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- Eye
○ Cornea - primary focusing device in the eye
▪ Largely collagen
▪ Bowman's membrane
□ Outermost surface
□ Strat squam, doesn't regenerate
□ ECTODERM
▪ Endothelium
□ Simple epithelium
□ NEURAL CREST
□ Right up against aqueous humor
Critical for transport from humor into cornea
Hydration of cornea is critical to transparency
○ Anterior chamber
▪ Filled with aqueous humor
▪ Ionic composition similar to plasma
▪ Maintains ocular pressure
▪ Feed cornea
○ Iris
▪ Open and close - adapt to intensity of light
▪ Autonomic control
▪ 2 sets of muscles
□ Circular
Contract to close iris
□ Radial
Contract to pull open
▪ Fully pigmented layer below iris surrounding ciliary process and continues
around the eye
□ Melanosomes made by cells that are NOT melanocytes
□ This pigment captures scattered light
If the inside of the eye was glistening, light would strike the
retina from all different angles
▪ Musculature - 2 layer epithelium
□ SM
□ And a layer of pigmented myoepithelial cells
□ Zonula fibers connect to processes and those process connect to the
lens
○ Lens
▪ Fine focusing knob of the eye
▪ Changes shape from somewhat flattened to somewhat ovoid
□ Dependent on tension from contractions from ciliary processes
3 sets of muscles
◊ Radial set
Contract, others relax - flat lens - distant vision
◊ Circular set
Contract - near vision
◊ Other set not discussed
Decreases with age
Source of aqueous humor
Histology Page 1
Source of aqueous humor
◊ Doesn't flow into eyeball bc vitreous humor is a gel
◊ Drains into canal of Schlemm
◊ Connects to venous drainage
○ Vitreous body
▪ Mostly GAG and hyaluronic acid
▪ Gelatinous
▪ Pushed up against the retina
▪ Not obstructive to light until later in age - floaters (precipitates)
▪ Shrinks with age
□ Starts pulling on the retina
Can pull the retina off the back of the eye - retinal detachment
◊ Repair - laser welding the retina back onto the RPE
○ Retina
▪ Neural retina facing inside
▪ RPE facing outside
○ Choroid
○ Optic stalk
▪ Optic nerve
▪ Blood vessels
□ Come in and course over the inside surface of the retina
○ Color detection
▪ Circulation in the retina
□ Nutrition coming from 2 directions
Vessels lying inside the eye send vessels into the retina down to
the level of the bipolar cell zone
These cells receive from optic stalk vessels
Rods and cones
◊ Receive vessels from choroid
◊ Transported by RPE
◊ Gives access to the rods and cones
▪ RPE
□ Tight junctions - RBB
□ Metabolism of inner parts of the retina
Separation of neural retina from RPE - neural retina will die
irreversibly
□ Blood vessels cannot circulate through here - would obstruct light
○ Fovea
▪ Light sensing CONES only
□ All other layers of neural retina are gone so that resolution is
maximized and not blocked by other cell type
□ Unimpeded light flow to cones - high resolution color vision
○ Phototransduction
▪ How is light converted into electrical signals
▪ Rods and cones are inhibitory
□ Their primary neurotransmitter is glutamate
□ In the dark they become depolarized
Leads to release of glutamate, which inhibits all transmission of
all connective neurons to the brain
□ In light Na channels are closed, so they cannot inhibit downstream
neurons, which transmit light perception to the brain
▪ Associated neurons
□ Are there for the purposes of mapping the retina (pixelation) - light
information coming from individual groups of rods and cones can be
Histology Page 2
information coming from individual groups of rods and cones can be
sent to the brain
▪ Muller cell
□ Like the glial cell of the retina
□ Critical in terms of nutritional support of neurons in the retina
Not really discernable in cross section
○ Innermost nuclear layer - ganglia
○ Inner layer - bipolar and Muller
○ Outer layer - rods and cones
○ Embryology
▪ Begins as outgrowth of embryonic brain - projects towards skin
□ Develops a bulb at the end
□ That optic swelling will pucker in on the end, creating optic cup
Single layer is puckered in to make two layers of cells adjacent
Innermost layer - neural retina
Outermost layer - RPE
□ Growth factors from cup trigger ectoderm to invaginate and initiate
development of the lens
Lens vesicle drops into optic cup
◊ Has a central space which will disappear as it condenses
into a ball
Lens triggers release of growth factors that cause remaining
overlying ectoderm to invaginate
Results in large, flat structure that does not break connection
with the surface
◊ Zone over lens - forms the cornea
▪ Tissue around the eye - embryonic mesoderm
□ Choroid, sclera, vasculature derived from it
□ Vasculature from outside RPE and inside choroid
○ Sclera
▪ White because it's collagen rich
▪ Very little cellular
- Kidney
○ Pyramid and associated ureter = a lobe in the kidney
○ Nephrons
▪ Connect to collecting ducts
▪ Every collecting duct and it's accumulation of nephrons = lobule
▪ Millions of nephrons - many are lost with age
○ Medullary component
▪ Draining of filtrate into ureter
▪ Final determination of water emission
○ Cortical tissue
▪ Contains glomeruli, convoluted tubules, and upper segments of loops of
Henle, beginnings of collecting ducts
▪ Medullary rays
□ Straight bundles of tubules
□ Represent straight parts of loops of henle and ocllecting ducts
▪ Cortical labyrinth
□ Glomeruli and convoluted tubules
○ Juxtamedullary nephrons
▪ Generation of osmotic gradient in medulla
▪ Long loops of Henle with long thin segments in medulla
□ Rarely do you see cortical nephron structure in medulla
Vasa recta
Histology Page 3
▪ Vasa recta
□ Circulation associated with juxtamedullary nephrons
□ A fraction of total kidney circulation
○ Interlobar artery to tufts to loop of Henle
○ Glomerulus
▪ Heavily fenestrated endothelium
□ Fluid is pushed through those holes
Some protein and peptide, but usually smaller ones
▪ GBM is encountered first
▪ Podocyte slits between individual extension of podocytes
□ Coats outside of every glomerular capillary
□ Able to be pulled close or extended
So the podocytes play and active role in the degree of filtration
taking place
Mutations in these proteins - strong negative effects on
glomerular filtration
○ Fluid drains into Bowman's capsule and from there into convoluted tubule
○ Extraglomerular mesangial cells
▪ Phagocytic
□ Clinical - accumulation within mesangial cells
▪ Hold together the capillary loops
○ Macula densa
▪ Part of the distal convoluted/straight tubule (occurs near the transition
from convoluted to straight)
▪ These cells have sodium chloride concentration sensors
□ Respond to low levels of sodium in filtrate
Blood pressure and electrolyte balance may be low, so the cell
emits paracrine factors to the juxtaglomerular cells on afferent
arteriole
◊ They produce renin
○ Histology
▪ Various types of sections - convoluted tubules in labyrinth
□ Big, scalloped = proximal, smaller = distal
▪ Medullary ray (can be adjacent to labyrinth)
□ Thick proximal and distal parts of the loop of Henle
□ Collecting duct - never found in labyrinth
Finding a collecting duct will confirm where we are
◊ Large, not scalloped
▪ Medulla
□ Lots of collecting ducts with the loop of Henle
□ Lots of thin segment, some thick
○ Reabsorption
▪ PCT - primary site of bulk reabsorption
□ Most water, glucose, AA, polypeptides are resorbed
□ Na - not hormone regulated, just constitutive
▪ Loop of Henle
□ Role of juxtamedullary loops of Henle in generating osmotic gradient
▪ Distal straight
▪ DCT - touches back to glomerulus and forms macula densa (some books say
straight)
▪ Collecting tubule to collecting duct
▪ Water reabsorption
□ Aquaporins
□ ADH
Histology Page 4
□ ADH
□ Aldosterone in sodium reabsorption
○ Renin-angiotensin
▪ Activated in the kidney by macula densa response to low sodium
▪ Renin cleaves angiotensinogen (from liver) to angiotensin I
▪ ACE cuts it to angiotensin II
□ Created locally, amount that is sufficient to be important in kidney
□ Dilation and constriction of afferent and efferent arterioles
□ Constrict arterioles throughout body and raises BP
□ Adrenals - stimulate aldosterone - will work on distal collecting tubule
Hormone driven sodium reabsorption
- Urinary tract/bladder
○ Epithelium lining ureters, urinary bladder, beginning of urethra - transitional
epithelium
▪ Allows for stretching without breaking
▪ Resistant to chaotropic effects of urea
○ Ureter
▪ Layers of SM - often 3 layers (2 layers closer to kidney)
□ Longitudinal
□ Middle circular
□ Inner longitudinal
▪ Peristaltic action
○ Bladder
▪ Transitional epithelium
▪ Non-discrete layers of muscle (contraction of a bag in multiple orientations)
- Digestive
○ Oral cavity
▪ Epithelia
□ Keratinized
□ Parakeratinized
□ Nonkeratinized
□ Lining
▪ Lips
□ Outside - skin
Strat squam kerat
□ Over vermillion border - keratinized epithelium converts to
parakeratinized epithelium
No full keratinization of cells
No stratum granulosum, no keratohyalin
Cells still have nuclei but are harder
□ Soft palate and lining mucosa - nonkeratinized
▪ Teeth
□ 3 mineralized layers
□ Enamel - hardest mineralized tissues in body
Created by ameloblasts
When teeth emerge from gums, no ameloblasts
So enamel is only produced while the tooth is below the gum line
As ameloblasts lay down enamel they are pushed to the outside
of the tooth
□ Dentin
Odontoblasts
Inner layer of dentin next to pulp - they still exist, dentin is
regenerable
□ Cementum
Histology Page 5
□ Cementum
Like bone
Cementoblasts
□ Collagen fibers - Sharpe's fibers - connect tooth to bone
□ Nerve and vascular supply - up center into pulp
□ Spongy bone - undergoing remodeling
Continually changes shape of tooth socket depending on forces
placed on it by the tooth
Orthodontics - place pressure on tooth so alveolar bone will
remodel itself in that direction
▪ Tongue
□ Anterior surface - strat squam keratinized
□ Bottom surface - nonkeratinized
□ Muscular - runs in all different direction
□ Glands in core of tongue
Some are mucous, some are serous
Called Von Ebner's glands
Ducts lead onto surface around papillae that are found there
□ Papillae
Filiform
◊ Mechanical activity
◊ Tips are keratinized
◊ Angular projection - curved towards back of the mouth (not
so much in humans)
Foliate
◊ Clustered next to one another
◊ Taste buds within epithelium
Fungiform
◊ Surrounded by filiform
◊ Taste buds
Circumvallate
◊ Surrounded by filiform
◊ Taste buds
Move food out of the crypts
▪ Salivary glands
□ All over the oral cavity
□ Minor salivary glands in soft palate and below tongue
□ Major salivary glands
Acinus
◊ Creates initial content of saliva
Ducts lead from the unit
◊ Intercalated and striated modify
◊ Secretory doesn't modify
Saliva matters
◊ Digestion enzymes
◊ Anti-microbial enzymes
Vs. pancreas
◊ No striated ducts in pancreas
◊ And there is a centroacinar cell with nucleus in pancreatic
acini
Duct in pancreas goes into the pancreas
Myoepithelial cells
◊ Surround acini and ducts
□ Parotid
Histology Page 6
□ Parotid
Completely serous
Some fat cells depending on age
□ Submandibular
Mixed
□ Sublingual
Almost completely mucous
Fewer striated ducts - less modification to mucus than serum
○ GI tract
▪ Inner mucosa
□ SM involved in manipulating inner linng
▪ Submucosa
▪ Muscularis externa
□ Inner - circular
□ Outer - longitudinal
□ Primarily involved in peristalsis
○ Esophagus
▪ Strat squam
□ Not keratinized in humans
▪ Submucosa - varying amounts of mucous glands
□ Esophageal mucus at top
□ Cardiac mucus at bottom
▪ Musc mucosa
□ Varies in thickness depending on region
▪ Externa
□ Varies in terms of relative amount of skeletal muscle present
Upper 1/3rd of esophagus - voluntary swallowing skeletal
Lower 2/3rds - peristalsis, SM
▪ GERD - abnormalities resulting from acid exposure in the stomach
□ Gaseous acid can get into esophagus and can be breathed into the
lungs
□ Metaplastic change first
□ Can convert into dysplastic change - esophageal cancer, Barrett's
esophagus
□ Interactions between stomach/esophagus and heart
○ Stomach
▪ Fundic glands
□ In fundus and antrum
▪ Epithelium is entire mucous
□ No absorption in the stomach
□ Mucus predominantly protects cell from acid
Bicarbonate rich, relatively thick mucus
▪ Crypts
□ Mucus from the mucous neck cells
That mucus is primarily within the cell to be released when it
gets to the top
◊ Not a thick mucus - fluid in these cells
▪ Fundic glands
□ Parietal - relatively unstained
HCl and intrinsic factor
Proton pumps are targets of many drugs
□ Chief cells - darker
Pepsinogen
□ Enteroendocrine
Histology Page 7
□ Enteroendocrine
▪ Cardiac glands
□ Predominantly mucous
□ More branched glands
▪ Pyloric glands
□ Predominantly mucous
□ Less branched
□ Distinguishable with colon - no absorptive cells in stomach
○ Intestine
▪ Peyer's patches
▪ Ganglia
□ If sandwiched between muscles - myenteric, Auerbach
Coordinates peristalsis
□ If under mucosa - submucosal, Meissner
Regulates inner fold contraction
▪ Duodenum
□ Sphincter between stomach and duodenum
□ Few goblet cells
□ Brunner's gland - bicarbonate-rich mucus that protects intestine
▪ Jejunum
□ Distinctive villi
□ More goblet cells
□ Lacteals - pick up chylomicra
Chylomicra prevent fat in blood from fusing
Also, recognition of LDLs and HDLs allow cells to take in fats
□ Fatty acids have to be broken down to cross membranes
□ Paneth cells
Defensins, anti-microbial peptides
□ Less absorptive, more mucous
▪ Ileum
○ Colon
▪ Lots of goblet cells
▪ Localized thickening of external layer of SM
○ Appendix
▪ Lymphatic follicles completely surround the lumen
□ Vs. Peyer's patches, which are only on one side
▪ Large amounts of mucous cells, as with rest of colon
○ Endocrine
▪ CCK - pancreas
▪ Gastrin - stomach acid
○ Liver
▪ Central vein
▪ Incoming artery
▪ Portal vein
▪ Vessels deliver blood directly into sinusoids
▪ Hepatocytes line the sinusoids for exchange of materials with the blood
▪ Bile flow
□ In canaliculi created by tight junctions between hepatocytes, forming
a channel
No epithelium, just hepatocytes
□ Flows into a specifically designed duct
□ Main bile duct in triad
▪ Hepatocytes
□ Polyploid, sometimes multinuclear
Histology Page 8
□ Polyploid, sometimes multinuclear
□ Limited amount of regeneration
□ Major producers of proteins in the blood
□ Take up many of the products from the digestive tract
▪ The lining of the sinusoids facilitates this exchange
□ Incomplete, fenestrated endothelium
□ Extensive folding of hepatocyte surfaces at endothelium
□ Macrophages - Kupffer cells
□ Ito cells - massive droplet of retinol
▪ Bile drainage
□ Down bile duct to sphincter that leads to the duodenum
□ Backup of this sphincter - leads into the gallbladder
○ Gallbladder
▪ Concentrates bile
▪ Major transporter of fluid from lumen to blood
□ CCK and gastrin stimulate
▪ Bile - compounds important in lipid digestion (keeps lipids in micellar
organization)
□ Bilirubin
▪ Reabsorbed and recirculated back to the liver after use in the intestine
▪ Solvent drag
□ Na-K ATPases pump sodium into basolateral space, water follows
□ Primary mechanism of water movement in the body
○ Pancreas
▪ Acini
□ With centroacinar cells
□ Produces zymogens
Inactive until they get to the duodenum
Products in ducts minimize activity of prematurely activated
zymogens
So the ducts are active
◊ Water, bicarb, and mucus
▪ Islets of Langerhans
□ A - glucagon
□ B - insulin
Majority of cells
□ D - somatostatin
□ Islet cell ratios are not identical throughout pancreas
- Male reproductive
Histology
Final Revi...
- Female reproduction
○ Secondary follicle
▪ Zona pellucida
▪ Pinkish layer around the oocyte
▪ Antrum grows to get segregation of the granulosa cells
□ Granulosa - all cells that aren't oocyte
Histology Page 9
□ Granulosa - all cells that aren't oocyte
□ Cumulus cells - in stalk and surrounding egg
Corona radiata - present around egg after ovulation
○ Corpus luteum
▪ After the egg is ovulated
□ Thecal cells remained behind
□ Outer granulosa cells
□ Cavity left behind
Vasculature invades
Cavity folds in on itself
▪ Granulosa lutein - larger cells - produce estrogen and progesterone
▪ Thecal lutein - smaller cells - produce androgen and progesterone
□ You cannot make estrogen without an androgen precursor
○ Fertilization
▪ A few hundred out of a few million end up in the entrance of the oviduct
with the egg
□ Only the normal shaped sperm
□ Sperm are transported here
▪ Sperm move to the egg
□ Capacitation
Calcium influx into sperm, cAMP activated, hypermotility
Sperm push through corona radiata
Bind to zona pellucida - acrosome reaction occurs here
Enzymes released, hole through zona pellucida
Sperm binds to oocyte plasma membrane
The membranes fuse
◊ Only sperm centrioles and nuclei stick around
◊ Mitochondria get rekt
▪ Cilia carry fertilized egg towards uterus
□ You can get peristalsis in both directions though
○ Uterus
▪ Proliferative
□ Entire endometrium is thinner
□ Glands are relatively tubular (they can distort)
□ Estrogen - stimulates mitotic proliferation
□ Progesterone - hypertrophy, but not mitosis
▪ Secretory
□ Glands tend to have wider lumen, irregular walls
□ Secretion product in the lumen
□ Endometrium is taller
□ Epithelium is ciliated down to the cervix
□ Progesterone - change in epithelium that allows implantation
▪ Menstruation
□ Whole endometrium is undergoing disintegration
▪ Cervical mucus
□ Becomes more viscous until ovulation
□ Then becomes viscous again under the influence of progesterone
○ Implantation
▪ Decidual cells develop just at the time that the zygote is coming down into
the uterus
▪ Decidual reaction - finish at the time of implantation
▪ Materials useful for nutrition of the zygote
▪ Are eaten
▪ Also influence the immune system
Histology Page 10
▪ Also influence the immune system
○ Placentation
▪ Early in the implantation phase the most important even is the
development of the sctb
▪ Sctb
□ Product of the cytotrophoblast
□ Daughter cells fuse with one another creating syncytium
□ More division --> more sctb
□ Sctb is the leading edge of invasion so the zygote can be drawn further
into the uterus
□ Initial source of gonadotropin that keeps the corpus luteum functional
LH levels have gotten so low that the corpus luteum is beginning
to deteriorate
◊ Otherwise corpus albicans, and endometrium sloughs off
Endometrium is maintained so implantation can continue
Until the placenta becomes steroidogenic on its own and no
longer relies on the corpus luteum
□ Spreads around entire invading zygote
□ Keeps piling up cells from the cytotrophoblast extending villi that
come around the invading embryo
□ Once the extraembryonic mesoderm develops, it develops under the
cytotrophoblast and creates a core of mesoderm in the center
□ From that mesoderm, circulation on the embryonic side of the
placenta develops
Vasculature and blood cells developing outside the embryo
While the same thing is happening in the embryo
The two vascular systems form
▪ The sctb has developed pockets - trophoblastic lacunae
□ The sctb will meet up with maternal capillaries in endometrium and
cut them - blood dumps right into trophoblastic lacunae surrounding
the villi
□ So maternal blood fills in these space
▪ The cytotrophoblast continues to poke out and form a shell around the
entire space, connecting the tips of every villus
□ Seals the blood spaces that maternal vessels are emptying into
□ Otherwise blood leaks back into uterine tissue
▪ Mature placenta
□ Villi sitting within lacunae filled with maternal blood
Maternal vessels stop at the shell
Only embryonic vessels within the open space
○ Histology
▪ Outer - chorion and amnion
▪ Inside - villi
□ Two layers - sctb on outside, cytotrophoblast inside
Mesoderm inside the cytotrophoblast
Hofbauer cells - phagocytes
Histology Page 11