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