Chase Findley, MSIV
Cell Cycle PhasesCell Cycle Phases
Checkpoints control transitions between Checkpoints control transitions between cell phases. Regulated by cyclins, cdks, cell phases. Regulated by cyclins, cdks, and tumor suppressors. and tumor suppressors.
Cell Cycle PhasesCell Cycle Phases Permanent cellsPermanent cells
Remain in G0, regenerate from Remain in G0, regenerate from stem cellsstem cellsNeurons, skeletal and cardiac muscle, RBC’sNeurons, skeletal and cardiac muscle, RBC’s
Stable cellsStable cellsEnter G1 from G0 when stimulatedEnter G1 from G0 when stimulatedHepatocytes, lymphocytesHepatocytes, lymphocytes
Labile cellsLabile cellsNever go to G0, divide rapidly with short G1Never go to G0, divide rapidly with short G1Bone marrow, gut epithelium, skin, hair folliclesBone marrow, gut epithelium, skin, hair follicles
Plasma Membrane Plasma Membrane CompositionComposition Asymmetric fluid bi-layerAsymmetric fluid bi-layer 50% cholesterol, 50% phospholipids50% cholesterol, 50% phospholipids Small amounts of protein, sphingolipids, Small amounts of protein, sphingolipids,
glycolipidsglycolipids High cholesterol or long saturated fatty High cholesterol or long saturated fatty
acid content increases melting acid content increases melting temperaturetemperature
Endoplasmic ReticulumEndoplasmic Reticulum RoughRough
Site of synthesis of Site of synthesis of secretory (exported) proteinssecretory (exported) proteins and N-linked and N-linked oligosaccharideoligosaccharide addition addition
In neurons, (In neurons, (Nissl bodiesNissl bodies) synthesize enzymes ) synthesize enzymes and peptide neurotransmittersand peptide neurotransmitters
Mucous secreting goblet cells and antibody Mucous secreting goblet cells and antibody secreting plasma cells are rich in RERsecreting plasma cells are rich in RER
Rough Endoplasmic Rough Endoplasmic ReticulumReticulum
Endoplasmic ReticulumEndoplasmic Reticulum
SmoothSmoothSite of synthesis of steroidsSite of synthesis of steroidsDetoxification of drugs and poisonsDetoxification of drugs and poisonsLiver hepatocytes and adrenal cortex are Liver hepatocytes and adrenal cortex are
rich in SERrich in SER
Smooth Endoplasmic Smooth Endoplasmic ReticulumReticulum
Golgi ApparatusGolgi Apparatus
““Distribution center” of proteins and Distribution center” of proteins and lipids from ER lipids from ER to plasma membrane, to plasma membrane, lysosomes, secretory vesicleslysosomes, secretory vesicles
Adds Adds mannose-6-phosphatemannose-6-phosphate to proteins, to proteins, targeting to targeting to lysosomelysosomeFailure results in I-cell disease, enzymes Failure results in I-cell disease, enzymes
secreted outside cellsecreted outside cell
Proteoglycan assembly and sulfationProteoglycan assembly and sulfation
Golgi ApparatusGolgi Apparatus
MicrotubulesMicrotubules Helical array of Helical array of polymerized dimers of polymerized dimers of αα
and and ββ tubulin tubulin Each dimer has 2 GTP boundEach dimer has 2 GTP bound Incorporated into flagella, cilia, mitotic Incorporated into flagella, cilia, mitotic
spindles, neuronsspindles, neurons Chediak-Higashi syndromeChediak-Higashi syndrome
Defect in microtubule polymerization with Defect in microtubule polymerization with decreased phagocytosisdecreased phagocytosis
Target of mebendazole, taxol, griseofulvin, Target of mebendazole, taxol, griseofulvin, vincristine, vinblastine, colchicinevincristine, vinblastine, colchicine
Cilia StructureCilia Structure
9+29+2 arrangement of microtubules arrangement of microtubules Dynein (ATPase) links peripheral 9 Dynein (ATPase) links peripheral 9
doublets, causes bending by differential doublets, causes bending by differential sliding of doubletssliding of doublets
Dynein=retrograde Kinesis=anterogradeDynein=retrograde Kinesis=anterograde Kartagener’s syndromeKartagener’s syndrome
Dynein defect, immotile Dynein defect, immotile cilia, infertility, recurrent cilia, infertility, recurrent infections infections
CollagenCollagen Most abundant protein in bodyMost abundant protein in body Organizes, strengthens extracellular matrixOrganizes, strengthens extracellular matrix Type IType I
Bone, skin, tendonBone, skin, tendon, dentin, fascia, cornea, dentin, fascia, cornea Type IIType II
CartilageCartilage, vitreous body, nucleus pulposus, vitreous body, nucleus pulposus Type III (Reticulin)Type III (Reticulin)
Skin, blood vessels, uterus, fetal tissueSkin, blood vessels, uterus, fetal tissue Type IVType IV
Basement membraneBasement membrane
Collagen SynthesisCollagen Synthesis Inside fibroblasts
Synthesis (RER)○ Translation of collagen α-chains (preprocollagen)
Hydroxylation (ER)○ Specific proline and lysine residues, requires
Vitamin CGlycosylation (Golgi)
○ Pro-α chain residues, formation of procollagen (triple helix of α-chains)
Exocytosis○ Procollagen exocytosed to extracellular space
Collagen SynthesisCollagen Synthesis Outside fibroblastsOutside fibroblasts
Proteolytic processingProteolytic processing○ Cleavage of terminal regions of procollagen, Cleavage of terminal regions of procollagen,
transforms into transforms into insoluble tropocollageninsoluble tropocollagenCross-linkingCross-linking
○ Reinforcement of many staggered tropocollagen Reinforcement of many staggered tropocollagen molecules by molecules by covalent lysine-hydroxylysine cross-covalent lysine-hydroxylysine cross-linkagelinkage, produces , produces collagen fibrilscollagen fibrils
○ Defective collagen synthesis causes Defective collagen synthesis causes Ehlers-Ehlers-Danlos syndrome.Danlos syndrome.
ElastinElastin
“Stretchy” protein Rich in proline, lysine Found in lungs, large arteries, elastic
ligaments α-1 antitrypsin inhibits elastase,
excessive elastase activity causes emphysema
Phosphotidylcholine Phosphotidylcholine (Lecithin) Function(Lecithin) Function Major component of Major component of RBC membranesRBC membranes, ,
surfactantsurfactant, , myelinmyelin, , bilebile Used in esterification of cholesterolUsed in esterification of cholesterol
Immunohistochemical Immunohistochemical StainsStains Connective TissueConnective Tissue MuscleMuscle Epithelial CellsEpithelial Cells NeuronsNeurons NeurogliaNeuroglia
Vimentin Desmin Cytokeratin Neurofilaments Glial fibrillary acid Glial fibrillary acid
proteinsproteins
Digestive Tract HistologyDigestive Tract HistologyMucosaMucosa
○ Contains epithelium, lamina propria, Contains epithelium, lamina propria, muscularis mucosa muscularis mucosa
○ Absorptive function, villaeAbsorptive function, villaeSubmucosaSubmucosa
○ Contains Contains submucosalsubmucosal nerve plexus nerve plexusMuscularis externaMuscularis externa
○ Contains Contains MyentericMyenteric nerve plexus nerve plexus○ Inner circular, outer longitudinalInner circular, outer longitudinal
Serosa/adventitiaSerosa/adventitia
Digestive Tract HistologyDigestive Tract HistologySubmucosal nerve plexiSubmucosal nerve plexi
○ SubmucosalSubmucosal layer layer○ Coordinates Coordinates secretionssecretions, blood flow, absorption, blood flow, absorption
Myenteric nerve plexiMyenteric nerve plexi○ Muscularis externa Muscularis externa layerlayer○ Coordinates Coordinates motilitymotility
Digestive Tract HistologyDigestive Tract HistologyBrunner’s GlandsBrunner’s Glands
○ Located in Located in duodenal submucosaduodenal submucosa○ Secrete Secrete alkaline mucousalkaline mucous, neutralize acidic , neutralize acidic
stomach contentsstomach contents○ Hypertrophy in peptic ulcer diseaseHypertrophy in peptic ulcer disease
Digestive Tract HistologyDigestive Tract HistologyPeyer’s PatchesPeyer’s Patches
○ Unencapsulated lymph tissue Unencapsulated lymph tissue in mucosa and in mucosa and submucosa of small intestinesubmucosa of small intestine
○ Take up antigen, stimulate local B cells to Take up antigen, stimulate local B cells to differentiate into differentiate into IgA-secreting plasma cellsIgA-secreting plasma cells
○ IgA secreted into lumenIgA secreted into lumen
Digestive Tract HistologyBarrett’s EsophagusBarrett’s Esophagus
○ Replacement of non-keratinized, Replacement of non-keratinized, squamoussquamous epithelium with epithelium with intestinal columnarintestinal columnar epithelium epithelium in distal esophagusin distal esophagus
○ Caused by acid reflux, may lead to Caused by acid reflux, may lead to adenocarcinomasadenocarcinomas
○ Example of Example of metaplasiametaplasia
Liver HistologyLiver HistologyZone 1Zone 1
○ PeriportalPeriportal○ Sensitive to Sensitive to toxictoxic
injuryinjuryZone 2Zone 2
○ intermediateintermediateZone 3Zone 3
○ Pericentral Pericentral ○ Sensitive to Sensitive to ischemic ischemic
injuryinjury
GI Secretory Cells (More thoroughly covered in GI session)
Parietal Cells (Stomach)○ Intrinsic factor
B12 absorption, destroyed in pernicious anemia
○ Gastric acid (HCl)Chief Cells
○ PepsinProtein digestion
Mucosal Cells○ Bicarbonate
G Cells○ Gastrin
ErythrocytesErythrocytes AnucleateAnucleate BiconcaveBiconcave
High surface area to volume ratio for easy gas High surface area to volume ratio for easy gas exchangeexchange
Life span: 120 daysLife span: 120 days Glucose energy sourceGlucose energy source
90% anaerobically degraded to lactate90% anaerobically degraded to lactate Membrane contains chloride-bicarbonate Membrane contains chloride-bicarbonate
antiport, involved in “physiologic chloride antiport, involved in “physiologic chloride shift”shift”
ErythrocytesErythrocytes
AnisocytosisAnisocytosisVarying sizeVarying size
PoikilocytosisPoikilocytosisVarying shapeVarying shape
ReticulocyteReticulocyteImmature erythrocyteImmature erythrocyte
○ Larger, bluish tingeLarger, bluish tinge
NeutrophilsNeutrophils
Multilobed nucleusMultilobed nucleus Mediate Mediate acute inflammatory responseacute inflammatory response PhagocyticPhagocytic Primary granules contain hydrolytic Primary granules contain hydrolytic
enzymes, lysozyme, myeloperoxidaseenzymes, lysozyme, myeloperoxidase Hypersegmented in B12/folate Hypersegmented in B12/folate
deficiencydeficiency
Neutrophils Normal Hypersegmented
Leukocytes
GranulocytesGranulocytesBasophils, eosinophils, neutrophilsBasophils, eosinophils, neutrophils
Mononuclear cellsMononuclear cellsLymphocytes, monocytesLymphocytes, monocytes
LymphocytesLymphocytes
Round, densely staining nucleusRound, densely staining nucleus Little cytoplasmLittle cytoplasm T & B lymphocytesT & B lymphocytes
T LymphocytesT Lymphocytes
Mediate Mediate cellularcellular immune response immune response Originate from stem cells in bone Originate from stem cells in bone
marrow, mature in marrow, mature in thymusthymus Differentiate into:Differentiate into:
Cytotoxic T cellsCytotoxic T cells○ MHC I, CD8MHC I, CD8
Helper T cellsHelper T cells○ MHC II, CD4MHC II, CD4
Suppressor T CellsSuppressor T Cells
B LymphocytesB Lymphocytes
Mediate Mediate humoralhumoral immune response immune response Originate from stem cells in bone Originate from stem cells in bone
marrow, mature in marrow, mature in marrowmarrow Migrate to peripheral lymph tissueMigrate to peripheral lymph tissue Differentiate into Differentiate into plasma cellsplasma cells, produce , produce
antibodyantibody when presented with antigen when presented with antigen Function as APC via MHC IIFunction as APC via MHC II
Mast CellsMast Cells
Mediate Mediate allergic reaction allergic reaction Contain histamine, heparin, Contain histamine, heparin,
chemotactic factorschemotactic factorsBind Bind IgEIgE to cell membrane to cell membrane
Found in Found in tissuetissue Cromolyn sodium Cromolyn sodium
prevents degranulationprevents degranulation
Eosinophils
MonocytesMonocytes
Kidney shaped nucleusKidney shaped nucleus Differentiates to macrophages Differentiates to macrophages in tissuein tissue
Macrophages
Phagocytic for bacteria, cell debris, senescent blood cells
Activated by gamma interferon Function as antigen presenting cell via
MHC II
Plasma Cells
Off-center nucleus, clock-face chromatin Abundant rough endoplasmic reticulum
and Golgi apparatus Differentiate from B cells, produce
antibody
Eosinophils
Bilobate nucleus Highly phagocytic for antigen-antibody
complexes Defend against helminth and protozoan
infections Elevated in allergies, asthma certain
neoplasms, collagen vascular diseases
Basophils
Bilobate nucleusBilobate nucleus Mediate Mediate allergic reactionallergic reaction
Contain histamine, heparin, leukotrienesContain histamine, heparin, leukotrienes
Found in blood
Epidermal LayersEpidermal Layers
*Langerhan’s cells are dendritic cells that function as APC’s in skin. *Langerhan’s cells are dendritic cells that function as APC’s in skin. Remember Remember Birbeck granulesBirbeck granules!!
Epithelial Cell JunctionsEpithelial Cell Junctions Zona occludens (tight junction)Zona occludens (tight junction)
Creates semi-permeable barrierCreates semi-permeable barrier Macula adherensMacula adherens
Small discrete points of attachmentSmall discrete points of attachment Gap junctionGap junction
Allows adjacent cells to communicate via Allows adjacent cells to communicate via metabolic/electrical processesmetabolic/electrical processes
HemidesmosomeHemidesmosomeAnchors cells to extracellular matrixAnchors cells to extracellular matrix
Integrin Integrin Maintains integrity of basement membraneMaintains integrity of basement membrane
Epithelial Cell Junctions
Skeletal Muscle Cell Skeletal Muscle Cell StructureStructure SarcomereSarcomere
Skeletal muscle unit from Skeletal muscle unit from Z line to Z lineZ line to Z line
A bandA bandArea of overlap of actin Area of overlap of actin
and myosin and myosin
I bandI bandArea of actin onlyArea of actin only
Contraction causes I band Contraction causes I band shortening, A band stays sameshortening, A band stays same
Skeletal Muscle Cell Skeletal Muscle Cell StructureStructure StriatedStriated Peripheral nucleiPeripheral nuclei Linear fibersLinear fibers
Cardiac Muscle Structure Striated Central nuclei Branching fibers Intercalated disks
Contain gap junctions which allow electrical impulse to pass between adjacent cells
Smooth MuscleSmooth Muscle
Non-striatedNon-striated Central, elongated nucleusCentral, elongated nucleus ““Network” muscle fibersNetwork” muscle fibers
Neuron Structure, Schwann Neuron Structure, Schwann CellsCells Individual Schwann
cells myelinate a single PNS axon
Impulse travels via saltatory conduction
Peripheral Nerve LayersPeripheral Nerve Layers EndoneuriumEndoneurium
Invests single nerve fiberInvests single nerve fiber PerineuriumPerineurium
Surrounds a fascicle of fibersSurrounds a fascicle of fibersMust be rejoined for limb re-Must be rejoined for limb re-
attachmentattachment EpineuriumEpineurium
Surrounds entire nerve, Surrounds entire nerve, and associated vesselsand associated vessels
OligodendrogliaOligodendroglia
Each oligodendroglia myelinates Each oligodendroglia myelinates multiple CNS axonsmultiple CNS axons
Predominate glial cell in Predominate glial cell in white matterwhite matter Destroyed in Destroyed in multiple sclerosismultiple sclerosis
MicrogliaMicroglia CNS CNS phagocytesphagocytes MesodermalMesodermal origin (all others origin (all others
from ectoderm)from ectoderm) Enlarge to large amoeboid cells Enlarge to large amoeboid cells
in response to tissue damagein response to tissue damage Fuse into multinucleated giant Fuse into multinucleated giant
cells when infected by HIVcells when infected by HIV
AstrocytesAstrocytes
Physical support and repair of axonsPhysical support and repair of axons K+ metabolismK+ metabolism Maintain blood-brain barrierMaintain blood-brain barrier
Sensory Corpuscles: Sensory Corpuscles: Meissner’sMeissner’s Small, encapsulated nerve endingsSmall, encapsulated nerve endings Dermis of palms, soles, digits (Dermis of palms, soles, digits (hairless hairless
skin)skin) Light discriminatory touchLight discriminatory touch
Sensory Corpuscles: Sensory Corpuscles: PacinianPacinian Large, encapsulated nerve endingsLarge, encapsulated nerve endings Deep skin layers at ligaments, joint Deep skin layers at ligaments, joint
capsules, serous membranes, capsules, serous membranes, mesenteriesmesenteries
Pressure, coarse touch, vibration, Pressure, coarse touch, vibration, tensiontension
Sensory Corpuscles: Merkel’s Cup-shaped nerve endingCup-shaped nerve ending Dermis of Dermis of fingertips, hair folliclesfingertips, hair follicles, hard , hard
palatepalate Light, crude touchLight, crude touch
Blood-Brain Barrier
Formed by:Tight junctions between nonfenestrated
capillary endothelial wallsBasement membraneAstrocyte foot processes
Blood-Brain BarrierBlood-Brain Barrier
Glucose and amino acids cross by carrier-mediated transport
Non-polar molecules cross more readily than polar molecules
Infection destroys tight junctions, leads to vasogenic edema
Renal StructureRenal Structure
Glomerular Structure
Sperm StructureSperm Structure Head (acrosome)Head (acrosome)
Derived from Golgi apparatusDerived from Golgi apparatus NeckNeck
Contains Contains mitochondria, mitochondria, energy supply from energy supply from fructosefructose
TailTailDerived from centriolesDerived from centrioles
SpermatogenesisSpermatogenesis
Occurs in seminiferous tubulesOccurs in seminiferous tubulesSertoli cells create blood-testis Sertoli cells create blood-testis barrier, prevent autoimmunitybarrier, prevent autoimmunity
SpermatogoniumSpermatogonium Diploid, 2NDiploid, 2N
Primary spermatocytePrimary spermatocyte Diploid, 4NDiploid, 4N
Secondary spermatocyteSecondary spermatocyte Haploid, 2NHaploid, 2N
SpermatidSpermatid Haploid, 1NHaploid, 1N
MitosisMitosis
Meiosis IMeiosis I
Meiosis IIMeiosis II
SpermatogenesisSpermatogenesis
Oogenesis Oogenesis
OogenesisOogenesis
Respiratory TreeRespiratory Tree
Conducting zoneConducting zoneWarms, humidifies, filters airWarms, humidifies, filters airSmooth muscleSmooth muscleAnatomic Anatomic dead spacedead spaceNose, trachea, pharynx, trachea, bronchi, Nose, trachea, pharynx, trachea, bronchi,
bronchioles, bronchioles, terminal bronchiolesterminal bronchioles
Respiratory zoneRespiratory zoneParticipates in Participates in gas exchangegas exchangeBronchioles, alveolar ducts, alveoliBronchioles, alveolar ducts, alveoli
PneumocytesPneumocytes
Type I pneumocytesType I pneumocytes97% of alveolar surface, 97% of alveolar surface,
line alveoliline alveoliResponsible for Responsible for gas gas
exchangeexchange
PneomocytesPneomocytes
Type II pneumocytesType II pneumocytesSecrete Secrete pulmonary pulmonary
surfactantsurfactantPrecursors to Type I and Precursors to Type I and
other Type II cellsother Type II cellsProliferate during lung Proliferate during lung
damagedamage
Bronchopulmonary Bronchopulmonary SegmentsSegments 1 Bronchopulmonary segment has:
1 tertiary (segmental) bronchus2 arteries (bronchial, pulmonary)Veins and lymphatics
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