Histology Lecture 2

Front 1

Define epithelium

Back 1

Avascular tissue that covers the exterior surface of the body and lines internal closed cavities and tubes
Makes up functional component of glands and act as receptors for smell, taste, hearing, and vision

Front 2

List the 4 characteristics of epithelial cells

Back 2

1) Free apical surface
2) Lateral cell-to-cell adhesions
3) Polarity
4) Sit on a basement membrane

Front 3

Define epitheloid tissue

Back 3

Looks like epithelium but lacks free apical surface

Front 4

List 5 fxns of epithelium

Back 4

1) Transport
2) Absorption
3) Secretion
4) Protection
5) Receptor

Front 5

What are the 3 criteria used to classify epithelium?

Back 5

1) Number of layers
2) Shape of cells on surface layer
3) Apical specializations

Front 6

What are the two number of layers used to classify epithelium?

Back 6

1) Simple- single layer of cells
2) Stratified- more than one layer of cells

Front 7

What are the three shapes of cells used to classify epithelium?

Back 7

1) Squamous- width of cell is greater than its height
2) Cuboidal- width, depth and height are all roughly equivalent
3) Columnar- height of cell is greater than its width

Front 8

What are the three apical specializations used to classify epithelium?

Back 8

1) Microvilli
2) Stereocilli
3) Cilli

Front 9

List 4 characteristics of epithelial dysplasia

Back 9

1) Occurs in response to persistant injury (or mutational change)
2) Usually regresses
3) Histiologically- variation in shape/size of cells; increase in size of nucleus; abnormal arrangement of cells within the epithelium
4) Usually seen but not limited to hyperplastic squamous epithelium (skin, bronchus, cervix, etc.)

Front 10

List 4 characteristics of carcinoma

Back 10

1) Cancer arising from epithelial cells
2) Malignant by definition
3) Carcinoma in-situ- no invasion through basement membrane
4) Named by appearance of cells, putative cell of origin, or presumptive organ of primary development

Front 11

Define microvilli

Back 11

1) Fingerlike projections that have a core of actin filaments (aka microfilaments) that insert into the actin filaments of the terminal web
2) Appearance can vary widely and usually covered by glycocalyx
3) Fxn is to increase surface area of cell

Front 12

Define stereocllia

Back 12

Unusually long microvilli that is found only in epididymis, proximal region of ductus deferens, and sensory (hair) cells of ear

Front 13

Define cilia

Back 13

1) Contains a core of microtubules NOT actin arranged into a axoneme
2) Number can vary from 1 to several hundred
3) Two types: motile or non-motile (aka primary)

Front 14

Describe the make-up of motile cilia

Back 14

9+2 array of microtubules- 9 outer doublet and 2 single central microtubules
Outer doublet composed of a complete A microtubule (13 protofilaments) and an incomplete B microtubule (10 protofilaments)

Front 15

Describe ciliary motility

Back 15

1) Occurs by bending axoneme. Inner and outer dynein arms of the A microtubule slide along the adjacent B microtubule. Dynein arms hydrolyze ATP to provide energy for microtubule sliding
2) Radial spokes interact with both the central microtubules and the A microtubule to regulate ATPase activity of dynein arms
3) Sequential activation of dynein arms allows cilium to bend
4) Cilia in successive rows start to beat so that each row is slightly more advnaced in cycle that following row

Front 16

Describe primary ciliary dyskinesia (immotile cilia syndrome)

Back 16

1) Broad group of autosomal recessive hereditary disorders affecting 1/20,000 births

Front 17

Describe Kartagener's syndrome

Back 17

Dynein arms are absent resulting in recurrent respiratory infections and male sterility.
50% of patients have situs inversus

Front 18

Describe Young's syndrome

Back 18

Radial spokes are absent or defective
Some defects observed in dynein arms
Result in recurrent respiratory infections and situs inversus

Front 19

Describe non-motile (primary) cilia

Back 19

1) Majority of cilia found on cells
2) Generally only one per cell
3) Contain an axoneme comprised of 9+0 array of microtubules
4) Non-motile; sensory function (cilia of kidney epithelium)

Front 20

Describe polycystic kidney disease (9+0 cilia)

Back 20

1) 1 in 800-1,000 white individuals is carrier
2) 4th leading cause of kidney failure in US
3) Due to defect in either formation or fxn of cilia of collecting ducts
4) Flow of urine bends the cilium, opening a mechanicosensitive Ca2+ channel. Influx of Ca2+ is first step of signal transduction pathway that ultimately regulates cell cycle
4) Result is formation of multiple expanding cysts in kidney that results in kidney failure

Front 21

Describe basal bodies (aka centriole)

Back 21

1) Found at base of cilia/flagella and template ciliary formation
2) If at nucleus and does not template ciliary formation, termed centriole
3) Composed of 9 sets of triplet microtubules (A, B, and C) that are continuous w/A and B microtubules of outer doublet. No central microtubules
3) Found as pairs arranged at right angles to each other
4) In LM, eosinophilic line at apical surface of cell underneath cilia

Front 22

Describe Bardet-Biedl syndrome

Back 22

1) Collection of genetically heterogenous disorders (at least 9 loci)
2) Due to defects in formation and/or functioning of basal bodies and/or cilia. Signaling pathways do not fxn
3) Characterized by congenital impairment, retinal degeneration leading to blindness, trunk obesity, cystic kidneys, polydactyly, situs inversus, and heart defects
3) Treatment includes kidney transplant and surgery to remove extra digits

Front 23

Define endothelium

Back 23

Simple squamous epithelium that lines vascular system

Front 24

Define mesothelium

Back 24

Simple squamous epithelium that lines walls and covers contents of closed cavities of body (abdominal, pericardial, and pleural cavities)

Front 25

Describe pleural mesothelioma

Back 25

1) Tumors that arise from parietal and visceral serous membranes of pleural, peritoneal, and pericardial cavities
2) Caused by occupational exposure to asbestos and has long latency period (25-40 years)
3) Symptoms include SOB, chest pain, and accumulation of pleural fluid
4) Treatment includes surgery, radiation, and chemo. Generally poor prognosis due to high metastasis to lymph nodes and other organs

Front 26

List and describe two types of special epithelium

Back 26

1) Psedostratified- appears stratified, however, all cells rest on the basement membrane. All cells do not extend to the free surface. Will always have either cilia or stereocilia
2) Transitional- aka urothelium; stratifed squamous that lines the lower urinary tract and can undergo distension

Front 27

What are three components of the junctional complex?

Back 27

1) Zonula occludens
2) Zonula adherens
3) Macula adherens

Front 28

Define junctional complex

Back 28

Main adhesive components between individual epithelial cells

Front 29

Describe the zonula occludens

Back 29

1) Most apical
2) Series of focal fusions that seals off intercellular space

Front 30

Name and describe 3 major groups of transmembrane proteins of the zonula occludens

Back 30

1) Claudins- backbone of each "strand"; sealing component; forms extracellular aqueous channel for paracellular transport
2) Occludin- transmembrane "signal transducer"; tumor supressor; regulates actic and paracellular pore permeability
3) Junction Adhesion Molecule (JAM)- associates with claudins

Front 31

What are some other cytoplasmic proteins of the zonula occludens? (besides the three major proteins)

Back 31

1) Scaffold proteins (ZO-1, ZO-2, ZO-3)
2) Actin binding proteins
3) Proteins involved in signal transduction

Front 32

What are the functions of the zonula occludens?

Back 32

1) Transport
2) Establishment of functional domains (barrier)
3) Restricts diffusion within plasma membrane

Front 33

Name and describe the 2 bacteria involved in the destruction of junctional complexes

Back 33

1) Enterotoxin of Clostridium- perfringes binds specific claudins which results in formation of a pore in the epithelial cell membrane leading to cell death
2) H. pylori binds to JAM at tight jxns; causes redistribution of occludin, JAM, and ZO-1; loss of epithelial polarization and tight junction fxn

Front 34

Name and describe 2 viruses involved in the destruction of junctional complexes

Back 34

1) Hep C- binds claudin allowing internalization of virus and ultimately liver cirrhosis
2) Reovirus- bind JAM allowing internalization of virus; frequent infections in children resulting in respiratory and GI disease

Front 35

Besides bacteria and virus, name and describe another cause of destruction of junctional complexus

Back 35

Parasites (house mite)- serine protease(s) destroy occludin and ZO-1; no longer functions as barrier and respiratory epithelium become vulnerable to allergens

Front 36

Describe cell adhesion molecules (CAMs)

Back 36

1) Utilized by anchoring junctions
2) Transmembrane proteins that form an essential part of every anchoring jxn on both lateral and basal surface
3) Interact with each other via extracellular domains
4) Have low strength adhesion allowing cells to adhere and dissociate
5) Interact with cellular cytoskeletan via their cytoplasmic domains
6) Define various tissues and stages of development by specific expression
7) Cadherins- zonula adherens; integrins- hemidesmosomes and focal adhesions

Front 37

Describe the zonula adherens

Back 37

1) Forms continuous band around cell
2) Site of strong cell-cell interaction beneath zonula occludens
3) Utilizes cadherin (Ca2+ dependent adhesion) to interact with actin cytoskeleton via actin binding proteins (ABPs); loss of cadherin in tumor cells associated with metastasis
4) Site of interaction with actin filaments; stretch across apical cytoplasm to form terminal web

Front 38

Describe fascia adherens

Back 38

1) Adheres cardiac muscle cells end-to-end
2) Similar composition to zonula adherens; also contains ZO-1

Front 39

Describe the macula adherens

Back 39

1) Major anchoring cell to cell jxn; provides particularly strong attachment
2) Spot welds on lateral domain of cell
3) Provides anchoring sites for intermediate filaments- keratin (aka tonofilaments)
4) Not a continuous band around cell; not always observed in sections
5) Fxns in dissipating physical forces throughout cell from attachment site
6) Composed of desmoplakins and plakoglobins (IF binding proteins)

Front 40

Describe communicating (gap) junctions (or nexus)

Back 40

1) Allows direct passage of signaling molecules
2) Found in epithelia, smooth muscle, cardiac muscle, and nerves
3) Transmembrane channels or pores in tightly packed array
4) Allows for low electrical resistance between cells (high current flow)
5) interacting cells each have 1/2 channel- connexon composed of 6 symmetrical subunits of connexin
6) Opening/closing of channel regulated by Ca2+ induced conformational changes in connexin; closes when internal Ca2+ high
7) Mutations in connexin genes associate with various diseases

Front 41

Describe Cx26

Back 41

Congenital deafness
K+ circulation in cochlear sensory epithelium

Front 42

Describe Cx46 & Cx50

Back 42

Identified in patients with inherited cataracts
Nutrients/waste from avascular lens

Front 43

Describe Cx32

Back 43

Associated with X-linked Charcot-Marie-Tooth Disease
Peripheral neuropathy

Front 44

Describe the basement membrane

Back 44

1) Visible in LM with PAS staining
2) Thin acellular layer composed of basal lamina, reticular lamina, and anchoring fibrils
3) Basal lamina consists of collagen Type IV (major component, 50%), laminin (glycoprotein, initiates assembly of basal lamina), inactin, and perlecan
4) Two layers: lamina densa (electron dense material between epithelium and CT; composed of type IV collagen, laminins, proteoglycans, glycoproteins) and lamina rara or lamina lucida (fixation artifact; clear area between basal lamina and cell; site of extracellular domains of fibronectin and laminin receptors)
5) Reticular lamina: reticular fibers (type III collagen)
6) Anchoring fibrils (type VII collagen)- anchors basal lamina to reticular lamina

Front 45

What are the 3 domains of collagen used in the assembly of type IV collagen?

Back 45

1) N-terminal 7S domain
2) Middle helical domain
3) C-terminal NC1 domain

Front 46

Describe the assembly of the type IV collagen superstructure

Back 46

1) Formation of NC1 trimer (type IV collagen protomer) via association of 3 NC1 domains
2) Formation of NC1 hexamer (type IV collagen dimer) via interaction of 2 NC1 trimers
3) Tetramer formed by interaction of 4 dimers via 7S domain
4) Superstructure formed by end-to-end interaction of multiple tetramers

Front 47

Name and describe two other molecules of basal lamina

Back 47

1) Entactin (sulfated glycoprotein)- links laminin with type IV collagen; contains additional domains that bind Ca2+ and interact with perlecan and fibronectin
2) Perlecan- proteoglycan that consists of protein core with side chains of heparan sulfate; responsible for most of volume of basal lamina; highly anionic therefore highly hydrated and has net negative charge; binds laminin, type IV collagen and entactin

Front 48

Describe the self-assembly of the basal lamina

Back 48

1) Initiated by both type IV collagen and laminins
2) Ca2+ dependent and integrin-mediated polymerization of laminin on basal cell surface
3) At same time, type IV collagen superstructure associates with laminin polymers via entactin
4) Laminin/type IV collagen scaffold provides binding site for other basal lamina molecules

Front 49

Describe a hemidesmosome

Back 49

1) Half of desmosome
2) Found where lots of mechanical stress and strong adhesion necessary between epithelia and CT

Front 50

Describe the structural features of a hemidesmosome

Back 50

1) Intracellular attachment plaque- adhesion protein- integrin; IF binding protein (desmoplakin-like); IF x-linking protein (plectin); BP230 (attaches IF to plaque); and protein linking IF w/integrins
2) No intermediate line
3) Extracellular space- site of interaction of integrins with laminin and type IV collagen

Front 51

Describe Bullous Pemphigoid (blistering disease)

Back 51

1) Autoimmune- antibodies against hemidesmosomes--> degradation
2) Onset at age ~65; rare in US, more common in Europe
3) Characterized by chronic, generalized blisters in skin causing epithelium to separate from CT
4) Diagnosed by presence of IgG directed against BP230
5) Treatment- corticosteroids and immunosuppressives

Front 52

Describe focal adhesions

Back 52

1) Cell- extracellular matrix anchoring jxn that anchors actin filaments (stress fibers) into basal lamina
2) Involved in dynamic changes of epithelial cells
3) Also found in non-epithelial cells such as fibroblasts and smooth muscle cells
4) Integrins interact with ABP, regulatory proteins, and extracellular matrix proteins (laminin and fibronectin)
5) Fxn as site of signal detection and transduction

Front 53

Describe infoldings of the basal cell membrane

Back 53

1) Located in fluid-transporting cell
2) Fxn to increase surface area
3) Site where mitochondria are concentrated (gives striated appearance)

Front 54

Describe, in general, glands

Back 54

Epithelial in origin
Develop by proliferation of epithelial cells and subsequent invagination into underlying CT

Front 55

List and describe the 3 classifications of glands

Back 55

1) Endocrine- lacks a duct system; product (hormone) is secreted into CT and enters bloodstream to travel to target cell
2) Paracrine- lacks a duct system and vascular transport of product; product secreted into extracellular space and diffuses through CT to affect cells within same epithelium
3) Exocrine- product is secreted directly onto epithelial surface or via duct; further classified based on mode of secretion

Front 56

List and describe the 3 classifications of exocrine glands

Back 56

1) Merocrine (eccrine) secretion- product released from cell via exocytosis (fusion of secretory vesicles with plasma membrane)
2) Apocrine- product releases along with entire apex of cell including cytoplasm
3) Holocrine- whole cell is released

Front 57

List and describe the classification of exocrine glands by cell number

Back 57

1) Unicellular- simplest; consists of single cells distributed among non-secretory cells
2) Multicellular- composed of more than one cell; subclassification based on arrangement of secretory cells and presence/absence of branching ducts

Front 58

Describe how to classify multicellular glands

Back 58

1) Determine if duct is branched
Unbranched= simple gland
Branched= compound gland
2) Determine shape of secretory portion
Shaped like tube= tubular
Shaped like flask= alveolar/acinar
Shaped like tube that ends in sac= tubuloalveolar

Front 59

List and describe secretory products of glands

Back 59

1) Serous- watery and primarily proteinacious
2) Mucous- lots of mucins (glycoproteins that form mucous upon hydration)
3) Mixed- contain both serous and mucous

Front 60

Define a serous demilume

Back 60

Serous cells found at base of acinus outside the mucous cell

Front 61

Define stroma

Back 61

CT component of glands
Encapsulates, divides, acts as barrier, site of innervation
Contains myoepithelial cells (contract to help deliver product into duct)

Front 62

Define parenchyma

Back 62

Functional component of gland
Includes secretory cells and ducts

Front 63

Describe Adenocarcinoma

Back 63

Form of carcinoma originating in glandular tissue
Cells to not have to appear glandular but do have to have secretory properties
Most common type of colorectal cancer

Front 64

What epithelium is derived from the surface ectoderm?

Back 64

Epidermis and derivatives
Anterior lobe of pituitary gland

Front 65

What epithelium is derived from neuroectoderm?

Back 65

Neural tube and derivatives (CNS- ependyma, pineal body, and neurohypophysis)
Neural crest and derivatives (PNS- ganglia, nerves/glial cells, and medullary cells of adrenal gland)

Front 66

What epithelium is derived from mesoderm?

Back 66

Epithelium of kidney and gonads
Mesothelium (lining of pericardial, pleural, and peritoneal cavities)
Endothelium
Adrenal cortex
Epithelium of seminiferous tubules and genital ducts
Atypical epithelium (adrenocortical cells of adrenal gland, leydig cells of testis, and lutein cells of ovary)

Front 67

What epithelium is derived from endoderm?

Back 67

Epithelium of respiratory system, alimentary canal, and extramural digestive glands (liver, pancreas, gall bladder)
Epithelial components of thyroid, parathyroid, and thymus glands

Front 68

Describe epithelial dysplasia

Back 68

Abnormal cell arrangement
Increased cell number
Increased size of nucleus

Front 69

Describe carcinoma

Back 69

Arises from epithelial cell
Named by appearance, organ, or cell affected
Carcinoma in situ (malignant but not invasive)

Front 70

Is alpha-actinin a motor protein?

Back 70

No

Front 71

What is primary cilia dyskinesia (immotile cilia syndrome)?

Back 71

No dynein arms
Situs inversus

Front 72

What is transcellular transport?

Back 72

Occurs across 1 epithelial cell
Requires specialized energy dependent carriers

Front 73

What is paracellular transport?

Back 73

Occurs across zonula occludens between 2 epithelial cells
Extent depends on "tightness"

Front 74

What do serous glands secrete?

Back 74

Proteins

Front 75

What do mucous glands secrete?

Back 75

Mucins (glycoproteins- carbohydrate-rich)