Transcript USMLE STEP I Review Week 1: Cell Bio & Histology

Chase Findley, MSIV
Cell Cycle Phases

Checkpoints control transitions between
cell phases. Regulated by cyclins, cdks,
and tumor suppressors.
Cell Cycle Phases

Permanent cells
 Remain in G0, regenerate from stem cells
 Neurons, skeletal and cardiac muscle, RBC’s

Stable cells
 Enter G1 from G0 when stimulated
 Hepatocytes, lymphocytes

Labile cells
 Never go to G0, divide rapidly with short G1
 Bone marrow, gut epithelium, skin, hair follicles
Plasma Membrane Composition
Asymmetric fluid bi-layer
 50% cholesterol, 50% phospholipids
 Small amounts of protein, sphingolipids,
glycolipids
 High cholesterol or long saturated fatty
acid content increases melting
temperature

Endoplasmic Reticulum

Rough
 Site of synthesis of secretory (exported) proteins
and N-linked oligosaccharide addition
 In neurons, (Nissl bodies) synthesize enzymes
and peptide neurotransmitters
 Mucous secreting goblet cells and antibody
secreting plasma cells are rich in RER
Rough Endoplasmic Reticulum
Endoplasmic Reticulum

Smooth
 Site of synthesis of steroids
 Detoxification of drugs and poisons
 Liver hepatocytes and adrenal cortex are
rich in SER
Smooth Endoplasmic Reticulum
Golgi Apparatus
“Distribution center” of proteins and
lipids from ER to plasma membrane,
lysosomes, secretory vesicles
 Adds mannose-6-phosphate to proteins,
targeting to lysosome

 Failure results in I-cell disease, enzymes
secreted outside cell

Proteoglycan assembly and sulfation
Golgi Apparatus
Microtubules
Helical array of polymerized dimers of α
and β tubulin
 Each dimer has 2 GTP bound
 Incorporated into flagella, cilia, mitotic
spindles, neurons
 Chediak-Higashi syndrome

 Defect in microtubule polymerization with
decreased phagocytosis

Target of mebendazole, taxol, griseofulvin,
vincristine, vinblastine, colchicine
Cilia Structure
9+2 arrangement of microtubules
 Dynein (ATPase) links peripheral 9
doublets, causes bending by differential
sliding of doublets
 Dynein=retrograde Kinesis=anterograde
 Kartagener’s syndrome

 Dynein defect, immotile
cilia, infertility, recurrent
infections
Collagen
Most abundant protein in body
 Organizes, strengthens extracellular matrix
 Type I

 Bone, skin, tendon, dentin, fascia, cornea

Type II
 Cartilage, vitreous body, nucleus pulposus

Type III (Reticulin)
 Skin, blood vessels, uterus, fetal tissue

Type IV
 Basement membrane
Collagen Synthesis

Inside fibroblasts
 Synthesis (RER)
○ Translation of collagen α-chains (preprocollagen)
 Hydroxylation (ER)
○ Specific proline and lysine residues, requires
Vitamin C
 Glycosylation (Golgi)
○ Pro-α chain residues, formation of procollagen
(triple helix of α-chains)
 Exocytosis
○ Procollagen exocytosed to extracellular space
Collagen Synthesis

Outside fibroblasts
 Proteolytic processing
○ Cleavage of terminal regions of procollagen,
transforms into insoluble tropocollagen
 Cross-linking
○ Reinforcement of many staggered tropocollagen
molecules by covalent lysine-hydroxylysine crosslinkage, produces collagen fibrils
○ Defective collagen synthesis causes Ehlers-
Danlos syndrome.
Elastin
“Stretchy” protein
 Rich in proline, lysine
 Found in lungs, large arteries, elastic
ligaments
 α-1 antitrypsin inhibits elastase,
excessive elastase activity causes
emphysema

Phosphotidylcholine (Lecithin)
Function
Major component of RBC membranes,
surfactant, myelin, bile
 Used in esterification of cholesterol

Immunohistochemical Stains

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Connective Tissue
Muscle
Epithelial Cells
Neurons
Neuroglia

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Vimentin
Desmin
Cytokeratin
Neurofilaments
Glial fibrillary acid
proteins
Digestive Tract Histology
 Mucosa
○ Contains epithelium, lamina propria,
muscularis mucosa
○ Absorptive function, villae
 Submucosa
○ Contains submucosal nerve plexus
 Muscularis externa
○ Contains Myenteric nerve plexus
○ Inner circular, outer longitudinal
 Serosa/adventitia
Digestive Tract Histology
 Submucosal nerve plexi
○ Submucosal layer
○ Coordinates secretions, blood flow, absorption
 Myenteric nerve plexi
○ Muscularis externa layer
○ Coordinates motility
Digestive Tract Histology
 Brunner’s Glands
○ Located in duodenal submucosa
○ Secrete alkaline mucous, neutralize acidic
stomach contents
○ Hypertrophy in peptic ulcer disease
Digestive Tract Histology
 Peyer’s Patches
○ Unencapsulated lymph tissue in mucosa and
submucosa of small intestine
○ Take up antigen, stimulate local B cells to
differentiate into IgA-secreting plasma cells
○ IgA secreted into lumen
Digestive Tract Histology
 Barrett’s Esophagus
○ Replacement of non-keratinized, squamous
epithelium with intestinal columnar epithelium
in distal esophagus
○ Caused by acid reflux, may lead to
adenocarcinomas
○ Example of metaplasia
Liver Histology
 Zone 1
○ Periportal
○ Sensitive to toxic
injury
 Zone 2
○ intermediate
 Zone 3
○ Pericentral
○ Sensitive to ischemic
injury
GI Secretory Cells
(More thoroughly covered in GI session)
 Parietal Cells (Stomach)
○ Intrinsic factor
 B12 absorption, destroyed in pernicious anemia
○ Gastric acid (HCl)
 Chief Cells
○ Pepsin
 Protein digestion
 Mucosal Cells
○ Bicarbonate
 G Cells
○ Gastrin
Erythrocytes
Anucleate
 Biconcave

 High surface area to volume ratio for easy gas
exchange
Life span: 120 days
 Glucose energy source

 90% anaerobically degraded to lactate

Membrane contains chloride-bicarbonate
antiport, involved in “physiologic chloride
shift”
Erythrocytes

Anisocytosis
 Varying size

Poikilocytosis
 Varying shape

Reticulocyte
 Immature erythrocyte
○ Larger, bluish tinge
Neutrophils
Multilobed nucleus
 Mediate acute inflammatory response
 Phagocytic
 Primary granules contain hydrolytic
enzymes, lysozyme, myeloperoxidase
 Hypersegmented in B12/folate
deficiency

Neutrophils

Normal

Hypersegmented
Leukocytes

Granulocytes
 Basophils, eosinophils, neutrophils

Mononuclear cells
 Lymphocytes, monocytes
Lymphocytes
Round, densely staining nucleus
 Little cytoplasm
 T & B lymphocytes

T Lymphocytes
Mediate cellular immune response
 Originate from stem cells in bone
marrow, mature in thymus
 Differentiate into:

 Cytotoxic T cells
○ MHC I, CD8
 Helper T cells
○ MHC II, CD4
 Suppressor T Cells
B Lymphocytes
Mediate humoral immune response
 Originate from stem cells in bone
marrow, mature in marrow
 Migrate to peripheral lymph tissue
 Differentiate into plasma cells, produce
antibody when presented with antigen
 Function as APC via MHC II

Mast Cells

Mediate allergic reaction
 Contain histamine, heparin,
chemotactic factors
 Bind IgE to cell membrane
Found in tissue
 Cromolyn sodium
prevents degranulation

Eosinophils
Monocytes
Kidney shaped nucleus
 Differentiates to macrophages in tissue

Macrophages
Phagocytic for bacteria, cell debris,
senescent blood cells
 Activated by gamma interferon
 Function as antigen presenting cell via
MHC II

Plasma Cells
Off-center nucleus, clock-face chromatin
 Abundant rough endoplasmic reticulum
and Golgi apparatus
 Differentiate from B cells, produce
antibody

Eosinophils
Bilobate nucleus
 Highly phagocytic for antigen-antibody
complexes
 Defend against helminth and protozoan
infections
 Elevated in allergies, asthma certain
neoplasms, collagen vascular diseases

Basophils
Bilobate nucleus
 Mediate allergic reaction

 Contain histamine, heparin, leukotrienes

Found in blood
Epidermal Layers
*Langerhan’s cells are dendritic cells that function as APC’s in skin.
Remember Birbeck granules!
Epithelial Cell Junctions

Zona occludens (tight junction)
 Creates semi-permeable barrier

Macula adherens
 Small discrete points of attachment

Gap junction
 Allows adjacent cells to communicate via
metabolic/electrical processes

Hemidesmosome
 Anchors cells to extracellular matrix

Integrin
 Maintains integrity of basement membrane
Epithelial Cell Junctions
Skeletal Muscle Cell Structure

Sarcomere
 Skeletal muscle unit from
Z line to Z line

A band
 Area of overlap of actin
and myosin

I band
 Area of actin only
Contraction causes I band
shortening, A band stays same
Skeletal Muscle Cell Structure
Striated
 Peripheral nuclei
 Linear fibers

Cardiac Muscle Structure


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
Striated
Central nuclei
Branching fibers
Intercalated disks
 Contain gap junctions which allow electrical impulse
to pass between adjacent cells
Smooth Muscle
Non-striated
 Central, elongated nucleus
 “Network” muscle fibers

Neuron Structure, Schwann Cells


Individual Schwann
cells myelinate a
single PNS axon
Impulse travels via
saltatory conduction
Peripheral Nerve Layers

Endoneurium
 Invests single nerve fiber

Perineurium
 Surrounds a fascicle of fibers
 Must be rejoined for limb re-
attachment

Epineurium
 Surrounds entire nerve,
and associated vessels
Oligodendroglia
Each oligodendroglia myelinates
multiple CNS axons
 Predominate glial cell in white matter
 Destroyed in multiple sclerosis

Microglia
CNS phagocytes
 Mesodermal origin (all others
from ectoderm)
 Enlarge to large amoeboid cells
in response to tissue damage
 Fuse into multinucleated giant
cells when infected by HIV

Astrocytes
Physical support and repair of axons
 K+ metabolism
 Maintain blood-brain barrier

Sensory Corpuscles: Meissner’s
Small, encapsulated nerve endings
 Dermis of palms, soles, digits (hairless
skin)
 Light discriminatory touch

Sensory Corpuscles: Pacinian
Large, encapsulated nerve endings
 Deep skin layers at ligaments, joint
capsules, serous membranes,
mesenteries
 Pressure, coarse touch, vibration,
tension

Sensory Corpuscles: Merkel’s
Cup-shaped nerve ending
 Dermis of fingertips, hair follicles, hard
palate
 Light, crude touch

Blood-Brain Barrier

Formed by:
 Tight junctions between nonfenestrated
capillary endothelial walls
 Basement membrane
 Astrocyte foot processes
Blood-Brain Barrier
Glucose and amino acids cross by
carrier-mediated transport
 Non-polar molecules cross more readily
than polar molecules
 Infection destroys tight junctions, leads
to vasogenic edema

Renal Structure
Glomerular Structure
Sperm Structure

Head (acrosome)
 Derived from Golgi apparatus

Neck
 Contains mitochondria,
energy supply from fructose

Tail
 Derived from centrioles
Spermatogenesis

Spermatogonium
 Diploid, 2N


Meiosis I

Meiosis II
Secondary spermatocyte
 Haploid, 2N

Mitosis
Primary spermatocyte
 Diploid, 4N


Spermatid
 Haploid, 1N
Occurs in seminiferous tubules
Sertoli cells create blood-testis
barrier, prevent autoimmunity
Spermatogenesis
Oogenesis
Oogenesis
Respiratory Tree

Conducting zone
 Warms, humidifies, filters air
 Smooth muscle
 Anatomic dead space
 Nose, trachea, pharynx, trachea, bronchi,
bronchioles, terminal bronchioles

Respiratory zone
 Participates in gas exchange
 Bronchioles, alveolar ducts, alveoli
Pneumocytes

Type I pneumocytes
 97% of alveolar surface,
line alveoli
 Responsible for gas
exchange
Pneomocytes

Type II pneumocytes
 Secrete pulmonary
surfactant
 Precursors to Type I and
other Type II cells
 Proliferate during lung
damage
Bronchopulmonary Segments

1 Bronchopulmonary segment has:
 1 tertiary (segmental) bronchus
 2 arteries (bronchial, pulmonary)
 Veins and lymphatics