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HISTOLOGY NOTES:
----------------------------------------------------------------------Trachea
? Pseudostratified columnar ciliated (PCC) epithelium with goblet cells,
mucoserous (mixed) glands
? C-shaped cartilages, smooth trachealis muscles dorsally
Bronchus
? PCC epithelium with goblet cells, mixed glands
? Plates of cartilage and smooth muscle bundles mixed
Bronchiole
? Columnar ciliated and secretory Clara cells, no goblet cells, no
glands
? Smooth muscle only
Respiratory bronchiole
? Cuboidal ciliated cells, alveoli in walls with type I and II cells
Alveoli
? Mixture of many type I (squamous, gas exchange) and few type II
(great, surfactant-secreting) epithelial cells
? Abundant surrounding capillaries
Major Intracellular Organelles (Be able to recognize on electron
micrographs):
Lysosome
? Lysosomal storage diseases (e.g., Tay-Sachs and many others)
? Few to hundreds/cell, round to irregular shape
? Surrounded by unit membrane
? Contains electron dense hydrolytic enzymes
? Degradation of phagocytosed materials and cell turnover
? Particularly abundant in neutrophils, macrophages, and liver
parenchymal cells
? Specific granules of granulocytes and acrosome of spermatozoon are
specialized lysosomes.
Peroxisome
? Abnormal in X-linked adrenoleukodystrophy and Zellweger syndrome
? Round
? Surrounded by unit membrane
? Contain urate oxidase, D-amino acid oxidase, catalase
? Involved in beta-oxidation of fatty acids
? Particularly abundant in liver parenchymal cells
Mitochondrion
? Abnormal mitochondria seen in Kearns-Sayre syndrome, MERRF, MELAS,
Leigh syndrome, and Lebers disease
? Few to hundreds/cell, usually elongated
? Have outer membrane and inner membrane
? Cristae are shelf-like projections from inner membrane. They increase
surface area. They are tubular in mitochondria in steroidogenic tissues,
e.g., Leydig cells, adrenal cortex, corpus luteum.
? Have dense bodies in matrix
? Site of oxidative phosphorylation, ATP synthesis

? Particularly abundant in muscle tissue, transporting epithelia, liver

parenchymal cells, secretory cells (e.g., pancreatic acinar cells)
Endoplasmic Reticulum (ER)
? Anastomosing plates and sheets of unit membranes, surrounding
flattened lumina
? Are either smooth (without attached ribosomes, SER, drug
detoxification and steroid synthesis) or rough (with attached ribosomes,
RER, protein synthesis for secretion).
? Contain enzymes and work bench for protein synthesis and steroid
synthesis
? RER often extremely abundant, especially in liver parenchymal cells,
pancreatic acinar cells, goblet cells, glandular cells, plasma cells,
motor neurons (as Nissl substance), i.e., cells that secrete proteins
and glycoproteins invariably have a lot of RER.
? SER often abundant in liver parenchymal cells (drug detoxification),
steroidogenic cells, and striated muscles as sarcoplasmic reticulum
Golgi Apparatus
? 5-10 flattened, unit membrane-bound sacs and numerous, smaller
membrane-bound vesicles
? Few to many/cell
? Often intermediate between RER and secretory granules in secretory
cells
? Curved structure with convex (cis-face, forming face) toward RER and
concave (trans-face, maturing face) toward secretory granules
? Contain glycosyltransferases and other enzymes for finishing and
packaging secretions initially synthesized in RER and destined for
secretion
? Involved in formation of lysosomes
? Abundant in neurons, plasma cells, protein secreting cells, goblet
cells, epididymal epithelium
Nucleus
? Present in most cells, except RBCs, 4-8m in diameter, often round but
variable shape
? Surrounded by double unit membrane (nuclear envelope) with pores to
allow passage of macromolecules synthesized in nucleus (e.g., m-RNA and
r-RNA) into cytoplasm
? Contains most of genome in DNA strands
? Chromatin can be darkly stained, condensed, inactivated
(heterochromatin) or lightly stained, decondensed, active (euchromatin)
? Contains nucleolus in synthetically active cells
Nucleolus
? Present in many cells actively engaged in protein synthesis
? Can be absent, when present often 1/nucleus
? Location of cistrons for synthesis of r-RNA
? Has fibrous central component (chromatin) and granular peripheral
components (r-RNA precursors)
? Prominent in liver parenchymal cells, motor neurons, many embryonic
cells, Sertoli cells, early stages of RBCs and WBCs in bone marrow, etc.
The Junctional Complex and Components
Junctional Complex
? Seen as terminal bars in light microscope
? Specialized for firm cell-cell adhesion between epithelial cells
? Usually (but not always) located on the apical boundary between cells,
near the luminal (apical) or free surface of the epithelium.
? Passes all the way around the apical surface of adjacent cells in a
belt-like fashion

? Isolates the luminal compartment from the lateral compartment between

cells and the deeper regions of an organ, below the basement membrane
? Consists of (from apical to basal) a zonula occludens (tight
junction), zonula adherens (adhesive junction), and a macula adherens
(desmosome)
Zonula Occludens
? Point of fusion of outer leaflets of plasma membrane
? Forms hydrophobic barrier between lumen and lateral intercellular
compartment
? Seen as wavy line of freeze-fracture etch preparations
? Prevents passage of materials from lumen to lateral compartment and
vice versa
? Passes all the way around the apical crown of a cell in a belt-like
fashion
? Can have several levels of leaflet fusion, producing redundant
barrier.
? Well developed in intestinal epithelium (preventing digestive enzymes
from breaking down cells). Important component of blood-brain and bloodtestis barrier.
Zonula Adherens
? Most commonly found just deep to the zonula occludens
? Belt-like, similar in this regard to the zonula occludens
? Outer leaflets now diverge, leaving 15-20 nm intercellular gap
? Site of intercellular adhesion
? Inner leaflets of membranes associated with actin-rich (presumably
reinforcing or motile) microfilaments
Macula Adherens (Desmosome)
? Most commonly found just deep to the zonula adherens
? Macular (spot-like) rather than zonular
? Adhesive function
? Intercellular gap 15-20 nm, with central lamina of adhesion (?)
protein
? Dense plaques cemented to inner (cytoplasmic) face of membrane
? Tonofilaments (bundles of intermediate filaments rich in keratin)
insert into these dense plaques
? Hemidesmosomes anchor the basal surface of some epithelial cells to
the basement membrane
Gap Junction (Nexus)
? Often a component of junctional complex, allows intercellular
communication
? Consists of six protein subunits arranged around an aqueous channel
? Adjacent cells often have patches of gap junction on their apposed
surfaces, creating aqueous channels for passage of water, ions, small
regulatory molecules, e.g. cAMP, between cells
? Also present between many other cell types, e.g. cardiac muscle cells,
neurons, lens, etc.
Lymphoid Tissue and Organs
Scattered Lymphocytes and Lymphoid Tissue
? B-cell function abnormal in Brutons agammaglobulinemia
? T-cell function abnormal in DiGeorge syndrome and AIDS
? Widely scattered free lymphocytes or small aggregates of lymphocytes
? Particularly abundant in skin, respiratory system, gastrointestinal
tract, and urogenital system
Lymph Nodules
? Are larger aggregates of lymphocytes
? Can have germinal centers
? Consist of lymphocytes, plasma cells, and macrophages

? Sites of lymphocyte differentiation into plasma cells

Palatine Tonsils
? Often inflamed in children
? Abundant lymph nodules in pharynx on either side of root of tongue
? Associated with stratified squamous unkeratinized epithelium covering
tonsillar crypts
Peyers Patches
? Collections of lymph nodules in GI tract
? Most abundant in ileum
Vermiform Appendix
? Inflammation and infection leads to appendicitis
? Collections of lymph nodules in cecal diverticulum
? Associated with simple columnar cecal epithelium with many goblet
cells
Lymph Nodes
? Become enlarged during infections and neoplastic diseases
? Widely distributed, numerous in neck, mediastinum, axilla, inguinal
region, mesenteries, and along major blood vessels
? Dedicated to immune surveillance of lymph
? Encapsulated with trabeculae projecting deep into organ away from
capsule
? Many afferent lymphatic (valved) vessels distributed peripherally
? One (or a few) efferent lymphatic vessel drains organ at hilus
? Arteries and veins enter and exit at hilus
? Lymph percolates in through afferent vessels, into subcapsular
sinuses, around germinal centers, and is collected in medullary sinuses
which empty into hilar efferent vessel(s)
? Cortex contains primary (inactive, darker) follicles and secondary
follicles (active, lighter germinal centers). The germinal centers
contain many B-cells, plasma cells, macrophages, and a few T-cells
? Paracortical regions are richer in T-cells
? Medulla contains medullary cords of closely packed lymphocytes, plasma
cells, macrophages, and medullary sinuses that carry lymph into efferent
lymphatic(s).
Thymus
? Congenital absence leads to DiGeorge syndrome and reduced T-cells
? Found in neck close to the thyroid
? Lobulated, each lobule has cortex and medulla
? Site of T-cell maturation
? Contains many endodermally derived (inferior branch of pharyngeal
pouch III) reticular epithelial cells, joined by desmosomes
? Reticular epithelial cells create microenvironment conducive to T-cell
differentiation
? Medulla characterized by hyaline aggregates of effete reticular
epithelial cells called Hassalls corpuscles
Spleen
? Enlarged in hemolytic anemias, e.g., sickle cell anemia
? Only intraperitoneal lymphoid organ, closely associated with fundus of
stomach
? Encapsulated by dense CT capsule with trabeculae projecting toward
center of organ and covered by mesothelium
? Consists of white pulp and red pulp
? Dedicated to immune surveillance of the blood and phagocytosis of
effete RBCs
? Red pulp contains many sinusoids and entrapped blood
? White pulp contains central artery surrounded by periarterial lymphoid
sheath (PALS)

? PALS and adjacent marginal zone rich in T-cells

? Germinal centers are located peripheral to the PALS and are richer in
B-cells
The Mononuclear Phagocyte System (MPS)
Common Feature of All Cells in MPS
? Derived from bone marrow
? Highly migratory
? Dedicated phagocytes
? Surface markers include Fc receptors, Il-2 receptors, and complement
receptors
? Secrete many immunomediators including Il-1, Il-6, TNF, interferon,
CSF, and erythropoietin
? Play key role in inflammation
MPS Family Members
? Monocytes (in blood, precursors of many macrophages)
? Pulmonary, pleural, and peritoneal macrophages
? Histiocytes
? Macrophages of lymph nodes and spleen
? Kupffer cells (hepatic sinusoids)
? Osteoclasts
? CNS microglia
? Cutaneous Langerhans cell
? Multinuclear giant cells (Langhans cells) in inflammation
Tissues Specialized for Contraction
General Features
? Cells specialized for forceful and repeated contraction.
? Unusually high concentration of the contractile proteins actin and
myosin.
? Contain contraction regulatory proteins such as calmodulin, troponin,
and tropomyosin.
? Striated varieties (skeletal and cardiac muscle), the muscle proteins
are arranged in highly organized arrays called sarcomeres, allowing for
my forceful and rapid contraction.
? Energy stored in ATP drives the conformational changes in proteins and
energizes movement.
Myoid Cells
? Similar to smooth muscle but usually isolated or in thin layer
? Surround seminiferous tubules, epididymal tubules near testis, and
acini of mammary glands and sweat glands.
? Often exist as single, stellate cells deep to the epithelial basement
membrane
Smooth Muscle
? One nucleus/cell, centrally place, not striated
? Make up a major component of wall of many visceral organs (except
heart) and wall of blood vessels
? Often closely associated with CT fibroblasts in wall of organ
? Controls diameter of lumen, blood pressure, motility of organ
? Calcium diffuses into cell and binds to calmodulin
? Calmodulin activates ATPase in myosin heads
? Myosin moves with respect to actin to generate force
Skeletal Muscle
? Duchenne muscular dystrophy and myasthenia gravis have direct effects
on skeletal muscle.
? Many nuclei/cell, peripherally placed, cells long and large,
unbranched, striated. Skeletal muscle fibers are an anatomic syncytium.
? Epimysium is CT capsule around entire gross muscle
? Perimysium is CT capsule around fascicles of muscle

? Endomysium is collection of fibroblasts that surround individual

muscle fibers (cells) and bind them together into coherent mass.
? Muscle fiber (cell) contains many myofibrils and is surrounded by a
sarcolemma (muscle cell membrane)
? Sarcolemma has deep surface invagination called T(transverse)-tubules
that carry action potential depolarization deep into sarcoplasm
? Each myofibril consists of many sarcomeres attached end to end
? Fewer mitochondria/cell than cardiac muscle
Sarcomere Structure and Contraction
? Sarcomere extends from Z-line to Z-line
? Sarcomere has thin (actin-rich) filaments inserting in Z-lines and
thick (myosin-rich) filaments intercalated between thin filaments.
? M-line marks middle of sarcomere and thick filaments
? A-band represents extent of thick filament myosin aggregatesremains
constant regardless of state of contraction
? I-band represents region of only thin filaments
- Shortest at maximal contract
- Intermediate at resting length
- Longest when stretched
? H-band is in middle of sarcomere, on either side of M-line. Length
varies with contraction in same way that I band does
? Myosin heads project away from thick filaments and latch on to thin
filaments
? During contraction, conformational change in myosin head causes thin
filaments to ratchet past thick filaments, moving Z-lines closer
together, shortening sarcomere, shortening myofibrils, shortening muscle
fibers, and causing entire gross muscle to contract.
? In stretched muscle, there is minimal overlap between thick and thin
filaments. Thus, H band is broadest here.
? Sarcoplasmic reticulum (SR) concentrates calcium and surrounds
myofibrils.
? T-tubule adjacent to two terminal cisternae of SR at triads (located
at A-I junction) by gap junctions
? Depolarization wave (from motor end plate) passes along sarcolemma,
down T-tubules, and triggers release of calcium from SR
? Calcium binds to troponin, causes conformation change in tropomyosin,
and exposes myosin head binding sites of actin.
? Myosin heads bind, change conformation, and pull actin filaments
closer to M-line, bringing Z-lines closer together and shortening
sarcomeres
Cardiac Muscle
? One nucleus/cell, centrally placed, cells small and branched, striated
? Individual cells firmly adherent and connected by gap junctions at
intercalated discs, meaning that cells are in ionic communication and
act in a coordinated fashion. Cardiac muscle is not anatomically
syncytial.
? Sarcomeres similar to those in skeletal muscle and work essentially
the same way
? There is a T-tubule, located over Z-lines, but it is associated with
less extensive SR cisternae.
? More mitochondria/cell than skeletal muscle
Frequently Tested Clinical Conditions Related to Histology/Cell Biology
Kartagener Syndrome
? Male, infertility, URI, situs inversus
? Cilia and flagella defective, lack dynein arms
Duchenne Muscular Dystrophy
? Young male, muscle weakness, elevated CPK

? Dystrophin defects lead to defective attachment of contractile

apparatus to cell membrane.
Myasthenia Gravis
? Female in 20s, weakness first in ocular muscles, progressive
? Autoantibodies to acetylcholine receptor
Achondroplasia
? Autosomal dominant inheritance, apparent at birth
? Long bones of limbs shortened and bowed, depressed nasal bridge.
Prominent forehead
? Defective fibroblast growth factor-3 receptor
Cystic Fibrosis
? Autosomal recessive inheritance, most common in Northern Europeans
? Chronic URI, wheezing, digestive difficulties, increased salt in sweat
? Abnormal transmembrane conductance regulator
Tay-Sachs Disease
? Autosomal recessive, most common in Ashkenazi Jews, French-Canadians
? Blindness, mental retardation, accumulation of ganglioside GM2
? Lysosomal defect in hexosaminidase A
Hereditary Spherocytosis
? Autosomal dominant in most common form
? Loss of spectrin leads to round, fragile RBCs and hemolytic anemia
Hurler Syndrome
? Autosomal recessive
? Coarse fascies, opaque cornea, mental retardation, excretes dermatan
sulfate and heparan sulfate in urine
? Lysosomal defect in alpha-L-iduronidase
Marfan Syndrome
? Autosomal dominant
? Long limbs, hyperextensibility of digits, associated with aortic
aneurysm
? Defective fibrillin
Osteogenesis Imperfecta (type I)
? Multiple fractures, blue sclera, hearing and dental problems
? Abnormal type I collagen
Brutons Agammaglobulinemia
? Male infant, repeated infections, nearly normal CBC
? B-cells absent so there are no plasma cells
DiGeorge Syndrome
? Newborn to young infant with fungal infections, craniofacial
anomalies, and tetany, reduced PTH
? T-cells lacking due to thymic hypoplasia
Collagen Types
General
? Most abundant protein in the human body.
? Linear tropocollagen molecule consists of three _-chains wrapped
around one another
? Types depend on different combinations of different _-chains and more
subtle biochemical differences
Type-I
? Abnormality leads to osteogenesis imperfecta (type I)
? Bones, tendons, fascia, organ capsules
? Striated fibers, ranging from thin to very thick
Type-II
? Hyaline and elastic cartilage, nucleus pulposus, vitreous body
? Thin fibrils
Type-III
? Abundant in lamina propria, liver, spleen, bone marrow

? Forms reticular (argyrophilic) fibers

Type-IV
? Abundant in basement membranes
? Associated with laminin and heparan sulfate
? Forms fine filaments not visible in light microscope
Type-V
? Wide distribution, small amounts
? Surrounds smooth and skeletal muscle
? Binds other fibrous collagens together
Type-VI
? Not abundant (except in cornea)
? Associated with types-I and III
? Structural role unclear
Type-VII
? In basement membranes, especially in skin
? Anchoring function in basement membranes
Type-VIII
? Associated with endothelial cell basement membranes
? Present in basement (Descemets) membrane of corneal endothelium
Type-IX
? Found in cartilage
? Involved in assembly of type-II collagen fibrils
Type-X
? Confined of cartilage
? Adjacent to hypertrophic chondrocytes in developing bone
? May play role in calcification
Odds and Ends
All Steroidogenic Tissues are similar in electron micrographs
? Prominent lipid droplets (stored cholesterol esters)
? Abundant SER (enzymes for steroid biosynthesis)
? Mitochondria with tubular cristae (produce ATP for steroid
biosynthesis)
? Examples:
- Adrenal cortex (largest lipid droplets in zona fasciculata)
- Corpus luteum
- Thecal cell of ovarian follicle
- Leydig cells
All Protein-Secreting Cells are similar in electron micrographs
? Prominent nucleolus (for synthesis of r-RNA precursors)
? Abundant RER (for assembly of polypeptide chains
? Abundant Golgi apparatus (for glycosylation and packaging of secretion
granules)
? Many mitochondria (for ATP for protein synthesis and vesicle
transport)
? Membrane-bound granules for secretion (often called zymogen granules)
? Examples:
- Plasma cells (secrete immunoglobulins)
- Motor neurons (secrete neurotransmitters)
- Pancreatic acinar cells (secrete digestive enzymes)
- Salivary glands
- Lacrimal glands
- Mammary glands
- Cells in parathyroid (secrete PTH)
- Chief cells in gastric glands (secrete pepsinogen)
- Adenohypophysis (secrete trophic hormones, e.g. LH, TSH, FSH)
Important Characteristics of Bone Marrow Cells

? Most primitive stem cells are rarest, largest, have pale staining
weakly basophilic cytoplasm, large uncondensed nuclei, and multiple
nucleoli
? Myeloblasts have large, uncondensed nuclei, several nucleoli and lack
nonspecific azurophilic) granules
? Promyelocytes have large, uncondensed nuclei, several nucleoli, and
azurophilic granules
? Myelocytes have large, uncondensed nuclei, usually one nucleolus, and
azurophilic granules and specific (neutrophilic, eosinophilic or
basophilic) granules
? Metamyelocytes have condensed, lobulated nuclei and both types of
granules
? Mature cells have fully condensed and lobulated nuclei and a
predominance of specific granules
? Proerythroblasts are large, round cells with several nucleoli and
basophilic agranular cytoplasm
? Basophilic erythroblast are smaller than proerythroblasts, nucleus
more condensed, nucleoli less prominent, cytoplasm intensely basophilic
due to numerous polyribosomes for hemoglobin synthesis
? Polychromatophilic erythroblasts have further nuclear condensation and
accumulation of acidophilic cytoplasmic hemoglobin, less cytoplasmic
basophilia that previous stage
? Orthrochromatic erythroblasts (normoblasts) have further nuclear
condensation, acidophilic cytoplasm because hemoglobin has replaced free
polyribosomes
? Once nucleus is extruded, you have mature RBC
? Reticulocytes are RBCs with remnants of basophilic polyribosomes in
cytoplasm They normally represent 1-2% of peripheral RBCs. Elevations
suggest hemolytic anemias