Histo Block B

initial unmineralized bone formed by osteoblasts

inhibits diffusion of nutrients, causing death of the chondrocytes in the cartilage model

an initial distinctive cuff of periosteal bone formed in the diaphysis of long bones during endochondral bone development

• nonlamellar bone; immature bone formed in the fetus
• stains more intensely due to increased ground substance (darker pink in decalcified prep)
• contains woven bone

• same as Haversion system
• surrounds a central Haversion canal

vascular and nerve supply of the osteon

they create cross connection between Haversian canals

appositional growth

• PTH: increases bone resorption; in pulses, increases bone formation
• calcitonin: decreases bonoe resorption
• gonadal steroids: decrease bone resorption & increase bone growth
• thyroid hormone: increases bone resorption

• bone tissue
• other connective tissues
• hematopoietic tissue
• fat tissue
• blood vessels
• nerve

• long
• short
• flat
• irregular

• compact bone mainly in diaphysis
• mainly spongy bone in the epiphyses

shell of compact bone with spongy bone & marrow in the center

two layers of compact bone with spongy bone in between

ex. vertebrae

• found on all bones EXCEPT on articular surfaces
• composed of dense fibrous connective tissue
• collagen fibers arranged parallel to surface of the bone
• inner layer contains osteoprogenitor cells

tissue lining the compact & spongy bone associated with the marrow cavity

• where ligaments & tendons attach to a bone
• the collage fibers of the periosteum extend into the circumferential lamellae

• mainly crystalline mineral salts & calcium present in the hyrdoxapatite
• matrix is laid down as unmineralized osteoid (secreted by osteoblasts)
• mineralization begins with secretes alkaline phosphatase (starting point for calcium & phosphate deposition)

• mainly type I collagen
• synthesized intracellularly as tropocollagen & then exported

• connective tissue characterized by a highly mineralized matrix
• contains mainly type I collagen
• contains lacunae connected by canaliculi

• osteoprogenitor cells: form new bone cells
• osteoblasts: sit on free edge & make matrix; mature into osteocytes
• osteoclasts: large & multinucleated
• bone lining cells: osteocytes

• Rest
• Ice
• Compression
• Elevation

• twisted
• conveys extra strength; withstands stress better; gives bone flexibility

• osteoblasts: bone marrow derived mesenchymal progenitors
• osteoclasts: bone marrow derived hematopoietic progenitors

• derived from mesenchymal stem cells in the marrow
• activated to become osteoblasts by CBFA1 transcription factor
• found in the innermost layer of the periosteum & endosteum

• capable of dividing
• secretory cells that produce type I collagen + bone matrix proteins
• respond to mechanicl stimuli to mediate bone growth & remodeling

newly formed bone matrix

• mature cells of bone
• surrounded by calcified extracellular matrix
• have long processes that pass through canaliculi
• "touch" other osteocytes via gap junctions
• maintain the bone matrix

• large, multinucleated cells
• responsible for resorption of bone matrix
• rest directly on bone tissue that is being removed
• derived from fusion of mononuclear hemopoietic progenitor cells
• form a syncitium
• rest in Howship's lacuna

shallow depression directly below an osteoclast

• the part of the cell in direct contact with bone matrix
• numerous deep plasma membrane infoldings

• adjacent to ruffled border of osteoclasts
• site of resorption & degradation

exocytosis of digested material in osteoclasts

• filled with lysosomes that contain hydrolytic enzymes
• demineralize the matrix by secreting hydrogen ions into extracellular space
• release carbonic anhydrase (converted into carbonic acid & hydrolytic enzymes like collagenase) to break down fibrous portion of bone
• resorption releases calcium & phosphorous into blood circulation
• after resorption is complete, osteoclasts undergo apoptosis (promoted by bisphosphonates & estrogen)

• resorption of calcium & phosphorous into blood circulation
• endocytosis: ruffled border has coated pits
• bone remodeling in response to stress

• osteons: consist of concentric lamellae
• Haversian/central canal: contain blood vessels & connective tissue
• lacunae: contain osteocytes
• canaliculi: connect osteocytes
• Volkman's/ perforating canals: contain blood vessels that travel from one Haversian canal to the next

• parathyroid hormone
• released when calcium levels are low
• stimulates osteoclasts to degrade bone & release calcium into the blood
• causes increased intestinal absorption of calcium
• causes the kidneys to retain calcium
• EXCEPTION - pulses of PTH increase bone formation

• near the surface of compact bone
• arranged parallel to the surface

represent remnants of older Haversian systems which have been partially destroyed as the bone tissue is remodeled or reorganized

• parathyroid hormone
• glucocorticoids
• thyroid hormone
• vitamin D metabolites (high doses)

• stimulates calcium salt deposition in bone
• released in response to high levels of calcium
• produced by thyroid gland
• stimulates osteoblasts to incorporate calcium (from bloode) into newly formed bone
• responsible for calcium storage

• calcitonin
• gonadal steroids

• growth hormone
• vitamin D metabolites (low doses)
• gonadal steroids

glucocorticoids

• efflux of calcium from bone
• decreased loss of calcium in urine
• enhanced absorption of calcium from intestine
• increased concentration of calcium in blood

• replacement of a hyaline cartilage model with bone tissue
• ossification begins as blood vessels invade the cartilage model, bringing osteoprogenitor cells
• a collar of bone is formed around the diaphysis (shaft)
• the matrix begins to calcify replace it with bone
• secondary ossification centers form in the epiphyses

cartilage cells undergo division & organize into distinct columns

• chondrocytes are metabolically active
• secrete VEGF which initiates vascular invasion
• cells become larger ("big & fluffy")

hypertrophied cells begin to degenerate & cartilage matrix becomes calcified

• calcified cartilage is resorbed & replaced with osteoprogenitor cells that differentiate into bone cells
• KILLS off cartilage EXCEPT at growth plate

• the cartilage zone left at each end of the marrow cavity
• allows bones to continue to grow in length & width
• when growth is complete, becomes the epiphyseal line

• occurs in flat bones
• embryonic mesenchyme condenses
• ossification occurs in numerous sites simultaneously
• both spongy & compact bone can arise via this mechanism

• as bone grows, it is constantly resorbed and remodeled
• osteoclasts eat away at center (cavity) as osteoblasts build diameter
• don't want bones to be too thick (heavy) or too thin (fragile)

• intramembranous ossification
• different random ossification centers eventually grow together to form a layer of bone

• growth in diameter
• new bone is added to the outside of bone & osteoclasts remodel inside of bone
• prevents bone from becoming too thick

• resorption
• reversal
• formation
• resting

• occurs all the time, especially in growth
• osteoclasts resorb & osteoblast reform new bone
• caused by mechanical stimulation
• ex. orthodontic appliances

• hematoma formation
• fibrocartilage callus formation
• bony callus formation
• bone remodeling

• compressional strength: greater than reinforced steel
• tensile strength: reinforced concrete
• torsional strength: LOW strength to endure twisting

• after initial injury, neutrophils & macrophages begin to clean up site of damage
• fibroblasts & capillaries proliferate and grow into site of injury
• loose CT (granulation tissue) is formed & becomes dense
• dense CT & cartilage cover bone at fracture site forming a callus
• callus helps to stabilize & bind together the ends of fractured bone
• osteoprogenitor cells within periosteum divide & differentiate into osteoblasts
• original callus tissue is replaced with new bone (bony callus)
• spongy bone is formed & some parts are replaced with compact bone

• ground reaction or impact forces like gymnastics & weight lifting have the highest effect on bone density
• the mechanical stress of exercise puts stress on the bone & increases bone density

• affects over 44 million people in the US
• responsible for 1.3 millions fractures/year
• low bone mass
• deteriorationg of both inner (trabecular) and outer (cortical) parts of bone
• 1 in 2 caucasion women will have an osteoporotic fracture
• 20% of patients with hip fractures will die within one year due to complications

• fractures of the vertebrae
• decrease in height
• scoliosis
• hip fractures
• minimal stress fractures
• loss of bone in the jaw (loose teeth of movement of teeth)

• gender (females)
• ethnicity (caucasian/asian)
• hormone levels (post menopausal)
• thin & small body frame
• family history
• lifestyle - smoker, alcohol consumption, lack of exercise, diet low in calcium

• reduced estrogen levels in postmenopausal women
• low estrogen causes increased RANK-L expression
• low estrogen causes increased osteoclast formation
• low estrogen causes excessive bone resorption
• NO SIGNAL for osteoclast apoptosis

• risk factors
• family history
• DXA scan: dual energy x-ray absorptiometry scan

• lifestyle changes - adequate calcium, weight bearing exercise, no smoking/drinking
• medication that stops bone loss & increases bone strength (bisphosphonates, calcium, pulses of PTH)

• inhibit osteoclast activity & promote osteoclast apoptosis
• released locally during bone resorption
• concentrated under osteoclasts
• may modulate signaling from osteoblasts to osteoclasts - decrease RANK-L expression, increase OPG expression

• antiresorptive agents
• bind to hydroxyapatite crystals in bone
• directly or indirectly inhibit osteoclasts
• inhibit bone mineralization (at sufficient doses)
• pharmacologically active only while on exposed bone surfaces
• remains bound in bone matrix for years

• osteoprotegerin (OPG)
• competitive inhibitor of RANK (binds to RANK-L)
• prevents stimulation of osteoclastogenesis

• inhaled calcitonin
• used daily (alternate nostrils)
• few side effects
• exhibits an optimum level, then loses efficacy

• things that cause new bone formation and/or inhibit bone resorption
• ex. estrogens, calcitonin, BMP 2/4, TGF beta, TPO, IL-17, PDGF, calcium

• Rx for osteoporosis - Forteo
• pulses of PTH increase bone formation
• increased osteoblast differentiation & activity
• decreased osteoblast apoptosis
• daily injectable - problems with compliance
• recombinant teriparatide
• must be used before bisphosphonates are started

• osteoporosis treatment designed to target RANK-L
• fully human monoclonal antibody (IgG2) that binds to RANK-L with high affinity & specificity
• blocks interaction of RANK-L and RANK
• NO osteoclast formation

• bisphosphonates: bind to bone mineral & disable osteoclasts (decrease RANK-L expression)
• denosumab: blocks osteoclast formation

• uric acid crystals in the joints
• side effect of treatment with thiazide anti-hypertensive medication
• predisposition - family history

• chronic, systemic autoimmune disease
• results in inflammation of synovial joint & destruction of cartilage and bone tissue
• 2-3X more common in women

articular cartilage wears out

• uncommon hormonal disorder
• develops when the pituitary gland produces too much growth hormone during adulthood
• bones increase in size - especially hands, feet & face
• affects middle aged adults

• autosomal dominant mode of inheritance
• mutations affect the synthesis or structure of type I collagen
• eight different types
• weak bones, susceptible to fractures, short statures
• blue tint to whites of eyes (blue sclera); multiple bone fractures; early hearing loss (deafness)
• location of mutation determines severity

• bony spicules in metaphysis
• poor ossification

• causes bones to grow larger and weaker than normal
• most common in spine, pelvis, skull & legs
• might affect one or several bones, but not entire skeleton
• more common in men than women
• common in older people
• symptoms - pain, enlarged bones, broken bones, damaged cartilage in joints

• conveyance of nutrients, wastes, regulatory molecules, humoral agents & cells
• homeostasis via thermoregulation & its buffering capacity
• related functionally, developmentally & genetically to connective tissue
• biochemically similar to lymph & interstitial fluid (plasma)

• formed elements: cells & cell fragments
• unformed elements: plasma (slightly alkaline, 90% water)

% volume of packed erythrocytes (RBCs)

layer of leukocytes (WBCs) & platelets

• more agranulocytes than granulocytes
• lymphocytes are more numerous than monocytes
• neutrophils > eosinophils > basophils

• anticoagulant (heparin or sodium citrate)
• prevents clot formation
• predominant components - albumin, fibrinogen, immunoglobulins, lipids (lipoproteins), hormones, vitamins & salts

• NO anticoagulant
• blood left to clot
• a protein-rich fluid lacking fibrinogen but containing albumin, immunoglobulins, & other components
• plasma LACKING fibrinogen

• combination of soluble proteins that become insoluble under certain conditions
• formed elements trapped in fibrin
• a fibrin-containing network trapping blood cells

• 90% water
• 8% protein (albumin, globulin, fibrinogen)
• 2% other solutes (electrolytes, nutrients, blood gases, etc.)

• erythrocytes
• leukocytes (agranulocytes & granulocytes)
• platelets

• total erythrocyte count
• total leukocyte count
• differential leukocyte count

• normal distribution of cells - 5000 to 9000/mm³
• number increases with infection (>10,000)

• 5 identified types of WBCs
• unique function in each individual case
• numbers/changes in numbers compared to normal distribution
• neutrophils: indicate bacterial infections
• eosinophils: indicate parasitic/skin infections; long term chronic infection

• red blood cells
• anucleated
• specialized for oxygen transport
• terminally differentiated cell
• 120 day life span
• replenished via hemopoiesis (blood cell production)

scanning electron micrograph of stack of RBCs

• 66% water
• 33% hemoglobin
• 1% lipids (carbohydrates & other proteins)

• each molecule is composed of 4 protein subunits (2 pairs of identical subunits)
• subunits consist of 4 main types of chains - alpha, beta, gamma, delta
• each subunit has a heme molecule
• trapped within heme is iron molecule (chelating agent)
• when oxygen is trapped on heme, iron turns red

• HbA: 96% (2 alpha, 2 beta chains)
• HbA2: 2% (2 alpha, 2 delta chains)
• HbF: 2% (2 alpha, 2 gamma chains)

• Limulus polyphemus
• has NO IRON in blood
• copper is chelating agent
• blood is blue/green

• position 6 on beta chain of hemoglobin has valine substituted for glutamic acid
• HbS: 2 alpha chains & 2 altered beta chains
• altered cell shape at low oxygen concentrations
• RBCs only last 30-40 days in circulation

cross linking molecule prevents further breakdown of tissue sample

• removal of water from tissue to use stain (soluble in organic solvents)
• tends to shrink tissue

RBC of less than 6um

RBC of greater than 9um

• ~8um diameter
• deformable, biconcave disc
• shape add 20-30% surface area
• total RBC surface area = 2000X exterior body area
• decreases diffusion distance for oxygen

rupture of erythrocyte membrane caused by hypotonicity of plasma (injection of water into cells) or hemolytic agents

• "spiky or spiny" appearance
• results from change/decrease in ATP concentration or fatty acid content
• NOT caused by hypertonicity of plasma

• ABO blood group: A, B, AB, O
• Rh blood group: Rh (D+) or Rh (D-)

• Rh (D+) mom develops antibodies against Rh (D-) baby
• anti-D immunoglobins

• surface antigen that lies on inside of RBC plasma membrane
• accessory protein for actin
• provides internal bracing for RBC membrane ("chain link fence")
• deficiencies/defects cause deleterious RBC morphological alterations (hereditary ellipsocytosis or spherocytosis)

• links IM protein band 3 to network of spectrin molecules
• anchor

• faciliates carbon dioxide exchanges
• anion transporter channel

• anion transporter
• major transmembrane protein exposed on outer surface of RBC

• any change in RBC size
• Ex: SICKLE CELL ANEMIA

change in RBC shape

decrease in hemoglobin content

increase in hemoglobin content

• decrease in hemoglobin content that results in inadequate oxygen provision to tissues
• primary anemia: RBC count down
• secondary anemia: RBC count constant, [Hb] down
• macrocytic anemia: RBC count down, RBC size up
• sickle cell anemia: change in Hb type, altered RBC shape (sickle)
• hereditary ellipsocytosis: RBC shape altered (elipse)
• hereditary spherocytosis: RBC shape altered (ball)

• lymphocytes & monocytes
• DO have primary granules (lysosomes)

• neutrophils, eosinophils, & basophils
• collectively referred to as microphages
• categorized via staining characteristics of secondary (specific) granules
• terminally differentiated
• non-mitotic
• heterochromatic nuclei

• white blood cells
• all terminally differentiated in peripheral blood
• non-mitotic
• nucleated
• NO hemoglobin
• arise, function & die within CT
• divided into agranulocytes & granulocytes

pathological increase in WBCs

pathological decrease in WBCs

• agranulocyte
• circulating immunocompetent cells
• small lymphocytes: 6-8um; 90% of LMCs
• large lymphocytes: 18um in CT
• comprise 30% of circulating WBCs
• circulate in blood ~8 hrs, go to CT sites & recirculate
• exposure to antigens stimulates mitosis
• produce effector & memory cells

• spherical, heterochromatic nucleus
• cytoplasm - basophilic
• usually have a few primary granules

• 15% of circulating lymphocytes
• variable life span
• responsible for humoral immune response
• has immunoglobin receptors in membrane
• differentiates into plasma cell in CT

• 80% of circulating lymphocytes
• responsible for cell mediated immunity
• memory cells - long lived
• effector cells

• 9-15um
• indented, moderately heterochromatic nucleus
• "foamy" nucleoplasm
• vacuolar cytoplasm (less basophilic)
• has primary granules (lysosomes)

• macrophage: connective & lymphoid tissue
• osteoclast: modified monocyte in bone
• alveolar macrophage: lung; pick up dust
• Kupffer cell: liver; move in & out of circulation

• bacterial phagocytosis
• bacterial inactivation via respiratory burst activity
• cytokine production to recruit helpers
• antigen processing & presentation
• foreign body giant cell formation

• 60-70% of circulating WBCs (most prevalent)
• 8 hrs in circulation, days in CT
• polymorphonuclear: lobed nucleus
• Barr body: female; extra X chromosome
• Stab form: immature neutrophil indicating severe infection

• primary: azure; lysosomes (contain peroxidase, acid phosphatase); develop first, work last; clean up
• secondary: specific; contain antimicrobial agents (lysozome, alkaline phosphatase, bactericides, opsonins); kill bacteria
• tertiary: specific; contain gelatinase & plasmalemma glycoproteins; facilitate contact with & phagocytosis of bacteria; destroy membranes

• release of contents of tertiary granules
• digestion of basal lamina, priming of secondary granules
• release of antimicrobial agents from secondary granules
• phagocytosis, fusion of endosome with primary granules
• form reactive compounds (superoxide, peroxide); respiratory burst activity
• leukotrine synthesis (recruitment)

• neutrophils
• monocytes
• fibroblasts
• basophils, eosinophils & lymphocytes (accumulate in chronic inflammatory reactions)

• 2-4% of circulating WBCs
• 10-14um
• bilobed nucleus
• eosinophilic cytoplasmic granules

• primary granules: azure
• specific granules: acidophilic (RED)
• major basic protein: active in antiparasitic functions
• lysosomal enzymes
• histaminases: antihistamine, counteracts basophil histamine
• aryl sulfatase: counteracts slow reacting substance of anaphylaxis (from basophils)

• increased in allergic reactions, parasitic & skin infections
• diurnal rhythm
• good at phagocytizing antigen-antibody complexes
• inefficient at bacterial phagocytosis
• respond chemotactically to basophils & mast cells
• counteract effects of basophil & mast cell degranulation

• 0.5-1% of circulating WBCs - RARE
• related functionally to mast cells
• 8-10um in diameter
• lobed nucleus - can be hidden by dark granules

• primary (azure)
• basophilic specific granules due to heparan sulfate content
• hydrolytic enzymes
• histamine: vasodilator, increases vascular permeability
• slow reacting substance: anaphylaxis (also vasodilator)
• eosinophil & neutrophil chemotactic factors

• degranulation
• Fc portion of IgE binds to membrane IgE receptor on mast cells & basophils (sensitization)
• on re-exposure, antigen binds bound IgE
• results in mast cell & basophil degranulation
• release of leukotrines & vasoactive substances counteracted by eosinophils

localized response of some vasoconstriction

systemic response, global vasoconstriction

• circulation time is 10 days
• cell fragments derived from megakaryocyte
• biconvex disc
• granulomere & hyalomere

• peripheral region
• contains microtubules for shape maintenance
• microfilaments for clot contraction

• central region; granules & membranous organelles
• alpha fibrinogen, clotting factors
• gamma ADP, ATP, serotonin, histamine - facilitate adhesion
• lambda  hydrolytic enzymes - function in clot resorption
• dense tubular system: similar to sER, sequesters calcium
• surface connected open canalicular system receives active components

• degranulation: occurs on contact with collagen
• conversion of thromboplastin - prothrombin - thrombin
• thrombin catalyzes the conversion of fibrinogen to fibrin
• involved in clotting reaction
• white thrombus: platelets only
• red thrombus: platelets + fibrin

• general classification for all blood cell development
• erythropoiesis:  erythrocyte development
• leukopoiesis: granulopoiesis & lymphopoiesis
• granulopoiesis: granulocyte development
• lymphopoiesis: lymphocyte development
• thrombopoiesis: platelet development

• Yolk sac phase
• liver phase
• splenic phase (concurrent with liver phase)
• adult phase

• 0-12 weeks
• cells from embryonic mesoderm (blood islands)
• seeds numerous colony forming units (CFUs)
• erythrocytes nucleated

• 4 weeks - 9 months
• liver hemopoietic
• produces nucleated RBCs

• 3-7 months
• concurrent with liver phase
• spleen hemopoietic
• lymphopoiesis continues postnatally

• 4 months - adult
• primarily bone marrow performs hemopoiesis

• myeloid tissue: tissue supporting RBC & WBC development (marrow)
• lymphoid tissue: tissue supporting lymphocyte development (lymphoid organs - ex. thymus, gut associated lymphatic tissue, lymph nodes)

• monophyletic / unitarian theory
• all blood cells arise from common stem cell (hemopoieic stem cell/HSC)

• colony forming unit
• hemocytoblast: cells capable of mitosis
• derived from mesenchymal reticular tissue
• potency variable
• small lymphocyte-like cell
• produces more differentiated stem cells responsive to different stimuli

• potential of what a given cell can differentiate into
• greater potency = greater number of potential developmental outcomes
• potency decreases as cells become more differentiated (also mitotic ability decreases)

• hematopoietic/pluripotent stem cell: from which all other blood cell types are derived
• multipotential hematopoietic stem cell: myeloid; found in bone marrow & lymphatic tissues
• progenitor cells: unipotential & self renewing; CFU
• precursor cell: unipotential; not self renewing
• mature blood cell

• erythropoietin
• granulocyte-monocyte colony stimulating factor (GM-CSF)
• granulocyte colony stimulating factor (G-CSF)
• monocyte colony stimulating factor (M-CSF)

• produced in interstitium of kidney
• hormone that stimulates production of CFU cells that give rise to RBCs

• granulocyte-macrophage colony stimulating factor
• source: T cells, endothelial cells, fibroblasts
• target: CMP, ErP, GMP, EoP, BaP, MKP, all granulocytes, erthryocytes

• granulocyte colony stimulating factor
• source: endothelial cells, monocytes
• target: ErP, GMP, EoP, BaP, MKP

• monocyte colony stimulating factor
• source: monocytes, macrophages, endothelial and adventitial cells
• target: GMP, MoP, monocytes, macrophages, osteoclasts

• erythropoietin
• source: kidney, liver
• target: CMP, MEP, ErP

• thrombopoietin
• source: bone marrow
• target: MKP, megakaryocytes

• medullary cavities of bone
• red marrow: hemopoietically active
• yellow marrow: reduced hemopoietic activity; adipocytes dominate

• stroma & free blood cells
• fibers: collagen & reticular fibers; some elastin
• fixed cells: fibroblasts, reticular cells, macrophages, adipocytes, osteoblasts, endothelial cells, etc.
• transient cells: developing blood cells in interstices of fixed cells & fibers

• development time - 14 days
• 6-10 hrs in circulation
• 1-2 days in connective tissue
• granulocytes more numerous than erythrocytes in marrow (shorter life span, longer developmental time)

• increased WBC release from marrow
• increased differentiation of WBCs from specific CFUs

• decrease in cell size & cytoplasmic basophilia
• increase in nuclear heterochromatiin & specific granule content
• increase in deformability & adhesiveness (sticky)
• increase in phagocytic activity & motility

• myeloblast
• promyelocyte
• myelocyte
• metamyelocyte
• mature granulocyte

lack of iron

lack of vitamin B12

• iron
• vitamin B12

• feedback loop
• increased peripheral RBC count decreases erythropoietin synthesis

decrease of oxygen in periphery/tissue increases production of erythropoietin (which increased CFU-E production to stimulate RBC production

• granulocyte/monocyte progenitor
• monocyte progenitor
• monocyte
• macrophage in lung, liver, bone or loose CT

• NK cell: cell mediated immunity
• T cell: cell mediated immunity
• B cell/ plasma cell: humoral immunity

• proerythroblast
• basophilic erythroblast
• polychromatophilic erythroblast
• orthochromatophilic erythroblast
• polychromatophilic erythrocyte/ reticulocyte
• erythrocyte

• megakaryocyte/erythrocyte progenitor
• megakaryocyte progenitor
• megakaryoblast
• megakaryocyte (stays in marrow)
• platelets

• largest cells in marrow
• lobed polyploid nucleus (32-64N generated by endomitosis)
• demarcation channels form in cytoplasm to define platelet boundaries
• cytoplasm protrudes into marrow channels & sheds platelets

• Lupus erythematosus: targets healthy cells of all body systems
• Hemolytic anemia: targets healthy RBCs
• Diabetes mellitus Type I: targets healthy beta cells of pancreas
• Hasimoto's thyroiditis: targets thryoid follicles

• group of cells, tissues, & organs that monitor body surfaces & internal fluid compartments
• react to potentially harmful substances
• lymphocyte: definitive cell of lymphatic system

• lymphocytes
• bone marrow
• diffuse lymphatic tissue (MALT)
• thymus
• lymphatic nodules
• lymph nodes
• spleen
• tonsils

• bone marrow
• diffuse lymphatic tissue (MALT)
• thymus
• site of antigen-independent proliferation & differentiation of immunicompetent cells ready to enter circulation

• lymphatic nodules
• lymph nodes
• spleen
• tonsils
• site of antigen-dependent activation of effector lymphocytes & memory cells

lymphocytes process antigens and decide whether or not to mount an immune response

• nonspecific
• physical barriers prevent entry of pathogens (skin)
• chemical defenses destroy pathogens (low pH of stomach)
• secretory substances neutralize pathogens (lysozymes of saliva)
• phagocytic cells eliminate pathogens (macrophages)

• specific: directed response towards specific invaders
• activation of immune effector cells results in immune "memory"
• humoral response: secretion of antibodies and subsequent destruction by immune cells
• cellular immune response: direct destruction of transformed cells by immune cells

• T cells: T lymphocytes
• B cells: B lymphocytes
• NK cells: natural killer lymphocytes

• cluster of differentiation markers
• unique cell surface molecules used to identify hematopoietic cells
• CD4 & CD8

• reticular cells
• monocytes
• granulocytes - basophils & eosinophils
• macrophages
• dendritic cells
• follicular dendritic cells
• Langerhans' cells - middle layer of epidermis
• epithelioreticular cells - thymus

• immunosurveillance
• immune response

• 70% of lymphocytes
• long lived
• mature
• immunocompetent
• constantly in motion
• hop out, check tissue, hop back in

• short lived
• migrate directly to tissue
• immature cells that have been activated/recruited
• complete their job then undergo apoptosis

• named for thymus, site of differentiation and "education"
• long lifespand
• 60-80% of circulating lymphocytes
• involved in cell-mediaetd immunity
• express T cell receptors - either CD4+ or CD8+

• express CD4
• subclassed based on secretion of cytokines
• TH1 or TH2 cells

particular type of cytokine

• affect function of lymphocytes & leukocytes
• autocrine: act on cell of origin
• paracrine: act on neighboring cells
• mimic hormones

• helper CD4+ T lymphocytes
• secrete IL-2, IFN-gamma, & TNF-alpha
• interact with cytotoxic CD8+ T cells, NK cells & macrophages
• cell-mediated immune response activated by intracellular pathogens 

• helper CD4+ T lymphocytes
• secrete IL-4, IL-5, IL-10, & IL-13
• interact with B lymphocytes
• antibody mediated immune response activated by extracellular pathogens

• express CD8
• kill target cells (virus infected, bacterial infected, cancer cells, & transplanted cells) by releasing perforins to degrade target cell membrane

• originate in thymus
• downregulate immune response to foreign & self-antigen
• suppress proliferation of T cells & B cells
• suppress antibody production
• inhibit cell-mediated response of T lymphocytes
• Rx: autoimmune disorders & transplant patients

• express ONLY T lymphocyte receptor
• neither CD4 or CD8
• develop in thymus
• migrate to epithelial tissue & remain there
• first line of defense: attack antigens before they enter the body

• named for bursa of Fabricus (bone marrow & MALT equivalent)
• variable lifespan based on function
• 20-30% of circulating lymphocytes
• produce & secrete immunoglobulins
• associated with humoral immunity
• express B cell receptors: membrane bound immunoglobulins
• express MHC II

• IgM: immature B cells
• IgD: mature B cells

• named for ability to kill certain targets
• 5-10% of circulating lymphocytes
• do NOT mature in thymus
• recognize transformed cells (virus, cancer, etc.)
• release perforins & granzymes (like cytotoxic T cells)

• first contact with particular antigen
• lag in response time
• lack of circulating B lymphocytes able to response initially
• subsequently, greater number of "memory B cells" remain in circulation for more rapid response

• more rapid response
• due to presence of "memory cells"
• basis for immunization & hypersensitivity reactions

Even dead viruses cause immune reaction to allow B cells to develop memory cells

• antibody mediated discharge of histamines from mast cells organism-wide
• eosinophils neutralize effects

mediated by antibodies produced by B lymphocytes or plasma cells

• mediated T lymphocytes
• protects against transformed and foreign cells

• major histocompatability complex
• transmembrane proteins
• display short peptides on surface of cell (bound internally then transported to surface)
• MHC I & II

• on surface of all nucleated cells & platelets (NOT RBCs)
• display fragments of all peptides actively synthesized in cell
• allow for elimination of abnormal host cells
• recognition of exogenous vs. endogenous cells
• present peptides to cytotoxic T cells (MHC I restricted)

• only on surface of antigen presenting cells
• display fragments of endocytosed foreing peptides
• present peptides to helper T  cells (MHC II restricted)

• macrophages
• Kupffer cells - perisinusoidal macrophages of liver
• dendritic cells
• Langerhans' cells
• B lymphocytes
• type II & III epithelioreticular cells - thymus

• means of passage back to blood for cells and large molecules from tissue spaces
• more permeable walls than blood capillaries
• blind capillaries in loose CT (epithelium of skin & mucous membranes)
• pass lymph through lymph nodes for entrapment, inspection & possible initiation of response

• lymphocytes move from one part of the body to the other
• via afferent lymphatics to node
• via efferent lymphatics from node ultimately to right lymphatic trunk or thoracic duct
• via blod to node through high endothelial venules (postcapillary venules)

• NOT enclosed by a capsule
• MALT: alimentary canal (GALT) or bronchial tree (BALT)
• contain large numbers of plasma cells & eosinophils
• found in subepithelial tissue (lamina propria)
• after contact with antigens, lymphocytes migrate to lymph nodes, undergo proliferation & differentiation, return as effector T and B cells

• localized concentrations of non-encapsulated lymphocytes within a reticular meshwork
• found in same areas as diffuse lymphatic tissue (subepithelial MALT)
• lack afferent vessels
• primary or secondary nodules

• uniform staining nodule without germinal center
• RARE

• germinal center
• mantle zone (corona)

• sign of lymphatic tissue response
• contains activated lymphocytes and follicular dendritic cells
• lighter staining - presence of lymphoblasts
• highly mitotic

large immature lymphocytes

contains small lymphocytes

• palatine tonsils
• pharyngeal tonsils (adenoids)
• lingual tonsils
• Peyer's patches - ilium
• vermiform appendix

• tonsilar crypts
• non-keratinized stratified squamous epithelium
• incomplete CT capsule
• secondary lymphatic nodules

• adenoids
• surface folds
• pseudostratified columnar epithelium
• lymphatic nodules

• skeletal muscle of tongue visible
• non-keratinized stratified squamous epithelium
• crypts

• collection of B & T lymphocyte rich nodule
• in ileum
• may also find solitary lymphatic nodules along rest of small & large intestine

• non-encapsulated lymphatic nodules
• lamina propria infiltrated by nodules & lymphocytes
• may be functionally associated with bursa of Fabricius (equivalent organs - bone marrow & MALT)
• amount of lymphatic tissue decrease with age

• small bean shaped organs
• present along lymphatic vessels everywhere in body (esp. axilla, groin, messenteries)

• afferent lymphatic vessels: transport lymph to node & can enter anywhere of the convex surface
• efferent lymphatic vessels: transport lymph away from node & exit at hilum

• capsule: dense connective tissue surrounding the node
• trabeculae: dense CT extending into the node
• reticular tissue: supporting meshwork throughout the node mainly composed of reticular cells & fibers

• indistinguishable from normal fibroblast
• produce type III collagen - forms reticular fibers
• have elongated cytoplasmic processes that wrap around the reticular fibers (isolate them from lymphocytes)
• attract B cells, T cells & dendritic cells

• dendritic cells
• macrophages
• follicular dendritic cells

• bone marrow derived
• antigen presenting cells
• monitor local environment for foreign substances
• have very high levels of MHC II
• very efficient antigen presentation to T cells

• phagocytic
• antigen presenting cells
• express MHC I & II
• not as efficient antigen presentation to T cells

• multiple thin cytoplasmic processes that express Fc receptors
• bind antibody-antigen complexes: retain these complexes on the surface for long time
• are NOT antigen presenting cells
• lack MHC II molecules

• cortex: outer portion of the node (exception - hilum)
• medulla: inner part of node
• lymphatic channels: sinuses
• high endothelial venules: postcapillary venules

• outer portion of the node (exception - hilum)
• dense mass of lymphatic tissue, lymphatic sinuses & lymph channels
• superficial cortex: contains primary & secondary lymph nodules
• deep cortex: free of nodules, rich in T cells

• nodular
• contains primary & secondary lymphatic nodules

• paracortex
• thymus-dependent cortex
• free of nodules
• rich in T cells

• inner part of the node
• consists of cords of lymphatic tissue, reticular cells & fibers and lymphocytes (mainly B), macrophages, dendritic cells & plasma cells

• supscapular (cortical) sinus: afferent lymphatic vessel drainage
• trabecular sinus: originate from subscapular sinus & connect to medullary sinus
• medullary sinus
• continuous endothelium adjacent to connective tissue
• discontinuous epithelium close to lymphatic parenchyma (not an open space)
• often contain pseudopods from macrophages to monitor lymph

• postcapillary venules lined by cuboidal or columnar epithelial cells in the deep cortex
• 90% of lymphocytes enter node - special receptos for antigen primed lymphocytes
• diapedesis: cause B & T cells to leave
• concentrate lymph through fluid & electrolyte gradients

• bilobed organ of superior mediastinum
• from 3/4th pharyngeal pouch
• derived from endoderm & mesenchymal mesoderm
• fully formed at birth - remains large until puberty
• gradually replaced by fat

• CT capsule & trabeculae
• thymic cortex
• thymic medulla
• blood vessels

• fibroblasts & collagen fibers
• plasma cels, lymphocytes, mast cells, adipose cells & macrophages
• blood vessels, efferent lymphatic vessels & nerves
• from thymic lobes - cortical caps over inner medullary tissue

• basophilic
• thymocytes: T lymphocytes
• macrophages: phagocytose all the T cells that fail thymic education
• epithelioreticular cells: type I, II, III

• large lymphocytes
• epithelioreticular cells: type IV, V, VI

• enter from the deeper part of the trabeculae
• carry a perivascular CT sheath containing reticular fibers, fibroblasts, macrophages, plasma cells

• provide the framework for the developing T cells
• similar function to reticular cells & reticular fibers (NOT found in thymus)
• have characteristics of epithelia (intercellular junctions, intermediate filaments)
• 6 types

• located at boundary of cortex & capsule or trabeculae or blood vessel
• tight junction: border between the thymic parenchyma & CT
• prevents developing T cells to move into the CT
• do NOT express MHC II

• located within the thymic cortex
• connect to other type II cells via desmosomes
• rich in intermediate filaments
• compartmentalize thymic cortex
• express MHC I & II

• located at the border of the cortex & medulla
• form a functional barrier between cortex & medulla
• express MHC I & II

• located at the border of the cortex & medulla
• form a functional barrier between cortex & medulla (with type III)

• located within thymic medulla
• connect to other type V cells over desmosomes
• compartmentalize thymic medulla

form Hassall's corpuscle

• most characteristic feature of the thymus
• isolated mass of concentrically arranged type VI cells
• contains keratinhyalin granules, intermediate filaments & lipid droplets
• center can contain keratin

• multipotent lymphatic stem cell migrates to thymic cortex
• maturation: expression of T cell receptors, CD4 or CD8
• positive selection: exposed to type II & III epithelioreticular cells; must recognize MHC complexes or undergo apoptosis
• surviving cells migrate to thymic medulla
• negative selection: exposed to type V epithelioreticular cell and self MHC complexes; survive if NO immune response is shown
• leave thymus as helper T cells (CD4+) or cytotoxic T cells (CD8+)

• protects lymphocytes from exposure to antigens
• endothelium: major structural component; highly impermeable occluding junctions; basal lamina & pericytes
• macrophages: catch the antigenic molecules escaping the parenchyma
• type I epithelioreticular cells: occluding junctions & basal lamina

• largest lymphatic organ (fist size)
• found in upper left quadrant of the abdominal cavity
• filters blood & lymph
• white pulp: immune system functions
• red pulp: hematopoietic functions
• "nonessential" organ

• antigen presentation by dendritic cells & macrophages
• activation & proliferation of B & T cells
• production of antibodies against antigens in blood
• removal of macromolecular antigens from blood

• removal & destruction of old/damaged/abnormal RBCs and platelets
• retrieval of iron from hemoglobin
• formation of RBCs during early fetal life
• blood storage (NOT in humans)

• capsule: dense CT
• trabeculae: dense CT extending into parenchyma of spleen
• myofibroblasts: contractile cell that produces CT fibers
• hilum: site where splenic artery & vein, nerves & lymphatic vessels enter
• splenic pulp: white & red based on functions

• consist of mostly lymphocytes
• branches of the splenic artery enter the white pulp (central artery)
• lymphocytes accumulate around central artery forming the periarterial lymphatic sheath
• contain mostly B cells in nodule
• T cells in area surrounding the nodule

• contains large number of RBCs
• splenic sinuses
• splenic cords (of Billroth) - connect splenic sinuses

• lined by very long endothelial cells
• few contact points between the cells
• no continuous basal lamina - wrap around endothelial cells
• large intercellular spaces allow RBCs to pass through

• cords of Billroth
• connect splenic sinuses
• consist of loose network of reticular cells & fibers
• contain RBCs, macrophages, lymphocytes, dendritic cells, plasma cells & granulocytes

• splenic atery enters into white pulp via the trabeculae
• sends branches into white pulp & sinuses at perimeter (marginal sinuses)
• splenic artery continues into red pulp
• branches into penicillar arterioles
• continue as arterial capillaries (sheathed by macrophages)
• empty into reticular meshwork of splenic cords
• blood cells re-enter circulation via splenic sinuses
• leave spleen via trabecular veins & ultimately splenic vein

• optic vesicle: invagination of neuroectoderm
• optic vesicle induces surface ectoderm to thicken and form lens placode
• optic cup develops two layers
• outer layer of optic cup: nonneural retina (pigmented cells)
• inner layer of optic cup: neural retina (retinal cells)

• corneoscleral coat: cornea & sclera
• uvea: iris, ciliary body, choroid & lens
• retina: fovea centralis with macula lutea & optic disc

• outer fibrous layer, mostly connective tissue
• sclera: posterior 5/6 of covering of the eye (white)
• cornea: transparent anterior covering of 1/6 of eye

point of transition from nonvisual part of retina to visual part of retina

• choroid: highly pigmented, vascular layer
• ciliary body: ring shaped swelling responsible for accomodation of lens
• iris: controls light
• lens

• anterior chamber: anterior to iris, posterior to cornea, communicates with posterior chamber
• posterior chamber: small space behind iris, naterior to lens
• vitreous chamber: space between posterior surface of the lens & neural retina

isotonic protein-filled fluid that flows between anterior & posterior chamber

• gelatinous media that fills vitreous chamber
• high in hyaluronic acid & collagen

bends light to focus on lens

• corneal epithelium: nonkeratinized stratified squamous; innervated by unmyelinated V1 free nerve endings; will regenerated
• Bowman's membrane: where epithelium rests, nonregenerative
• corneal stroma: highly arranged perpendicular collagen fibers; transparent; contains myelinated nerves of V1
• Descemet's membrane: supports corneal endothelium; robust regeneration
• corneal endothelium: simple squamous; nonregenerative; mediates metabolic activity of cornea (hydration)

• point of transition from cornea to sclera
• corneal epithelium thicks & provides a source of stem cells (regenerative properties of corneal epithelium)
• Bowman's membrane disappears
• episcleral vessels appear

• suprachoroid lamina (lamina fusca): closely associated with choroid
• substantia propria (Tenon's capsule): most pronouced part; important in providing socket for prosthetic eyes
• episcleral layer: close to fat

• uvea: key for draingage
• nonpigmented epithelium of ciliary processes produce aqueous humor
• released into posterior chamber
• drains to anterior chamber
• drains to iridocorneal angle
• filters into trabecular meshwork/ spaces of Fontana
• drains into canal of Schlemm
• empties into episcleral veins, then superior & inferior opthalmic veins

• space between outer & inner layers of optic cup before fusion
• separates pigmented & nonpigmented epithlial cells of ciliary processes
• apical portions of cells are FACING EACH OTHER
• basal lamina on OUTSIDE of nonpigmented epithelial cells anchors zonula fibers

• produces aqueous humor
• basal portion of cells associated with zonula fibers (connect to lens)

associated with stroma of ciliary body (vasculature)

• blocked canal of Schlemm
• increases intraocular pressure
• can damage optic nerve
• impedes flow of light through cornea

CONSTRICTS - constrictor pupillae m.

DILATES - dilator pupillae m.

• parasympathetic control of iris
• shrink iris/ decrease pupil diameter
• CN III carries preganglionic parasympathetic fibers
• ciliary ganglion sends postganglionic parasympathetic fibers

• longitudinal muscle of iris
• sympathetic control
• dilates iris/ increase pupil diameter
• preganglionic sympathetic fibers from IMLCC of T1-T5
• superior cervical ganglion sends postganglionic sympathetic fibers (travels through long & short ciliary nerves)

• constrictor pupillae m.
• dilator pupillae m.
• anterior pigmented myoepithelium
• posterior pigment epithelium
• stromal cells, fibroblasts, vasculature

• anterior pigmented myoepithelium: from outer layer of optic cup; some contractile properties associated with dilator pupillae m.
• posterior pigmented epithelium: from inner layer of optic cup

• thick basal lamina (lens capsule): acts like basement membrane; where zonula fibers from ciliary processes insert
• supscapular epithelium: simple cuboidal OR squamous arrangement; divides in germinal zone
• lens fibers: at equatorial region, epithelial cells elongate & lose nucleus to become lens fibers

• specific cytoplasmic proteins filensin and crystallin
• with aging - proteins accumulate & cloud or turn yellow

• aqeuous humor bathes lens & supplies nutrients to it under normal circumstances
• inadequate nutrients cause lens to become opaque (formation of cataracts)
• Rx - artificial lens

control shape of lens (accomodation)

• largely smooth muscle - ciliary muscle (under parasympathetic control)
• 3 indistinguishable layers
• ciliary processes: nonpigmented & pigmented epithelium
• ciliary epithelium communicate via gap junctions, held together tightly by desmosomes

• ciliary muscle contracts
• ciliary body with inserted zonular fibers moves closer to lens
• tension in zonular fibers reduced
• lens relaxes/ becomes more round

• ciliary muscle relaxes
• ciliary body moves away from lens
• tension on zonular fibers increases
• lens flattens

• Bruch's membrane: separates chroid from retina
• choriocapillaries: smallest capillary bed closest to retina
• choroid: extensive vasculature, fibroblasts & immune cells, pigment cells, etc.

• lamina vitrae
• border of uvea (choroid) & retina

• accumulation of pigment between Bruch's membrane and RPE
• may lead to retinal degeneration

• thickening of Bruch's membrane
• drusen - accumulation of pigment
• atrophy of retina
• depigmentation of retinal pigmented epithelium
• obliteration of capillaries
• ruptured blood vessels

• yellowish pigment that accumulates between Bruch's membrane & RPE
• cause of macular degeneration & possible retinal detachment

• non-neural retina: posterior pigmented cells of the iris & nonpigmented epithelial cells associated with the ciliary processes
• neural retina: cells that actually detect the photons of light & transmit information to the brain

• retinal pigmented epithelium
• layers of rods & cones
• outer limiting membrane
• outer nuclear layer
• outer plexiform layer
• inner nuclear layer
• inner plexiform layer
• ganglion cell layer
• layer of optic nerve fibers
• inner limiting membrane

detect photons of light

• minority photoreceptor type
• lower sensitivity to light, higher acuity
• 3 photopigments: red, green, blue
• highest density towards fovea centralis
• responsible for photopic or daytime vision
• discs where photons reside are continuous with plasma membrane

• predominant photoreceptor type
• high sensitivity to light
• 1 photopigment: grey
• decreased density towards fovea centralis
• associated with scotopic vision (nighttime/low light)
• associated with peripheral vision
• discs that hold photopigments are enclosed within a membrane separate from the plasma membrane

• red-sensitive:  ~560 nm
• green-senstive:  ~530 nm
• blue-sensitive: ~420nm

• opsin + Vitamin A chromophore
• cones: iodopsin
• rods: rhodopsin (scotopsin + retinal)

• inability to distinguish the differences between certain colors
• results from absence of color-sensitive pigment in the cone cells of the retina
• most problems are inherited & present at birth
• red-green color blindness: most common type; red & green seen as same color

• receive input from photoreceptors
• 3 rod photoreceptors to 1 bipolar cell
• 1 cone photoreceptor to 1 bipolar cell
• leads to higher acuity in cone

• form the scaffolding for the retina; span nearly the entire length
• outer limiting membrane: apical end of cell
• inner limiting membrane: basal end of cell

• horizontal cells: modulate signals between bipolar & photoreceptors
• amacrine cells: module signals between bipolar cells & ganglion cells
• inner plexiform cells: send signals from inner plexiform layer to outer plexiform layer

• fovea centralis: high concentration of cones for visual acuity; tilted outer layers permit light to reach photoreceptors directly
• macula lutea: around fovea
• optic disc: blind spot

• RPE
• layer of cones ONLY
• outer nuclear layer
• outer plexiform layer
• NO inner retinal layers

• blind spot of eye: devoid of photoreceptors
• central retinal artery: branch of opthalmic artery supplying retina
• optic nerve fibers go back towards CNS through lamina cribosa (fenestrations in sclera)

• area of transition between retina & optic disc
• sclera has fenestrations to allow axons to leave optic disc

• bulbar & palpebral parts
• both parts have stratified columnar epithelium with goblet cells

• conjunctiva
• orbicularis oculi m.
• levator palpebrae superioris m.
• tarsal glands
• sebaceous glands
• apocrine glands
• accessory lacrimal glands
• eyelash

• located within tarsal plate (CT of stroma)
• pronounced duct system
• secrete "oily" tear into eye

• common sweat glands associated with eyelashes
• similar morphology to tarsal/Meibomian glands

• large cavity
• eosinophilic cell types

• located on superior part of eyelid
• basophilic cells with simple cuboidal arrangement

• skin & derivatives
• forms external covering of the body
• largest organ of the body
• constitutes 16-20% of total mass

• hair & nails
• glands - sweat, sebaceous, mammary
• variations found in animal world - NOT normally found in humans

• blubber
• feathers, beaks, claws
• quills
• horns, dermal plates
• horse hooves
• skin folds

• protective barrier: pathogenic organisms, dessication/hydration, UV light (some chemicals can be absorbed)
• regulation of body temperature: sweating through evaporation & insulation through vasoconstriction
• excretory: sweat glands
• sensory: brings information about external environment to individual
• endocrine: converts precursor molecules into hormonally active molecules (ex. Vitamin D)
• diagnostic information: color, patterning
• dermatoglyphics: personal ID through fingerprints & footprints
• GOOD FOR ECONOMY

• yellow: jaundice, liver problem
• blue (cyanosis): respiration or circulatory distress
• dry/cracked skin/ rashes: many different problems

• epidermis
• dermis

• keratinized stratified squamous epithelium
• ectodermal origin
• avascular

• irregular fibroelastic CT
• mesenchymal in origin
• vascular

• subcutaenous CT - more loose than dermis
• superficial fascia
• contains variable amounts of adipose tissue
• allows for mobility
• epidermis invaginates into dermis & hypodermis

• in areas of most abrasion
• palm of hand, soles of feet, fingertips, toes
• hairless
• abundant sweat glands
• thick keratinized layer - epidermis is thicker than thin skin

upper portion of the back (thick dermis)

• stratum corneum
• stratum granulosum
• stratum spinosum
• stratum basale (germinativum)

• stratum corneum
• stratum lucidum
• stratum granulosum
• stratum spinosum
• stratum basale (germinativum)

• most superficial layer
• consists of squamous, dead, anucleated keratinocytes filled with keratin
• forms a protective barrier

• only found in THICK skin
• highly refractile
• cannot see any cells
• process of keratinization is well advanced

• from one to several layers thick
• cells contain basophilic keratohyalin granules

• thickest layer
• composed of cells with numerous spinous process connected by desmosomes
• prickle cells: image due to artifact of fixation

• single layer of cells resting on a basal lamina
• stem cells (keratinocytes) arise by mitosis
• proliferation of keratinocytes must keep pace with the rate of desquamination
• contains varying amounts of melanin

• keratinocytes
• melanocytes
• langerhans' cells
• merkel's cells

• predominant cell type of epidermis
• produces keratin - 85% of total volume of fully differentiated cell
• keratin filaments aggregate into tonofilaments
• bundles of tonofilaments form tonofibrils
• as cells approach the surface, they begin to form keratohyalin granules
• apoptosis begins & soft keratin is formed

• contain filaggrin & trichohyalin
• promotes formation of tonofibrils (keratinization)

allows enzymatic breakdown of desmosomes holding keratinocytes together

• cells of stratum spinosum form lamellar bodies
• lamellar bodies secrete their contents (sphingolipids, ceramides, & other lipids) through exocytosis onto the cell surface between stratum granulosum & corneum
• lipid envelope: barrier to fluids
• envelop maintains as cells approach the surface

•  tyrosinse - DOPA - melanin
• enzyme: tyrosinase

• premelanocytes formed in golgi
• content of melanin increases with chemical transformation of tyrosine to DOPA and then to melanin
• melanosomes migrate to tips of processes of melanocytes
• melanosomes bud off & are phagocytized by keratinocytes
• pigment donation
• cytocrine secretion

• number of melanocytes in light skin is the same as in dark skin
• light skin: melanin is degraded rapidly by lysosome activity; found only in basal layer of the skin
• dark skin: melanin is distributed throughout the epidermis

• cannot be seen in routine sections
• function as antigen-presenting cells - involved in delayed hypersensitivity reactions (allergic dermatitis)
• contain HIV - relatively resistant to effects of HIV; serve as reservoir for virus
• contain birbeck granules
• part of mononuclear phagocytic system

• not easily seen in routine sections
• situated primarily in fingertips, oral mucosa, and base of hair follicles
• processes extend up between keratinocytes
• unmyelinated nerve fibers form merkel cell-neurite complexes that function as mechanoreceptors (sense light touch)
• merkel cell carcinoma: extremely aggressive

• papillary layer
• reticular layer

• immediately under the epidermis
• loose CT
• loose network of collagen, reticular & elastic fibers
• cell types - fibroblasts, macrophages, etc.
• thin layer

• varying thickness
• irregular dense CT
• bundles of collagen fibers
• fewer cells than papillary layer
• langer's lines: bundles of collagen fibers that allow minimal scarring (surgical importance)

• dermal papillae: projections into epidermis
• epidermal ridges (rete ridges): projections of epidermis into dermis
• projections are more numerous in thick skin than in thin skin
• hemidesmosomes: link intermediate filaments of the cytoskeleton to fibers in the papillary layer (anchoring filaments)

• free nerve endings: in epidermis around hair follicles (fine touch, pain, heat & cold)
• merkel's cell: merkel's cell-neurite complex (light touch)
• pacinian corpuscle: deep dermis, hypodermis (pressure & vibration)
• meissner's corpuscle: papillary layer of dermis under hairless skin (touch)
• ruffini's corpuscle: displacement of collagen bundles
• Krause's end bulb: papillary layer (pressure)

• infections (fungal & bacterial)
• infestations
• pigmentary disorders
• drugs & chemicals
• tumors
• weedwacker's dermatitis

• antimicrobial peptides
• inflammation
• re-epithelialization: mitosis & mobilization of keratinocytes
• subsequent repair of the underlying tissues
• deeper wounds require involvement of hair follicles

• first degree: surface of skin is damaged, but epidermis is still intact
• second degree: burn extends through epidermis into dermis; blisters variable
• third degree: both epidermis & dermis are destroyed; grafting likely necessary

• eccrine sweat glands
• apocrine sweat glands
• hair follicles & hair
• sebaceous glands
• nails

• helps regulate body temperature
• secretions similar to ultrafiltrate of blood
• sodium & water resorbed in the duct - hypotonic secretion
• excretory function: sweat contains sodium chloride, urea, uric acid & ammonia
• thermoregulatory sweating: cholinergic innervation; loss of water & electrolytes (K+ and Mg2+) can be excessive
• emotional sweating: adrenergic innervation; sympathetic stimulation

• secretory segment: extremely tortuous
• clear cells: secrete a watery component containing glycogen which reaches lumen via intercellular canaliculi
• dark cells: secrete a proteinaceous solution
• myoepithelial cells: help expel secreteion from the gland

• stratified cuboidal epithelium
• cells smaller & darker than secretory portion
• cells end when duct enters the epithelium & epithelial cells form duct wall

• large lumen, coiled tubular glands (may branch)
• found in axilla, areola, nipple of mammary glands & genital area
• secretory portion: simple cuboidal cells found with myoepithelial cells
• duct: stratified cuboidal cells (2-3 cells thick); no resorption of fluid takes place
• secretory function: linked to sex hormones (secrete pheromones)

• hair grows in cycles
• hair is formed by the hair follicle
• attached to each follicle is a sebaceous gland & a bundle of smooth muscle (arrector pili m.)
• dermal papilla: tuft of loose CT with vessels & nerves at the bottom of the follicle
• matrix cells: surround papilla; form germinative layer from which hair arises; cells increase in number & hair grows

• glassy membrane
• external root sheath
• internal root sheath - henle's layer, huxley's layer, cuticle
• hair - cortex & medulla

• muscle & gland attached to same side of the hair follicle
• muscle aids in secretory process; its contraction makes hair stand up & causes goose bumps
• gland produces sebum (oily substance that coats the hair & skin)
• holocrine secretion: cell accumulates secretion & ultimately dies & entire cell is secreted

• essentially controlled by genetics and ethnicity
• black, brown, blonde - varying amount of pigments
• gray & white (loss of melanins)
• eumelanin: black-brown pigment
• pheomelanin: red pigment
• round hair - straight
• flat, elliptical hair - curly

• anagen: active growth (90% involved) 3-7 years or longer
• catagen: growth stops; 1-2 weeks (1-2% involved)
• telogen: no more growth; club hair; 3 months (10-14% involved)
• eyebrows have shorter times

hair loss

• androgenetic alopecia: male patterned hair loss; genetic control of hair pattern
• alopecia areata: unexplained loss of hair
• alopecia universalis: total loss
• chemical alopecia: exposure to chemicals (chemotherapy)

• hard keratin
• rests on nail matrix (bed)
• eponychium: cuticle
• hyponychium: skin under tip of nails

• covered in enamel & dentin
• clinical crown: part of tooth visible, not covered by gingiva
• anatomical crown: extends down to where enamel ends & cementum begins on the root of the tooth

structure covered in dentin

surrounds root and dentin at root of tooth

• crown
• root
• cementum
• pulp & pulp chamber
• apical foramen
• peridontium
• periodontal ligament
• alveolar bone

• central soft core of the tooth
• coronal portion: pulp chamber
• radicular portion: root canal & lateral canals

• where blood vessels and nerves enter the tooth
• pathway between peridontium and the pulp

• periodontal ligament: holds tooth in place; extends from cementum to alveolar bone
• alveolar bone: bone that tooth sits in

• central incisor
• lateral incisor
• canine
• 1st premolar
• 2nd premolar
• 1st, 2nd, 3rd molars
• 32 teeth in total

• ameloblasts
• odontoblasts
• cementoblasts
• cementocytes
• CT cells (fibroblasts, cells of the pulp)

• formation of enamel
• originally from ectoderm
• sloughed off when tooth erupts - new enamel is not formed

• formation & maintenance of dentin
• exist after eruption to maintain dentin layer
• decrease in number with age

• formation of cementum
• secrete cementum until they become incorporated in the matrix
• become cementocytes (cells within cementum containing canaliculi)

• lateral lamina: downgrowths from maxillary and mandibular cavities
• successional lamina: projection off of bud that will form permanent tooth; begins to grow before birth
• dentin forms first (from mesenchymal tissue)
• enamel forms over dentin (from ectoderm)

• extremely hard
• brittle - maintained by underlying resilient dentin; easily fractured with destruction of dentin
• translucent: color from light yellow to grayish white
• varying thickness
• mineralized tissue - 96% mineral (hydroxyapatite), 4% organic & water
• NO collagen

• progressive destruction of bone
• result from dissolution of hydroxyapatite crystal in enamel

• no regeneration: non-vital tissue
• wears progressively with age
• increased discoloration: increased organic deposition; change in color of underlying dentin
• reduced permeability: decrease in pore size, increase in crystal size, reduced water content
• increase in fluoride content

• 70% inorganic - hydroxyapatite crystals
• 20% collagen fibers & other proteins
• 10% water
• softer than enamel but harder than bone
• slightly elastic: protection for enamel
• contains tubules
• yellowish

• contains densely packed dentinal tubules - from pulp to DEJ/DCJ
• odontoblastic process: like an osteocyte process
• encased in mineral
• odontoblasts line pulp cavity
• dentin conforms to general shape of the tooth

• formation of enamel
• amelioblasts differentiate from ectoderm in long, vertical cell lines
• Tome's process: covers enamel
• direct secretion & calcification of enamel completed by amelioblasts

• febrile diseases
• tetracycline-induced: incorporated into enamel; may present as brown band; may also cause enamel hypoplasia
• fluorosis: above 5ppm will cause enamel mottling

• odontoblasts secrete dentin
• odontoblasts have a process which extends from the cell body to the DEJ
• these processes reside in dentinal tubules
• the process usually occupies 1/3 of the length of the tubule
• odontoblasts secrete dentin throughout the life of a tooth - do NOT die after eruption; pulp cavity deminishes in size

• before dentin calcifies
• "mantle" dentin

• surrounds the root of the tooth
• two types - acellular and cellular
• acellular: predominant cementum
• cellular: located at base of the root
• secreted by cementoblasts in lacunae and have canaliculi which project towards the periodontal ligament
• 45-50% hydroxyapatite
• 50% collagen

• composed of three basic components
• periodontal ligament (membrane): comprised of collagen fibers, very dense, runs from cementum of root to alveolar bone (attached by Sharpey's fibers)
• cementum: surrounds the root
• alveolar bone: alveolar process

• odontoblasts
• fibroblasts
• undifferentiated ectomesenchymal cells
• macrophages & lymphocytes

• fibers: collagen type I & type II
• ground substance: glycosaminoglycans & glycoproteins
• water

• nerves travel in dentinal tubules & are stimulated by occurances in the enamel
• odontoblasts act as receptor for stimulus
• hydrodynamics - movement of fluids in canal upsets odontoblasts

• lines the oral cavity
• mostly stratified squamous non-keratinized epithelia
• underlying lamina propria
• submucosa

• orthokeratinized: apical cells full of keratin, no nuclei (skin)
• non-keratinized: apical cells retain nuclei, wet surface (esophagus)
• parakeratinized: moderate keratin, apical cells with picnotic nuclei; wet surface (gingiva)

• lining mucosa: non-keratinized, soft palate, cheek, lips, ventral tongue
• masticatory mucosa: parakaratinized & orthokeratinized;  hard palate & gingiva
• specialized mucosa: keratinized papillae; dorsum of tongue

• lips
• cheeks - lining mucosa with sebaceous glands
• alveolar mucosa - lining mucosa; mucogingival junction with gingiva
• gingiva - masticatory mucosa
• hard palate - masticatory mucosa
• soft palate - lining mucosa

• vermillion border: red area of lips
• transition between skin & oral mucosa
• Fordyce's spots: white spots; sebaceous glands within oral cavity

epithelial cells + lamina propria

• keratinocytes
• melanocytes
• Langerhans cells
• Merkel cells

• papillary layer: loose connective tissue underlies epithelia
• reticular layer: deep dense irregular connective tissue

• papilla: filiform, fungiform, foliate, circumvalate
• taste buds
• salivary glands

• extrinsic: muscles originate outside tongue; moves tongue in and out
• intrinsic: muscles originate in the tongue & insert in the tongue; alters shape of the tongue

• basal cells (type IV)
• dark cells (type I)
• light cells (type II)
• intermediate cells (type III)

• four cell types: basal, dark, light, intermediate
• cells have long microvilli that project into tast pore
• receptors on microvilli
• taste is actually dependent more on smell
• accessory cells: neuroepithelial cells, supporting cells & basal cells

• protection: lubricant, mucous protects epithelia of oral mucosa, clearance of sugars from mouth, form salivary pellicle on enamel
• buffering: maintains pH
• digestion: salivary amylase breaks down starch, lipase breaks down fat; dilutes gastric chime prior to entering GI tract
• taste: dissolves food; mediates taste through saliva; gustin aids growth & maturation of taste buds
• antimicrobial: histatin, lysozyme, lactoferrin, antibodies
• maintenance of tooth integrity: remineralization through calcium binding proteins & saturation of calcium and phosphate ions

• histatin: antibacterial protein
• lysozyme: hydrolysis of bacterial cell walls
• lactoferrin: binds free iron, required by some bacteria for growth
• antibodies: secretory IgA; agglutinate microorganisms; prevents adhesion to oral tissues

• parotid
• submandibular
• sublingual
• minor salivary glands
• Fordyce's spots

• largest salivary gland
• between ear & ramus of mandible
• peripheral branches of CN VII facial
• duct opens near maxillary second molar

• posterior part of the floor of the mouth
• tucked up against medial aspect of the mandible
• duct opens beneath tongue, lateral to lingual frenulum

• floor of the mouth - between tongue & teeth
• ducts open into raised sublingual folds
• often intermingles with submandibular gland ducts

• between 600-1000
• small discrete masses throughout oral mucosa
• except within the gingiva & anterior hard palate
• mucus glands except serous glands of von Ebner (circumvallate papilla)
• NONE in gingiva
• protective effect on enamel - help form the acquired pellicle
• important for lubrication of oral cavity

sebaceous glands on inside of lip

• compound tubuloalveolar (acinar) glands: excretory duct, striated duct, intercalated ducts
• terminal acinar: tubules secrete mucus; acini secrete serous fluid; serous demilunes present
• cell types: mucous cells, serous cells, myoepithelial cells

• artifact of preparation/fixation
• serous cells capping over serous-mucus cells
• inner acinus of mucus cells (light by H&E)
• outer layer of serous cells (dark by H&E)

• forms capsule
• projects into the gland
• subdivides gland into lobules
• cells - mainly fibroblasts; numerous plasma cells that contribute antibodies to saliva

• serous cell: secretes proteins, intensely stained by H&E, prominent Golgi apparatus
• mucous cell: secretes mucin, stains lightly
• myoepithelial cells

• minor mucosal glands have slow continuous secretion
• major serous glands have stimulated secretion
• B-adrenergic (sympathetic) stimulation: protein secretion
• L-adrenergic & cholinergic stimulation (parasympathetic): water & electrolyte release

• reduced salivary output with age: fatty degeneration, fibrosis, lymphocyte accumulation, reduced productive epithelial cells
• oncocytes: granular, acidophilic epithelial cells; increase with age; may give rise to neoplasms

• parotid gland: 100% seromucous
• submandibular gland: 80% seromucous; 20% mixed serous demilunes
• sublingual gland: mostly mucus acini; some mixed serous demilunes

• small diameter
• connected to the acini
• myoepithelial cells
• short cuboidal cells
• similar in staining to acini
• prominent in parotid gland (serous)
• secrete bicarbonate
• absorb chloride

• columnar cells
• central nuclei
• eosinophilic
• prominent striation in basal region
• prominent basal lateral infoldings
• removes Na+ from salivary secretions
• secrete bicarbonate
• makes saliva hypotonic
• flow rate

• transitions from simple columnar to stratified columnar
• pseudostratified intermediary
• makes saliva more hypotonic

• outer ear: auricle & external acoustic meatus
• middle ear: converts sound waves to mechanical vibrations
• inner ear: functions in equilibrium

collect & slightly amplify sound; localize sound in vertical direction

• pinna
• external component of the ear
• shape attributed to elastic cartilage
• lined with thin skin, hair follicles, sweat glands & sebaceous glands

conduct sound to the tympanic membrane

• air filled space leading from auricle to tympanic membrane/ eardrum
• lateral 1/3: S-shaped elastic cartilage continuous w/ that of the auricle; contains hair follicles, sebaceous glands & ceruminous glands
• medial 2/3: thin skin atop petrous portion of temporal bone; fewer hair cells & glands

• ear wax = sebum from sebaceous glands + desquaminated epithelial cells from skin
• function: lubricate ear & impede entry of foreign particles
• may prevent otitis media (inflammation/infection of outer ear)

converts sound waves from outer ear to mechanical vibrations in inner ear

• air filled space called tympanic cavity within temporal bone
• lateral boundary: tympanic membrane
• medial boundary: bony wall of inner ear

• separates outer ear from middle ear
• outer layer: keratinized stratified squamous epithelium (EAC)
• middle layer: radial & circumferential CT fibers (except at pars flaccida)
• inner layer: mucous membrane covered in simple cuboidal epithelium (continuous w/ auditory tube & mastoid antrum; becomes respiratory epithelium)

• malleus, incus & stapes
• manubrium of malleus is embedded in the tympanic membrane
• freely moveable synovial joints b/w malleus & incus and b/w incus & stapes
• stapes acts as a piston attached to oval window

auditory ossicles can become ossified and fracture; which leads to conductive hearing loss

outer ear - tympanic membrane - malleus - incus - stapes - oval window

• tensor tympani: increases tension on tympanic membrane (CN V3 innervation)
• stapedius: dampens movement of stapes at oval window (CN VII innervation)

• bony labyrinth
• membranous labyrinth
• vestibulocochlear nerve (CN VIII)
• facial nerve (CN VII)

three connected spaces (vestibule, semicircular canals, cochlea) within petrous portion of temporal bone bathed by perilymph

• central oval space of bony labyrinth connected to semicircular canals & cochlea
• vestibular ganglion: vestibular portion of CN VIII
• contains oval window
• contains utricle & saccule of membranous labyrinth

vestibule + semicircular canals

attachment of stapes; transmits vibratory motion of airwaves into fluid waves within inner ear

compensatory mechanism to dissipate energy from motion of fluid

• extend from the vestibule anterior at right angles to each other
• lateral: detects angular acceleration in horizontal plane
• anterior & posterior: detect vertical acceleration
• ampulla: swelling at end of semicircular canal closest to vestibule

• anterior spiral extension from the vestibule; cochlea
• contains round window
• cavity of spiral - cochlear duct
• spiral ganglion: cochlear portion of CN VIII

• lies within the bony labyrinth
• divided into the cochlear & vestibular labyrinth
• bathed by endolymph

• function: equilibrium & balance
• semicircular ducts: lie inside the semicircular canals
• utricle: continous w/ semicircular duct

• fluid produced by stria vascularis
• contained w/in membranous labyrinth
• high in K+

• fluid contained w/in bony labyrinth
• similar to extracellular fluid in content

• function: hearing
• cochlear duct: cavity of spiral; lies inside cochlea
• contains spiral ganglion (cochlear portion of CN VIII)
• saccule: continuous w/ cochlear duct

hair cells: modified columnar epithelial cells grouped by innervation (type I & II)

patches of hair cells in the utricle & saccule that detect gravity & linear acceleration

• stereocilia: large microvilli; multiple tightly packed groups of actin per hair cell
• kinocilium: one large cilium (9+2 arrangement) per hair cell on UTRICLE (vestibular system only)
• otoconia: calcium carbonate crystals embedded on gelatinous membrane (otolithic membrane) that add weight & impact gravitational movement of hair cells

• hair cells act as stretch receptors
• stereocilia bend according to change in gravity (directional response)
• cell membrane is stretched
• K+ channels are opened, allow K+ to flow into cell
• K+ stimulates increase in Ca2+ concentration
• release of neurotransmitters may be followed by action potential in nerve

patches of hair cells in the ampulla of semicircular canals that detect angular acceleration

• stereocilia: large microvilli made of actin; multiple per hair cell
• kinocilium: one large cilium (9+2 arrangement) per hair cell
• cupula: gelatinous fluid in duct causes cupula to drag behind and bend hair cells due to inertia
• NO otoconia

• one long continuous ribbon of hair cells within cochlear labyrinth
• NO kinocilium
• inner row: 1 hair cell (with microvilli)
• tunnel of Corti: contains cortilymph
• outer row: 3-5 hair cells
• supported by pharyngeal cells

• sense of rotation without equilibrium
• signifies dysfunction of vestibular system
• causes may include viral infection, drugs & tumors

caused by excessive stimulation of utricle

• caused by blockage of cochlear aqueduct
• increase in endolymphatic pressure causes dizziness & ringing in ears

• detects sound, not movement
• 2 & 3/4 turns
• high frequencies detected at base
• low frequencies detected at apex

• separates rows of hair cells of spiral organ of Corti
• formed by pillar cells
• bathed in cortilymph

• arises from spiral limbus
• sits on top of hair cells
• causes deflection of hair cells when sound is detected - NOT directionally dependent

• spiral bony part of cochlea
• contains vestibular portion of CN VIII branches as they exit osseous lamina to form spiral ganglia

• scala vestibuli: bony labyrinth filled w/ perilymph; separated from scala media by vestibular/Reisser's membrane
• scala media: membranous labyrinth filled with endolymph; cochlear duct
• scala tympani: bony labyrinth filled with perilymph; separated from scala media by basilar membrane

separates scala vestibuli & scala media

separates scala media & scala tympani

• ONLY vascularized endothelium in the body
• sits on the outer wall of the scala media; opposite from entrance of nerve fibers
• supported by spiral ligament
• produces endolymph & functions in K+ transport

connection between scala vestibuli & scala tympani

• area of tympanic membrane is 17X larger than oval window
• cone shape of tympanic membrane (center - umbo)
• mechanical advantage of levers created by auditory ossicles