clinical cytogenetics sample types: chromosomes can be studied from any cell actively
dividing and where a nucleus is present.
Bone Marrow - Rapid method for chromosome diagnosis. Used to diagnose newborns
with suspected lethal disorders and when leukemia is suspected. unstimulated
Peripheral Blood - Analyses on lymphocytes from small blood sample. Must be
stimulated to divide.
If unstimulated, used to study interphase cells

Fibroblast - Established from skin biopsy, abortus, or autopsy. Takes 1-2 weeks. Useful
when blood tests are normal and mosiacism is suspected.
Amniocentesis - Standard for prenatal diagnosis. Amniotic fluid collected at 16-18 weeks
gestation. Results take 10-14 days.
Chorionic Villus Sampling (CVS) - 1st trimester biopsy of placenta. 10-14 days, risk of
miscarriage is about 1.0%
Banding Methods:
Q Banding- Quinacrine is fluorescent and stains A-T rich sequences.
G-Banding- Most common stain in routine cytogenetics. Stain with Giemesa produces
alternate light and dark bands. GC rich=light bands, AT rich= dark bands
C-Banding- stains the constituitive heterochromatin darkly and euchromatin light. Used
mainly to stain the centromeres.
Fluorescence in situ hybridization (FISH)- application of a probe directly onto a
metaphase chromosome spread or interphase nucleus. DNA probe is labeled with reporter
molecule and detected with an antibody to that molecule. *Method of choice for detecting
microdeletion syndromes.
Probes:
Single copy/Locus specific probes
Sub-telomere-specific probes
Alphoid or centromeric repeat probes
Whole chromosome (painting) probes

G-banding
- Use phyohemaglutinin (PHA) to induce mitosis in T cells
- Colcemid, toxic to microtubules, to arrest division after 72 hours
- Hypotonic solution of KCl to swell nucleus
- Fix cells and stain with Giemsa

Euploidy: normal balanced set of chromosomes

Diploidy: normal number of chromosomes in a somatic cell (46 for humans)
Haploid: chromosome number in gametes
Aneuplodies: unbalanced number with missing or additional chromosomes (2n-1 or +1, such as trisomy 21)
Triploid: 3 haploid sets, can happen by
1. egg fertilized by 2 sperm
2. fertilization by diploid sperm
3. non disjunction in egg (associated with advanced maternal age)
Down's Syndrome Clinical Signs
- Single transverse crease on hand because hand does not move a lot in utero
- Sandal toe
- Heart and GI issues
Female with rob(14;21) Down syndrome- 21 is stuck on 14
Female carrier of rob(15;21)- normal because has one 21 and other is stuck on 15
Trisomy 13 Clinical Signs
- Holoprosencephaly- left and right brain does not separate
- Small eyes
- Severe intellectual deficits
- Heart valve defects
- Iris coloboma

FISH- complementary stretch of DNA probe is labeled and hybridized onto a cell.
Can be used to ID specific chromosomal regions that have been deleted or
duplicated

1. Generalized mosaicism
2. Confined placental mosaicism
3. Fetal mosaicism

CYTOGENETICS II

Numerical abnormalities - numerical errors due to nondisjunction include trisomies and monosomies. Other
errors include triploidy (69 chromosomes) and tetraploidy (92). Most polyploid conceptuses are
spontaneously aborted. Triploidy most often occurs when 1 normal egg is fertilized by 2 sperm. Tetraploidy
occurs through a post-zygotic error of DNA replication, duplicating all the chromosomes.
Mosaicism- resulting mixture of two or more cell lines in an individual that occurs very early in embryonic
or pre-embryonic life. - When an individual has 2 or more cell populations with a different chromosomal makeup
- Happens after fertilization. One cell divides normally but another has nondisjunction or something

Ex:
45X/46XX
Mosaic female with normal cell line and abnormal (45X) line.
46XY/47, XY, +21 Male with mosaic karyotype of a normal and trisomy 21 cell line.

Gonadal Mosaicism- also called germinal mosaicism, affects organs involved in meiosis: ovaries and testes.
Structural Chromosome Abnormalities:
Ring- deletion of
terminal short and
long arm and
unstable ends join

Terminal Deletions- result from one break in one chromosome arm. Segment containing the centromere is
replicated and passed on to daughter cells. Accentric fragment is lost. Most common is the 5p- syndrome,
cri-du-chat. 46,XX,del(4)(p15.2)=Wolf Hirschhorn Syndrome
Interstitial Deletions- 2 breaks in one chromosome arm. Accentric fragment between the two arms is lost.
sticky ends rejoin. Includes Prader-Willi, DiGeorge, Williams, and Smith-Magenis syndromes.
22q11.2- DiGeorge- heart disease, prominent nose, long fingers, learning difficulties, cleft palate

Reciprocal Translocations- 2 breaks occur in 2 different chromosomes at the same time. Broken ends
exchange and rejoin and no material is lost. This is a balanced rearrangement. However, individuals are at
risk or producing abnormal gametes through segregation errors during meiosis.
Robertsonian Translocations- form between 2 acrocentric chromosomes (13, 14, 15, 21 & 22) Breaks occur
in the short arm and the long arms fuse, forming a stable dicentric chromosome. Accentric fragments are
lost. No phenotypic affect to losing the short arms. However, carriers are again at risk of abnormal
segregation at meiosis. 5% of Downs cases are due to a Robertsonian Translocation.
Inversions- form from 2 breaks in one chromosome. The piece between the breaks inverts and rejoins, thus
a balanced rearrangement. During meiosis, however, a loop structure forms to accommodate the inverted
segment, which may result in abnormalities if recombination occurs within the loop.
1-Paracentric inversion- inverted segment does not span centromere. (within one arm) Abnormalities from
recombination result in dicentric and acentric chromosomes, which do not produce viable offspring.
Dicentric and acentric made during crossing over

2-Pericentric inversion- inverted segment spans and often displaces the centromere. Recombination results
in deletions and duplications
Cryptic chromosome abnormalities- submicroscopic subtelomeric chromosome defects found in 7.4% of
children with moderate to severe mental retardation and in .5% of children with mild MR. Many of these
families have a positive history for MR and early pregnancy losses.
CHIP technology- Looking at small chromosomal regions and performing thousands of FISH assays at
once to detect chromosome imbalances in one single experiment. Allows analysis of chromosome material
at the 1-3 megabase level. Rapid testing for detecting trisomy 13, 18 and 21
Williams Beuren Syndrome- Interstitial deletion of 7q11.23- cardiovascular disease (stenosis), hypercalcemia, lack of elastin gene, over friendly

- 3 or more miscarriages can be indication for

chromosomal analysis

Normal Chromosome
Microarray Results

- Microarray process- compare genomic DNA to control DNA. Produces an array profile
- Should be +- 0.2
- Abnormalities are +-0.6

- The basic assumption of a CGH experiment is that the ratio of the binding of test and control DNA is proportional to the ratio of the concentrations of sequences in the two samples.
- Y axis is log of the ratio
Limits of Microarray Technology
- Can not detect balanced rearrangements, only deletions/insertions
- Does not provide info on location of additional copy
- Copy # variations may be pathogenic or not

Chapter Four General Histology

BLOCK 1 CORE CONCEPTS
THREAD: CELL BIOLOGY/HISTOLOGY
CONTRIBUTORS: KATHARINE JONES, WALTER QUIROGA, VIKRAM SHENOY & GABRIEL DE
LA GARZA

TABLE OF CONTENTS:
SKIN I
SKIN II
CONNECTIVE TISSUE
CARTILAGE & ADIPOSE
BONE I
BONE II
JOINTS
IMMUNE SYSTEM I
IMMUNE SYSTEM II

SKIN I AND II
Six Functions of Skin:
1) Barrier
2) Sensory Organ
3) Thermoregulation
4) UV Protection
5) Immune (SALT: Skin Associated Lymphoid Tissue)
6) Sexuality (Apocrine and sebaceous glands in dermis secrete pheromones)
Three Layers of Skin:
1) Epidermis: epithelial layer resting on basement membrane
A) Thick skinnon hairy with very thick epidermis
B) Thin skinhairy with thin epidermis
2) Dermis: papilla project into epidermis to keep layers from sliding past each other,
capillary beds, Meissners corpuscles
A) Lower dermisdense irregular connective tissue
B) Upper dermisloose connective tissue housing ecrine, apocrine and
sebaceous glands
3) Hypodermis: dense irregular connective tissue with fat, Pacinian corpuscles
Five Layers of the Epidermis:
1) Stratum Basale: Contacts basement membrane, consists of keratinocytes=STEM
CELLS, mitotically active, desmosomes hold keratinocytes together,
hemidesmosomes and focal contacts hold keratinocytes to basement membrane
2) Stratum Spinosum:
A. Tons of DESMOSOMES for strong cohesion and barrier against friction,
gives characteristic spiny appearance
B. Filaggrin bundles intermediate filaments (cytokeratincalled
tonofilaments in skin) into tonofibrils
C. Mitotic in that some cells may divide to produce more spinosum cells
3) Stratum Granulosum: WATER BARRIER through Odland bodies containing
phospholipids of skins water barrier, keratinohyalin formed into characteristic
GRANULES of this layer
4) Stratum Lucidum: Cannot see histologically, LYSOZYMES BURST, nucleus
and organelles dissolve, keratohyalin cements tonofibril bundles together,
desmosomes still intact
5) Stratum Corneum: layer of DEAD keratinocytes
A. stratum compactumstill desmosomes
B. stratum disjunctumupper most layer, no more desmosomes,
desqamation (stem cell to desquamation = 30 days)
Types of Secretion:
1) Merocrine: exocytosis into extracellular space
2) Apocrine: apical portion of cell ruptures but cell anneals and lives
3) Holocrine: cell death in secretion

Three Glands in Skin:

1) Sebaceous glands: acinar, NO lumen, secrete lipid pheromones by holocrine
secretion, no myoepithelial cells, associate with every hair follicle and also
without hair follicles in lips, glans penis, glans clitoris, areola of breasts, glands
develop at puberty
2) Apocrine glands: coiled tubular (simple cuboidal or columnar), LARGE lumen,
secrete proteinaceous pheromones by merocrine secretion, stratified cuboidal
duct, myoepithelial cells, always associated with hair follicles but are only in
circumanal region, genitalia, areola of breasts, axillae, develop at puberty
3) Ecrine glands: coiled tubular, SMALL lumen, light cells=ion pumpers, dark
cells=secrete mucous by merocrine secretion, stratified cuboidal duct (basophilic),
myoepithelial cells, important for thermoregulation
Three Non-keratinocytes in Epidermis:
1) Merkel cell: sensory function
2) Melanocyte: NEURAL CREST ORIGIN!!, vimentin positive
3) Langerhans cell: MONOCYTE ORIGIN!!, vimentin positive
**Pathology of Epidermis**
Pemphigus (loss of adhesion between cells), Bullous pemphigus (loss of adhesion with
basement membrane), Psoriasis (thickening of skin and subsequent cracking down to
dermis), Squamous cell carcinoma, Basal cell carcinoma (neither are very invasive due to
cell-cell junctions), Melanoma (extremely invasive because no cell-cell contacts)

CONNECTIVE TISSUE
The 3 components of Connective Tissue (CT): cells, fibers, and ground substance.
Extracellular Matrix (ECM)
C
E
L
L
S

Fibroblasts- synthesize the fibers (collagen, elastin) and ground substance (GAGs, proteoglycans, multiadhesive
proteins) of the ECM. Also produce growth factors.
Macrophages- are mature monocytes in the CT, which came from hematopoietic stem cells. Participate in
phagocytosis, antigen-presentation, resistance to infections and tumors
Mast Cells- stores chemical mediators (histamine [vsdln, bronchocxn], heparin [anticoagulates w/antithrombin],
eosinophil chemotactic factor of anaphylaxis) of inflammatory response in basophilic secretory granules.
99.998% of IgE (from plasma cells) is bound to mast cell surface receptors and blood basophils. 2 populations:
CT mast cells (skin, peritoneum) & mucosal mast cell (intestinal mucosa, lungs)
Plasma Cells- come from B lymphocytes and synthesize antibodies.
Adipose- store fat and produce heat
Leukocytes- cross capillary walls from blood by diapedesis during inflammatory response (mediated by mast
cells and basophils). None return to blood, EXCEPT for lymphocytes.

F
I
B
E
R
S

Collagen- strength/organize ECM; generally found either as tropocollagen filaments < fibrils < fibers < bundles.
A) Collagens forming Long Fibrils (aka Collagen Fibers) forms bones, dentin, tendons, organ capsules, and
dermis. Type 1 most abundant throughout body (point mutation leads to osteogenesis imperfecta); Type 2
unique to cartilage; Type 3 forms reticular fibers. (Types 1, 2, 3, 5, & 11)
B) Fibril-associated Collagens short collagens attaching collagen fibrils to each
other and ECM. (Types
9, 12, & 14)
C) Network-forming Collagen forms meshwork unique to lamina densa of basal lamina. (Type 4)
D) Collagen forming Anchoring Fibrils anchors collagen fibers to basal lamina, e.g. hold epidermis (stratum
basale) to dermis (lamina reticularis). (Type 7)
Collagen Synthesis
1) 1, 2 chain translation into RER (preprocollagen signal cleavage procollagen)
2) Hydroxylation of proline & lysine (Vit. C dependent, lack of it leads to scurvy)
3) Glycosylation of hydroxylysine
4) Triple helix assembly of procollagens ( 1, 1, 2) with registration peptides
5) Packaging and glycosylation in Golgi and eventual exocytosis into extracellular space
6) Procollagen registration peptide removal (at N- & C-termini) turns it into tropocollagen, which
self assembles into polymeric collagen fibrils and fibers (fibril aggregates)
Elastin- gives ECM resilience, stretches w/ tension, made of elastin & fibrillin, hydrolyzed by elastase, and
mutation in elastin gene causes Marfan syndrome.

G
R
O
U
N
D
S.

Ground Substance highly hydrated mix of GAGs, proteoglycans, and multiadhesive glycoproteins. Fills space
b/w cells & fibers, has regulatory functions, acts as adhesive, lubricates, and is barrier to invaders.
GAGs linear, unbranched polymer of dissacharide units that are very hydrated and negatively charged; 5 types
Proteoglycans GAGs bonded to a protein core; proteoglycans attached to hyaluronic acid chain form
proteoglycan aggregates, such as aggrecan in cartilage.
Multiadhesive Glycoproteins protein w/branched carbohydrate moiety; have role in cellular adhesion.
A) Fibronectin made chiefly by fibroblasts, has binding cites for cells, collagen, and GAGs.
B) Laminin participates in adhesion of epithelial cells to basal lamina, which is rich in laminin.
*Cells use integrin to bind to collagen, fibronection & laminin extracellularly and with actin intracellularly
THREE
Loose (Areolar) CT
Lots of cells
Vascular
Small Type I bundles in random
Stroma
Dense, regular CT
Few cells
Avascular
Large Type I bundles in parallel
Tendons
MAJOR
Dense, irregular CT
Few cells
Vascular
Large Type I bundles in random
Perichondrium, periosteum,
TYPES
epineurium, epimysium
OF CT

CARTILAGE & ADIPOSE

CARTILAGE 1) Dense, irregular CT perichondrium sheath provides vascularity,
innervation, & lymph drainage.
2) Perichondrium has Type I collagen, fibroblasts, & chondroblasts.
3) Chondroblasts secrete collagen & ECM and become chondrocytes,
which may divide into isogenous groups and use anaerobic
glycolysis. Chondrocytes receive nutrients from perichondrium by
diffusion and mechanical compression of tissue.
4) Articular cartilage at ends of bones is sustained by synovial fluid,
NOT perichondrium.
5) Growth by 2 processes: interstitial growth (mitotic division of
preexisting chondrocytes, important in articular cartilage) &
appositional growth (differentiation of perichondrial cells, more
important of the two).
Type
Hyaline

Elastic
Fibrocartilage
(intermediate b/w
dense CT &
hyaline)

Characteristics
Chondrocytes arranged
in groups within
basophilic matrix of
Type II collagen
Chondrocytes within
matrix of Type II
collagen & elastic fibers.
Chondrocytes arranged
in rows in acidophilic
matrix of Type I
collagen bundles in rows

Perichondrium
Present except
at articular
surfaces
Present
Absent

Locations
Articular ends of long
bones, ribs, templates for
endochondral bone
formation
Pinna of ear, auditory canal,
epiglottis, laryngeal
cartilages
Intervertebral discs, pubic
symphysis.

ADIPOSE 2 types
Unilocular Adipose (yellow fat) richly vascularized & innervated w/in reticular fiber network.
1) Stores liver-made triglycerides transported by VLDL and cholymicrons. Lipoprotein lipase
(activated by insulin) releases FFA & glycerol for diffusion across capillary into adipocyte, where
they are re-esterified to triglycerides.
2) Sympathetic NS indirectly innervates adipose tissue by releasing norepinephrine, which
stimulates AC & cAMP to activate hormone-sensitive lipase. This hydrolizes TGs into FFA &
glycerol, which are transported back to the liver.
Multilocular Adipose (brown fat) color due to capillaries and mitochondria
1) Important in first months of postnatal life b/c it produces heat through norepinephrine stimulation
and thermogenin (ATP uncoupler) in mitochondria.
2) Sympathetic NS directly innervates this tissue.

BONE I & II AND JOINTS

Types of bone
-Woven/primary(embryonic) Random collagen I fibers
- First bone formed in development, fracture
repair and disease(padgets, bone cancer)
- Lamellar/secondary (adult) Parallel collagen I fibers
(woven bone is remodeled into Lamellar)
____________________________________________________
-Cortical / compact bone high density
-Trabecular / spongy / cancellous bone Inner meshwork
of bone struts.
- histologically both have same structure

Haversian system/osteon- complex of concentric lamellae surrounding

haversian canal. Adjacent lamellae have collagen
fibers perpendicular to each other.
- Outer(near periosteum), Inner(around marrow cavity)
and Interstitial (older lamellae after remodeling)
lamellae
- Volkmanns canal- perforate the lamellae- lined with
endosteum. Link haversian canals, periosteum and
marrow cavity.

Cell Types Osteoblasts deposition.inhibited by PTH, vit. D needed for synth.

of osteoid glycoproteins, vit. C needed for
collagen I synth.
- Osteocytes- found in lacunae.
Was previously an osteoblast,
canaliculi connect adjacent
lacunae. Osteocyte cell
processes traverse canaliculi.
- Osteoclasts resorption of
bone. Multinucleated,
monocyte origin. Found in
howships lacuna. PTH acts
on osteoblast which
stimulates osteoclast.
Calcitonin inhibits indirectly.
- Osteoprogenitor cell Becomes
osteoblast on activation. Lining cell found
on endosteum (internal lining) or
periosteum (external lining). Bundles of
periosteal collagen fibers Sharpeys
fibers.

HistongenesisIntramembranous ossification
- Source of flat bones, frontal & parietal bones, mandible, maxilla
- Takes places within condensations of mesenchymal tissue in regions called primary ossification
center. Cells differentiate into osteoblasts. Multiple ossification centers grow radially and fuse.
Endochondral ossification
- Forms long and short bones
- Takes place within hyaline cartilage that resembles bone to be formed. Bone collar is formed first.
- Primary ossification centers in the diaphysis, after bone collar is formed and blood vessels
penetrate.
- Secondary ossification centers- In the epiphyses
Epiphyseal cartilage (or plate) connects epiphyses to diaphysis divided into 5 zones
1- Resting Zone, 2- Proliferative zone, 3- Hypertrophic cartilage zone, 4- calcified cartilage zone, 5ossification zone. (refer fig. 8-16 in junq)
Joints
1- Diarthroses - Allows movement.
- capsule and articular cavity.- synovial membrane, articular cartilage
- synovial fluid- hyaluronic acid from cell of synovial layer.
- fluid serves for exhange of nutrients and o2 and co2
- Negative charges of GAGs help bring H2O back in on release of pressure from joint.
2- Synarthroses no movt. or very little.
i- Synostosis- bones united by bone tissue- skull bones are typical
ii- Synchondrosis- Bones united by cartilage- hyaline type. Eg- Epiphyseal plate, rib to sternum
iii- Syndesmosis- Bones joined by dense connective tissue ligament- symphysis pubis.
3- Amphiarthroses- Intervertebral disc.

IMMUNE SYSTEM 1 AND 2

Reaction types
Innate mechanisms
o barriers, mucous, protease inhibitors, etc.
Adaptive mechanisms
o programmed cells with memory
Two types of tissues
Primary lymphoid tissues-where immune cells are made and programmed
o Bone marrow and Thymus
Secondary lymphoid tissues- where the immune response takes place
o Lymph nodes, Spleen, Tonsils and diffuse lymphoid tissue
Two Functional Divisions
Cellular Immunity Division
o Programmed cells directly kill abnormal cells
Humoral Immunity Division
o Circulating antibodies, the cells that produce them and the cells that respond to
them
Antibodies
Antibody - circulating glycoproteins that recognize and interact with specific antigens, binding to the epitope of the antigen on its Fab region and binds
an immune cell at the Fc region
Class

IgM

Morphol.

General Function

Made By

Location

Fc Region Binds
To

Misc

pentamer

Activates complement system, a 20

plasma P system that stim other N,
giving rise to sets of P that opsonize
(coat the outside of the pathogen)
causing recognition by phagocytes and
direct lysis

plasma cells

soluble in plasma
and in the B
lymphocyte
membrane

Stuff that will

activate the
complement
system

1st class secreted into

the blood in an immune
resp.

plasma cells

blood, lymph,
intestinal lumen

Macrophages and
neutrophils

Major class in blood

(75-80% of blood
antibody)
only class that can
pass to fetus via
placenta
also in breast milk

Agglutinates antigens/pathogens to
prevent access to body (protects
mucosas from proteosysis)

plasma cells

secretions
(including
breastmilk)
released in lamina
propria, transported
across secretory
epithelium

pathogens

principle class in
secretions

monomer

Activates mast cells and basophils to

trigger cytokine, histamine and heparin
release. Activates eosinophils in
response to a parasitic infection

plasma cells

Bound on cell
surface

Mast cells,
Basophils,
Eosinophils

causes allergies

monomer

Receptor to antigens triggering B cell

activation

plasma cells

surface of B
lymphocytes

IgG

monomer

IgA

dimer bound
by protein J
which also
aids
secretion

IgE

IgD

Mainly stim. phagocytosis (make

phagocytosis more appealing) by/to
macphg and neutrophils but also aids
activation of complement system

expressed
only expressed on
developmentally after
cell surface
IgM on mature B cells

T lymphocytes - Develop and are selected in the thymus. They mediate cellular and cytotoxic immunity. T cells have cell surface receptors that recog antigen bound on a cell
surface to a MHC complex of proteins. Also aid in the proliferation of other B and T lymphocytes to stimulate the humoral response

Cell

Function

Activated By

Cytotoxic T cells
(CD8+)

kill infected cells or cells

expressing abnormal P
by damaging the M with
perforin

contact with an
abnormal cell
expressing MHC I

Cells of the Immune System

Activation Causes
clonal expansion of
other cytotoxic T cells,
cytotoxic memory T
lymphocytes, and
perforin production

secretes cytokines
(interleukins) and
Antigens bound to MHC clonal expansion of
growth factors to
II class of surface P on Helper T, retainment of
Helper T cells (CD4+) modulate the activity
memory CD4+ and
APCs (Dendritic cells
of and aid in clonal
and Langerhans cells) production of cytokines
expansion of other T
and B lymphocytes
Clonal expansion and
Antigens that bind to
differentiation into
mediate the humoral
their IgM or IgD
plasma cells (which
B Lymphocytes
response and ssecrete
receotors, cytokines
secrete lots of
circulating antibodies secreted by Helper T in
antibodies) and retain
a close proximity
some as memory B
kill viral infected and
Fc region of IgG
release of perforins to
Natural Killer
cancer cells in a
antibodies (and a lack of cause apoptosis and
Lymphocytes
nonspecific manner
MHC I)
lysis
phagocytosis and lysis
phagocytosis and lysis
pathogen coated with
Macrophages
of pathogens coated by
of pathogens coated
IgG or complement P
IgG
ingest and destroy
pathogen coated with
ingest and destroy
Neutrophils
bacteria
IgG or complement P
bacteria
Mast cells and
Basophils

mediate
allergy/inflammatory
responses

histamine and heparin

pathogen or allergen
specific to their surface release and release of
IgE
chemoattractants

Activates

B and T cells via

cytokine secreton

nothing

Origin

Misc

Bone Marrow

develop in the thymus

Bone Marrow

develop in the thymus

Bone Marrow

Cell surface has IgD

and IgM
some stick around as
memory cells

Bone Marrow
leave marrow as
monocytes and mature
in tissue
Bone Marrow

Bone Marrow

have IgE rec

LYMPH TISSUES
Thymus - primary lymph tissue
Cortextight tight tight blood-thymus barrier
o consists of
endothelial cells and their basal
lamina
epithelial reticular cells and their
basal lamina
fibroblasts and ECM
o enables proper programming of T cells
programming of T cellso positive selection for recognition of
MHC complex
o negative selection for recognition of self
o 90% removed, remaining 10% move to medulla and exit via vasculature
Medulla
epithelial reticular cells
o highly branched w/ desmosomes
o provide lattice for developing T cells
o remnants form Hassalls Corpuscles
Lymph Nodes - secondary lipoid tissue
contain B lymphocytes, T lymphocytes, Plasma
cells, and macrophages
Secondary nodules contain germinal centers w/
developing B lymphocytes
Lympocytes enter through High Endothelial
Venules (HEV)
Lymph Vessels
very leaky vessels with one-way valves

Spleen secondary lymphoid tissue

APCs, macrophages, reticular cells, lymphocytes
Blood enters open circulation via PALS in white pulp, traverses red pulp (Billroths
cords) and exits into closed circulation
Note White pulp actually more basophilic, contains more red than red pulp
Also responsible for destruction of old red blood cells
o Iron-free heme is metabolized to bilirubin

MALT Tonsils: secondary lymphoid tissue

Skin: Langerhans, macrophages, lymphocytes, tight junctions
Colon: Peyers patches
Respiratory:
Immune System Components 2004 (Rowley)
Legend:
= antigen

= antibody

Memory T CD 4+ cells

= major histocompatability
complex
final result

Helper
CD 4+
T lymphocyte

Study Guide

= T cell receptor
Plasma Cell

interleukins
= cytokines

Cytotoxic
CD 8+
T lymphocyte
interleukins

+
+

clock face nucleus

secretes antibodies

Memory T CD8+ cells

proliferation
proliferation
proliferation
IgA

+ complement
system

IgG

+ macrophage,
neutrophil

agglutinates antigen
(secretions)
B lymphocyte

IgE
+ mast cells,
basophils

removes
antigen

TCR

Release of histamine,
IgM
heparin, chemotatic factors

protease cascade

CD 8+
T lymphocyte

TCR

IgD
MHC-II

phagocytosis
of antigen, cell
protease destroys
antigen, cell

vessel dilation and

vascular permeability
Inflamation to bring in
more components
Dendritic Follicular Cell
(in lymph node)

Dendritic Antigen Presenting Cell

(found everywhere)
mononuclear phagocyte system

kills the presenting cell

IgM

CD 4+
T lymphocyte

secrete perforins

Memory
B cells

MHC-I

All nucleated cells

Chapter Five Muscle

BLOCK ONE CORE CONCEPTS
THREAD: CELL BIOLOGY/HISTOLOGY
CONTRIBUTORS: AMIT SINGH & SAMIT SONI

TABLE OF CONTENTS:
MUSCLE STRUCTURE I
MUSCLE STRUCTURE II
MUSCLE FUNCTION I
MUSCLE FUNCTION II
MUSCLE FUNCTION III

MUSCLE STRUCTURE & FUNCTION

General
Nuclei
Cells Present
Junctions

Skeletal
long cylinder, register, 2 peripheral nuclei
epi,peri,endomysium, 2% mito, No lipid
droplets, collagen type I, III, IV
many peripherally located
satellite, fibroblast, myofiber, endothelial
myofibroblast
focal contacts @ terminal z line

Force

post mitotic; limited w/ help of satellite cells

no hyperplasia
focal contact ECM

IF
Proteins
excluding Ca++
regulation

Desmin
-actinin (Z line), actin, myosin, tropomyosin,
troponin, dystrophin, nebulin, titin, cap z,
creatine phosphate (M line), integrin

Innervation

neuromuscular jxn; motor unit=neuron+

fibers; triad @ A-I jxn

Regeneration

Cardiac
boxcar, register, no epi/perimysium, lipid
droplets, 40% mito, 1-2 central nuclei,
collagen type I, III, IV
1-2 centrally located, with halos
myofibers, endothelial, myofibroblast, fibroblast
desmosomes, adherent jxns in transverse portion & gap
jxn in lateral portion (intercalated disc)
post mitotic No regeneration

Smooth
fusiform, 1 central nucleus, RER, mito,
golgi, vesicles, ECM: collagen type I, III, IV
No striations
1 centrally located
myofibers, endothelial, myofibroblast, fibroblast
focal contacts (focal densities @ membr)
gap jxn
mitotic active regeneration, hyperplasia

intercalated disc (cell-cell)

focal contacts (in all directions) ECM

Desmin
-actinin, actin, myosin, tropomyosin,
troponin, vinculin, integrin, cadherins,
connexins, titin, cap z, creatine phosphate
NO: nebulin actin ( 1 micron avg )
varicosities (NT diffuses to pacer unit),
Diad @ z line

Desmin
NO: nebulin, titin, cap z, troponin
YES: isofroms of tropomyosin, caldesmon,
-actinin, actin, myosin, vinculin,
connexins, integrins
unitary: as one unit, few varicosities (ex:
uterus, bladder)

type I- red: lots of mito & myoglobin (for marathons)

multiunit: tremendous specificity, more

type II- white: little mito & NO myoglobin (for sprinters)

varicosities (ex: iris, blood vessels)

NT diffuses

Calcium Regulation:
SKELETAL:
- Here we have a TRIAD of T-tubule and terminal cisternae
at A-I junction
- Basically, two proteins here, Dihydropyridine and
Ryanodine
- What happens:
1. Get a depolarization that travels down T-Tubule System
2. Causes a conformational change in dihydropyridine
which will
3. Physically pry open ryanodine1 receptor located on
Sarcoplasmic Reticulum membrane
4. Calcium (which was bound to Calsequestrin) is released
through the Ryanodine 1 receptor.
5. Once out, Calcium can bind to troponin C to do its thang
or Calcium can also cause Calcium induced Calcium
release by interacting with the Ryanodine 1 receptors
and opens them up to release Calcium from SR.
-How to get rid of it:
-Calcium can also come back into Sarcoplasmic
Reticulum via Calcium ATPase
TAKE HOME MESSAGE: ALL calcium in skeletal
muscle comes INTRACELLULARLY!

CARDIAC
- rememberhere we have a DIAD at Z line
- also, you have piss-poor Sarcoplasmic Reticulum
herewhy, you ask? Because the calcium here is mostly
EXTRACELLULAR so you dont need a GREAT
sarcoplasmic reticulum
- What happens:
1. Depolarization event travels through T-tubule
system
2. Causes a conformational change of
Dihydropyridine in T-Tubule which
opens it allowing extracellular Ca2+ to enter
3. Once in, Ca2+ will bind Troponin C and do
its thang
4. Calcium can also cause a small amount of
Calcium induced Calcium release from SR
via Ryanodine 2 but this is minimal and
serves as a boost.
- How to get rid of it:
- by way of Ca2+ ATPase in SR or
extracellularly

SMOOTH
- 3 ways to raising Ca2+ levels, 2 of them are from
extracellular sources, 1 is intracellular
Extracellular:
1. Mechanosensitive receptor (unique calcium mechanical
receptor) opens in response to stretching and allows
extracellular Ca2+ in
2. Voltage sensitive receptor in Caveloa; in response to
some electrical signal opens up and allows Ca2+ in
- once inside this calcium will cause Calcium Induced
Calcium Release from Ryanodine 3 receptors on
Sarcoplasmic Reticulum (nonpinocytotic)
Intracellular:
1. G-protein related: G-protein through signal transduction
will cause release of IP3 which can bind to Ryanodine 3
receptor on SR membrane (nonpinocytotic) and cause
Ca2+ induced Ca2+ release of intracellular calcium from
remnant SR.
How to get rid of it:
- use Ca2+ ATPase in SR, tiny vesicles, or Na/Ca cotransport channel on smooth muscle membrane

Chapter Six Nervous System

BLOCK 1 CORE CONCEPTS
THREAD: CELL BIOLOGY/HISTOLOGY
CONTRIBUTORS: CARRIE ESHELBRENNER, LUCIA LIFSCHITZ, MICHELLE PHILLIPS &
RENEA STRUM

TABLE OF CONTENTS:
INTRODUCTION TO NERVOUS SYSTEM
NERVOUS SYSTEM I
NERVOUS SYSTEM II
NERVOUS SYSTEM II
AUTONOMIC NERVOUS SYSTEM I
AUTONOMIC NERVOUS SYSTEM II

NERVOUS SYSTEM I-III

Embryonic Origin of Nervous System: ECTODERM (epithelial so has basal lamina)
Neural Plate (invaginates, becomes) Neural Groove
(pinches off to form) Neural Tube w/ tissue masses on both sides, the Neural Crest
(Neural Crest is surrounded by basement membrane that becomes the Glia Limitans)

Neural Tube:
Becomes BRAIN and SPINAL CORD hollow portion
central canal

ventricles of brain
spinal cord

NEURONS:
Motor = VENTRAL (neurofilament)
PREganglionic Autonomics (Para/Sympa) (neurofilament)
NEUROGLIA
Oligodendrocytes (GFAP)
Fibrous Astrocytesmostly WHITE matter (GFAP)
Protoplasmic Astrocytesmostly GREY matter (GFAP)
Ependymal cells (GFAP)
OTHER CELLS FOUND in CNS (INVADERS)
Microglia (monocyte invaders) (vimentin)
Endothelium (vascular invaders) (vimentin)
Perivascular Macrophages (invader) (vimentin)

Neural Crest:
Gives rise to PERIPHERAL NERVOUS SYSTEM and the MENINGES (lining of the
outer surface of the brain and spinal cord). People with defects in the neural crest will
suffer from Prader-Willi Syndrome.
NEURONS:
Sensory neurons = DORSAL (neurofilament)
POSTganglionic Autonomics (Para/Sympa) (neurofilament)
VIMENTIN POSITIVE CELLS
Schwann cells
Satellite cells around sensory somas in DORSAL root ganglion
Pia Cells (meningothelial cells)
Arachnoid cells
Dura
Melanocytes (skin pigmentation)

Odontoblasts (enamel formation)

Parts of a Neuron
Part

Dendrite
Soma/
Perikaryon
Myelinating
Cell

Dendrite

Nucleus
Axon
Hillock

Axon

Soma/Perikaryon
Synaptic
Terminal/
Bouton

Nucleus

Axon

Axon Hillock

Synaptic Terminal/Bouton
Actual photomicrograph of motor neuron (PT stain); Schematic
diagram of the ultrastructure of a neuron (see Junq 9-5 for labels)

Characteristics
Receive stimuli from the
environment, sensory cells, other
neurons; usually short; taper as
they subdivide
Contains nucleus and surrounding
cytoplasm, exclusive of cell
processes; Nissil bodies (RER);
Golgi around periphery of nucleus;
mitochondria scattered throughout;
increasing lipofuscan (residue that
builds up when lysozymes cannot
digest all of the material) with
aging; intermediate filament =
neurofilament
Large; circular; euchromatic; darkstaining nucleolus
Carries signal to target cell; most
neurons have only one; very long;
constant diameter; little branching;
diameter of axon to propagation
of action potential; may be
myelinated (see below)
Pyramidal shaped region where
axon originates; determines
diameter of axon
Can transmit a chemical or
electrical signal; contains synaptic
vesicles; numerous mitochondria;
types: (1) axodendritic (2)
axosomatic (3) axoaxonic

Structure of Axon
*Centrosome sits in axon hillock and gives rise to a bank of microtubules (10 microns) with + end pointing towards synapse
*Similar backs arise down the length of the axon; no MTOC
*Fast axonal transport moves proteins along microtubules
Anterograde kinesin motor 200 mm/day
Retrograde dynein motor 300 mm/day
*Slow axonal transport carries actin and tubulin molecules to bouton
Gel-sol transformation 1 mm/day enzyme gelsolin momentarily cleaves actin filaments-creates area of low viscosity

Types of Neurons
Bipolar Neurons:
One dendrite, one axon
Found in cochlear ganglia, vestibular ganglia, retina, olfactory mucosa
Interneurons
Multipolar Neurons:
More than two cell processes
Most neurons of the body
Motor efferents
Pseudounipolat Neurons:
Dendrite fused to axon (wave of depolarization bypasses soma)
Found in spinal ganglia and most cranial ganglia

Myelination
General Process:
Microtubule polymerization causes myelinating
cell to turn about the axon as lipid proliferates
E face fuses with E face to form intraperiod line
P face fuses with P face, squeezes cytoplasm
out, forms main dense line
Cytoplasm percolates through the myelin as
clefts of Schmidt-Lanterman link remnant
cytoplasm at rim of myelinating cell with that
along the axon/myelinating cell interface
(See Junq 9-30 for labels)

Myelinates
Origin
Intermediate Filament
Mitotic?
Number of Cells
Myelinated
Proteins of Fusion
Node of Ranvier
Basal Lamina?

Oligodendrocyte
CNS
Neural tube
GFAP
Yes
Myelinates many axons
simultaneously
MBP (myelin basic protein) and
PLP (proteolipid protein)
No extra covering (no need for
one because these axons are
within the BBB)
No (difficult to regenerate axon)

Schwann Cell
Peripheral nervous system
Neural Crest
Vimentin
Yes
Myelinates only one neron
PO and PP-22
Schwann cells send out
paranodal processes to protect
the nodes
Yes-secreted by Schwann cells
(allows for axonal regeneration)

AUTONOMIC NERVOUS SYSTEM I & II

INTRODUCTION TO EMBRYOLOGY
Week 1: Fertilization

Blastocyst

Fertilization occurs in the ampullary region of the

fallopian tube
Capacitation: sperm conditioning, enters zona
radiata
Acrosome reaction: protein rxn after binding
zona pellucida
Fusion: sperm + oocyte
Cell divides, decreasing on size (blastomere) until
reach 16 cells (morula)
Morula travels to the uterus, fluid enters the zona
pellucida and creates a cavity (blastocele) and the
morula becomes a blastocyst.
Embryoblast: Inner cells
Trophoblast: Outer cells
Blastocyst hatches from zona pellucida (ready to
implant)

Clinical Correlations
Pelvic Inflammatory Disease
STD (gonorrhea or
chlamydia)
Purulent infection in
fallopian tubes can cause
narrowing and prevent
migration of fertilized egg

Abnormal Implantation
Ectopic: Fallopian tube
Placental Previa: near cervix
(placenta will cover cervix)
Ovarian (rare)
Intra-abdominal (rare)

EARLY DEVELOPMENT
Week 2: The Week of Twos (Bilaminar Disc)

Clinical Correlations

Trophoblast differentiates into 2 layers

Cytotrophoblast: inner layer, proliferates
Syncytiotrophoblast: outer later, invades
endometrium and maternal capillarities and
makes HCG*

Hydatiform mole (benign) or

Choriocarcinoma (malignant)
Abnormal growth of
trophoblast without
embryonic tissue
Fusion sperm to anucleate
oocyte
High HCG (detected at Day
14)

Embryoblast differentiates into 2 layers

Hypoblast: next to blastocyst cavity
Epiblast: next to amniotic cavity
Extra-embryonic mesoderm from new yolk sac
cells from 2 layers
Extra-embryonic somatopleuric mesoderm:
next to cytotrophoblast and amnion

Extra-embryonic splanchnopleuric
mesoderm: next to yolk sac
Two cavities form as a result of new mesoderm
layers
Chorionic cavity: space between the
splanchnopleuric and somatopleuric extraembryonic mesoderm
Amniotic cavity: between epiblsat and extra-

embryonic somatopleuric mesoderm

Secondary (Definitive) Yolk Sac:
Hypoblast cells migrate along inside of exocoelomic
cavity (along primary yolk sac) and pinch it off
exocoelomic cysts

NEURULATION
Neurulation (begins on Day 18 thru Week 4)
Neural Plate: thickening of ectoderm (now called
neuroectoderm) induced by notochord. This IS Neurulation
Neural Folds: Elevation of neural plate edges and depression of
mid region (neural groove)
Neural tube: the edges to move towards the midline and fuse
(starts at the 5th somite and progresses cranially and caudally)
Neural crest cells: lateral border or crest of neural fold that
migrate away to give rise to a variety of cells
Crainial neural plate will become forebrain and midbrain
Caudal neural plate will become hindbrain and spinal cord but
needs Wnt-3a and FGF to activate
Tube remains open until the cranial neuropore closes at day 25
and the caudal neuropore closes at day 27 (final step of
neurulation!!)

Clinical Correlations

Failure of caudal neuropore to close:

Spina bifida
Spina bifida occulta (covered by
skin)
Failure of cranial neuropore to close:
Encephalocele
Anencephaly

Chapter 8 Anatomy & Radiology of the

Extremities
BLOCK 1 CORE CONCEPTS
THREAD: ANATOMY/EMBRYOLOGY/RADIOLOGY
CONTRIBUTORS: TRAVIS TAYLOR, EDWIN BUTLER, ROHAN WAGLE, BO ALLAIRE & RYAN BOECK

TABLE OF CONTENTS:
ANTERIOR CHEST WALL
POSTERIOR CHEST WALL
BRACHIAL PLEXUS
ARM
FOREARM
HAND
CLINICAL HAND

CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON
MICHAEL EPSTEIN

HIP
THIGH
LEG
FOOT
CASES OF THE KNEE

CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON
CASSIUS BORDELON

INTRO TO RADIOLOGY
RADIOLOGY UPPER EXTREMITY
RADIOLOGY LOWER EXTREMITY

ALFRED WATSON, JR.

ALFRED WATSON, JR.
ALFRED WATSON, JR.

Anterior Chest Wall

Muscle
Pec minor
Pec major

Innervation
Medial pec. n.
Lateral & medial pec n.

Major Action
Depression of glenoid
Adduction

Posterior Chest Wall

Muscle
Trapezius
Latissimus Dorsi
Teres major
Levator scapulae
Rhomboid major & minor

Innervation
CN XI
Subscapular n.
Subscapular n.
Dorsal scapular n.
Dorsal scapular n.

Major Action
Elevation of shoulders
Adduction
Adduction
Retraction of scapula
Retraction of scapula

Shoulder
Muscle
Innervation
Major Action
Serratus anterior
Long thoracic n.
Protraction of scapula
Deltoid
Axillary n.
Abduction of shoulder
Supraspinatus
Suprascapular n.
Abduction of shoulder
Infraspinatus
Suprascapular n.
External rotation
Teres minor
Axillary n.
External rotation
Subscapularis
Subscapular n.
Medial rotation
-Bursae: subdeltoid/subacromial allows the head of the humerus to slide under the deltoid and corachoacromial arch
-Ligaments: coracoacromial, coracoclavicular, costoclavicular

BRACHIAL PLEXUS
Proximal

Distal

Dorsal scapular
suprascapular

C5

Lateral pectoral

Musculocutaneous

C6

Axillary

C7

Radial
Median
subscapular

C8
Ulnar

T1

Long thoracic

Roots
(2 nerves)
Real

Trunks
(1 nerve)
Texans

Medial pectoral

Divisions
(0 nerves)
Drink

Cords
(3 nerves)
Cold

Branches
(5 nerves)
Beer

-Erbs palsy = tearing of C5

-Klumpkes palsy = tearing of T1
Arm
Muscle
Coracobrachialis
Biceps brachii

Innervation
Musculocutaneous n.
Musculocutaneous n.

Brachialis
Triceps

Musculocutaneous n.
Radial n.

Major Action
Adduction
Flexion of shoulder & elbow &
supination
Flexion of elbow
Extension of elbow

-Ligaments: Transverse humearal

-Quadrangular space: Axillary nerve & posterior humeral circumflex a.
-Triangular space: circumflex scapular a.
-RUM @ West Coast Tequila Univ.
Radial -> Wrist drop; Ulnar -> Claw hand; Median -> Thenar atrophy & Ulnar deviation

Proximal Arm
Subclavian
1) Transverse cervicle
2) Suprascapular

Distal Arm
Axillary
1) Lateral Thoracic
2) Subscapular
a. Thoracodorsal
b. Circumflex scapular
(in triangular space)
3) Anterior humeral circumflex
4) Posterior humeral circumflex

Brachial
1) Profunda brachial

Forearm
Muscle
Extensor carpi radialis longus
Extensor carpi radialis brevis
Extensor carpi ulnaris
Extensor digitorum communis
Extensor digiti minimi
Extensor indicus proprius
Extensor pollicis longus
Extensor pollicis brevis
Abductor pollicis longus
Suppinator
Flexor carpi radialis
Flexor carpi ulnaris

Extensors
Innervation
Radial n.
Radial n.
Radial n.
Radial n.
Radial n.
Radial n.
Radial n.
Radial n.
Radial n.
Radial n.
Flexors
Median n.
Median n.

Major Action
Extension of wrist
Extension of wrist
Extension of wrist
Extension of digits 2 -5
Extension of digit 5
Extension of digit 2
Extension of digit 1
Extension of digit 1
Abduction of digit 1
Supination of forearm
Flexion of wrist
Flexion of wrist

Palmaris longus
Flexor digitorum superficialis
Flexor digitorum profundus
Flexor pollicis longus
Pronator teres
Pronator quadratus

Median n.
Median n.
Median n. & ulnar n.
Median n.
Median n.
Median n.

Flexion of wrist
Flexion of digits 2 -5
Flexion of digits 2 -5
Flexion of digit 1
Pronation of forearm
Pronation of forearm

-Ligaments: Annular, medial collateral

-interosseus membrane: between radius and ulna

Hand
Muscle
Flexor pollicis brevis
Abductor pollicis brevis
Opponens pollicis
Adductor pollicis
Interossei
Lumbricals

Innervation
Median n.
Median n.
Median n.
Ulnar n.
Ulnar n.
Ulnar n. & Median n.

-carpal tunnel covered by flexor retinaculum

-palmar aponeurosis
-Bones of wrist mnemonic: Some Lovers Try Positions That They Cant Handle

Major Action
Flexion of digit 1
Abduction of digit 1
Opposition
Adduction of digit 1
Flex the MPs & extend IPs
Palmars = adduct (PAD), Dorsal =
abuct (DAB)

CLINICAL ANATOMY OF HAND

Brachial Plexus
Newborn
Erbs C5-6 (Shoulder dysfunction)
Klumpke C8-T1 (Horners sign) (Hand dysfunction)
Adult
Upper downward tx
Lower abduction
Shoulder Dislocation
Axillary nerve (no shoulder abduction)
Suprascapular nerve (Shoulder dysfunction)
Rotator Cuff
Ext. rotators (infraspinatus and teres minor)
Int. rotators (subscapularis)
Abduction (Supraspinatus)
Impingement Syndrome (Supraspinatus)
Biceps Rupture
Long head (elderly)
Distal insertion tears

no surgery
surgery

Parsonage-Turner
Acute brachial neuritis (caused by viral infection
nerves)

impairment of radial and median

Tennis Elbow
Lateral epicondylitis
- responds to steroid injection
Medial epicondylitis (responds to steroids)
RUM/WCTU
Radial Nerve: distal 1/3 humerus fracture can damage this unable to extend wrist
Median Nerve
Carpal Tunnel
- roof = transverse flexor retinaculum
- floor = carpal bones
- 9 tendons and median nerve
- syndrome numbness and tingling, thenar atrophy, weakness in grip
Anterior interosseous paralysis
- from anterior interosseous nerve that goes to pronator quadratus, thumb, and index
finger cant pinch finger to thumb

Hip
Muscle
Gluteus maximus
Gluteus medius
Gluteus minimus
Tensor fascia lata
Biceps femoris
Semitendinosus
Semimembranosus
Piriformis
Obturator internus
Quadratus femoris

Innervation
Inferior gluteal n.
Superior gluteal n.
Superior gluteal n.
Superior gluteal n.
Sciatic n.
Sciatic n.
Sciatic n.
Nerve to piriformis
Nerve to obturator internus
Nerve to quadratus femoris

Major Action
Extension of hip
Abduction
Abduction
Weak abduction
Flexes knee & extends hip
Flexes knee & extends hip
Flexes knee & extends hip
Weak external rotation of thigh
External rotation of thigh
External rotation of thigh

-Ligaments: sacrospinous, sacrotuberous, iliolumbar, iliofemoral (Y ligament of Bigalow), Transverse acetabular,

round ligament (ligamentum teres), retinacular ligaments (carry blood supply to head of femur)

Thigh
Muscle
Iliopsoas
Sartorius
Rectus femoris
Vastus lateralis
Vastus medialis
Vastus intermedius
Adductor magnus
Adductor brevis
Adductor longus
Gracilis
Pectineus

Anterior compartment
Innervation
Femoral n. & lumbar plexus
Femoral n.
Femoral n.
Femoral n.
Femoral n.
Femoral n.
Adductor compartment
Obturator n. & Sciatic n.
Obturator n.
Obturator n.
Obturator n.
Femoral n.

Major Action
Powerful flexion of hip
Flexion of hip & knee
Flexion of hip & Extension of knee
Extension of knee
Extension of knee
Extension of knee
Adduction of hip
Adduction of hip
Adduction of hip
Adduction of hip
Adduction of hip

-Pes anserina: Say Grace before Tea -> Sartorius, Gracilis, Semitendinosus
-femoral triangle: NAVEL -> Nerve, Artery, Vein, Empty space, Lymphatics

Leg
Muscle
Fibularis longus
Fibularis brevis
Tibialis anterior
Extensor hallucis longus
Extensor digitorum longus
Gastrocnemius
Soleus
Popliteus
Tibialis posterior
Flexor digitorum longus
Flexor hallucis longus

Evertor compartment
Innervation
Superficial fibular n.
Superficial fibular n.
Extensors
Deep fibular n.
Deep fibular n.
Deep fibular n.
Flexors
Tibial n.
Tibial n.
Tibial n.
Tibial n.
Tibial n.
Tibial n.

Major Action
Eversion
Eversion
Extension of ankle & Inversion
Extension of 1st toe & ankle
Extension of toes 2-5
Flexion of knee & ankle
Flexion of ankle
Flexion of knee
Flexion & Inversion
Flexion of 1st toe
Flexion of toes 2-5

-Popliteal fossa: 1) sciatic -> tibial & fibular n. 2) popliteal a. ->anterior & posterior tibial a.
-Tarsal tunnel: Tom, Dick, & A Very Nervous Harry
-Greater Saphenous: from femoral vein to anterior foot surface -> used for coronary bypass
-Ligaments of knee: ACL, PCL, lateral & medial collaterals
-Lateral (O-shaped) & medial (C-shaped) meniscus of knee

Foot
-Ligaments: medial collateral (deltoid), lateral collateral (anterior fibulo-talar, posterior fibulo-talar, & lateral fibulocalcaneal), spring ligament (plantar calcaneal-navicular), long plantar
-Stirrup of foot: Fibularis longus & Tibialis posterior
-Bones of foot: Calcaneus (heel), Talus, Navicular (boat-shaped), Cuneiforms (lateral, medial, & intermediate), Cuboid,
Metatarsals & phlanges

CASES OF THE KNEE

ACUTE
distinct event
audible pop
sharp pain
inability to continue
marked swelling
locking
instability

CHRONIC
insidious onset
non-painful popping
dull ache and pain
usually can continue
may swell minimally
stiffness
giving way
activity related
90% of acute cases deal with:
PCL
ACL
Medial Collateral ligament
Dislocated Patella (moreso in women due to wider hips, thus quadratus muscles have a
wider starting point and pull the patella laterally; Vasus Medialus Obliques prevents against
this action by stabilizing the patella medially)
Meniscus
Fracture
Lateral Meniscus has 2 points of attachment, whereas Medial Meniscus has 3 points of attachment,
therefore you are more likely to tear your Medial Meniscus.

INTRODUCTION TO RADIOLOGY
X-ray - Excite phosphors on screen, which in turn provides 99% of film exposure
Ranking of absorption of x-rays from least to most
Air < Fat < Water < Barium
Standard positions- Lateral, Oblique, and AP views
Contrast studiesGI-barium, air, and water soluble (ex: iodine). Water soluble in GU and vascular as
well
Computed Tomography (CT)-x-rays at various angles with detectors, computer combines information to
produce cross sections
Interventional Procedures/Angiography-useful in imaging arteries/veins, atherosclerosis, tumors, traumas
of organs/vessels
Magnetic Resonance Imaging (MRI)-magnetic fields cause changes in magnetic spins of protons which
can be measured, useful for CNS, musculoskeletal, abdomen, pelvis, vascular

RADIOLOGY OF THE UPPER EXTREMITY

Bone parts-epiphysis (head), metaphysis (region on diaphyseal side of epiphyseal plate), diaphysis (shaft),
Growth is at epiphyseal plate, epiphysis growth is circumferential
Metaphyseal growth is elongation of bone shaft, growth stops when epiphysis and metaphyses fuse
Joint types- cartilaginous (ex: primary-rib/manubrium, secondary-manubrium/sternum),
Fibrous (ex: Skull bones or Interosseus membrane), and synovial (ex: shoulder or knee)
Radiographic points: Distal clavicle, acromion, coracoid process, glenoid fossa, greater
and lesser tuberosities
Differential diagnosis: Supposedly explains 95% of aberrant findings
C ongenital
I nfections
N eoplastic
T rauma
Bone abnormalities: Trauma (fracture,dislocation), arthritis, tumors, infection, congenital
Remainder of lecture was review of anatomy of upper extremity-see Harvey

RADIOLOGY OF THE LOWER EXTREMITY

Cant break pelvis in just one place (pretzel example)
Pubic symphysis-cartilage
Nerves come out of arcuate lines of sacrum
Dislocation-like femoral head coming out of ball and socket totally
Sublexation-partially comes out, but still articular surface against articular surface
Diastasis-two bones connected to each other split apart (like at pubic symphysis or sacro-iliac joint)
happens often with motorcycle accidents or delivery of large babies
120 to 130 degree angle between femur neck and shaft
Condyle- epiphysis and metaphysic
Blood from knee injury will collect in suprapatella bursa
2 cruciate ligaments keep tibia from going anteriorly or posteriorly relative to femur
Fabella-normal variant bone at knee joint
Infrapatellar ligament goes to tibial tuberosity
FBI sign- if injure knee, blood and marrow come out, marrow (has lots of fat) floats to top, creates
Fat/Blood Interface, seen with horizontal x-ray
Fibula creates ankle joint, but doesnt carry much weight
Interrosseus membrane can transfer force and cause additional fractures