Chase Findley, MSIV

Cell Cycle Phases

 Checkpoints control transitions between cell phases. Regulated by cyclins, cdks, and tumor suppressors.

Cell Cycle Phases

 Permanent cells   Remain in G0, regenerate from stem cells Neurons, skeletal and cardiac muscle, RBC’s  Stable cells  Enter G1 from G0 when stimulated  Hepatocytes, lymphocytes  Labile cells  Never go to G0, divide rapidly with short G1  Bone marrow, gut epithelium, skin, hair follicles

Plasma Membrane Composition  Asymmetric fluid bi-layer  50% cholesterol, 50% phospholipids  Small amounts of protein, sphingolipids, glycolipids  High cholesterol or long saturated fatty acid content increases melting temperature

Endoplasmic Reticulum

 Rough  Site of synthesis of secretory (exported) proteins and N-linked oligosaccharide addition  In neurons, ( Nissl bodies ) synthesize enzymes and peptide neurotransmitters  Mucous secreting goblet cells and antibody secreting plasma cells are rich in RER

Rough Endoplasmic Reticulum

Endoplasmic Reticulum

 Smooth  Site of synthesis of steroids  Detoxification of drugs and poisons  Liver hepatocytes and adrenal cortex are rich in SER

Smooth Endoplasmic Reticulum

Golgi Apparatus

 “Distribution center” of proteins and lipids from ER to plasma membrane, lysosomes, secretory vesicles  Adds mannose-6-phosphate to proteins, targeting to lysosome  Failure results in I-cell disease, enzymes secreted outside cell  Proteoglycan assembly and sulfation

Golgi Apparatus

Microtubules

 Helical array of polymerized dimers of α and β tubulin  Each dimer has 2 GTP bound  Incorporated into flagella, cilia, mitotic spindles, neurons  Chediak-Higashi syndrome  Defect in microtubule polymerization with decreased phagocytosis  Target of mebendazole, taxol, griseofulvin, vincristine, vinblastine, colchicine

Cilia Structure

 9+2 arrangement of microtubules  Dynein (ATPase) links peripheral 9 doublets, causes bending by differential sliding of doublets  Dynein=retrograde Kinesis=anterograde  Kartagener’s syndrome  Dynein defect, immotile cilia, infertility, recurrent infections

Collagen

 Most abundant protein in body  Organizes, strengthens extracellular matrix  Type I  Bone, skin, tendon , dentin, fascia, cornea  Type II  Cartilage , vitreous body, nucleus pulposus  Type III (Reticulin)  Skin, blood vessels, uterus, fetal tissue  Type IV  Basement membrane

Collagen Synthesis

 Inside fibroblasts   Synthesis (RER) ○ Translation of collagen α-chains (preprocollagen) Hydroxylation (ER) ○ Specific proline and lysine residues, requires Vitamin C  Glycosylation (Golgi) ○ Pro α chain residues, formation of procollagen (triple helix of α-chains)  Exocytosis ○ Procollagen exocytosed to extracellular space

Collagen Synthesis

 Outside fibroblasts  Proteolytic processing ○ Cleavage of terminal regions of procollagen, transforms into insoluble tropocollagen  Cross-linking ○ Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross linkage , produces collagen fibrils ○ Defective collagen synthesis causes Ehlers Danlos syndrome.

Elastin

 “Stretchy” protein  Rich in proline , lysine  Found in lungs, large arteries, elastic ligaments  α-1 antitrypsin inhibits elastase, excessive elastase activity causes emphysema

Phosphotidylcholine (Lecithin) Function  Major component of RBC membranes , surfactant , myelin , bile  Used in esterification of cholesterol

Immunohistochemical Stains

 Connective Tissue  Muscle  Epithelial Cells  Neurons  Neuroglia  Vimentin  Desmin  Cytokeratin  Neurofilaments  Glial fibrillary acid proteins

Digestive Tract Histology

 Mucosa ○ Contains epithelium, lamina propria, muscularis mucosa ○ Absorptive function, villae  Submucosa ○ Contains submucosal nerve plexus  Muscularis externa ○ Contains Myenteric nerve plexus ○ Inner circular, outer longitudinal  Serosa/adventitia

Digestive Tract Histology

 Submucosal nerve plexi ○ Submucosal layer ○ Coordinates secretions , blood flow, absorption  Myenteric nerve plexi ○ Muscularis externa layer ○ Coordinates motility

Digestive Tract Histology

 Brunner’s Glands ○ Located in duodenal submucosa ○ Secrete alkaline mucous , neutralize acidic stomach contents ○ Hypertrophy in peptic ulcer disease

Digestive Tract Histology

 Peyer’s Patches ○ Unencapsulated lymph tissue in mucosa and submucosa of small intestine ○ Take up antigen, stimulate local B cells to differentiate into IgA-secreting plasma cells ○ IgA secreted into lumen

Digestive Tract Histology

 Barrett’s Esophagus ○ Replacement of non-keratinized, squamous epithelium with intestinal columnar epithelium in distal esophagus ○ Caused by acid reflux, may lead to adenocarcinomas ○ Example of metaplasia

Liver Histology

  Zone 1 ○ Periportal ○ Sensitive to toxic injury  Zone 2 ○ intermediate Zone 3 ○ Pericentral ○ Sensitive to ischemic injury

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 ○ Pepsin  Protein digestion  Mucosal Cells ○ Bicarbonate  G Cells ○ Gastrin

Erythrocytes

 Anucleate  Biconcave  High surface area to volume ratio for easy gas exchange  Life span: 120 days  Glucose energy source  90% anaerobically degraded to lactate  Membrane contains chloride-bicarbonate antiport, involved in “physiologic chloride shift”

Erythrocytes

 Anisocytosis  Varying size  Poikilocytosis  Varying shape  Reticulocyte  Immature erythrocyte ○ Larger, bluish tinge

Neutrophils

 Multilobed nucleus  Mediate acute inflammatory response  Phagocytic  Primary granules contain hydrolytic enzymes, lysozyme, myeloperoxidase  Hypersegmented in B12/folate deficiency

Neutrophils

 Normal  Hypersegmented

Leukocytes

 Granulocytes  Basophils, eosinophils, neutrophils  Mononuclear cells  Lymphocytes, monocytes

Lymphocytes

 Round, densely staining nucleus  Little cytoplasm  T & B lymphocytes

T Lymphocytes

 Mediate cellular immune response  Originate from stem cells in bone marrow, mature in thymus  Differentiate into:  Cytotoxic T cells ○ MHC I, CD8  Helper T cells ○ MHC II, CD4  Suppressor T Cells

B Lymphocytes

 Mediate humoral immune response  Originate from stem cells in bone marrow, mature in marrow  Migrate to peripheral lymph tissue  Differentiate into plasma cells , produce antibody when presented with antigen  Function as APC via MHC II

Mast Cells

 Mediate allergic reaction  Contain histamine, heparin, chemotactic factors  Bind IgE to cell membrane  Found in tissue  Cromolyn sodium prevents degranulation

Eosinophils

Monocytes

 Kidney shaped nucleus  Differentiates to macrophages in 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 nucleus  Mediate allergic reaction  Contain histamine, heparin, leukotrienes  Found in blood

Epidermal Layers

*Langerhan’s cells are dendritic cells that function as APC’s in skin. Remember Birbeck granules !

Epithelial Cell Junctions

     Zona occludens (tight junction)  Creates semi-permeable barrier Macula adherens  Small discrete points of attachment Gap junction  Allows adjacent cells to communicate via metabolic/electrical processes Hemidesmosome  Anchors cells to extracellular matrix Integrin  Maintains integrity of basement membrane

Epithelial Cell Junctions

Skeletal Muscle Cell Structure  Sarcomere   Skeletal muscle unit from Z line to Z line A band Contraction causes I band shortening, A band stays same  Area of overlap of actin and myosin  I band  Area of actin only

Skeletal Muscle Cell Structure  Striated  Peripheral nuclei  Linear fibers

Cardiac Muscle Structure

    Striated Central nuclei Branching fibers Intercalated disks  Contain gap junctions which allow electrical impulse to pass between adjacent cells

Smooth Muscle

 Non-striated  Central, elongated nucleus  “Network” muscle fibers

Neuron Structure, Schwann Cells  Individual Schwann cells myelinate a single PNS axon  Impulse travels via saltatory conduction

Peripheral Nerve Layers

 Endoneurium  Invests single nerve fiber  Perineurium   Surrounds a fascicle of fibers Must be rejoined for limb re attachment  Epineurium  Surrounds entire nerve, and associated vessels

Oligodendroglia

 Each oligodendroglia myelinates multiple CNS axons  Predominate glial cell in white matter  Destroyed in multiple sclerosis

Microglia

 CNS phagocytes  Mesodermal origin (all others from ectoderm)  Enlarge to large amoeboid cells in response to tissue damage  Fuse into multinucleated giant cells when infected by HIV

Astrocytes

 Physical support and repair of axons  K+ metabolism  Maintain blood-brain barrier

Sensory Corpuscles: Meissner’s  Small, encapsulated nerve endings  Dermis of palms, soles, digits ( hairless skin)  Light discriminatory touch

Sensory Corpuscles: Pacinian

 Large, encapsulated nerve endings  Deep skin layers at ligaments, joint capsules, serous membranes, mesenteries  Pressure, coarse touch, vibration, tension

Sensory Corpuscles: Merkel’s

 Cup-shaped nerve ending  Dermis of fingertips, hair follicles , hard palate  Light, crude touch

Blood-Brain Barrier

 Formed by:  Tight junctions between nonfenestrated capillary endothelial walls  Basement membrane  Astrocyte foot processes

Blood-Brain Barrier

 Glucose and amino acids carrier-mediated transport cross by  Non-polar molecules cross more readily than polar molecules  Infection destroys tight junctions, leads to vasogenic edema

Renal Structure

Glomerular Structure

Sperm Structure

 Head (acrosome)  Derived from Golgi apparatus  Neck  Contains mitochondria, energy supply from fructose  Tail  Derived from centrioles

Spermatogenesis

    Spermatogonium  Diploid, 2N Primary spermatocyte  Diploid, 4N Secondary spermatocyte  Haploid, 2N Spermatid  Haploid, 1N  Mitosis  Meiosis I  Meiosis II Occurs in seminiferous tubules Sertoli cells create blood-testis barrier, prevent autoimmunity

Spermatogenesis

Oogenesis

Oogenesis

Respiratory Tree

 Conducting zone  Warms, humidifies, filters air  Smooth muscle  Anatomic dead space  Nose, trachea, pharynx, trachea, bronchi, bronchioles, terminal bronchioles  Respiratory zone  Participates in gas exchange  Bronchioles, alveolar ducts, alveoli

Pneumocytes

 Type I pneumocytes  97% of alveolar surface, line alveoli  Responsible for gas exchange

Pneomocytes

 Type II pneumocytes  Secrete pulmonary surfactant  Precursors to Type I and other Type II cells  Proliferate during lung damage

Bronchopulmonary Segments

 1 Bronchopulmonary segment has:  1 tertiary (segmental) bronchus  2 arteries (bronchial, pulmonary)  Veins and lymphatics