Simple Squamous Epithelium

Simple Squamous Epithelium

At a glance

• Single, flat cell layer on a basement membrane built for rapid exchange and frictionless surfaces.
• Found wherever slick lining or ultrathin barrier is needed: vessels, mesothelium, alveoli, Bowman capsule, inner cornea.
• Key hazards: loss exposes collagen/tissue factor (clotting), thickening impairs exchange, and poor regeneration in some sites (cornea/endocardium).
• Go-to markers: CD31/ERG/vWF for endothelium; calretinin/WT1/podoplanin for mesothelium; keratin profile varies by site.

Jump to sections

• Generalities
• Endothelium / endocardium
• Mesothelium (pleura, pericardium, peritoneum)
• Pulmonary Alveolar Lining – Type I Pneumocyte
• Parietal Layer of Bowman Capsule / Thin Segment of Loop of Henle
• Corneal endothelium
• Lymphatic Endothelium
• Vestibular system and endolymphatic areas (inner ear)
• Specialized serosal/mesothelial modifications
• Corneal trabecular/angle related flat lining (ocular drainage areas)

Corneal endothelium

What it is: single layer of squamous to low cuboidal cells on the posterior surface of the cornea (facing anterior chamber). Embryologically neural crest, not surface ectoderm, but histologically a simple flat lining.

Why it is still in the family: it is a single cell layer, flattened, on a basement membrane (Descemet membrane), forming a barrier.

Key functions:

• Barrier to aqueous humor (so anterior chamber fluid does not just soak the corneal stroma).
• Active pump (Na⁺/K⁺ ATPase, carbonic anhydrase) that moves fluid out of corneal stroma into anterior chamber.
• Reason: to keep cornea relatively dehydrated (deturgescent) so it stays transparent.

Why it matters in pathology:

• If you lose cells (Fuchs endothelial dystrophy, trauma, surgery), the pump capacity drops.
• Fluid enters corneal stroma.
• Cornea swells.
• Transparency goes down.

Special points:

• Sits on Descemet membrane (specialized BM).
• Tight and adherens junctions present.
• Cells do not regenerate well in adults, they enlarge and spread instead.

Corneal trabecular/angle related flat lining (ocular drainage areas)

Some parts of the anterior chamber angle are covered by very attenuated endothelium-like cells.

Why: aqueous humor has to exit through here, so the lining cannot be bulky.

Pathology angle: in glaucoma workups or angle-closure specimens, knowing that the lining is supposed to be very thin keeps you from calling it atrophic.

Endothelium / endocardium

1. Location / extent

Lines all blood vessels and cardiac chambers (inside arteries, veins, capillaries, atria, ventricles, valves).

Why: blood must never touch raw connective tissue — that would trigger clotting — so the body keeps a continuous endothelial film.

Forms a continuous, noninterrupted luminal surface (a smooth inner tube).

Why: any gap or rough spot = turbulence + platelet adhesion.

When blood touches the layer under the endothelium, the body reads that as “the vessel wall is broken.”

Here’s why:

1. Exposed collagen: The connective tissue has collagen fibers. Platelets have receptors that bind collagen. When they see collagen, they stick and get activated.
2. von Willebrand factor (vWF): vWF binds to collagen and then to platelets. This makes platelet sticking even stronger, especially when blood is moving fast.
3. Tissue factor (TF): Cells under the endothelium carry tissue factor. When TF meets factor VII in the blood, it starts the coagulation cascade → thrombin → fibrin → clot.
4. No more endothelial “brakes”: Healthy endothelium makes NO, prostacyclin, and shows thrombomodulin. All of these tell platelets “stay calm.” When endothelium is gone, those anti-clot signals disappear, so platelets can activate more easily.

So: exposed collagen + vWF + tissue factor + loss of anti-clot signals = clotting.

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2. Surface property

Nonthrombogenic luminal surface (doesn’t make blood clot in normal state).

Why: endothelium expresses substances that tell platelets “do not stick here,” so blood stays fluid despite constant contact.

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3. Secretory / regulatory products

Antithrombotic factors: prostacyclin (PGI₂), nitric oxide (NO), thrombomodulin.

Why: PGI₂ and NO inhibit platelet aggregation and cause local vasodilation; thrombomodulin turns thrombin from procoagulant into anticoagulant mode.

Prothrombotic factors (on injury/activation): von Willebrand factor (vWF), tissue factor.

Why: if the endothelium is damaged, it must be able to start coagulation quickly to seal the breach — so it keeps “emergency” procoagulant tools.

Vasoactive factors: NO, prostacyclin (vasodilators); endothelin-1 (vasoconstrictor).

Why: endothelium can fine-tune vessel diameter on site, matching flow to local needs.

Inflammation/leukocyte traffic: P-selectin, E-selectin, ICAM-1, VCAM-1 (expressed when activated).

Why: under infection or injury, you want leukocytes to stop and exit — these adhesion molecules are the “brakes.”

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4. Cytoplasmic organelles / ultrastructure

Weibel–Palade bodies (elongated granules storing vWF and P-selectin).

Why: lets the cell release vWF fast for platelet adhesion and P-selectin for leukocyte rolling, without having to make them from scratch.

Many pinocytotic vesicles (lots of small transport bubbles).

Why: endothelium often moves material across itself (blood → tissue, tissue → blood); vesicles make that efficient.

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5. Permeability / exchange

Regulated paracellular and transcellular transport (not just open leak).

Why: tissues need nutrients, but you must not flood the wall with plasma proteins — controlled leak prevents edema.

Permeability can increase in inflammation (junctions loosen).

Why: inflamed tissues need plasma proteins and WBCs — temporary leakiness helps defense.

Capillary specializations (continuous, fenestrated, sinusoidal)

Why: different organs need different “tightness” — brain needs very tight, endocrine organs need more open, liver/spleen need very open.

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6. Hemodynamics / mechanical adaptation

Shear-stress sensitive (can “feel” flow).

Why: high, steady flow → keep antithrombotic/anti-inflammatory state; disturbed/low flow → can switch to a more adhesive, pro-atherogenic state.

Can realign cytoskeleton with flow

Why: aligning with flow reduces drag and mechanical injury.

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7. Endocardial specifics

Same endothelial phenotype but adapted to cardiac chambers (subject to pulsatile, sometimes turbulent flow).

Why: the heart has changing pressures and valve motion — the lining must be extra smooth and well attached.

Covers valves, chordae, trabeculae as one sheet

Why: if valve surfaces were naked CT, you’d get thrombus and fibrosis on every beat.

Controls short-distance diffusion from chamber blood to subendocardial tissue

Why: inner myocardium can grab a bit of oxygen/nutrients from the chamber, but only if the lining is thin and intact.

Overlies subendocardial fibrous tissue ± Purkinje fibers

Why: protects the conduction system from direct blood contact and from mechanical abrasion.

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8. Immunohistochemistry (site-specific)

Positive: CD31 (PECAM-1), CD34, von Willebrand factor (vWF), ERG, FLI-1.

Why: these are the standard endothelial markers; if a flat cell stains for these, you can call it endothelial.

Often positive: vimentin.

Why: endothelium behaves more like a modified mesenchymal cell than like surface skin epithelium.

Usually negative: broad cytokeratins.

Why: helps you say “this is endothelium” and not mesothelium or metastatic carcinoma in a cavity.

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9. Basement membrane / subendothelial layer

Endothelium sits on a thin basement membrane over subendothelial CT

Why: CT gives elasticity and strength to the vessel wall, basement membrane gives the anchor.

Endocardium: endothelium → fibroelastic CT → deeper layer with conducting elements (Purkinje)

Why: needs both a smooth blood-contact surface and a protected conduction layer.

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10. Functional summary (extra for this site)

• Maintains blood fluidity (keeps platelets quiet in normal flow)

  Why: thrombosis inside a normal vessel is dangerous; the default state must be anticoagulant.

• Initiates hemostasis when injured

  Why: same cell must be able to flip to “repair mode” instantly.

• Modulates vascular tone

  Why: the vessel wall can’t react properly without endothelial signals.

• Controls leukocyte entry

  Why: you only want WBCs to exit where there is trouble.

• Provides very low-friction surface for high-speed blood flow (especially in heart)

  Why: reduces mechanical damage and clot formation.

SPECIAL GUEST

Atrial endocardial specialized zones

We already did endocardium, but in some areas (for example over valves, chordae) the lining can become a bit thicker or have subendothelial cushions.

Why: mechanical stress is higher.

Still: the luminal face is a simple squamous endothelial sheet.

Pathology angle: when you see organizing thrombus or fibroelastosis, you need to know what the original lining was.

Generalities

1. Architecture

Single continuous layer of flattened epithelial cells (only one layer, cells are very thin and tile-like)

Why: one layer + very thin = shortest possible diffusion path, so gases/fluids/solutes can cross quickly.

Cells polygonal to irregular in surface profile (if you look from above, they look like uneven paving stones)

Why: this shape lets cells pack together tightly and cover a surface with no gaps.

Cytoplasm markedly attenuated (cell body is so thin that on H&E you mostly see the nucleus)

Why: less thickness = less distance for diffusion = faster exchange.

Nuclei centrally located, oval to elongated, often bulging into the lumen (the nucleus is in the middle, a bit long, and is the thickest part you see)

Why: nucleus has to stay somewhere; pushing it into one spot keeps the rest of the cell as thin as possible.

Supported by an intact basement membrane (there is always a thin protein sheet underneath that they sit on)

Why: the cells are so thin they need a stable “floor” to attach to, and the basement membrane also filters and guides repair.

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2. Cytologic Features

Cytoplasm scant, pale eosinophilic (little pink cytoplasm is visible)

Why: these cells don’t need big volumes of cytoplasm to do their job; staying thin is more important than storing stuff.

Cell borders inconspicuous on H&E (you cannot easily see where one cell ends and the next begins)

Why: tight packing + thin cytoplasm = borders blend → makes a smoother, less turbulent surface.

Nuclei with finely granular chromatin, inconspicuous nucleoli (normal-looking nucleus, not dark and ugly, no big nucleolus)

Why: this is a resting/lining epithelium, not a rapidly proliferating tumor; so nuclei look bland.

Minimal pleomorphism in normal locations (cells all look about the same when normal)

Why: uniformity = healthy lining; variation would suggest injury, activation, or neoplasia.

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3. Polarity and Attachment

Apical surface directed toward lumen/body cavity/vascular space (the top side faces blood, air, or serous fluid)

Why: this is the side that does the exchange or provides a frictionless surface.

Basal aspect rests on basement membrane with hemidesmosomal attachment (ultrastructural) (the bottom side is glued to the basement membrane by special attachment points)

Why: prevents the sheet from peeling off when fluid/blood flows over it.

Adjacent cells joined by apical junctional complexes forming a continuous lining (cells are locked to each other at the top so the sheet does not leak easily)

Why: even though the cells are thin, the body still needs to control what slips between them.

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4. Junctional Complexes

These keep the sheet continuous and regulate what passes between cells.

Why: thin cells alone would be too fragile; junctions make the lining mechanically strong and selectively leaky.

Tight (occluding) junctions / zonula occludens

Proteins: occludin, claudins, JAMs (the molecules that seal the space between cells)

Why: they form the actual seal — without them, plasma/serous fluid would just leak through.

Scaffold: ZO-1, ZO-2, ZO-3 (adaptor proteins that link the seal to the inside of the cell)

Why: they anchor the seal to the cytoskeleton so it doesn’t tear with flow.

Function: regulates paracellular permeability (decides how much can sneak between two cells)

Why: some organs need more leak (inflammation), some need less (blood); this is the control point.

Adherens junctions / zonula adherens

Proteins: E-cadherin, catenins (classic cell-to-cell glue)

Why: they make neighboring cells actually stick, not just touch.

Linked to actin cytoskeleton (connected to the internal “wires” of the cell)

Why: tying adhesion to actin lets the epithelium resist stretching.

Function: maintains lateral cell-to-cell adhesion (keeps the sheet from pulling apart)

Why: a lining is useless if it rips every time blood/air moves over it.

Desmosomes / maculae adherentes

Proteins: desmogleins, desmocollins (desmosomal cadherins)

Why: these are the “spot weld” cadherins — stronger in one point.

Plaque: desmoplakin, plakoglobin (anchor plate on the inside)

Why: connects the weld to the cell’s inner skeleton so it can take shear.

Function: spot-strength against shear stress (good for places with flow or rubbing)

Why: endocardium, vessels, serosa all get mechanical stress — desmosomes stop microtears.

Gap junctions

Proteins: connexins (form channels)

Why: cells can pass ions/small signals quickly.

Function: intercellular communication (little doors for ions and small molecules)

Why: helps coordinate responses (e.g. inflammation, repair) across the sheet.

Basal attachment (hemidesmosomes, integrins)

Function: secure attachment to basement membrane (keeps the epithelium from lifting off)

Why: without this, flow would detach the lining and you’d expose the connective tissue → clot/inflammation.

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5. Basement Membrane

Continuous basement membrane present (always there in normal lining)

Why: provides a uniform support so the super-thin cells can stay flat.

Composed of type IV collagen, laminin, entactin/nidogen, heparan sulfate proteoglycans (typical basement membrane proteins)

Why: this combo gives both strength (collagen) and adhesion sites (laminin/integrins).

Functions: structural support, selective barrier, scaffold for regeneration (it holds, filters, and guides regrowth)

Why: when the surface is damaged, cells can crawl along this “map” to reline the area.

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6. Cytoskeleton

Actin microfilaments in subcortical network (thin filaments right under the membrane that help keep the flat shape)

Why: actin lets the cell spread very thin without collapsing, and it links to junctions.

Intermediate filaments: cytokeratins typical of simple epithelia (CK8, CK18, CK19) (these are the epithelial “identity” filaments)

Why: give tensile strength and tell you by IHC “this is epithelial.”

Microtubules present for intracellular transport (tracks to move vesicles and organelles)

Why: even thin cells still need to move stuff across from basal to apical sides.

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7. Immunohistochemistry (depends on anatomic subtype)

Generic simple epithelial profile (when it is really an epithelial lining):

Positive: pan-cytokeratin (AE1/AE3), CK8/18, CK19, EMA (epithelial membrane antigen) (this confirms it is epithelial)

Why: these keratins/EMA are the standard markers labs use to prove “this lining is epithelial.”

Negative: CD45 and other hematolymphoid markers (helps rule out inflammatory/hematologic cells)

Why: tells you this isn’t a lymphoma or just a sheet of inflammatory cells.

Vascular/endocardial lining (endothelium-like):

Positive: CD31, CD34, von Willebrand factor (vWF), ERG, FLI-1 (classic endothelial markers)

Why: these prove the flat cell is vascular in origin, not mesothelial or metastatic.

Often positive: vimentin (mesenchymal-type filament)

Why: endothelium is more “mesenchymal-like” than true surface epithelium.

Usually negative: epithelial cytokeratins (this helps separate endothelium from mesothelium or carcinoma)

Why: really important in effusions/heart/vascular lesions to know what lining you’re seeing.

Mesothelium (serosal simple squamous):

Positive: CK5/6, calretinin, WT-1, D2-40 (podoplanin), often EMA (mesothelial panel)

Why: this panel tells you “this flat lining is mesothelium” and not metastatic adenocarcinoma.

Use: distinguishes reactive/benign mesothelium from metastatic carcinoma on pleura or peritoneum.

Why: that’s a common real-life differential.

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8. Vascularity and Nutrition

Epithelium itself is avascular (no blood vessels inside it)

Why: there is no room — cells are too thin.

Nutrition and oxygen arrive by diffusion from underlying connective tissue (it eats/drinks from below)

Why: thickness is so small that diffusion is enough.

Extreme thinness facilitates diffusion (this is why this morphology is chosen)

Why: thin cell = fastest way to move substances without using energy.

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9. Functional Correlation

Specialized for rapid trans-epithelial exchange (very good for gases, water, small solutes)

Why: this is the main reason this type exists — quick passage.

Provides smooth, low-friction, often nonthrombogenic lining (good for blood flow or serous fluid)

Why: flat, sealed surface prevents turbulence, platelet sticking, and friction.

Barrier function present but relatively permeable (not as tight as stratified or columnar mucosa)

Why: if it were too tight, you’d lose the whole point (fast exchange).

In endothelium/endocardium: contributes antiplatelet, anticoagulant, and anti-inflammatory surface (helps prevent clots and keeps blood “calm”)

Why: blood must stay fluid inside vessels/heart; the lining actively helps.

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10. Regeneration and Injury

Low baseline proliferative activity (not dividing all the time)

Why: normal lining under normal flow doesn’t need constant replacement.

Capable of spreading and proliferating to cover denuded areas (can heal by flattening and dividing)

Why: flat cells can migrate quickly over a defect and reseal it.

Regeneration is more orderly when basement membrane is preserved (if the floor is intact, repair is nicer)

Why: cells follow the basement membrane like a guide; if it’s gone, healing is slower and messier.

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11. Typical Anatomic Correlates

Vascular and cardiac luminal surfaces (endothelium, endocardium-like) (inside vessels and inside heart)

Why: blood needs a smooth, nonclotting surface.

Serosal surfaces: pleura, pericardium, peritoneum (mesothelium) (lining of body cavities)

Why: moving organs need a slippery, thin cover.

Pulmonary alveolar type I cells (gas-exchange surface)

Why: oxygen and CO₂ must cross with almost no distance.

Renal corpuscle parietal layer and thin nephron segments (filtration-friendly areas)

Why: filtration and reabsorption require very thin walls.

Lymphatic Endothelium

Location / role

• Lines all lymphatic capillaries and larger lymphatic vessels.
• Why: lymph has to drain easily from tissues back to blood, so the lining must be very permissive.

Epithelium

• Simple squamous endothelium (flat, single layer), but thinner and looser than blood vascular endothelium.
• Why: lymphatics start as “pickup tubes” in tissues — they must let fluid in, not keep it out.

Permeability / openings

• Initial lymphatic capillaries have overlapping endothelial cells that act like one-way flaps.
• Why: when interstitial pressure rises, the flaps open → fluid, proteins, even cells enter; when pressure drops, they close → lymph doesn’t leak back.

Basement membrane

• Often discontinuous or very thin.
• Why: partial BM makes it easier for big molecules (proteins, chylomicrons) to get in.

Anchoring filaments

• Endothelial cells are tied to surrounding CT with anchoring filaments.
• Why: when tissue swells and pulls, these filaments tug the lymphatic open → promotes drainage.

Junctions

• Have junctions, but less tight than blood vessel endothelium.
• Why: goal here is uptake, not strict barrier.

Immuno

• Positive: D2-40/podoplanin, LYVE-1, Prox1, VEGFR-3 (lymphatic markers).
• Why: these help you say “this flat vessel is lymphatic, not venous.”
• Negative or weaker: CD34/CD31 may be weaker/variable in some lymphatics compared to blood vessels.
• Why: useful when identifying lymphatic invasion by tumors.

Function summary

• Collect excess interstitial fluid and proteins → prevent edema.
• Why: proteins can’t easily go back into blood capillaries; lymphatics are the route.
• Allow immune cell trafficking (APCs, lymphocytes) to nodes.
• Why: immune system needs a highway from tissue to lymph node.
• Return chyle (lipid-rich lymph) from gut to circulation.
• Why: big lipid particles need a low-resistance vessel.

So: same simple squamous idea, but looser, leakier, and flap-like because its job is pickup, not containment.

Mesothelium (pleura, pericardium, peritoneum)

1. Location / extent

Lines closed body cavities: pleural, pericardial, peritoneal (covers lungs, heart, abdominal organs).

Why: these organs move and rub; they need a slippery, uniform cover.

Forms a continuous sheet over both organ surface (visceral) and cavity wall (parietal).

Why: two smooth facing surfaces ↓ friction during breathing, heartbeat, gut motion.

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2. Surface property

Smooth, low-friction, glistening surface (looks shiny).

Why: secretes a small amount of serous fluid → organs can slide without damaging each other.

Can absorb serous fluid and particulates.

Why: cavity must stay clean and at the right volume; mesothelium can take fluid back.

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3. Secretory / absorptive activity

Produces lubricating serous fluid (hyaluronate-rich).

Why: reduces shear between moving organs (e.g. lung vs chest wall).

Can increase fluid and adhesion molecule expression during inflammation.

Why: in peritonitis/pleuritis, you want immune cells to reach the site and fluid to dilute irritants.

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4. Junctions / integrity

Tight and adherens junctions maintain a sealed, continuous lining.

Why: prevents uncontrolled leak of peritoneal/pleural fluid into submesothelial tissue.

Desmosomes add mechanical strength.

Why: diaphragmatic motion, cardiac motion, peristalsis all tug on this layer.

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5. Submesothelial connective tissue

Mesothelium sits on thin CT with vessels, lymphatics, nerves.

Why: easy access to lymphatics = easy drainage of cavity fluid and cells.

Lymphatic stomata (esp. on diaphragm, pleura).

Why: let peritoneal/pleural fluid and even cells enter lymph directly → cavity “self-cleans.”

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6. Immunohistochemistry (mesothelial phenotype)

Positive: CK5/6, calretinin, WT-1, D2-40 (podoplanin), often EMA.

Why: this combo says “this flat lining is mesothelium,” not vascular endothelium or metastatic carcinoma.

Negative or different from endothelium (CD31, vWF):

Why: helps distinguish reactive mesothelial proliferation from vascular lesions.

Can coexpress keratin and vimentin.

Why: mesothelium has both epithelial and mesenchymal-like traits.

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7. Plasticity / repair

Mesothelial cells can flatten, migrate, and repopulate denuded areas quickly.

Why: serosal injuries (surgery, infection) need fast relining to prevent adhesions.

If basement membrane / submesothelial layer is damaged → fibrosis and adhesions.

Why: loss of the smooth mesothelial cover makes raw CT stick to nearby structures.

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8. Functional roles (extra for serosa)

1. Lubrication

   Why: primary role — keeps moving organs from abrading.

2. Barrier

   Why: limits spread of infection/tumor across cavity, at least early.

3. Transport / immune participation

   Why: mesothelium can present antigens and recruit inflammatory cells during peritonitis/pleuritis.

4. Source of growth factors

   Why: helps healing of underlying CT and vessels.

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9. Pathology relevance (why we care)

Reactive mesothelial hyperplasia can mimic carcinoma cytologically.

Why: knowing the mesothelial marker set prevents overcalling malignancy.

Mesothelium is the cell of origin of malignant mesothelioma.

Why: its IHC profile is the key to diagnosis.

Parietal Layer of Bowman Capsule / Thin Segment of Loop of Henle

Location:

• Lines the outer wall of the renal corpuscle (the “cup” around the glomerulus).
• Why: you need a thin, smooth lining to form the urinary (Bowman) space without adding resistance.

Epithelium:

• Simple squamous cells (flat, single layer).
• Why: filtrate from the glomerulus needs to collect easily in this space — a thin wall keeps the space open.

Nucleus / cytoplasm:

• Flattened nucleus bulging slightly into the space; scant cytoplasm.
• Why: same logic as other flat epithelia — stay thin.

Basement membrane:

• Continuous, sits on a thin layer of CT.
• Why: stabilizes the capsule so it doesn’t collapse when pressure changes.

Function:

• Structural/containing, not filtering — the filtration happens at the glomerular tuft (fenestrated endothelium + GBM + podocytes).
• Why: parietal layer’s job is basically to collect what was already filtered, not to filter again.

Continuity:

• At the urinary pole it becomes simple cuboidal epithelium of the proximal convoluted tubule.
• Why: filtrate now needs active transport → switch from flat (passive) to cuboidal (active).

Pathology note:

• In some GN, parietal cells proliferate → crescents.
• Why: they are the cells sitting in that space, so they are the ones that respond.

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2) Thin Segment of Loop of Henle

(descending and parts of ascending thin limb)

Location:

• Nephron segment that dives into the medulla as a very thin tubule.
• Why: this part is for passive water/solute movement, not heavy transport.

Epithelium:

• Simple squamous epithelium, even thinner than the parietal layer in some species.
• Why: the medullary gradient works best when the tubular wall does not get in the way.

Cell features:

• Very thin cytoplasm, small nucleus that bulges into lumen.
• Few organelles.
• Why: less machinery = more room for diffusion.

Basement membrane:

• Present, delicate.
• Why: keeps the tubule from collapsing in the high-osmolar medulla.

Function:

• Descending thin limb: highly permeable to water, less to solutes.
  • Why: water needs to leave to concentrate tubular fluid, following the hypertonic medulla.
• Ascending thin limb (where present): relatively impermeable to water, more to NaCl.
  • Why: helps generate/maintain the medullary gradient without letting water follow.

Junctions:

• Tight junctions present but not as “tight” as in distal nephron.
• Why: you want controlled paracellular movement to build the gradient.

Vascular proximity:

• Runs near vasa recta.
• Why: countercurrent exchange needs close apposition of thin epithelia and thin vessels.

Pulmonary Alveolar Lining – Type I Pneumocyte

1. Location / extent

Covers ~90–95% of the alveolar surface (but is fewer in number than type II cells).

Why: gas exchange needs a huge, very thin surface; type I cells spread out like wallpaper.

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2. Architecture / shape

Extremely flattened, simple squamous cell with long cytoplasmic extensions.

Why: the flatter the cell, the shorter the diffusion distance for O₂ and CO₂.

Nucleus occupies a small bulged area; rest of cell is ultra-thin.

Why: keeps most of the surface at minimum thickness, but still gives a place to store organelles.

Forms part of the blood–air barrier together with capillary endothelium and fused basement membranes.

Why: gas has to cross as few layers as possible — air → type I cell → BM → capillary endothelium → blood.

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3. Blood–air barrier components

1. Type I pneumocyte cytoplasm (epithelium).

2. Fused basal laminae of pneumocyte and capillary endothelium.

3. Capillary endothelial cell.

   Why: fusing the two basement membranes removes extra thickness → faster diffusion.

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4. Junctions

Tight/occluding junctions between adjacent type I cells and with type II cells.

Why: prevents alveolar fluid from flooding the air space; keeps surface mostly air, not edema fluid.

Desmosome-like adhesions for mechanical stability during breathing.

Why: alveoli stretch and recoil every breath; lining must not tear.

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5. Relationship to type II pneumocytes

Type I cells do not make surfactant; type II cells do.

Why: division of labor — type I stays thin for gas exchange, type II stays plumper to secrete.

Type II cells can proliferate and replace type I after injury.

Why: type I cells themselves have poor regenerative capacity.

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6. Cytoplasm / organelles

Very few organelles, clustered near nucleus.

Why: keeping organelles in one thicker zone lets the rest of the cell stay ultra-thin.

Pinocytotic vesicles may be present.

Why: small-scale transport and turnover of membrane at the air–liquid interface.

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7. Vascularity / proximity to capillaries

Capillaries run immediately beneath the type I pneumocyte.

Why: puts blood as close as possible to inhaled air; in some areas only two thin cells + fused BM separate them.

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8. Function

Primary role: gas exchange (O₂ in, CO₂ out).

Why: ultra-thin cytoplasm + fused BM → minimal diffusion distance → very fast exchange.

Secondary role: participates in keeping alveolar fluid minimal (via tight junctions).

Why: fluid layer that is too thick would slow gas exchange.

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9. Immuno / markers (may vary by lab, but in principle)

• Epithelial markers (cytokeratins): positive (it is epithelium).

  Why: confirms epithelial origin, helps separate from endothelial cells in studies.

• Aquaporin-5, T1α/podoplanin (RTI-40 in rodents), caveolin-1 often used in research to mark type I.

  Why: these relate to water movement and specialized membrane domains needed for gas exchange.

• Negative for surfactant proteins (SP-A, SP-B, SP-C) compared with type II.

  Why: confirms it is the thin exchange cell, not the secretory surfactant cell.

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10. Injury / disease relevance

Highly sensitive to toxins, smoke, viral injury.

Why: they are large, thin, and have little “reserve” cytoplasm.

Loss of type I → denudation of alveolar surface → edema into alveoli.

Why: without the tight, thin epithelium, capillary fluid can enter the air space.

Repair depends on type II→type I differentiation.

Why: type I won’t repopulate efficiently on its own.

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11. Summary (site-specific “why”)

• So flat: to shorten diffusion path.
• So fused with endothelium: to remove extra layers.
• So junctional: to keep air space dry.
• So dependent on type II: because the thin cell can’t afford to be a factory too.

Specialized serosal/mesothelial modifications

Even within mesothelium, there are small regional tweaks.

Pleura and peritoneum with dense microvilli

• Reason: increase surface area for fluid exchange and absorption.
• Pathology angle: in peritonitis or carcinomatosis, this thin layer is the first to react or to get covered by tumor.

Peritoneal “milky spots” (omentum)

• Surface is mesothelial, but immediately under it are clusters of immune cells.
• Reason: the omentum helps sample peritoneal fluid.
• Pathology angle: explains why peritoneal tumors often seed omentum.

So still simple squamous on top, but doing more immune and fluid work than the “vanilla” pleura/peritoneum.

Vestibular system and endolymphatic areas (inner ear)

You can meet very thin, squamous to low cuboidal epithelium in:

• endolymphatic duct and sac
• parts of vestibular system

Why it is there: this lining participates in fluid regulation (endolymph resorption, immune-surveillance like jobs) in a very confined space, so it stays thin.

Pathology angle (why a resident cares):

• Some inner ear lesions or inflammatory processes can change this epithelium to a more reactive, cuboidal, or stratified look.
• In otologic specimens, recognizing that the normal lining can be very flat helps you not to overcall “denudation”.