MCAT Biology

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MCAT Biology
2013-12-23 23:16:02

MCAT Barron's flash card for biology
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  1. Enzyme Structure and Function
    • -Enzymes are highly selective catalysts for biochemical reactions; remain unchanged
    • Provide alternative reaction pathway that requires less activation energy
    • Alter rate of reaction, not position of equilibrium
    • May have nonprotein cofactor
    • Enzyme's active site specifically binds substrate
    • Enzyme-substrate complex changes shape
    • Rate of reaction dependent on enzyme and substrate concentration
    • -Addition of substrate won't increase reaction rate if all active sites are bound(rate-limited)
    • -With unlimited substrate and correct pH and temperature, rate of reaction is proportional to enzyme concentration
  2. Enzyme Inhibition
    • Enzymes are proteins that may denature at suboptimal temperature or pH
    • Inhibitors may decrease or stop catalytic activity by disrupting enzyme's active site
    • Competitive Inhibitors:
    • -Compete with substrate for enzyme's active site
    • -Addition of more substrate will speed up reaction rate to reach its maximal rate(Vmax)
    • Noncompetitive Inhibitors:
    • -Alter the enzyme by binding to another portion of it, not the active site
    • -Addition of substrate will not allow Vmax to be reached
  3. Metabolism
    • Set of chemical reactions that enable organisms to harvest and use energy
    • -Catabolic reactions: "break down" substrates to gain energy (e.g.-glycolysis)
    • -Anabolic reactions: "build up" molecules, expend energy (e.g.-amino acid synthesis)
    • Substrate: reactant that is consumed/changed by an enzyme to produce a product
    • Typical reaction:
    • -Only middle step is irreversible
    • -E+S⇌ES→EP⇌E+P
  4. Glycolysis
    • Basic universal metabolic pathway for utilization of glucose, results in 2 molecules of pyruvate
    • -Utilized by aerobic (oxygen-utilizing) and anaerobic organisms
    • -Occurs in cytoplams
  5. Krebs Cycle/Citric Acid Cycle
    • -Utilized by aerobic organisms; occurs in mitochondrial matrix
    • -Involved int he chemical conversion of carbohydrates, fats, and proteins into carbon dioxide and water to generate a form of usable energy (in the form of ATP, NADH and FADH2)
    • -2 Pyruvate (glycolysis) decarboxylated in mitochondria → 2 acetyl CoA + 2NADH +2CO2
    • -Acetyl CoA then enters the Krebs Cycle
    • -Two turns of cycle (1 acetyl CoA per cycle) yield: 2 ATP (from GTP), 6 NADH, 2 FADH2, 4 CO2
  6. Lipids and Proteins Feed into Citric Acid Cycle
  7. Electron Transport Chain
    • Couples electron donor and an electron acceptor
    • Hydrogen ions are transferred across the inner mitochondrial membrane into the intermembrane space, through a set of mediating biochemical reactions
    • -Hydrogen ions build up in the intermembrane space and create a gradient
    • The hydrogen ion gradient flows through ATP synthase into the matrix, to produce adenosine triphosphate(ATP)
  8. Electron Transport Chain
  9. Nucleotide Structure and Function
    • Nucleotide's three components:
    • -Pentose sugar: 5-carbon ring
    • -Nitrogenous bases: on 1' carbon of pentose sugar
    • --Pyrimidines: 6-membered ring
    • ---cytosine, uracil, and thymine
    • --Purines: 6-membered ring fused to a 5-membered ring
    • ---adenine and guanine
    • -One to three phosphate groups (attached to 5' carbon)
    • --High-energy, used to fuel reactions
    • Nucleotides form long chains by covalently attaching and polymerize in the 3'→5' direction

    • -3' carbon attached to a hydroxyl (-OH) group
    • -5' carbon attached to a phosphate
    • -Phosphate and hydroxyl groups react→ covalent bond
  10. DNA (Deoxyribonucleic Acid)
    • Purine bases: adenine(A) and guanine(G)
    • Pyrimidine bases: cytosine(C) and thymine(T)
    • DNA molecule consists of two double-stranded molecules in a double-helix structure
    • -5' end of one strand lies next to 3' end of another
    • -Strands are complimentary and loosely held together by hydrogen bonds and may dissociate without breaking individual strands
    • -Complementary bases:
    • --A pairs with T
    • --G pairs with C
    • Semiconservative model of DNA replications: two strands dissociate and each one is used as a template for production of complementary strand
  11. Prokaryotic DNA Replication
    • Single origin of replication
    • Topoisomerase: nicks double helix of DNA and releases coiling to allow replication to begin
    • Primase: makes RNA primer for DNA Polymerase III (which makes new DNA) to use as a starting point
    • -Deoxynucleotides (DNA) add on to one another in the 5'→3' direction
    • Leading strand: continuous complementary strand produced in the 5'→3' direction
    • Lagging strand must be completed in short segments (Okazaki fragments), which is them unified by DNA ligase
    • Exonuclease: "proofreads" each added nucleotide
    • DNA polymerase I: removes the RNA primer laid down by primase
  12. DNA Repair
    • Repair mechanisms to prevent genetic errors that lead to harmful mutations
    • Sources of damage include gamma rays, X-rays, UV light, chemicals, free radicals
    • Damages include deamination (C→U), mismatch during DNA synthesis, backbone breaks, cross-links
    • Three major DNA repair mechanisms:
    • -Base excision: removal of damaged bases occurs daily; several DNA glycosylases and enzymes identify damaged bases and DNA polymerase beta replaces them
    • -Nucleotide excision: differs from base excision because several adjacent nucleotides are removed and replaced also
    • -Mismatch repair: corrects mismatch of normal bases paired incorrectly
  13. Recombinant DNA
    • Artificially created/altered
    • Two or more pieces of DNA form a recombinant molecule
    • -Same restriction enzyme used on both pieces of DNA to cut them at a specific point
    • -Overhanging portion: sticky ends that will hybridize with another complementary DNA strand→ recombinant molecule
    • Gene cloning:
    • -In vitro: polymerase chain reaction (PCR) used to replicate DNA for analysis
    • -In vivo:
    • --Plasmids: carry circular DNA, enter bacteria, and replicate
    • --Cultured cells transformed with a human gene manufacture products for human therapy
  14. Ribonucleic Acid (RNA)
    • RNA has -OH groups at 2' and 3' of ribose ring; DNA has only -OH at 3' carbon
    • three types:
    • -Messenger (mRNA): DNA transcribed to mRNA in nucleus; template for protein
    • -Ribosomal (rRNA): four different types
    • -Transfer (tRNA): transfers specific amino acids to ribosome for protein synthesis
    • --Specific tRNAs for each amino acid
    • --Base pairing within molecule causes clover leaf shape
    • --Four key regions:
    • ---Aminoacyl attachment site for amino acids
    • ----Amino acids attached by aminoacyl tRNA synthetases
    • ---Anticodon (three bases) binds complementary mRNA
    • ---T loop
    • ---D loop
  15. Genetic Code and Transcription
    • Central dogma: DNA→RNA→protein
    • Transcription (DNA→mRNA):
    • -Promoter region binds RNA polymerase
    • --Promoter regions are "conserved sequences"
    • -DNA double helix opens so that one DNA strand can be a template for RNA polymerase
    • --RNA chain elongation proceeds in 5'→3' direction until terminator sequence reached
    • -Transcripts "processed" in nucleus of eukaryotes:
    • --Introns: unused portions of RNA are spliced out; exons: coding regions of mRNA
    • Poly-A sequence at 3' end and 5' cap added for stability and for recognition as mature/ready for translation
  16. Ribosomes
    • In eukaryotes, translation begins at 5' cap of mRNA where initiator tRNA loaded into P-site of small ribosomal subunit with initiation factors
    • Ribosomes composed of >50 proteins and rRna
    • One large and one small ribosomal subunit:
    • -Small subunit joins correct tRNA to mRNA
    • -Large subunit catalyzes peptide bond formation of growing protein
  17. Ribosome-Binding Sites
    • Each ribosome has four binding sites:
    • -One for mRNA codon
    • -Three for tRNAs:
    • --A-site: tRNA binds
    • --P-site: high-energy bond between amino acids and tRNA broken; bond formed between amino acids and growing peptide chain
    • --E-site: tRNA "exits"
  18. Translation
    • Mature mRNA leaves nucleus via nuclear pore complex (eukaryotes)
    • -mRNA binds small ribosomal subunit at start codon (AUG)
    • --AUG codes for methionine
    • --Large ribosomal subunit binds complex
    • --tRNA brings amino acids to complex
    • ---peptide bond formed→growing polypeptide
    • -Each amino acid coded for by 1 to 6 codons
    • --20 different amino acids; 64 different codons (redundancy of code)
    • --Wobble Hypothesis: first two bases bind tRNA
    • Three possible reading frames/protein
    • -Correct reading frame necessary for correct protein production
    • Ribosome dissociates at stop codons (UAA, UAG, UGA)
    • mRNA degraded by RNAses
  19. Prokaryotes and Eukaryotes: Differences in Transcription and Translation
    • In prokaryotes:
    • -mRNA is not spliced; no poly-A tail or 5' cap
    • -Bacterial cells do not have introns; genes are uninterrupted sequences
    • -Ribosome binds at ribosome-binding sequence to begin translation because no 5' cap
    • -mRNAs are polycistronic (several proteins encoded in 1 mRNA)
    • In eukaryotes:
    • -mRNA is interrupted by introns that are removed by sliceosomes
    • --snRNPs (small nuclear ribonucleoproteins) combine with small nuclear RNA and other proteins to form spliceosome
    • -5' cap and poly-A tail needed for export to cytoplasm for nucleus
    • -Ribosome binds 5' cap at translation
    • -1 mRNA makes 1 protein
  20. Structure of Eukaryotic Chromosomes
    • Double-stranded DNA packaged with protein (histones and nonhistone proteins) into chromatin
    • -Chromosomes: highly coiled chromatin
    • --Prokarytoes: circular DNA; no chromosomes
    • 46 chromosomes in most human cells
    • -22 pairs of homologous chromosomes and XX(female) or XY(male)
    • Histones package DNA into nucleosomes (first level of chromosome packing)
    • -Each histone is an octamer with two of each histone protein (H2A, H2B, H3, H4)
    • -beads on a string: nucleosomes separated by linker DNA
    • Coiling is dynamic
    • Euchromatin: areas of chromosomes-expressing genes; less tightly packed during interphase
    • Heterochromatin: highly coiled; not expressed
  21. Chromosomes and Cancer
    • Centromeres: region of mitotic chromosome holding sister chromosomes together
    • -Site of kinetochore formation, mitotic spindle binds
    • Telomeres: characteristic DNA sequence replicated at chromosome ends; prevents shortening with replication
    • -Telomeric DNA sequences bind telomerare (adds copies)
    • --Lagging strand completes replication without losing essential genes
    • Cancer caused by failure of normal cellular control→immortal cells
    • -Disruption of growth factors, receptors, signaling pathways, DNA repair/damage response, cell cycle regulation, apoptosis
    • --Oncogene: damaged proto-oncogene; one mutation→malignancy
    • --Tumor suppressor gene: normally prevents cancer; two mutations cause disinhibition of cell division→malignancy
  22. Gene Expression
    • Pathway from DNA→protein can be regulated at many levels; control of transcription is most important
    • Trascription controlled by regulatory DNA sequences
    • -Work in conjunction with gene regulatory proteins to "switch on" genes
    • Gene expression depends on cell type, surroundings, age, and extracellular signals/hormones
    • Repressors proteins interact with regulatory DNA sequence to prevent RNA polymerase II from binding
    • Activator proteins promote binding of RNA polymerase II
    • -Classic example- lac operon in E.coli
    • --Activator protein CAP and lac repressor work on single promoter region (lac operon)
  23. Mendelian Genetics
    • Studied pea plants; two laws describing inheritance
    • -First law: segregation of characteristics (one allele expressed/gemete)
    • -Second law: independent assortment (genes for characteristic independently inherited)
    • Phenotype: appearance of an organism
    • Genotype: genetic makeup
    • -Completely dominant gene will determine phenotype
    • Gene: region of DNA controls a discrete hereditary characteristic
    • Alleles: alternative forms of gene; diploid cells have 2 alleles each occupying same locus (position) of homologous chromosomes
    • -Homozygous: identical alleles for given gene
    • -Heterozygous: different alleles
    • Wild type: typical of an organism in natural conditions
    • Recessive trait: phenotype produced by a homozygous recessive allele
    • -Albinism is autosomal recessive; child has disease if inherits gene from both parents
    • Complete dominance: dominant gene always fully expressed if present
    • Incomplete/partial dominance: heterozygous genotype expressed as intermediate phenotype
    • Codominance: heterozygous individuals expresses both phenotypes
    • Penetrance: proportion of individuals with a gene expressing certain phenotype
  24. Meiosis
    • Only occurs in gametogenesis (in ovaries and testicles)
    • Human cells have 46N chromosomes
    • Through 2 cell divisions (meiosis I and II), 4 haploid (23N) cells are made
    • -In males- primary spermatocyte (46N)→4 sperm (23N)
    • -In females- primary oocyte→1 ovum and 3 polar bodies
    • Meiosis promotes genetic variability:
    • -Homologous chromosomes independently assort during meiosis I
    • -Maternal and paternal DNA exchanged in meiosis I during crossover
    • Mitosis→identical daughter cells
    • Meiosis→genetically diverse gametes
  25. Punnet Square
    • Punnet square: predicts genotype of offspring
    • -Method of analyzing possible allele combinations based on parents' genotypes
  26. Meiosis-Segregation of Genes
    • Meiosis generates 4 nonidentical haploid cells
    • -Meiosis I: chromosomes duplicated (sister chromatids), maternal and paternal homologous chromosomes align
    • --Crossover: recombination; homologous chromosomes may exchange DNA
    • ---Chiasmata form, stabalizing the 4 chromatids until separated in anaphase I
    • -Linkage: 2 genes lie close on a chromosome, inherited together
    • --Genes far apart participate in recombination frequently, also likely to be inherited together as genes on different chromosomes
    • --Used for gene mapping
    • Meiosis errors leads to incorrect number of chromosomes in gametes (aneuploid)
    • -Trisomy 21 (Down's syndrome) due to nondisjunction (homologs don't separate)
  27. Sex-Linked Characteristics
    • Karyotype: display of all 46 human chromosomes
    • -Normal- 22 somatic pairs, 2 sex chromosomes
    • --Exceptions exists, including Kleinfelter's syndrome
    • Y chromosome:
    • -Contains SRY region/ sex-determining region; presence produces male→testes development
    • -Small; many non-vital genes
    • -Y-linked disorders: colorblindness, hemophilia, and so on
    • X chromosome:
    • -Normal females contain two; only one active, other is a barr body
    • Cytoplasmic inheritance: maternal mitochondrial DNA is always inherited due to prescence in egg
    • -Sperm have mitochondria in tail, which falls off after fertilization
  28. Mitosis
    • Somatic cells; results in two identical daughter cells
    • Nuclear division+cytokinesis
    • Five phases:
    • -Interphase: cell growth, DNA synthesis, chromosomes replicated, not easily visible in nucleus
    • -Encompasses G1, S, and G2 of cell cycle
    • -Prophase: chromosomes tighten, nucleoli disappears, centrioles→opposite ends, mitotic spindle forms
    • -Metaphase: nucleur membrane dissolves during prometaphase, microtubules attach to kinetochores, spindle fibers align chromosomes along metaphase plate
    • -Anaphase: chromatids polarize, spindle fibers become indistinct
    • -Telophase: chromatids on opposite poles, nuclear membrane forms, spindle fibers disappear, chromosomes indistinct
    • --Cytokinesis: separation of cytoplasm, completes division
  29. Analytical Methods
    • Hardy-Weinberg principle: "punnet square for a population"
    • -Based on concept of genetic equilibrium in population
    • -Calculate frequency of particular alleles based on frequency of autosomal recessive disease
    • --p2+2pq+q2=1
    • ---p: frequency of dominant allele
    • ---q: frequency of recessive allele
    • Test cross: breeding of organism expressing dominant trait with one expressing recessive trait; determining genotype
    • F1 (filial 1) generation: first generation bred from two closely related species/strains
    • F2 generation: progeny of F1
    • Back cross: breeding of recessive homozygote and F1 generation
  30. Mutation
    • Heritable change in DNA; advantageous or deleterious
    • Induced by mutagen or spontaneous:
    • -Polymerase errors, exonuclease malfunction
    • -Base alterations/damage: tautomerization, deamination, oxidation, alkylation
    • -Spontaneous frameshift mutations: likely in areas of nucleotide repeats
    • May be large (chromosomal) or small (point mutaitons)
    • Point mutations:
    • -Base-pair substitutions
    • --Transitions: purine→purine; pyrimidine→pyrimidine
    • --Transversions: purine→pyrimidine or pyrimidine→purine
    • ---Silent: inconsequential
    • ---Missense: wrong amino acid will be inserted/substituted
    • ---Nonsense: lead to a shortened protein from early termination
    • -Frameshift mutations
    • --Insertion/deletion of nucleotide changes reading frame
  31. Fungi
    • One of the five kingdoms of organisms
    • Unlike plants, no photosynthesis and cell walls contain chitin
    • All have at least one nucleus; generally haploid for most of life cycle
    • All can reproduce asexually and some sexually too
    • Differ in level of cellular organization
    • Asexual reproduction:
    • -Spores, fragmentation, fission, budding, simple cell division
    • Sexual reproduction important for genetic variability of fungi
    • -Nuclear membrane remains intact throughout cycle
    • -Haploid nuclei are formed and brought together(plasmogamy)
    • -Some have specialized sex cells that produce gametes
  32. Structure of Viruses
    • Typically contain nucleic acid to encode genetic information
    • -Circular or linear
    • -Double stranded or single stranded
    • Viruses may require reverse transcriptase or other enzymes that it carries within it
    • Outer protein capsid surrounds nucleic acid
    • -Protein subunits usually form icosahedral or helical shape
    • -Single or multilayered
    • May contain additional structures
    • -Bacteriophages have sheaths to transmit nucleic acid across bacteria cell wall
    • Viruses that infect eukaryotic cells may have lipid bilayers outside capsid with special viral proteins within it
  33. Viral Sturcture
  34. Viral Life Cycle
    • Reproduce only within suitable cells
    • Bacteriophages (viruses-infecting bacteria) have two replication strategies:
    • -Lytic: virus replicates rapidly, bacterial cell wall bursts
    • -Lysogenic: copy of viral genome incorporated into host cell chromosome, replicated within host DNA
    • --Switch to lytic in order to produce new bacteriophages
    • Viruses infecting animal cells are similar, may also "bud" off without killing host
    • -Incorporated viral sequences may cause new proteins to be expressed
    • Retroviruses: ssRNA viruses infecting human cells
    • -Reverse transcriptase makes DNA copies→incorporated into host chromosomes
    • Transduction: transfer of DNA by viruses
  35. Prokayotic Cell Structure
    • Unicellular, form colonies
    • Nuclear area: circular DNA semi-anchored to plasma membrane
    • -No nuclear envelope separating genetic material
    • -Complexed with proteins; no histone-DNA complexes
    • -Plasmids, episomes may be present
    • Cytoplasm
    • -Free ribosomes, organelles absent
    • --Chromatophores present in some photosynthetic bacteria
    • Plasma membrane (phospholipid bilayer)
    • -No glycolipids, cholesterol
    • Cell wall complex: outside plasma membrane
    • -Gram(+): thick, peptidoglycans
    • -Gram(-): also have lipopolysaccharides, porins, periplasmic space
    • --Ion passage highly regulated
    • -Flagella (propel the cell), pili, slime layer may be present outside
  36. Prokaryotic Cells
    • Classified by shape:
    • -Bacilli (rod), Spirilli (spiral), Cocci (round)
    • Reproduce by binary fission (asexual): cell contents duplicated, septum formed→two identical daughter cells
    • -Exponential growth
    • Smaller than eukaryotes, highly adaptable
    • Symbiotic relationship with other organisms
    • -Parasitism: type of symbiotic relationship; one organism helped, other exploited
    • Aerobic organism: can survive/grow in oxygen-containing environment
    • -Obligate: needs oxygen
    • Anaerobic: does not need oxygen, may die if present
    • -Obligate: needs no oxygen
    • -Facultative: may use if present
  37. Prokaryotic Cell Genetics
    • DNA replication, transcription, and translation in cytoplasm
    • Single promoter controls series of genes (transcribed as single RNA) = operon
    • Transcription initiated by RNA polymerase and sigma factors, complex and bind to promoter sequence
    • -Activator/repressor proteins: located upstream/downstream from promoter, affect RNA polymerase binding
    • -Termination frequently occurs after RNA base-pairs itself→"hairpin loop"
    • Translation occurs before transcription is complete
    • -Usually occurs without modification
    • -Requires mRNA, tRNA, ribosomes
    • -Terminated when protein termination factors recognize termination codons
    • --Ribosomal subunits dissociate
  38. Eukaryotic Cells
    • Distinguishing features of eukaryotic cell:
    • -Membrane-bound organelles, nucleus, meiotic division
    • The nucleus contains DNA and enzymes necessary for transcription
    • -Compartmentalizes the genetic information
    • -Surrounded by nuclear membrane/envelope (lipid bilayer)
    • --Serves as a physical barrier, nuclear pores selectively allow certain proteins and RNA to pass through
    • -Nucleolus: spherical mass of dense granules within nucleus; may be multiple
    • --Specialized regions of chromosomes containing genes for ribosome and RNA synthesis
    • Membrane-bound organelles include mitochondria, endoplasmic reticulum, golgi apparatus, lysosomes
  39. Membrane-Bound Organelles I
    • Mitochondria: energy-producer of cell; most ATP produced here through aerobic metabolism
    • -Two membranes: outer (smooth) and inner (folded)
    • -Matirx within inner membrane where Krebs cycle occurs
    • -Proton gradient across inner membrane drives ATP production
  40. Membrane-Bound Organelles II
    • Lysosomes: spheres housing hydrolytic enzymes to digest cell waste and foreign bodies
    • Endoplasmic reticulum (ER):
    • -Rough: flattened membranes with ribosomes, produces proteins to be packages or exported (lysosomal enzymes, secreted proteins)
    • -Smooth: no ribosomes, site of steroid and phospholipid synthesis
    • Golgi bodies: smooth, flattened membranes
    • -Cis face receives vesicles from rough ER
    • -Trans face buds off vesicles
  41. Eukaryotic Plasma Membrane
    • Surrounds cytoplasm, contains cell contents
    • -Cell wall: may surround plasma membranes of plant cells; made of pectin
    • Differs from prokaryotic plasma membrane; contains glycolipids and cholesterol
    • Fluid mosaic model: phospholipid bilayer with associated macromolecules (integral/peripheral proteins, glycoproteins, lipids, glycolipids, cholesterol)
    • -Hydrophobic proteins and lipids move laterally within hydrophobic protion of lipid bilayer
    • Glycoproteins have oligosaccharide groups attached
    • Animal cells often have glycolipids on outer membrane surface, which also have complex oligosaccharide groups attached
    • -Oligosaccharides form a coating over cell
    • --Involved in binding of neutrophils
    • --Protects cell from complement (part of immune response)
  42. Passive Transport
    • Does not require energy expenditure (ATP)
    • Simple diffusion: particles move across the cell membrane down their chemical gradient (from more to less)
    • -Water, carbon dioxide, and oxygen move via simple diffusion
    • -Osmosis: type of simple diffusion in which water moves from areas of low-solute concentration (hypotonic) to high-solute concentration (hypertonic)
    • Facilitated diffusion: cell utilizes a protein channel or carrier to facilitate movement of particles down their concentration gradient (no ATP required)
    • -Facilitated diffusion will not work if there is no electrochemical gradient
  43. Energy-Requiring Transport
    • Cell energy needed to move particles across cell membrane against the cell's electrochemical gradient
    • -Useful when materials needed by the cell faster than they passively diffuse
    • Active transport: Protein carrier facilitates movement across the membrane, requires ATP
    • -sodium/potassium exchange pump: transmembrane protein pump that moves three sodium ions of the cell and two potassium ions in
    • --Powered by ATP
    • Endocytosis: cell membrane engulfs extracellular molecules and brings then into the cell by forming a new membrane-bound vesicle
    • Exocytosis: processed cell materials exported out of the cell, bud off of plasma membrane
  44. Intercellular Connections
    • Cell connection within tissues; allows communication necessary for function
    • Gap junction (nexus): communicating junction
    • -Small channels connect cytoplasm of two cells
    • -Rapid communication between cells via ions (e.g.-neurons)
    • Tight junctions (zona occludens): membranes of two adjoining cells fused together
    • -Creates an impermeable fluid barrier
    • Adherens junctions: protein complexes that anchor epithelial cells to each other, more basal than tight junctions
    • Desmosomes/Macula adherens: junctional complex; helps resist shearing forces, found in simple and stratified epithelium and muscle cells
    • -Hemidesmosomes: join cell to basal lamina
  45. Membrane Potential
    • Membrane voltage/electrical potential: potential energy resulting from the work of separating ions across the membrane
    • Maintained through action of ion channels, pumps, transporters within membrane
    • -Sodium/Potassium -ATPase keeps extracellular Na+ concentration high
    • Cell membrane is permeable to many ions (via channels)
    • -Each ion has a different permeability and contributes to the resting membrane potential of the cell
    • --Each ion has unique equilibrium potential and will diffuse across the membrane in attempt to reach it
    • Membrane potential: weighed average of each contributing ion's equilibrium potential and permeability (usually ~60 to ~80 mV but differs among cell types)
  46. Cytoskeleton
    • Gives cell stability and ability to move; unique to eukaryotes
    • Fiber types:
    • -Microfilaments: thread-like fibers, 3-6nm in diameter, composed of protein actin
    • --Associate with myosin, aid in muscle contraction
    • --Allow cellular movement and cleavage
    • -Microtubules: cylindrical tubes, impart cell structure, 20-25nm in diameter, composed of protein called tubulin (alpha and beta)
    • --Give cell structure
    • --Attach to centromeres during mitosis
    • ---Centioles organize microtubules during mitosis
    • --Within flagella and cilia: "9+2" microtubule structure
    • -Intermediate filaments: intermediate size (10nm) give tensile strength
  47. Extracellular Matrix
    • Connective tissue surrounding/supporting cell
    • ECM has three components
    • -Structural proteins:
    • -Collagen: >20 kinds, rod-like protein
    • --Type I: skin, tendon, bone
    • --Type II: cartilage
    • --Type III: skin, muscle
    • -Elastin: gives flexibility
    • -Specialized proteins: fibrillin, fibronectin (attach cells to ECM), and laminin (anchors cells to basal lamina)
    • -Proteoglycans: proteins with branching sugars; glycosaminoglycans (GAGs)
    • --Hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, heparan sulfate, keratin sulfate
    • --Diverse and important functions ranging from anticoagulation (heparin) to joint lubrication (hyaluronic acid)
  48. Phases of Cell Cycle
    • Ordered set of events leading to mitosis
    • Cells not growing and dividing are not in cell cycle (they are in G0)
    • Stages are G1->S->G2->M
    • -G1: growth of cell contents
    • -S: DNA synthesis
    • -G2: Cell contents checked and repaired
    • -M: mitosis
    • Cell cycle regulation is complex; loss of control->cancer
    • -Cdk and other cyclins control movement from G1->S or G2->M
    • -p53 blocks progression through cell cycle in cells with damaged DNA; if severe→
    • apoptosis
    • -p27 protein binds to cyclin and Cdk, blocking entry into S phase
  49. The Cell Cycle
  50. Neuron Structure I
    • Specialized cells of nervous system
    • Cell body: site of nucleus and organelles
    • -"Grey matter"
    • -Metabolically active
    • Dendrites: extensions of cell body's cytoplasm
    • -Increases surface area and synaptic communication
  51. Neuron Structure II
    • Axons
    • -One per neuron
    • -Attached to cell body by axon hillock
    • -Synapses with neurons or at other specialized cells
    • -Up to 1 meter long
    • -May have myelin sheath, which increases propagation of signal; increases resistance across membrane
    • --Myelin sheath produced by:
    • ---Oligodendrocytes in CNS
    • ---Schwann cells in PNS
    • --Nodes of Ranvier: gaps in myelin sheath
  52. Neuron Conductivity
    • Synapses: site of communication between two neurons
    • -Usually between axon and dendrite, separated by a synaptic cleft
    • --Axons have terminal buttons at their ends
    • ---Buttons have synaptic vesicles with neurotransmitters (e.g.- acetylcholine, dopamine, norepinephrine, serotonin, GABA)
    • ---Traverse the cleft and communicate with post-synaptic dendrite
    • Classification of neurons:
    • -Multipolar neurons (most common type): single axon, many dendrites; integrate information from many other neurons; somatic and visceral motor
    • -Pseudounipolar neurons: one dendrite, one long axon; somatic and visceral sensory neurons
    • -Bipolar neurons: one dendrite, one axon at opposite poles of cell; specialized sensory neurons (e.g.- smell, sight, taste, hearing)
  53. Action Potential
    • Temporary change in membrane permeability →electrical signal
    • Resting membrane potential of neurons: 70 mV
    • Stimulus changes permeability of membrane to Na+ and K+ →depolarization (cell becomes +)

    • Threshold for signal propagation (point of no return)
    • -All-or-none response
    • -Na+ rushes in (limited by ENa and closing Na+ channels), causing positive charge inside (+40 mV)
    • -K+ channels open to compensate, K+ rushes out (limited by EK and closing K+ channels)
    • -Channels close again, cell repolarizes as ions pumped back to resting potential
    • -Refractory period: Na+ channels cannot reopen, another AP cannot be generated
    • AP lasts milliseconds in neurons (slightly linger in myocardium)
  54. Neuron Transmission
    • Signals sent by nerves have an addictive effect =summation
    • -Single stimuli unlikely to evoke a response, but multiple stimuli increase the chance of an excitatory postsynaptic potential (EPSP)
    • -Temporal summation: successive stimulation of one nerve (over short period of time)
    • -Spatial summation: stimulation of several different fibers added together
    • Excitatory and inhibitory nerve fibers maintain fine physiologic balance
    • -Example: sympathetic ("fight or flight") and parasympathetic nervous ("rest and digest") systems regulate airway dilation and restriction along with many other functions
    • --Antagonistic control
  55. Neuron Organization
    • Cell bodies of neurons typically are in the central nervous system (CNS) and organized into specialized areas called cortexes
    • Ganglion: cluster of neuron cell bodies outside of the CNS
    • Cortex: neuron cell bodies layered on the brain ("grey matter")
    • -"White matter" composed of axons (fatty myelin appears white)
    • CNS neurons surrounded by supportive/helper cells called neuroglia
    • -Astrocytes: have perivascular feet, compose blood-brain barrier
    • -Oligodendrocytes: deposit myelin
    • -Microglia: phagocytes
    • PNS neurons surrounded by:
    • -Schwann cells: myelinate PNS
    • -Satellite cells: surround ganglia
  56. The Central Nervous System: Cerebrum
    • CNS: brain and spinal cord
    • Brain has three main parts: 1) cerebrum 2) brainstem 3)cerebellum
    • -Cerebrum: governs intelligence, behavior, consciousness, speech, and writing
    • --Two hemispheres (longitudinal fissures between them); joined by corpus callosum
    • --Gyri: folds on the surface
    • --Sulci/fissures: depressions between the folds
    • --Five lobes on each hemisphere
    • ---Frontal: major motor areas (motor speech)
    • ---Parietal: controls sensory input
    • ---Occipital: controls vision
    • ---Temporal: hearing (receptive speech)
    • ---Insula (cortex within Sylvain fissure): emotions and feelings
  57. Brain Anatomy
    • Frontal lobe: located anteriorly
    • Parietal lobe: located posterior to central sulcus and superior to occipital lobe
    • Occipital lobe: most inferior and posterior portion
    • Temporal lobe: inferior to Sylvian fissure
    • -Sylvain fissure = lateral sulcus in figure at right
  58. CNS: Brainstem
    • Four parts:
    • -Midbrain: auditory and visual relay center, controls eye movement (oculomotor nucleus), pupillary constriction, and accommodation
    • -Pons: contains tracts for cerebral and cerebellar communication, controls facial movement and sensation, tearing,and so on.
    • -Medulla oblongata: directly above the spinal cord; controls many reflexes, respiration, heartbeat, and blood vessel tone
    • -Diencephalon: divided into:
    • --Thalamus: essential relay center, controls integration of movement (among basal ganglia, cerebrum, cerebellum), processes sensory input (except smell)
    • --Hypothalamus: links nervous and endocrine systems (secretes hormones to stimulate pituitary gland), controls temperature, sleep, blood pressure, thirst, hunger, stress, and so on.
  59. Brainstem Anatomy
  60. CNS: Spinal Cord Anatomy
    • Cord is less than 1 inch in diameter; 18 inches long; continues from the base of the skull to L2
    • -Two enlargements: cervical and lumbar (limb areas)
    • Protected by vertebral column
    • -Lumbar punctures are safe because only terminal roots--cauda equina--are below this level
    • Protected by surrounding cerebral spinal fluis and meninges (dura, arachnoid, and pia)
    • -Pia is closest to cord/brain
    • -Cerebrospinal fluid (CSF) within subarachnoid space (between pia and arachnoid)
    • 31 pairs of spinal nerves exit through intervertebral foramina
    • -8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal
  61. CNS: Spinal Cord Organization
    • Cross section of the spinal cord looks like a butterfly surrounded by white matter
    • -Grey matter contains multipolar neuron cell bodies divided into dorsal and ventral horns
    • --Dorsal (posterior) horn: sensory
    • --Ventral (anterior) horn: motor
    • -White matter contains myelinated axons
    • Dorsal root ganglion: contains cell bodies of pseudounipolar neurons
    • -Axons attach to the spinal cord via the dorsal root
    • Ventral root: contains axons from multipolar motor neurons from ventral horn
    • White matter: divided into funiculi (dorsal, lateral, and ventral), which contains tracts
    • -Tracts: organized fibers with common function; run superiorly and inferiorly
  62. Spinal Cord Cross Section
  63. Peripheral Nervous System Organization
    • PNS made up of somatic and autonomic components
    • Somatic nervous system: controls voluntary muscle movement
    • Autonomic nervous system (ANS): maintains homeostasis, involuntary muscle movement, innervates smooth muscles and glands
    • -ANS divided into parasympathetic and sympathetic systems
    • --Sympathetic: "fight or flight"; increases heart rate, increases blood pressure, dilates bronchial tree, constricts blood vessels, decreases digestion, relaxes bladder,and dilates pupils
    • --Parasympathetic: "rest and digest"; decreases heart rate, decreases blood pressure, constricts bronchial tree, increases digestion, contracts bladder, and constricts pupils
  64. Somatic Peripheral Nervous System
    • Somatic portion consists of cranial nerves and peripheral nerves
    • Cranial nerves: 12 pairs exit the brain; sensory, motor, and autonomic fibers within them:
    • -CN I- Olfactory, CN II- Optic, CN III- Oculomotor, CN IV- Trochlear, CN V- Trigeminal,
    • -CN VI- Abducens, CN VII- Facial, CN VIII- Vestibulocochlear, CN IX- Glossopharyngeal
    • -CN X- Vagus, CN XI- Accessory, CN XII- Hypoglossal
    • Spinal nerves: 31 pairs; contain sensory and motor fibers within protective sheaths (endoneurium, perineurium, epineurium)
  65. Sensory Pathway
    • Consists of a 3-neuron chain (primary, secondary, and tertiary)
    • Primary neuron: pseudounipolar neuron with cell body in the dorsal root ganglion
    • -Peripheral process within spinal nerve
    • -Central process synapses with secondary neuron in CNS
    • Secondary neuron: multipolar neuron, cell body within CNS
    • -Axon decussates (crosses) at midline of spinal cord
    • -Ascends to thalamus and synapses with tertiary neuron
    • Tertiary neuron: multipolar cell body in thalamus
    • -Axon -> sensory cortex
  66. Voluntary Motor Pathway
    • 2-neuron pathway from cerebral cortex -> muscle
    • Upper motor neuron (UMN):
    • -Multipolar cell body within cerebral cortex
    • -Axon decussates at level of medulla
    • -Synapses with LMN in ventral horn of spinal cord
    • Lower motor neuron (LMN):
    • -Multipolar cell body in ventral horn of cord
    • -Axon leaves spinal cord via ventral root
    • -Travels within spinal nerve to a skeletal (voluntary) muscle
    • -Terminates at motor end plate
  67. The Reflex Arc
    • Reflex: involuntary, almost instantaneous movement in response to a stimulus
    • -May be autonomic or somatic
    • -Monosynaptic or polysynaptic
    • Motor reflex arc has five elements:
    • -Receptor, sensory neuron, association neuron, motor neuron, effector muscle
    • Example: Patellar reflex ("knee jerk")
    • -Patellar tendon tapped -> muscle spindle activation in quadriceps tendon -> sensory neuron in spinal cord -> interneuron -> motor neuron -> quadriceps muscle extends knee
  68. Muscle Cells
    • Excitable cells that propagate action potential along cell membrane and contract
    • Three types:
    • -Skeletal: striated, long, hundreds of nuclei, no gap junctions, contract in response to acetylcholine released by motor neuron, less energy efficient, controlled at level of actin
    • --Motor unit: motor neuron and the muscle fibers it innervates
    • -Cardiac: striated, intercalated disks ="functional syncytium," spontaneously depolarize
    • --Special cells in sinoatrial node contract at an automatic rate
    • ---Autonomic fibers can alter this rate
    • -Smooth: spindle-shaped cells, one nucleus, may be interconnected by gap junctions (allows slow peristalic movement), nerve endings secrete neurotransmitters, very energy efficient, controlled by phosphorylation of myosin
    • --Muscle of internal organs, blood vessels, airway, and so on
  69. Muscle Organization
  70. Myofiber Structure
    • Sarcolemma: plasma membrane
    • Sarcoplasm: surrounds individual myofibrils within myofiber
    • Myofiber: one multinucleated cell
    • -Composed of myofibrils, which contain thick and thin myofilaments (responsible for striated appearance)
    • --Thick filaments= myosin; Thin filaments= actin
    • --Proteins tropomyosin and troponin aid in contraction
    • --Relaxation is carried out by elastic fibers
    • -Myofibrils divided into sarcomeres, the smallest contractile unit
  71. Myofiber Organization
    • Sarcoplasm: contains smooth ER (sarcoplasmic reticulum), golgi bodies, and mitochondria, which surround myofibrils
    • -Sarcoplasmic reticulum: responsible for concentrating calcium ions within its lumen
    • --Associated with sarcotubules (tubular network)
    • --Terminal cisternae: enlarged areas of sarcoplasmic reticulum, continuous with sarcotubules
    • --T-tubules: perpendicular invaginations of sarcolemma, connect to the terminal cisternae
    • ---T-tubules transmit depolarization of sarcolemma→terminal cistern→leads to release of calcium by sarcoplasmic reticulum
    • Triad: T-tubule and two adjacent terminal cisterns
  72. Excitation of a Muscle Cell
    • Action potential propagated through an alpha motor neuron
    • Reaches the motor neuron terminal, causing calcium influx through calcium-dependent channels
    • Acetylcholine vesicles released in response to calcium influx, cross the synapse to the motor end plate (specialized portion of sarcolemma)
    • Sodium/potassium channels are opened at motor end plate
    • Sodium rush procedures an end-plate potential that spreads in both directions along the sarcolemma
    • Depolarization of T-tubles, which are connected to sarcoplasmic reticulum, causes calcium to be released into the sarcoplasm, carries depolarization into myofibrils
  73. Muscle Contraction
    • Calcium released from sarcoplasmic reticulum into sarcoplasma
    • Calcium binds to troponin C (present in actin of thin filaments)
    • -Alters shape of tropomysin -> exposing myosin binding site
    • --Normally, tropomysin blocks myosin from binding
    • Actin and myson bind, forming cross-bridgs that pivot
    • -Cross-bridges broken by consumption of ATP by myosin ATPase
    • Thick and thin filaments slide over each other -> muscle contraction
    • -Thick and thin filaments never change length
    • -"H" and "I" bands narrow; "A" bandwidth constant
  74. Muscle Contraction
  75. Contractions and Tetanus
    • Isometric contraction: no change in length, increasing muscle tension
    • -Additional/active tension does not change muscle length
    • Isotonic contraction: change in muscle length, constant tension
    • -Eccentric contraction: muscle actively lengthening
    • --Example- lowering an object
    • -Concentric contraction: muscle actively shortening
    • --Example- lifting a weight
    • Tetanus: when multiple stimuli are sent to a muscle it may not be able to relax in between stimuli, which leads to summation (increased force of contraction)
    • -Tetanus results when the muscle is in a constant state of contraction
  76. Types of Muscle Fibers
    • Muscles contain varying combinations of these types of fibers:
    • -Type I (red) fibers: slow twitch, contract slow and fatigue slowly, these are endurance muscles, energy derived from aerobic metabolism
    • --Legs of a chicken are red meat; these muscles are important for endurance
    • -Type II (white) fibers: fast twitch; contract quickly but fatigue easily, energy mainly from anaerobic metabolism, low myoglobin content, contain few mitochondria
    • --Think of white meat on a chicken
    • -Intermediate fibers: share qualities/features of white and red fibers
  77. Muscle Attachment and Movement
    • Tendons attach muscles to bone
    • Antagonist/agonist muscle pairs allow opposing motion
    • Extension: increasing joint angle
    • Flexion: decreasing joint angle
    • Supination/pronation: rotation of forearm or foot
    • Abduction: movement away from the body
    • Adduction: movement toward body
    • Circumduction: circular movement of ball-and-socket joint
    • Rotation: body moves around its axis; atlas rotates on axis
    • Opposition: example- thumb touching first finger
    • Foot motion:
    • -Eversion: soles pointing laterally
    • -Inversion: soles pointing midline
  78. Anatomical Planes
    • Anatomical position: patient standing upright, feet together, arms at side with the palms facing forward; right and left refer to the patient's right and left
    • Planes:
    • -Median/Midsagittal plane: right and left are mirror images
    • -Sagittal plane: parallel to the midsagittal plane on either side
    • -Coronal/frontal plane: divides the body into anterior and posterior sections
    • -Transverse/horizontal planes: divide the body into cross sections
  79. Anatomical Terms
    • Proximal: closer to center of body
    • Distal: farther from center of body
    • Dorsal/posterior: on the back
    • Ventral/anterior: belly side
    • Caudal/inferior: toward the feet
    • Cephalad/superior: toward the head
    • Supine: lying on the back with hands up
    • Prone: lying on stomach
    • Medial: toward the middle of the body
    • Lateral: away from midline
  80. The Skeletal System: Organization
    • Human skeleton is an endoskeleton, provides:
    • -Internal structure, support, protection of organs, site of production of blood cells, storage of calcium and minerals
    • 206 bones, as well as cartilage
    • -Bones may be fused or connected at joints
    • Split up into axial and appendicular skeletons
    • Axial contains: bones of skull, vertebral column, ribs and sternum, middle ear bones, and hyoid
    • Appendicular skeleton consists of:
    • -Pectoral girdle and upper extremities
    • -Pelvic girdle and lower extremities
  81. Axial Skeleton
    • Skull:
    • -8 pairs of fused bones (parietal, temporal, maxillary, palatine, zygomatic, lacrimal, inferior cohcha, nasal)
    • -6 unpaired (frontal, occipital, ethmoid, sphenoid, vomer, mandible)
    • --Mandible is the only movable bone
    • Vertebral column: 26 bones from base of skull to pelvis, separated by intervertebral discs, supported by ligaments
    • -7 cervical (atlas=C1, axis=C2); 12 thoracic; 5 lumbar; sacrum; coccyx
    • -Spinal cord lies within
    • Ribs and sternum:
    • -12 pairs of ribs attached to T1-T12
    • -7 pairs articulate with bony sternum; 3 pairs attached by cartilage to sternum; 2 "floating" ribs
  82. Appendicular Skeleton: Upper Extremity
    • Shoulder girdle: clavicle and scapula
    • Arms: humerus, radius (lateral), and ulna (medial)
    • Hands:
    • -carpal bones, 5 metacarpal bones, phalanges
    • -thumb and 2 (distal and proximal) phalanges
    • -other fingers have 3 (distal, middle, proximal) phalanges
  83. Appendicular Skeleton: Lower Extremity
    • Pelvic girdle: ischium, ileum, and pubic bones
    • Legs: femur, tibia (medial), fibula (lateral)
    • Foot:
    • -7 tarsal bones, 5 metatarsal bones, phalanges
    • -big toe has 2 (distal and proximal) phalanges
    • -other toes have 3 (distal, medial and proximal) phalanges
  84. Bone Structure
    • Bone is connective tissue containing specialized cells within rigid, calcified matrix
    • -Specialized cells include:
    • --Osteocytes: located within lacunae, connected by canaliculi
    • --Osteoblasts: bone-forming cells
    • --Osteoclasts: break down/remodel bone
    • -Bone matrix (largest component of bone; stores calcium and phosphate):
    • --Organic component: collagen fibers, ground substance (glycoproteins)
    • --Inorganic component: minerals; mostly calcium phosphate (hydroxyapatite)
    • Bone marrow: centralized cavity, contains fat and specialized progenitor cells (produce blood cells)
    • Periosteum: fibrous connective tissue that surrounds bone
  85. Bone Structure
  86. Types of Bone
    • Compact Bone:
    • -Firms the surface of most bones
    • -Densely packed osteons/Haversian systems
    • --Haversian canals run parallel to long axis of bone, contain blood vessels
    • ---Surrounded by lamellae (concentric rings)
    • --Blood vessels interconnect via Volkmann's canals (perpendicular to Haversian canals)
    • --Osteocytes lie within spaces between lamellae called lacunnae
    • --Canaliculi: small canals within matrix; radiate from lacunae to Haversian canals
    • Spongy/Cancellous Bone:
    • -Within inner cavity of long bones, flat/irregular bones, vertebrae
    • -Consists of traceulae, forming a lattice-work
    • --Bone marrow within spaces, lined by endosteum
  87. Cartilage
    • Specialized connective tissue composed of chondrocytes that produce extracellular matrix consisting of:
    • -Collagen
    • -Elastin
    • -Ground substance (proteoglycans)
    • Collagen has no blood vessels, chondrocytes are fed by diffusion; therefore this tissue heals slowly
    • Three types of cartilage with varying amounts of above components:
    • -Elastic cartilage: high elastin; found in pinna of ear and epiglottis
    • -Hyalin cartilage: hard cartilage; forms articular surface at end of bones; found in nose, larynx, and sternum
    • -Fibrocartilage: abundant type I collagen; found in intervertabral discs, pubic symphysis
  88. Joints
    • Bones articulate with each other at joints
    • -Classified by type, structure, and function
    • Functional Classification:
    • -Synarthrosis: permits no movement; mostly fibrous (sutures of the skull)
    • -Amphiarthrosis: slightly moveable; mostly cartilaginous joints (intervertebral joints and pubic symphysis)
    • -Diarthrosis: synovial joints that are the most moveable joints in the body (shoulder, knee, hips), classified into categories based on type of movement (hinge, ball and socket, gliding)
    • -Fibrous capsule encases the joint
    • -Hyaline cartilage lines articular surface
    • -Synovial membrane produces a serious, lubricating fluid (synovial fluid)
  89. Tendons and Ligaments
    • Ligaments connect bones to each other
    • -Strong fibrous bands keep joint stable and limit range of motion
    • Tendons connect muscles to bones
  90. The Circulatory System: Overview
    • Includes heart, blood vessels, blood, and lymphatic vessels
    • Functions to transport oxygen and nutrients throughout the body, as well as hormones and other important blood agents, removes waste from tissues and initiates clotting if bleeding occurs
    • Blood vessels are lined by endothelium
    • -Flow: arteries -> arterioles -> capillaries -> venules -> veins -> right heart -> lungs -> left heart -> arteries
    • Lymph is composed of fluid that has left the capillaries and has been reabsorbed by lymphatic channels
    • -Lymph emptied back into veins by lymphatic ducts
  91. The Heart
    • Specialized, 4-chambered (2 atria and 2 ventricles) muscle that propels blood through blood vessels
    • Layers of the heart:
    • -Endocardium: lines interior of the heart (epithelial cells)
    • -Myocardium: heart muscle
    • -Epicardium: exterior of the heart; visceral pericardium (epithelial cells)
    • Beats an average of 60-80 beats per minute and each beat consists of periods of relaxation and contraction of the ventricles and atria
    • -Atrial systole: atria contract first (propel blood into ventricles)
    • Ventricular systole: ventricles then contract to propel blood through pulmonary artery and aorta
    • -Diastole: heart relaxed (myocardium fed during diastole by coronary arteries)
  92. Electrical System of the Heart
    • Cardiac muscle has automaticity and will beat on its own
    • -Purkinje fibers: specialized muscle fibers that conduct beat from SA node
    • During normal sinus rhythm, conduction starts in SA node
    • -SA node (within right atrium) -> AV node (septum of right ventricle) -> bundle of His -> right/left bundle branches -> Purkinje fibers
    • Cardiac nerves of parasympathetic and sympathetic nervous system alter rate of the heart
    • -Parasympathetic (vagus nerve): decreases force and rate, constricts coronary circulation
    • -Sympathetic: increases force and rate, dilates coronary arteries
  93. Blood Flow Through the Heart
    • The heart moves blood through two circuits: pulmonary and systemic circulation
    • Oxygen-poor blood returns to heart from systemic circulation via the superior and inferior vena cava -> right atrium -> tricuspid valve -> right ventricle -> pulmonary semilunar valve -> main pulmonary artery (only artery carrying deoxygenated blood in the body)
    • Blood is oxygenated in the lungs and returned through pulmonary veins (only veins carrying oxygenated blood) to the left atrium -> mitral valve/bicuspid valve -> left ventricle -> aotra -> arteries of body
    • Left ventricle is thicker: pumps against high-systemic pressures
  94. Heart Acts as a "Double Pump"
    • Systolic blood pressure: pressure within blood vessels when heart is contracted (~120 mmHg)
    • Diastolic blood pressure: pressure within vessels when heart is relaxed (~80 mmHg)
  95. Capillary Beds
    • Capillaries: body's smallest blood vessels; lined by a single layer of epithelial cells
    • Gas and nutrient exchange occurs via diffusion, driven by osmotic and hydrostatic gradients (Starling equation)
    • -Osmotic gradient: determines water's movement across a permeable membrane
    • --Driven by difference in impermeable solute concentration within extracellular and intracellular space (albumin: major plasma protein, maintains adequate osmotic pressure)
    • -Hydrostatic gradient: determined by arterial and venous pressures
    • --Highest at arteriolar end of capillary bed, lowest in venules
    • Precapillary sphincters: smooth muscle ring that dilate/contract; determine peripheral resistance and regulate flow to a tissue
  96. Blood Composition
    • Composed of blood cells within plasma
    • Plasma (55 percent of blood volume)
    • -90 percent water
    • -Proteins: albumin (important for maintaining osmotic pressure), globulin, fibrinogen, antibodies, hormones
    • --Fibrinogen -> fibrin to form clots
    • --Serum=plasma after fibrinogen has been clotted
    • -Electrolytes and nutrients
    • Blood cells (45 percent of blood volume)
    • -Red blood cells, platelets, white blood cells
  97. Red Blood Cells
    • Red blood cells (RBCs)/Erythrocytes: biconcave discs produced in bone marrow; no nucleus when mature
    • -Hemoglobin binds to oxygen (oxyhemoglobin) and transports it from lungs to tissues
    • -Transports CO2 from tissue to lungs
    • -100 days life span, then removes by spleen
    • -RBC membrane has >30 antigens, most importantly: Rh antigen (+ or -) and blood group (A, B, O) antigen
    • --Blood Type A= AA or AO genotype
    • --Blood Type B= BB or BO genotype
    • -Blood Type AB= AB (co-dominant alleles)
    • --Universal recipients: no anti-A or anti-B antibodies
    • --Blood Type O= OO
    • ---Universal donor
  98. Oxygen Dissociation Curve
    • Hemoglobin: metalloprotein that binds oxygen (binds to heme) and CO2 (binds to carboxyl groups on amino acids)
    • -CO2 has different binding site, affects hemoglobin's affinity for oxygen
    • Adult hemoglobin (Hemoglobin A) has two alpha and two beta subunits
    • Oxygen dissociation curve is sigmoidal due to the cooperative binding of oxygen (oxygen binds easier when other peptide chains bound)
    • Bohr effect: oxygen dissociation curve shifts to the right in the presence of decreased pH and increased carbon dioxide -> oxygen given up to tissues easier
    • Curve also affected by changes in temperature and DPG (metabolic organic phosphate)
  99. White Blood Cells/Leukocytes
    • Have nuclei
    • Five types categorized into granulocytes and agranulocytes
    • Granulocytes have membrane-bound enzymes (granules) that act on endocytosed materials
    • Three types of granulocytes named after staining properties:
    • -Neutrophils: most abundant WBC, multilobed nucleus, firswt responders to bacterial and fungal infections; neutrophils   -> pus
    • -Eosinophils: bilobed nucleus, active in parasitic infections and allergic reactions
    • -Basophils: large, blue-staining granules containing histamine and heparin
    • Agranulocytes:
    • -Lymphocytes: (B cells, T cells, and NK cells), produced in lymphoid tissue and bone marrow
    • -Monocytes: become macrophages in tissue, important in phagocytosis of pathogens
  100. Platelets and Clotting
    • Platelets are fragments of megakaryocytes (large platelet precursor cells in bone marrow), adhere to each other and to blood vessels to stop bleeding
    • Thromboplastin released from platelets
    • -Reacts with prothrombin and calcium in the blood -> thrombin
    • -Thrombin is a protease that cleaves fibrinogen -> fibrin
    • --Fibrin is insoluble and holds the clot together
    • Body's clotting cascade kept in balance by natural anticoagulation proteins such as heparin and antithrombin III
    • Aspirin can predispose to bleeding through deactivation of platelet's clotting mechanism
  101. Lymphatic System
    • Major functions:
    • -Equalization of fluid distribution, returns fluid to blood
    • -Transports proteins and large fat molecules
    • -Site of lymphocyte production, important for immune function
    • Lymph is similar to blood plasma in composition but higher in lymphocytes
    • -Lymph drained from digestive tract (chyle) is high in fat
    • Unlike cardiovascular system, lymphatic system has no pump, moved by peristalsis
    • -Movement aided by valves and contraction of nearly skeletal muscles
    • -Lymphatic fluid joins venous circulation at thoracic duct (near left sublavian vein) and right lymphatic duct
  102. Lymph Nodes
    • Interspersed along the lymphatic channels
    • Size ranges from a few millimeters to 1-2 cm; enlarge during infectious or cancerous process in response to presence of antigens
    • Filter lymph, produce lymphocytes
    • Lymph node structure:
    • -Cortex: contains lymphoid follicles; site of production/maturation of B lymphocytes
    • --T lymphoytes found in deep cortex
    • -Inner medulla: filled with cords of lymphocytes (B cells, plasma cells)
  103. Lymphoid Organs
    • Sites of lymphocyte development
    • Critical role in capturing pathogens
    • -Two types:
    • --Lymphoid tissue within organs and cavities
    • ---Peyer's patches (in ileum)
    • ---Appendix
    • ---Tonsils
    • --Lymphoid tissue that monitors blood and lymph
    • ---Lymph nodes
    • ---Spleen: blood passes through the spleen, which is rich in lymphocytes and macrophages
    • ----Destroys old red blood cells
    • ----Destroys encapsulated microorganisms
  104. Immune System
    • Barrier layers of skin and organs provide primary protection against infection
    • Innate immunity: less specific, doesn't require previous exposure to a pathogen
    • -Example: NK cells, complement, neutrophils are capable of recognizing generic/common features of pathogens
    • --Not specific, less effective than adaptive mechanisms
    • Adaptive immunity: requires previous exposure, develops while an infection is initially fought by innate mechanisms
    • -Primary immune response: occurs during first encounter with an organism
    • --Slow, less efficient
    • -Secondary immune response: fast, body has "memory" or organism
  105. Immunization
    • Bypasses primary immune response so host can respond quickly to pathogen
    • Passive immunity: preformed antibodies transferred to an organism, temporary immunity is conferred
    • -Breast feeding passes mother's IgA antibodies to child
    • Active immunity: generates long-lasting, more effective immunity (IgG and IgM) by organism being exposed to weakened pathogen (general mode for vaccinations)
    • -Subsequent exposure results in secondary immune response
  106. Adaptive Immune Response
    • Two types:
    • -Cell-mediated response
    • -Antibody-mediated response/humoral
    • Cell-mediated response: targets virus-infected and cancer cells, foreign or transplanted cells
    • -Involves T lymphocytes that kill cells targeted by immune system
    • Antibody-mediated response: targets viruses, bacteria, foreign molecules
    • -Foreign molecules activate B lymphocytes that become plasma cells
    • --Produced specific antibodies to bind to surface of target cells
    • --Presence of antibodies triggers complement activation or phagocytosis by neutrophils
  107. Antibodies
    • Produced by plasma cells
    • Subdivided into classes/isotypes based on the heavy chain, which has a constant and variable region
    • -Constant region is the same in antibodies of same isotypes
    • Light chain (may be kappa or lambda)
    • Isotypes:
    • -IgA: found in mucosal surfaces (gut, respiratory tract)
    • -IgD: cell surface receptor on inactivated B lymphocytes
    • -IgE: involved in allergy in defense against parasites
    • -IgG: provides majority of immunity, crosses placenta
    • -IgM: activated in early stages of B-cell activation
  108. T cells
    • Majority produced in bone marrow; differentiate in the thymus
    • Antigen-presenting cells: present portions of foreign proteins to helper T cells (Th cells) and activate them
    • Helper T lymphocytes: stimulate cytotoxic T cells (Tc cells) and B lymphocytes
    • Cytotoxic T lymphocytes: recognize MHC I (major histocompatibility complex I) patterns
    • -Destroys cells that are recognized by T-cell receptors by triggering apoptosis (programmed cell death)
  109. The Respiratory System
    • Provides gas exchange at alveolar membrane; removes inhaled particles; humidifies and warms air
    • Movement of air during inspiration:
    • -nose or mouth -> pharynx (nasopharynx and oropharynx) -> larynx -> trachea -> left and right mainstream bronchi -> left and right lungs (containing intrapulmonary bronchi -> bronchioles -> alveoli)
    • Inspiration: contraction of diaphragm (innervated by phrenic nerve: C3, C4, C5) leads to expansion of thoracic cavity and decreased intrathoracic pressure, air rushes in 
    • -Normal breath/tidal volume= 500mL
    • Expiration: passive relaxation of diaphragm leads to decreased intrathoracic volume (and increased pressure)
    • -Lungs have elastic recoil, decreased by smoking and amphysema
  110. Gas Exchange
    • Alveoli surrounded by large capillary network, allowing for diffusion of gases across respiratory membrane (alveolar wall and basement membrane (BM), BM of pulmonary capillary, pulmonary capillary endothelium)
    • Gas exchange occurs only at alveoli; remainder of bronchial tree is anatomical dead space
    • Surfactant: lowers surface tension; keeps alveoli from collapsing
    • -Due to the small radius of alveoli, the inflation pressure (p) would be very high but surfactant has a very low surface tension (T)
    • -Amount of pressure needed to oppose surface tension and maintain inflation is determined by the Law of Laplace: p=2T/radius
  111. Gas Transport
    • Oxygen transported in the form of oxyhemoglobin
    • -Affinity for hemoglobin affected by
    • --pH
    • --temperature
    • --concentration of 2,3-diphosphoglycerate (DPG)
    • --carbon dioxide
    • Carbon dioxide may be dissolved in plamsa, bound to hemoglobin (on carboxyl groups of amino acids) or converted to bicarbonate ions (due to carbonic anhydrase on red blood cells)
    • Inspired are is approximately 21 percent oxygen
    • -Partial pressure of humidified oxygen in trachea = 760mmHg (sea level) - 47 mmHg (partial pressure of water in air) = 713 mmHg * .21 (21% oxygen) = 150 mmHg
  112. Airway Anatomy
    • The right lung has three lobes, and the left lung has only two because the heart takes up space
  113. Respiration Regulation
    • Respiratory Center (in medulla): controls inspiration and expiration
    • -Spontaneous rhythm of 12-15 breaths/minute
    • --Modulated by centers in pons and medulla and stretch receptors in lungs
    • Carotid and aortic bodies (peripheral chemoreceptors): sense arterial pH and PO2 changes
    • Increased arterial PCO2 (hypercapnia) sensed by peripheral chemoreceptors and center in medulla (PCO2 diffuses across CSF) -> increased respirations to remove CO2
    • Ventilation is more sensitive to hypercapnia (high PCO2) than to hypoxia (low PO2) or acidosis
    • Smooth muscle in airway walls innervated by sympathetic and parasympathetic nerves
    • -Parasympathetic -> bonchoconstriction; increased airway resistance
    • -Sympathetic -> bronchodilation
  114. Endocrine System
    • Hormones: molecules that provide very specific control at the cellular level
    • -May be peptides, amino acids, proteins, fatty acids
    • Carried within blood and diffuse from capillary beds to target cells
    • Unlike the nervous system, effects are slow and long-lasting
    • -Steroid hormones enter nucleus of cells and affect transcription
    • Neuro-endocrine relationship:
    • -Hypothalamus stimulates pituitary gland, which secretes hormones to stimulate endocrine organs (thyroid, parathyroid, pancreas, adrenals, testes/ovaries)
    • -Regulated via negative feedback
    • -Hormones from endocrine organs decrease secretion of stimulatory hormones from hypothalamus and pituitary
  115. The Pituitary Gland
    • Pituitary gland:
    • -Anterior pituitary (adenohypophysis)
    • --Originates from Rathke's pouch (oral epithelium)
    • --Connected via pituitary portal system to hypothalamus
    • --Produces: adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, endorphins
    • ---Remember FLAT PEG to help you recall anterior pituitary hormones
    • -Posterior Pituitary (neurohypophysis)
    • --Hormones produced by hypothalamus; direct neuronal connections
    • --Secretes: oxytocin and antidiuretic hormone (ADH)
  116. Growth Hormone and Prolactin
    • Secreated by anterior pituitary
    • Growth hormone (GH):
    • -Stimulates liver to release IGFs -> bone growth
    • -Inhibited by somatostatin
    • -Hypersecretion -> gigantism if ossicifation is incomplete; acromegaly if completed (in adults)
    • -Hyposecretion -> dwarfism
    • Prolactin:
    • -Promotes and maintains lactation
    • --Works along with estrogen and progesterone
    • -Helps maintain corpus luteum
  117. The Thyroid and TSH
    • Thyroid stimulating hormone (TSH): anterior pituitary
    • -Produced in response to TRH (hypothalamus)
    • -Stimulates thyroid to secrete T3 and T4/thyroxin
    • -Hypersecretion ->hyperthyroidism
    • --Weight loss, exopthalmos, tachycardia
    • --Goiter: enlarged thyroid due to inflammation or cancer
    • -Hyposecretion -> hypothyroidism (hypo=low)
    • --Cretinism in children
    • --Adults: low energy, weight gain, mental slowness
    • Thyroid gland (located in anterior neck)
    • -Fillicles utilize iodine to produce T3 and T4
    • --Control metabolism, organ growth, and nervous system activity
    • -C cells/parafollicular cells produce calcitonin, which decreases blood calcium
    • --Remember: calcitonin tones down calcium
  118. Parathyroid Glands
    • Four small glands located on posterior aspect of thyroid gland
    • Secrete parathyroid hormone (PTH), which:
    • -Has antagonistic relationship with calcitonin
    • -Stimulates osteoclasts to break down bone and increase blood calcium levels
    • -Increase absorption of calcium by the intestines
    • -Stimulates vitamin D production, which aids in calcium absorption
    • -Promotes calcium reuptake in the kidneys
  119. The Adrenal Glands and ACTH
    • Adrenocorticotropic hormone (ACTH) from anterior pituitary in response to corticotropin releasing hormone (CRH) from hypothalamus
    • Signals adrenal cortex to produce glucocorticoids, adrenal androgens
    • Adrenal glands (atop kidneys)
    • -Cortex: mesodermal origin; three zones from outer to inner:
    • --Zona glomerulosa: mineralocorticoids (aldosterone)
    • ---Regulates salt/electrolyte balance
    • --Zona fasciculata: glucocorticoids (e.g., corticosterone, cortisone)
    • ---Regulates sugar, fat, protein metabolism
    • --Zona reticularis: adrenal sex hormones (17 ketosteroids)
    • ---Increase hair, masculinization
    • --Remember levels of cortex: GFR=salt, sugar, sex (the deeper you go, the sweeter it gets)
    • -Medulla: neural crest origin; secrete epinephrine and norepinephrine
  120. Adrenal Disease
    • Adrenal insufficiency: caused by trauma to adrenals, autoimmune process (Addison's disease) or necrosis of glands
    • -Due to inadequate steroid production patients have
    • --Low blood pressure and low serum sodium (from low aldosterone)
    • --Deficient glucocorticoids -> weakness
    • --Low immune function
    • --Bronze skin due to increased melanocyte-stimulating hormone (same precursor as ACTH)
    • ---ACTH increased because no negative feedback from adrenals
    • Hyperadrenalism:
    • -Excess aldosterone -> muscle weakness/paralysis, hypertension, renal failure
    • -Excess corticosteroids (Cushing's syndrome) -> moon face, skin thinning, muscle weakness, central obesity
    • -Excess adrenal androgens -> virilism
  121. Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)
    • FSH and LH produced by anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from hypothalamus
    • FHS and LH work synergistically to maintain fertility
    • FHS:
    • -Females: stimulates ovary to produce a primary follicle -> mature Graafian follicle
    • --Follicle grows, releases inhibin, which inhibits FSH
    • --FSH stimulates granulosa cells to produce estrogen (estradoil)
    • -Males: stimulates production of androgen-binding protein by sertoli cells of testes (essential for spermatogenesis)
    • LH:
    • -Females: LH surge -> ovulation
    • --Converts ruptured follicle -> corpus luteum (produces progesterone)
    • -Males: acts on Leydig cells of testes to produce testosterone
  122. Female Fertility Cycle
    • As estrogen and progesterone concentrations increase in the blood, FSH and LH are inhibited
    • -LH keeps the corpus luteum, which produces progesterone, functioning
    • -If pregnancy occurs, the placenta begins to produce progesterone, if not, the uterine lining sheds (menstruation) and a new cycle begins
  123. Female Reproductive System
    • Ovaries: stimulated by FSH and LH; produce eggs
    • -Eggs are released from follicles, picked up by fibra at the end of the fallopian tubes
    • Breasts: accessory organs containing mammary glands; respond to prolactin to produce milk
  124. Male Reproductive System
    • Testes: produce sperm, which mature and are stored in the epididymis
    • Semen: contains sperm and other fluids secreted by other accessory glands:
    • -Prostate: adds fructose, acid phosphatase, citric acid, calcium, fibrinolyson
    • -Seminal vessicles: phosphorylcholine
    • -Bulbourethral glands: produce "pre-ejaculation," which neutralizes acidic environment of urethra before ejaculation
    • Vas Deferens: carries sperm from testes to the urethra
  125. Gametogenesis
    • Occurs within gonads
    • Most of the cells of the body are diploid (46 chromosomes), except for gametes (sperm and egg), which are haploid (23 chromosomes)
    • -Reduction in number of chromosomes occurs during gametogenesis when primary spermatocyte and primary oocyte undergo meiosis
  126. Spermatogenesis
  127. Oogenesis
  128. Embryogenesis
    • Fertilization: joining of sperm and egg to form a zygote; occurs in ampulla of fallopian tube
    • -Sperm binds zona pellucida of secondary oocyte, causing acrosomal reaction (releases enzymes to help penetrate the zona)
    • -Penetration triggers the cortical reaction (makes egg impermeable to other sperm)
    • --Fast block driven by rapid depolarization
    • --Slow block caused by calcium release
    • -Nuclei of sperm and secondary oocyte fuse
    • --Male pronucleus forms and tail of sperm falls off (site of male mitochondria)
    • --Secondary oocyte completes meiosis II -> ovum
    • ---Ovum's nucleus is female pronucleus
    • -Pronuclei fuse -> zygote
  129. First Week of Development
    • Cleavage: series of mitotic divisions of zygote; first divisions occur within fallopian tube
    • Zygote -> blastula (composed of blastomeres-2 cells, 4 cells, 8 cells- totipotent until 8-cell stage) -> 320cell morula (with inner/outer cell masses) -> blastocyst (occurs when fluid forms within cavity of morula)
    • Blastocyst will implant in uterine cavity around day 7
    • -Inner cell mass -> embryoblast (will become the embryo)
    • -Outer cell mass -> trophoblast (part of the placenta)
  130. Gastrulation
    • Occurs during the embryonic period (weeks 3-8)
    • Process that leads to establishment of primary germ layers (ectoderm, endoderm, mesoderm) from which all human cells arise
    • -Cells migrate through the primitve groove to form these layers
  131. Primary Germ Layer Derivatives
    • Ectoderm: skin, inner ear, and external auditory meatus, external nasal passages, enamel, gums, adenohypophysis (anterior pituitary), lens of eye, cells of mammary gland, lining of lower anus, vestibule of vagina, distal male urethra
    • -Neuroectoderm: central and peripheral nervous systems, pineal gland and posterior pituitary, adrenal medulla
    • -Neural crest: ganglia, pia, and arachnoid (meninges), melanocytes
    • Mesoderm: muscles and connective tissue, blood, bone marrow, cortex of adrenals, serous organ membranes, dura and microglia
    • Endoderm: epthelium of GI tract, thyroid, thymus, epithelium of respiratory tract, lining of genitourinary system
  132. Neurulation
    • Formation/closure of neural tube
    • Notochord signals overlying ectoderm -> neuroectoderm and neural plate
    • -Neural plate folds -> neural tube (open at both ends at neuropores), some cells become neural crest cells
    • --Rostral (toward head) neural tube -> brain
    • --Caudal (toward feet) end -> spinal cord
    • --Lumen 0f tube -> ventricles, central canal of cord
    • During week 4, rostral neural tube forms:
    • -Prosencephalon
    • --Telencephalon: cerebral hemispheres
    • --Diencephalon: thalamus, hypothalamus, most of eye
    • -Mesencephalon: midbrain
    • -Rhombencephalon
    • --Metencephalon: pons, cerebellum
    • --Mylencephalon: medulla
  133. Twinning
    • Fraternal twins are dizygotic twins
    • -Two separate eggs were fertilized by different sperm
    • -May be different sexes
    • Monozygotic twins are identical and always the same sex
    • -Blastocyst's inner cell mass split into to, forming two genetically identical embryoblasts (inner cell mass)
    • --Conjoined twins: inner cell mass does not separate completely and the blastocyst develops into two identical humans separated by some amount of tissue
  134. Fetal Circulation
    • Oxygenated blood from the placenta delivered via umbilical vein
    • Umbilical arteries carry deoxygenated blood back to the placenta
    • -Umbilical cord has AVA (2 umbilical arteries and 1 vein)
    • Oxygenated blood bypasses hepatic circulation through the ductus venosus (becomes ligamentum venosuum after birth)
    • Much of oxygenated blood passes from right atrium to left atrium through foramen ovale, bypasses nonfunctioning fetal lungs
    • -Foramen ovale closes at birth when baby takes first breath and pulmonary pressures drop
    • Ductuc arteriosus connects pulmonary artery to aorta, allows blood from pulmonary circulation to rejoin systemic circulation
    • -Becomes ligamenum arteriosum
  135. Integumentary System (Skin, Hair, Nails, Glands)
    • Skin is a protective barrier against external environment; made of epidermis and dermis
    • -Protects against dehydration from fluid loss
    • -Excretes wastes and fluids via sweat
    • -Primary sense organ for somatic sensation (touch, pressure, temperature, pain)
    • -Allows conversion of vitamin D precursors (7-dehydrocholesterol) -> vitamin D
    • Glands: structures containing secretory cells
    • -Sebaceous glands: acinary type; secrete lipid-rich sebum into hair follicles
    • -Sweat glands:
    • --Eccrine: distributed almost everywhere on the body, secrete sweat
    • --Apocrine: larger glands; secrete viscous sweat from pubic area, axilla, and around breasts
  136. Skin Structure
  137. Hair and Nails
    • Hair: composed of keratin; covers entire body except for palms, soles, glans of penis, labia minora, sides of finger and toes
    • -Composed of a shaft that is attached to a root within the hair follicle
    • --Connective tissue papilla has a rich blood supply
    • --Erector pili: smooth muscles that contract to raise hair (causes "goosebumps")
    • Nails: composed of keratinized epithelium; helps to shape distal digits and provide protection
    • -Composed of nail body that is attached at the nail root
    • -Cuticle and eponychium are thickened stratum corneum that surround the nail and extend over its edges
    • -Lanula: white area at base of the nail, continuous with the root
    • -Hyponichium: thickened skin at distal end of nail plate
  138. The Digestive System
    • Extraction of nutrients from food begins with ingestion
    • -Food is chewed and moistened with saliva and mucus to form a bolus
    • --Saliva is formed by the three pairs of salivary glands in the mouth (parotid, submandibular, sublingual)
    • ---Amylase and disacchiridase (maltase) in saliva begin to break carbohydrates into glucose
    • -Epiglottis protects the airway during swallowing; prevents aspiration of food into trachea
    • -Swallowing involves sequential contraction of pharyngeal muscles to move bolus from oropharynx into espphagus
    • --Upper one-third of esophagus is skeletal muscle (voluntary); middle one-third is mixed; lower one-third is smooth muscle (involuntary)