CIRCULATORY SYSTEM

1. General structures of blood vessels

Blood vessels are structurally adapted according to physiologic requirements.

- Pulmonary aa (low-pressure system) has thinner walls than do systemic aa (high-
pressure system) such as carotid or renal artery
- They constitute a continuous system, and some overlapping of classification is to be
expected.
- Arteries + veins: different thickness, different structures of walls

Cavity organ: tubular, with a lumen. 


Lumen: is coated by 1 layer of simple squamous epithelium 
 

N: flattened
C: thin layer

Each blood vessel has 3 layers with different structures (tunics = coats).

Lumen: may contain blood vessels.


Walls of blood vessel = arteries + veins: 1. Intima 2. Media 3. Adventitia

1. TUNICA INTIMA


- Consists of a layer of endothelial cells, lining the vessels interior surface and
resting on the basal lamina.
- Under this endothelium: subendothelial layer consisting of LCT that may
contain smooth muscle cells
- When present, both CT + smooth muscle cells tend to be arranged
longitudinally
- In aa, the intima is separated from the media by an internal elastic lamina
which is composed of elastin. It has gaps (fenestrae) that allows substances to
diffuse to and nourish cells deep in the vessel wall.

2. TUNICA MEDIA

- Consists chiefly of concentric layer of helically arranged smooth muscle
cells  muscular layer.
- Between the smooth muscle cells you can find elastic fibers + lamellae +
reticular fibers + proteoglycans.
- Smooth muscle cells are the cellular source of the ECM.
- In large aa: a thinner external elastic lamina is often found, separating the
media from the outer tunica adventitia.
- In capillaries + post-capillary venules, the media is replaced by pericytes.

3. TUNICA ADVENTITIA
- Consists of longitudinally arranged collagen fibers + elastic fibers
- Collagen type I  in adventitia, Collagen type III  in media, rich in
reticular fibers
- The adventitia layer gradually becomes continuous with the enveloping CT
of the organ through which the vessel runs.

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Vasa vasorum
- In large aa: vasa vasorum branch profusely in the adventitia and the outer part of the
media.
- It provides metabolites to the adventitia + media in larger vessels, since the layers
are too thick to be nourished solely by diffusion from the lumen.
- More frequent in vv than in aa.
- Greater abundance of vasa vasorum  paucity of O2 + nutrition substances in
venous blood.
- Can arise from branches of the artery they supply or from neighboring aa.
- Lymphatic capillaries can penetrate the media of vv, but they are present in aa only
in the adventitia.

Innervation
- Vasomotor nn: Larger aa are supplied with a network of unmyelinated sympathetic
nerve fibers whose neurotransmitter is norepinephrine (vasoconstrictor). The
neurotransmitter must diffuse to affect the smooth muscle cells in media.
- Gap junctions between smooth muscle cells of the media propagate the response to
the neurotransmitter to the inner layers of muscle cells.
- In vv, nerve endings are found in both the adventitia + media, but the overall density
of innervation is less than in aa.
- aa of skeletal muscles also receive a cholinergic vasodilator nerve supply.
- Afferent sensory nerve endings in aa include baroreceptors (in arch of aorta +
carotid sinus) + chemoreceptors (in carotid body + aortic body).

Drawing

2. Elastic Arteries – structure and ultrastructure, localization and function

- Compromise the major distribution vessels and include the aorta + the innominate
(brachiocephalic artery*) + common carotid artery* + subclavian artery* + most of
the pulmonary arterial vessels.
* = Branches of aorta
- The elastic artery has a yellow color from the accumulation of elastin in the tunica
media.
- Functions in stabilizing blood flow.

Tunica intima:
- Endothelium (simple squamous epithelium) with basal membrane.
- Subendothelial CT with collagen fibers + elastic fibers + smooth muscle cells. The
subendothelial layer CT contains scattered fibroblasts + other cells with an
ultrastructure like smooth muscle cells  Myointimal cells.
- Internal elastic lamina
- Tight junctions + gap junctions.

- Myointimal cells + fibroblasts are probably involved in elaboration of the EC

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components. Myointimal cells are not invested by basement membrane and are thus
not epithelial in nature. With increasing age, myointimal cells accumulate lipid and
the intima progressively thickens  represents early changes of Atherosclerosis.

Tunica media:
- Thickest layer and most elastic. Also very well developed.
- Perforated wavy, elastic laminae arranged concentrically (the number increases with
age: 40 in newborn, 70 in adult).
- Between these laminae you can find collagen + smooth muscle cells
- Few fibroblasts are present.
- Collagen fibers + elastic fibers are produced by smooth muscle cells.
- No external laminae

Tunica adventitia:
- Thinner than tunica media, but well developed
- Made of CT + fibroblasts.
- Has some elastic fibers present.
- Contains vasa vasorum (penetrate the outer ½ of the tunica adventitia) + nervi
vascularis.

3. Muscular Arteries- structure and ultrastructure, localization and function

- The main distributing branches of the arterial tree: radial a + femoral a + coronary a
+ cerebral a  most aa.
- They have the same basic structure as elastic aa but the elastic tissue is reduced to a
well defined, fenestrated elastic sheet; internal elastic lamina, and a less defined;
external elastic lamina.
- Sometimes the internal elastic lamina is duplicated.

Tunica intima
- Endothelium.
- Subendothelial layer  CT = collagen fibers + elastic fibers + smooth muscle cells
- Internal elastic lamina: thick + wavy

Tunica media
- Thickest layer, which contains up to 40 layers of smooth muscle cells.
- The number of layer diminishes as the artery becomes smaller.
- Elastic laminae + collagen fibers are present.
- External elastic lamina.

Tunica adventitia
- Thick CT layer, almost the same as tunica media in thickness.
- Collagen fibers + elastic fibers are present.
- Function: Distribution of blood + the smooth muscle cells of the vessel wall is under
the control of the sympathetic NS and adrenal medullary nn.
- Few fibroblasts + vasa vasorum + nerve fibers can also be found.

4. Arterioles -structure and ultrastructure, localization and function

- Arterioles are the terminal branches of the arterial tree, which supply the capillary

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beds. They are generally less than 0.5 mm.
- Arterioles are key control point for blood flow.
- The flow of blood through capillary beds is regulated mainly by the arterioles, which
supply them.
- Contraction of the circulatory arranged smooth muscle fibers of the arteriolar walls
reduces the diameter of arterioles throughout the body markedly in peripheral
resistance to blood flow and the arteriolar compartment of the circulatory system. It
has an important role in the regulation of systemic blood pressure.

Tunica intima
- Subendothelial layer is very thin.
- Endothelial lining + little collagenous CT + thin internal elastic lamina (disappears
under diameter of 50 micrometer).

Tunica media
- Almost entirely composed of smooth muscle cells: 1-5 concentric layers.
- No external elastic laminae.

Tunica adventitia
- Sparse and poorly developed.
- It is almost as thick as the tunica media and merges with the surrounding
collagenous tissue.
- No vasa vasorum.

5. Veins and venules -structure and ultrastructure, localization and function

- The venous system merely functions as a low pressure collecting system for the
return of blood from the capillary networks to the heart. Blood flow in the vv occurs
passively down a pressure gradient towards the heart.
- The vv are classified as: large/medium/small.
- Thin wall with an oval, big lumen.
- Large vv + medium vv usually accompany large aa + medium aa.
- Large vv + medium vv have same layers in wall: tunica intima + tunica media +
tunica adventitia.
- A wall of a vein is much thinner than a wall of an artery.
- Some vv may have valves to prevent backflow.

Large veins
- Large vv such as the femoral vein + renal vein have a relatively thick muscular wall,
consisting of several layers of smooth muscle separated by collagen fibers.

Tunica intima
- Endothelium.
- Basal lamina and thin subendothelial CT.
- Internal elastic lamina.

Tunica media
- 4-5 layers of smooth muscle cells + collagen fibers + fibroblasts.
- No distinct layer/border.

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Tunica adventitia
- Is the thickest and best developed layer
- Has smooth muscle cells + collagen fibers + fibroblasts + some elastic fibers.

Medium veins
- Medium vv have valves in their interior.
- A valve:
- 2 semilunar folds of the tunica intima that project into the lumen.
- Composed of elastic CT + lined on both sides by endothelium.
- Only occur in vv >2 mm in diameter, especially those draining extremities.

Tunica intima
- Endothelium + basal lamina + thin subendothelial CT + internal elastic lamina.

Tunica media
- Very thin with smooth muscle bundles + fibroblasts + reticular fibers + elastic
fibers.

Tunica adventitia
- Thicker than tunica media.
- Has CT + some smooth muscle cells (longitudinally arranged) + thick collagen
fibers (which merge with the surrounding collagenous tissue).

Venules
- Endothelium + basal lamina.
- Pericytes: contractile, replacing the media. They are modified muscle cells, have
numerous extensions, role: phagocytosis and contraction  loose endothelial
junctions.
- Sensitive to histamine and serotonin: High permeability to fluid during allergic and
inflammatory reactions.
- No real tunica media, just 1-2 layers of smooth muscle.
- Tunica intima is devoid of elastic fibers.
- Thicker muscular wall.
- A poorly developed internal elastic lamina.
- The tunica adventitia continues with the surrounding collagenous CT.

Post-capillary venules
- Diameter larger in post-capillary venules (25-30 micrometer) than capillaries (7-9
micrometers).
- Pericytes may be present with an elongated nucleus.

6. Ultrastructure of blood capillaries

- Site of most nutrient and gas exchange between tissue and blood.

Continuous capillaries
- CT + muscle tissue + nervous tissue + exocrine glands.
- Diameter: 7-9 micrometers (like a RBC), round lumen.
- 1 nucleus/cross section.
- Are composed of: a single layer of endothelial cells + basal membrane + collagen

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fibers + pericytes (surround endothelial cells).
- Numerous pinocytotic vesicles are present on both surfaces of capillaries. These
vesicles are responsible for the transport of macromolecules in both directions across
the endothelial cells.
- Small cytoplasmic flaps, called marginal folds, extend across the intercellular
junctions at the luminal surface.
- Exchange occurs by: passive diffusion + pinocytotic vesicles.
- In capillaries of the continuous endothelial type, the basement membrane is thought
to present little barrier to exchange between capillaries and surrounding tissues.

Fenestrated capillaries – discontinuous

- are found in intestine + kidney + endocrine glands (tissues with rapid exchange of
substances).
- Are characterized by the presence of large fenestrated pores in the wall of
endothelial cells.
- The fenestrae are 60-80 nanometers, and are closed by a diaphragm, which is thinner
than a cell membrane.
- A continuous basal lamina is present.

Sinusoid capillaries
- Large diameter: 30-40 nanometers.
- Found in liver + bone marrow + spleen + endocrine glands.
- The endothelial wall is discontinuous as the endothelial cells show multiple
fenestrae without diaphragms.
- Basal lamina is discontinuous.

7. Classification of blood capillaries

Continuous
- Non-fenestrated, have tight junctions (most tissues)
- The endothelial cells form an uninterrupted lining.
- CT + muscle tissue + nervous tissue + exocrine glands
- Diameter: 7-9 micrometer
- Composed of a single layer of endothelial cells + basal membrane + pericyte.
- Numerous pinocytotic vesicles are present on both surfaces of capillaries.
- These vesicles are responsible for the transport of macromolecules in both directions
across the endothelial cells  transcellular pathways.

Discontinuous

Sinusoidal
- Endothelial cells don’t form a continuous interface between lumen + surrounding
tissues.
- No diaphragm.

Drawing

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Fenestrated
- Endothelial cells contain large pores of fenestrations (diameter: 60-80 nm) closed by
a diaphragm.
- Basal lamina is discontinuous.
- Found in intestine + kidney glomerulus + endocrine gland + lymph nodes.
- Diameter: 30-40 nm.

Drawing

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LYMPHOID SYSTEM

8. The immune system basics: cell types, functions

- Lymphatic system = Groups of cells + tissues + organs, that function to protect our
body surfaces + internal fluid compartments, from invasion and damage by harmful
substances (foreign cells + microbes + viruses + parasites).

The immune system is able to:

- Differentiate between self (own) and non-self (foreign + modified seld) structures 
specificity.
- Respond: immune response  fights against pathogens.
- Remember AGs over long periods of time.

Cells of the immune system:

- Lymphocytes: T + B + NK
- AG-presenting cells (APC): dendritic cells + macrophages + B lymphocytes 
control the activation of T cells.

Neutrophils
- The cells of the immune system, especially lymphocytes, are scattered throughout
the body either as isolated cells, as non-encapsulated aggregations in the GI tract +
respiratory tract + other tracts (mucosal associated lymphoid tissue or MALT) or
within the lymphoid organs namely the thymus + lymph nodes + spleen.

Immune system:
- Humoral immunity  B lymphocytes: responsible for AB production.
- Cell-mediated immunity  T lymphocytes: functions as cytotoxic cells directly
killing abnormal body cells.

- The specificity of the immune system is entirely attributable to the remarkable

chemical structure of AG receptors on lymphocytes, namely surface immunoglobulin
(sIg), on B cells, and, T cell receptor (TCR) on T cells.
- Supporting cells, which interact with lymphocytes have a role in the presentation of
AG to lymphocytes and the regulation of the immune response.
- These include: monocytes + macrophages + neutrophils + basophils + reticular cells
+ eosinophils + dendritic cells + follicular dendritic cells + Langerhans’ cells +
epithelia-reticular cells.
- Also, stromal cells (specialized epithelial cells), provide the environment for many
immune reactions to occur by secreting specific substances that regulate growth +
migration + activation of effector and supporting cells.
- Different types of cells can be identifies by specific cluster of differentiation (CD)
markers on their surface.
- CD markers are either expressed during one phase of differentiation or during
activation; CD markers are present throughout life.

9. LYMPHOID TISSUE: STRUCTURE, VARIETIES

The lymphoid tissue consists of:

- Numerous immune system cells: lymphocytes + APC (dendritic cells, macrophages,

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B lymphocytes)
- Stroma (body): reticular cells + reticular fibers.
- Reticular cells: cell body with oval, euchromatic nucleus. Has long, thin processes
that contact each other (desmosomes).

2 main tissue architecture types:

- Diffuse: uniform appearance.
- Follicular: consists of lymphoid follicles.

2 types of lymphoid tissues:

- Encapsulated (has CT capsule): spleen + thymus + lymphnodes.
- Un-encapsulated (or partly capsulated): tonsils + Peyer’s patches (usually in the
small intestine) + lymphoid nodules in GI tract + respiratory tract + urinary and
reproductive tracts.

10. OVERVIEW OF LYMPHOID ORGANS: DEFINITION,

CLASSIFICATION, and EXAMPLES

Central primary lymphoid organ:

- Where lymphoid precursor cells undergo AG independent proliferation and
differentiation:
- T cells in thymus
- B cells in bone marrow (Primary!)
Peripheral secondary lymphoid organ:
- Where functional lymphocytes go including lymph nodes + spleen + Peyer’s patches
+ lymphoid nodules of GI and other tracts
- Lymphocytes contact AGs and divide and differentiate into effector B cells and T
cells.
- Memory cells forms, which circulate for years to provide extended immunity.

11. T LYMPHOCYTES: ORIGINS, DIFFERENTIATION, SUB-

POPULATIONS

- Lymphocytes are small cells, about 70% of the lymphocytes in the circulation.
- They participate in a cycle which they exit the systemic circulation to enter the
lymphatic tissue: they are responsible for immunologic surveillance of surrounding
tissues. And then they return to the systemic circulation.
- These 70% represent mostly long-lived, mature T cells that have developed that
capacity to recognize and respond to foreign AGs and are in transit to form one site of
lymphatic tissue to another.
- The remaining 30% in blood vessels don’t circulate between lymphatics and
systemic circulation. These are short-lived, immature cells or activated cells destined
for a specific tissue. They can leave capillaries and migrate directly to the tissues
(especially into CT that underlines the lining epithelium of respiratory + GI +
urogenital tracts, as well as into intercellular spaces of these epithelia).
- These are the cells that recognize foreign AG, they can distinguish self from non-
self, because they have surface AG receptors.
- Recognition of their specific AG drives differentiation and proliferation to produce a
highly specific and effective clone.
- Memory lymphocytes can persist for many years  this is only when vaccination

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works.

T lymphocytes (T cells)
- A thymus-derived (or processed) lymphocyte.
- Immunologically immature T cells migrate from the bone marrow to the thymus,
where they develop into mature T (thymus-dependent) cells.
- Immature T cells proliferate in the thymus acquiring a variety of surface markers to
become mature (naive) lymphocytes, having as yet had no contact with AG.
- At this stage of development, T cells with the ability to react to the body’s own
normal constituents (self AG) are either destroyed or suppressed resulting in self-
tolerance.
- Clones of mature T cells then populate the peripheral lymphoid tissue (lymph nodes,
MALT and spleen) and form here continuously circulating T cells via the bloodstream
in a constant guest for AG.
- On encountering AG, T cells effect AG destruction either by direct cytotoxic
activity or indirectly via activation of B-lymphocytes and macrophages.
- About 75% of circulating lymphocytes.
- Diameter: 6-15 micrometers (comparable to a RBC)
- Small T lymphocytes – scanty cytoplasm.
- Large activated lymphocytes – more cytoplasm, azurophillic granules.

T lymphocytes are subdivided by the presence of different surface markers:

T helper cells (TH):
- These T cells ‘’help’’ other lymphocytes to perform their effector functions by
secreting a variety of peptide or protein chemical messengers called interleukins.
- Such functions include: activation of B cells to produce AB, regulation of cytotoxic
T cells and activation of macrophages to mount a chronic granulomatous
inflammatory (delayed type hypersensitivity) response.
- T helper cells express CD4 surface markers.
- They induce and coordinate the responses of the cytotoxic T cell + other cells of the
adaptive immune response  cytokine factories.
Cytotoxic T cells:
- These lymphocytes function in the killing of virus-infected and malignant cells.
- They express CD8 surface markers.
- They require interaction with TH cells to become activated and to undergo
proliferation for cytotoxic functions.
Suppressor T cells (TS):
- These cells are responsible for switching off the immune response when the
initiating stimulus is removed and for suppressing immune responsiveness to self
AGs.
- They express CD4+ and CD25+ surface markers.
Gamma/delta T lymphocytes:
- They possess a distinct TCR on their surface made of one gamma-chain and one
delta-chain.
- Most other TCRs are composed of 2 glycoprotein chains: alpha and beta TCR-
chains.
- They develop in the thymus and migrate into various epithelial tissues (e.g. skin,
mucosa, intestines, vagina). Once they colonize epithelial tissue, they don’t
recirculate between blood and lymphatic tissue.
- They are positioned at interfaces of external and internal environments, and,

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functions as the first line of defense against invading organisms.
- They encounter AG on the surface of the epithelial cells even before it enters the
body.
Lymphocytes recognize their specific AGs in association with major
histocompatibility AGs:
- TH cells recognize AG that is presented in association with:
- MCH class II
- TC cells recognize AG that is presented via:
- MCH class I

12. B LYMPHOCYTES: ORIGINS, DIFFERENTIATION, SUB-

POPULATIONS

- B-lymphocytes are derived from precursors in the bone marrow but also undergo
maturation/differentiation in bursa equivalent organs (bone marrow and GALT).
- Exposure to AG results in clonal proliferation in the peripheral lymphoid tissues
with the production of AB-secreting plasma cell and B memory cells.
- About 20-30% of the circulating lymphoid pool.
- B-lymphocytes are characterized by their ability to synthesize ABs, glycoproteins,
which bind to specific AGs. These are immunoglobulins IgG + IgA + IgD + IgM +
IgE.
- In some cases, immunoglobulins are secreted and circulate in the blood.
- In others, they remain bound to the surface of the B lymphocyte where they behave
as AG receptors, activating the B cell when the appropriate AG is encountered an
binds with the AB.
- Activation of B cells requires the help of TH responding to the same AG.
- Once activated, B cell terminally differentiate into plasma cells.
- A few cells from the clone mature to become memory cells, small long-lived,
circulating lymphocytes, which are able to respond quickly to any subsequent
challenge with the same AG.
- AB production during this secondary immune response occurs much more rapidly, is
of much greater magnitude and produces IgG rather than IgM.
- B-lymphocytes express MCH class II molecules, which are important for presenting
AG to T cells.
- Their CD markers are: 9, 19 and 20.

13. ANTIGEN PRESENTATION: CELLS INVOLVED, MECHANISMS

-  B-lymphocytes (although not a part of the mononuclear phagocytic system),

macrophages (from macrophage-monocyte system) and dendritic cells.
- AG presenting cells take up foreign material and process the AG by breaking it
down into molecular fragments of a form capable of recognition of T-lymphocytes.
- Processed AG is then passed to the plasma membrane for presentation to appropriate
lymphocytes.
- This process is enhanced by the intimate relationship of the lymphocyte plasma
membranes to those of the APC cytoplasmic extensions.
- The shapes of APCs vary according to the arrangements of cells in the different
tissues.
- Vascular endothelial cells + dermal fibroblasts + thyroid epithelial cells + brain
astrocytes may present AGs also to T-lymphocytes.

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Dendritic cells (DC); interdigitating DC:
- Langerhan’s cells + Germinal center of dendritic cells + follicular dendritic cells
(not considered APC because they lack MCH II molecules. They present AG through
fc receptors of AB. They interdigitate between B cells in the germinal centers).
- Located in peripheral tissues of lymphoid tissues.
- They can be activated in inflammatory conditions.
- Have the ability to uptake, process and present AGs to T cells.
- The are ‘’professional’’ APCs.
- The Langerhan’s cells of the skin migrate from their site of Ag uptake in the skin to
regional lymph nodes where they become paracortical interdigitating dendritic cells
 Mobile APCs.
- DC are the most efficient in APC and are able to present any form of protein AG on
both MCH I and MCH II molecules.
- Inflammatory response  sequester the AG, physically digest it with enzymes
secreted by neutrophils. They phagocytize and degrade the AG in the cytoplasm of
macrophages.
- Degradation of macrophages  may lead to subsequent presentation of a portion of
the AG to immune-competent lymphocytes to elicit a specific immune response.

- Specific immune responses are either primary or secondary. When immune-

competent cells encounter foreign AG, a specific immune response to the AG is
generated.

- Primary immune response: body’s first encounter with AG. Characterized by a lag
period of several days before ABs (mostly IgM or specific lymphocytes directed
against the invading AG can be detected in the blood).
- Initial response to an AG is initiated by only one or few B cells that have been
programmed to respond to that specific AG. After this initial response, a few AG-
specific B cells remain in circulation as memory cells.

- Secondary immune response is usually more rapid + more intense (characterized by

higher levels of secreted ABs, usually IgG class) than the primary response because
of presence of specific B cells already programmed to responds to that specific AG.
- Secondary responses is the basis of most immunizations for common bacterial and
viral diseases. Some AGs (e.g. penicillin and insect venoms) may trigger an intense
secondary immune response that produces hypersensitivity reaction or even
anaphylaxis. ABs themselves don’t kill/destroy invading AGs; they simply mark them
for destruction by cells of the immune system.

14. THYMUS: DEFINITION, GENERAL HISTOLOGY

- The thymus is a large, bi-lobed, flattened, lymphoid organ located in the superior-
anterior mediastinum. Develops bi-laterally from the 3rd (sometimes 4th) brachial
pouch.
- It is most active during childhood after which it undergoes slow involution.
- Central lymphoid organ, double embryonic origin: epithelial and mesenchymal.
- Thin capsule, lobular organization as trabeculae.
- Trabeculae contain blood vessels + lymphatic vessels + nn.
- In addition to collagen fibers + fibroblasts, the CT of the thymus contains variable

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numbers of plasma cells + granulocytes + lymphocytes + mast cells + adipose cells +
macrophages.
- Each lobule has a cortex (greater cell density) which many T-lymphocytes +
medulla (lighter stained, less cellular).
- Cortex: many young T-lymphocytes (thymocytes) + macrophages + epithelial
reticular cells, with large euchromatic nucleus.
- Medulla: more epithelial reticular cells, fewer lymphocytes.
Mature T-lymphocytes leave from here to the spleen and lymph nodes.
Hassal’s corpuscles: concentric layers of flattened epithelial reticular cells. Function
is unknown.
- The epithelial cells of the thymus not only provide a mechanical supporting
framework for the lymphocyte population, but in the cortex tend to envelop the
lymphocytes performing some kind of ‘’nurse’’ function promoting T cell
differentiation, proliferation and subset maturation.
- Furthermore, the epithelial cells secrete at least 3 hormones and humoral factors,
which regulate T cell maturation and proliferation within the thymus and in other
lymphoid organs and tissues.
- After puberty, thymus undergoes involution and has increased amount of CT and
adipocytes.
- The trabecular establish domains in the thymus: thymic lobules. They are not true
lobules, but cortical caps over portions of the highly convoluted and continuous inner
medullary tissue.
- The lobular arrangement of the cortical cap and medullary tissue superficially
resembles a lymphatic nodule with a germinal center.

Thymocytes
- Precursor lymphocytes, from the bone marrow, which enter the thymus via blood.
- They proliferate and mature in the thymus but only 1-3% survive the selection
process that allows mature T cells to enter the peripheral circulation.
- Specialized APCs scan for T cells that may self react, these cells are killed as to
prevent auto-immunity (negative selection).
- Progenitor T cells (thymocytes) that recognize MCH class I molecules but not self-
AG are positively selected for development.
- This is where the entire repertoire of AG specific T cells is generated (the TCRs is
created here).
Thymic parenchyma contains developing T cells in an extensive meshwork formed by
epithelia-reticular cells. The outer portion: thymic cortex, basophilic because of the
closely packed T-lymphocytes, N: intensely stained. These T-lymphocytes
(thymocytes) occupy spaces within the meshwork. Macrophages are also dispersed
among the cortical cells. The developing T cells arise from CFU-Ls, which originate
from bone marrow. As development continuous within thymus, the cells derived from
CFU-Ls pass through a series of developmental stages that are reflected by their
expression of different CD molecules.

Epithelio-reticular cells have features of both epithelial + reticular cells: they provide
a framework for the developing T-lymphocytes. Reticular CT cells and their fibers,
are not present in the thymic parenchyma. Epithelio-reticular cells exhibit certain
features characteristic of epithelium such as intercellular junctions and intermediate
filaments. There are 6 types, recognized on the basis of their function: 3 types in the
cortex + 3 types in the medulla.

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- Type I epithelio-reticular cells: located at boundary of cortex + CT capsule, but also
b/w the cortical parenchyma + the trabeculae. They also surround adventitia of
cortical blood vessels. Function: Separate the thymic parenchyma from the CT of the
organ. The occluding junctions between these cells reflect their function as a barrier
that isolates the developing T cells from the CT of the organ (that is: the capsule,
trabecular, perivascular CT).

- Type II epithelio-reticular cells: Located within the cortex. TEM reveals maculae
adherents (desmosomes) that join long cytoplasmic processes of adjacent cells. The
cell body + cytoplasmic processes contain abundant intermediate filaments. B/c of
their processes these cells are stellate. The nucleus is large, lightly stained in H&E b/c
of abundant euchromatin (because of nucleus type II cells can easily be identified).
Type II cells compartmentalize the cortex into isolated areas for the developing T
cells. Unlike type I cells, type II express MCH I and MCH II molecules which are
involved in thymic cell education.

- Type III epithelio-reticular cells: located at boundary of cortex + medulla. TEM

reveals occluding junctions between sheet-like cytoplasmic processes of adjacent
cells. Like type I cells, type III cells create a functional barrier; in this case, b/w the
cortex + medulla. Like type II cells, they also possess MCH I and MCH II molecules.

(- Macrophages: reside within the thymic cortex. Responsible for phagocytosis of T

cells that do not fulfill thymic education requirements. These T cells are programmed
to die before leaving the cortex. About 98% of the T cells undergo apoptosis and are
then phagocytosed by the macrophages. Macrophages are easily seen in PAS
(Periodic acid-Schiff) reaction b/c of their numerous large lysosomes. They are
therefore sometimes called PAS cells.)

- Type IV epithelio-reticular cells: They are located between cortex + medulla close to
type III cells. Possess sheet-like processes with occluding junctions between adjacent
cells, but also between type III cells. In co-operation with type III cells, they create
the barrier at the cortico-medullary junction.

- Type V epithelio-reticular cells: located throughout medulla. Like type II cells

located in the cortex, processes of adjacent cells are joined by desmosomes to provide
cellular framework of medulla + to compartmentalize groups of lymphocytes. These
nuclei contrast markedly with the densely staining lymphocyte nuclei.

- Type VI epithelio-reticular cells: form the most characteristic feature of the thymic
medulla: thymic Hassall's corpuscles. They are isolated masses of closely packed,
concentrically arranged type VI epithelio-reticular cells that exhibit flattened nuclei.
TEM studies of these cells reveal kerato-hyalin granules, bundles of cytoplasmic
intermediate filaments, and lipid droplets. The cells are joined by desmosomes. The
center of a thymic corpuscle may display evidence of keratinization. They are
functionally active multicellular components of the medulla. They produce
interleukins 4 and 7, that function in thymic differentiation and education of T
lymphocytes.

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Functions:
- Development of immune-competent T-lymphocytes derived from bone marrow.
Differentiation of the 2 T cell subsets: T helper cells and T cytotoxic/suppressor cells.
- Proliferation of clones of mature naïve T cells to supply the circulating lymphocyte
pool and peripheral tissues.
- Development of immunological self-tolerance.
- Secretion of hormones and other soluble factors, which regulate T cell maturation,
proliferation and function within the thymus and peripheral tissues.
- Thymic hormones also regulate the development of peripheral lymphoid organs and
tissues. For example: Thymulin, thymopoietin and thymosine.
- Haemopoiesis is an important function of the thymus during fetal development.

Blood-thymus barrier:
1) non-fenestrated endothelium, thick basal lamina and 2) reticular cell sheath type I
form the barrier found in the cortex, separating proliferating thymocytes from the
blood. 3) Macrophage in the surrounding perivascular CT also takes part in forming
this barrier. Antigenic molecules that escape from the capillary lumen into the cortical
parenchyma may be phagocytosed by macrophages residing in this tissue.

Organization of a thymic lobule:

- The thymus is a highly lobulated invested by a loose collagenous capsule, from

which short interlobular septa containing blood vessels radiate into the substance of
the organ.
- The thymic tissue:
- deeply basophilic outer cortex.
- inner eosinophillic medulla.
 distinction between the 2 is most marked in early childhood.
- The cortex is packed with lymphocytes accounting for its basophilia, the medulla
contains fewer lymphocytes.
- The epithelial framework of the medulla is relatively coarse and bulky, the
interstices being much smaller than these of the cortex and therefore accommodating
fewer lymphocytes.
- The epithelial framework of the cortex is more delicate and finely branched than that
of the medulla (sometimes described as reticular).

15
- In the center of the medulla are eosinophillic, lamellated Hassal’s corpuscles
representing degenerated epithelial cells.
- Numerous small branches of the internal thoracic and inferior thyroid arteries enter
the thymus via the interlobular septa, branching of the cortico-medullary junction to
supply the cortex and medulla.
- The cortical capillaries are of the continuous endothelium type whereas those of the
medulla and septa may be fenestrated.
- Post-capillary venules in the cortico-medullary region: cuboidal endothelium which
allows passage of lymphocytes into and out of the thymus.
- The venous and lymphatic drainage follows the course of the aa.
- The inner surface of the thymus capsule and septa is invested by a continuous layer
of thymic epithelial cells resting on a basement membrane.
- The epithelium also forms sheaths around the blood vessels forming a barrier to the
entry of antigenic material into the system of spaces within the epithelial framework
 blood-thymus barrier.
- Sympathetic and para-sympathetic fibers derived respectively from (S) chain and
phrenic nn accompany the vessels.
- Some serve vasomotor functions but many terminate in the medulla 
neuroendocrine function.
- The thymic cortex contains macrophages, which engulf dead lymphocytes.
- Several mitotic figures of lymphoblasts in the outer cortex.

15. LYMPHOID FOLLICLES: STRUCTURE, DISTRIBUTION

- Nodules of densely packed lymphocytes located in all peripheral lymphoid tissues,

most lymphocytes are B cells.
- Lymphatic nodule consisting of mainly small lymphocytes: primary nodule. But
most nodules are secondary, and have distinctive features.

Distinct areas:
- Mantle zone/corona: outer ring of small lymphocytes that encircles the germinal
center. Darker stained, mainly small resting lymphocytes.
- Germinal center: defines secondary or reactive lymphoid follicles. Lighter stained,
larger activated B cells – centroblasts and centrocytes, with cleaved nuclei.
- The B-lymphocytes in the superficial cortex are mainly naïve B cells and B memory
cells.
- The resulting lymphoblasts of the germinal center are Follicle center cells.
- The center of the follicle is less intensely stained than the corona because the cells
are larger and less closely packed together.
- The product of follicular B-lymphocyte activation and proliferation is an expanded
population of B memory cells and not the formation of plasma cells. Differentiation
of plasma cells is a result of T cell/B cell interaction in the para-cortex with the AB-
secreting plasma cells migrating directly to the medullar cords where they are
conveniently situated for secretion of AB into the efferents.
- Germinal center bordering cells form a capsule like structure of stromal cells of the
periphery of the germinal center. This prevents the entry of T cells. Activated
lymphocytes entering the node via afferent lymph, pass readily into germinal centers
 that’s why is open at its superficial aspects.
- Accessory cells in the superficial cortex: involves in AG processing
- Tangible body macrophages

16
 - Follicular dendritic cells
- Marginal zone macrophages
- NK cells

Lymph nodules are usually found in structures associated with alimentary canal, i.e.
tonsils + ileum + vermiform appendix  dispersed singly in random manner. In
alimentary canal: some aggregations of nodules are found in specific locations:
- Tonsils: form a ring of lymphatic tissue at the entrance of oropharynx  pharyngeal
tonsils (adenoids) (roof of pharynx) + palatine tonsils (the tonsils, on either side of
pharynx) + lingual tonsils (base of tongue). Palatine tonsils consist of dense
accumulation of lymphatic tissue located in mucous membrane. Squamous epithelium
that forms the surface of tonsils dips into underlying CT in numerous places
forming tonsilar crypts. The walls usually possess numerous lymph nodules.
- Peyer's patches: located in ileum, consist of numerous aggregations of lymphatic
nodules containing T and B-lymphocytes. Also, numerous isolated single (solitary)
lymph nodules are located along both large and small intestines.
- Vermiform appendix: arises from cecum. Lamina propria is heavily infiltrated with
lymphocytes and contains numerous lymphatic nodules.

Diffuse lymphatic tissue+ lymphatic nodules are named according to the region(origin
they are found in:
- Alimentary canal: gut-associated lymphatic tissue (GALT)
- Bronchial tree: bronchus-associated lymphatic tissue (BALT)
- Mucosa-associated lymphatic tissue (MALT) includes GALT + BALT: found in
female reproductive tract (MALT) where mucosa is exposed to external environment.

16. LYMPH NODES: STRUCTURE AND FUNCTIONS

- Most lymphocytes are located in encapsulated, highly organized structures called

lymph nodes.
- They are interposed along the larger regional vessels of the lymph vascular system.
- Lymph nodes tend to occur in groups, particularly in areas where the lymphatic
converge to form larger trunks as in the neck + axilla + groins + lung hila + para-
aortic areas + abdominal mesenteries.

Functions
1) Non-specific filtration of particulate matter and microorganisms from lymph by the
phagocytic activity of macrophages, thus preventing exogenous material from
reaching the general circulation.
2) Interaction of circulating lymphocytes with AG containing lymph as it is filtered
through the narrow confines of the node. Initiation of an immune response may
require the involvement of AG presenting cells.
3) Aggregation, activation and proliferation of B-lymphocytes in response to
appropriate antigenic stimulation. This leads to plasma cell formation and AB
production.
4) Aggregation, activation and proliferation of T-lymphocytes with induction of
cytotoxic immune responses after appropriate antigenic stimulation.

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Structure
- Cortex: highly cellular
- Medulla: less cellular
- The lymph node is encapsulated by dense collagenous tissue from which trabeculae
extend for a variable distance into the substance of the node.
- Afferent lymphatic vessels divide into branches outside the node, pierce the capsule
to drain into a narrow space: Subcapsular sinus, beneath the cortex.
- From here, cortical sinuses pass towards the medulla.
-  medullary sinuses, converge upon the hilum in the concavity of them.
- Lymph drains from the hilum  efferent lymphatic vessels  thoracic.
- The parenchyma of the lymph nodes consist of an open meshwork.
- Reticular fibers which provides support for an ever changing population
lymphocytes.
- The cortex consists of densely packed lymphocytes and forms extrinsic medullary
cords, which projects into the medulla between the medullary sinuses.
- In the outer cortex, lymphocytes form a variable number of densely packed
lymphoid follicles many of which show less dense germinal center. HEPV  high
endothelium post-capillary venules: specific adhesion molecules that select lymph
that will enter the organ.
- The deep cortex (para-cortical zone) is devoid of lymphoid follicles.
- Medulla
- cell cords (lymphocytes, plasma cells)
- sinuses which joint o form efferent vessels
- Capsule of dense irregular CT, incomplete septa
- Lymph sinuses: subscapular  inter-follicular  medullar.
- HEPV, high endothelium post-capillary venules.

Organization:

17. SPLEEN: DEFINITION, GENERAL HISTOLOGY

- The largest lymphatic organ.

Functions:
- 1) production of immunological responses against AGs.
- 2) removal of particulate matter and aged or defective blood cells, particularly
erythrocytes, from the circulation.

- The structure of the spleen provides for intimate contact to be made between blood

18
and immunologically active cells.
- The spleen is difficult to study due to rapid autolysis.
- Consists of many macrophages, for RBC phagocytosis.
- Thick capsule of DCT with trabeculae dividing into pulps incompletely.
White pulp – lymphoid tissue
- The splenic artery divides into branches, which enter the spleen hilum  arterioles
in the parenchyma.
- Associated with the arterioles  peri-arteriolar lymphoid sheaths.
- T lymph masses are located around arterioles, B lymph follicles (adjacent to
arterioles.
- Reticular epithelial cells and macrophages.
Red pulp – found between sinusoids and has cell cords (Billroth’s cords) with mainly
macrophages, reticular fibers and reticular epithelial cells.
- Reticular cells with cords of cells between sinuses.
- Cords have macrophages, monocytes, lymphocytes, plasma cells, RBCs and
granulocytes.
- Sinuses have irregular lumen incomplete endothelium and basal lamina.
Marginal zone – forms border between the red and while pulp, where lymphocytes
leave blood to enter white pulp and RBCs and plasma cells to enter red pulp.
- The capsule is thickened at the hilum and is continuous with CT, which sometimes
contains smooth muscle, which exerts a rhythmic, pumping action, clearing the spleen
of blood and allowing it to ac as a reservoir.
- In humans, only a few smooth muscle cells persist.

18. BLOOD CIRCULATION IN SPLEEN

- Arterial blood supply from the splenic artery, it branches into several trabeculae that
enter the hilum of the spleen.
- These branches enter the parenchyma of the spleen as control aa.
-  Branch into marginal sinuses; continue into the red pulp where it branches into
several  Penicillar arterioles.
- Open circulating model: Penicillar arterioles open into medullary sinuses.
- Closed circulating model: Blood cell leave sinuses, then reenter, but it is
described as a continuous vascular chain.

Functions:
1) Filtration of blood – removal of antigenic material and cellular debris by
macrophages and dendritic cells, concentrated and presented to lymphocytes in the
white pulp.
2) Lymphocyte cells – both T and B-lymphocytes are activated in the spleen . Plasma
cells migrate from the white pulp into the red pulp where they secrete
immunoglobulins into venous blood.
3) Destruction of old/damaged RBCs. Phagocytosed by macrophages and the
hemoglobin is broken down.

19. MUCOSE-ASSOCIATED LYMPHOID TISSUE (MALT): DEFINITION,

EXAMPLES, and GENERAL HISTOLOGY

- Lymphoid tissue is distributed throughout the GI tract either as a diffuse

lymphocytic infiltrate or as large discrete non-capsulated aggregations such as in the

19
tonsils and intestinal Peyer’s patches.
- In the large aggregations, follicles may form with germinal centers similar to those
of lymph nodes.
- Smaller follicular aggregations and diffuse lymphocytic infiltrates are also seen in
the tracheo-bronchial tree and genitourinary tract.
- This mass of lymphoid tissue is considered to be a lymphoid organ  MALT.
- The epithelium overlying all MALT aggregations is specialized for the sampling of
luminal contents for AG, and acts as the equivalent of the afferent lymphatics of
lymph nodes.
- The lymphatics associated with MALT are all efferent, passing to regional lymph
nodes (tonsilar, mesenteric, hilar), along with the lymphatics of the tract well.
- MALT is formed during fetal life but germinal centers do not develop until after
exposure to AG at birth.
- The amount of MALT is maximal during childhood  atrophy in adulthood.
- When AG is encountered, it is carried to local MALT tissue or regional lymph nodes
where it evokes the relevant immune response.
- Lymphocytes, ABs and plasma cells then pass via circulation to the GI and
respiratory mucosae where they await antigenic challenge.
- IgA is secreted mostly in MALT.

Examples:
- Lymphoid nodules, tonsils (palatine, pharyngeal, lingual, Peyer’s patches)
- Tonsils: incompletely encapsulated lymphoid nodules.
- Palatine: covered by str. sq. non-ker. epith., crypts underlying CT barrier
- Pharyngeal: covered by ciliated pseudostr. epith., no crypts.
- Lingual: smaller, at base of tongue, covered by str. sq. non-ker. epith, one
crypt in each nodule.
- Peyer’s patches: Lymphoid nodules in the lamina propria of the ileum. Crypts 
contribute to vulnerability to infections.

20
RESPIRATORY SYSTEM

20. The respiratory epithelium

Ciliated pseudostratified columnar epithelium with goblet cells

- The cilia move the mucous and the trapped particles towards the oral cavity.
- Cilia continue into the respiratory portion well past the mucus producing cells to
prevent the mucus from accumulating.

- Deeper in the bronchial tree the epithelia undergoes transition.

- First to simple columnar – in the first bronchioles.
- Then to simple cuboidal – in the terminal bronchiole.
- And then to simple squamous epithelium – in the alveoli.
- The Goblet cells disappear at the level of terminal bronchioles.

The respiratory epithelium consists of 5 cell types:

Ciliated columnar cells

- Possess about 300 cilia at the apical pole.
- Cilia beat at 1000-1500 cycles per minute.
- Contains numerous mitochondria.

Goblet cells
- Unicellular mucus glands.
- Accumulated mucus at the apical pole.

Brush cells
- Columnar cells.
- Squat microvilli with filaments that stretch into the cytoplasm about 120-140
microvilli/cell: pear-shaped, wide base and narrow microvillus apex.
- High density at the bronchiolar alveolar junction, a location prominently involved
with trapping inhaled particles of airway pollutants.
- Brush cells might be involved in chemosensing or presenting AGs, thus involved in
innate immunity.

Basal cells
- Smallest, round.
- Lie on the basal lamina.
- Do not reach the apical surface of the epithelium.
- Are though to divide and differentiate into the other cell types.

Small granular cells

- Resemble basal cells.
- Have finer-like cytoplasmic extensions which reach the airway lumen.
- Lightly stained.
- Contain small granules with a dense core at the basal pole.
- Considered a population of the diffuse neuro-endocrine system.
- Release polypeptide hormones and/or catecholamines that are thought to function in
reflexes regulating the airway of vascular calibers.
- Abundant cytoplasm.

21
- Related with neuro-epithelial bodies.
- Silver staining.

21. Nasal cavity mucosa

- The nasal mucosa consists of a pseudostratified columnar ciliated epithelium, which

numerous goblet cells supported by a richly vascular lamina propria containing serous
and mucus glands.
- These features reflect the functions of the nasal mucosa, processes that begin in the
nasal cavities and continue throughout the conducting portion of respiratory tract.
- Particulate matter in inspired air is trapped in a thin layer of surface mucus secreted
by the goblet cells of the surface epithelium and the mucus glands of the lamina
propria.
- Coordinated, wave-like beating of cilia propels mucus with trapped particles
towards the pharynx where it is swallowed and inactivated in the stomach.
- The entrance to the nasal cavity, the nasal vestibule, is lined by skin, which has short
coarse hairs called Vibrissae, which trap large particles before they, reach the nasal
mucosa.
- The temperature of inspired air is adjusted to that of the body by heat exchange
between the air and blood flowing in a rich plexus of thin-walled venules in lamina
propria.
- A mucosa similar to this also lines the nasopharynx + paranasal sinuses + auditory
tubes.

Nasal cavity
- Is divided into 2 mucus-coated passages by a midline septum  Hyaline cartilage.
- The cavernous nasal cavity or fossa is separated into 2 cavities by the median nasal
septum, which is bony.
- Nostrils = Choanae
- Nasal cavity is divided into 3 functional parts:
- The vestibule: about 1.5 cm.
- Walls – of cartilage.
- Lined with a keratinized stratified epithelium  stiff hairs, which filter large
particles + sebaceous glands.
- The lamina propria attached to the periosteum
- Has serous and mucus glands.
- Veins from thin-walled, dilated sinuses/cavernous bodies – become engorged
and leaky during infections and allergies. The lamina propria becomes
distended swelling of the mucus membrane, and this results in restriction of
the air passage.
- Extending from both lateral walls are 3 curved plates of bone: superior + middle +
inferior conchae.
- The superior choanae is covered by olfactory epithelium.
- The middle and inferior conchae are covered by respiratory epithelium
- The choanae function by: creating turbulence or air + increase contact are
between the air and epithelium (allowing mucus to trap particles, moistening
and warming of the air).

22
22. Olfactory mucosa

The olfactory epithelium:

- Covers: The roof of the nasal cavities and extends laterally overlying the superior
conchae and medially over the superior portion of the nasal septum.
- Is composed of pseudostratified epithelium without goblet cells.
- Includes 3 cell types: olfactory (sensory) cells + supporting cells + basal cells.

- Olfactory (sensory) cells are bipolar neurons.

- The dendrite reaching the surface forms an apical vesicle from which
extend modified olfactory cilia – non-motile bathed by serous secretions of
glands from the lamina propria.
- Un-myelinated axons from the basal portion of the cells, which aggregate as
small nn.
- Supporting cells provide physical and metabolic support.
- Columnar, more apical nuclei.
- Contain a yellow lipofuchsin, which gives the mucosa its natural yellow-
brown color.
- Have luminal microvilli.
- Basal cells
- Small, round cells though to give rise to new supporting and sensory cells.

Lamina propria
- LCT, beneath the epithelium
- Un-myelinated olfactory nn
- Blood vessels
- Lymphatic vessels
- Branched tubulo-alveolar glands: Bowman’s glands  its secretion is a solvent for
the odoriferous substances.

23. Trachea – general organization

- Is a short tube (10-12 cm) with a diameter of about 2 cm.

- It bifurcates into the 2 main bronchi.
- 10-12 C-shaped ring of hyaline cartilage, like stacked horseshoes.
- The posterior opening of the cartilage rings are bridged by fibro-elastic ligament and
smooth trachealis muscle.

Epithelium
- The respiratory epithelium of the trachea is tall, pseudostratified and ciliated and
contains goblet cells.
- In response to the irritation of tobacco smoke, the epithelium commonly undergoes
morphological change to a stratified squamous form with consequent loss of Ciliary
action, metaplasia. (Ciliary activity is essential for continuous movement of the
glandular secretions towards the pharynx.)
- The tracheal epithelium is supported by a basement membrane.

Lamina propria
- LCT with many elastic fibers, which condense at the deep border of the lamina
propria to form an elastic membrane.

23
- Highly vascular.
- Diffuse lymphoid tissue.

Submucosa
- Underlying the lamina propria.
- Contains muco-serous glands (submucosal glands), which decrease in number in the
lower parts of the trachea.
- Supplement the secretions of cells in the epithelium.
- More numerous in the posterior part.
- Diffuse lymphatic tissue and lymphatic nodules.
- The submucosa ends with the perichondrium of tracheal cartilages.

Tunica fibro-musculo cartilaginea

- The trachea if a flexible tube of fibro-elastic tissue and cartilage, which permits
expansion in diameter and in length during inspiration, and passive recoil during
expiration.
- The trachea is stabilized by 16-20 C-shaped cartilages (hyaline cartilage covered by
perichondrium).
- These rings support the mucosa and prevent the tracheal collapse during inspiration.
- Bands of smooth muscle cells, trachealis muscle + CT + fibers, join the free ends of
the rings posteriorly  contraction of trachealis muscle decreases tracheal diameter,
thus assists in increasing intra-thoracic pressure during coughing.
- Longitudinal collagen and elastic fibers (annular ligaments) link the individual
cartilages – allow both the lengthening and shortening of the trachea (swallowing).

Pulmonary tree
- The trachea bifurcates at the carina, behind the sternum, to produce the 2 main
bronchi (2 on the left, 3 on the right).
- The lobar bronchi again bifurcate, and so on for about 23-24 generations.
- The first 16 or so of these generations act merely as conduits for passage of gas, and
together constitute the conducting tone.
- Beyond the 16th generation, alveoli start to appear in the airway walls, becoming
more numerous until the process terminates in an acinus consisting of a large
collection of alveoli:
- 2 primary bronchi enter the lungs.
- 3 intrapulmonary/lobar bronchi on the right, 2 on the left.
- Bronchioles  terminal bronchioles.

Drawing

24
24. Primary bronchi – general histology

- The basic structure of the bronchi is similar to that of the trachea, but differs in
several details:
- The respiratory epithelium is less tall and contains fewer goblet cells
- The goblet cells have darkly stained, granular cytoplasm.
- The lamina propria is denser with a large quantity of elastin in its more
superficial layers
- The lamina propria is separated from the submucosa by a discontinuous layer
of smooth muscle which become more prominent progressively in smaller
airways – also contains lymphoid nodules (BALT).
- The submucosal layer contains fewer sero-mucus glands.
- The cartilage framework is arranged into flattened, interconnected plates
rather than discrete C-shaped rings as in the trachea.

- The main bronchi  lobar bronchi  segmental bronchi.

- The bronchi are conductive structures of a size down to about 1 mm.
- Bronchial branches are accompanied by branches of the pulmonary a, n and lymph
vessels.
- The bronchi usually travel in inter-segmental and interlobular sheaths of CT.

25. Intrapulmonary bronchi – general histology

- The mucosa similar of that of trachea

Respiratory epithelium
- The bronchial epithelium is pseudostratified; the bases of all the cells extending
down to the basement membrane, although not all the cells reach the luminal surface.
- The ciliated cells have large nuclei, which stain poorly.
- Goblet cells stain most strongly due to their content of mucus.

Lamina propria
- Contains a layer of smooth muscle, which becomes more prominent as one
approaches the respiratory portion.
- Contains elastic fibers.
- Contains lymphoid nodules – bronchi associated lymph tissue (BALT).
- Contains mast cells – containing darkly stained granules, which contain histamine
and heparin. When AG-AB complexes are formed on their cell membranes, they
release histamine  smooth muscle constriction and vasodilation  mucosal
swelling. (In bronchioles these phenomena  asthma)

- The submucosa presents glands.

- The cartilage
- Encircle completely the lumen of the large bronchi.
- Forms isolated plates around the entire circumference, in the small bronchi.
- As the bronchi diminish in diameter, the structure progressively changes to more
closely resemble that of large bronchioles.
- In tertiary, segmental bronchi:
- The respiratory epithelium is tall columnar, with little pseudo-stratification,
less goblet cells.

25
 - Lamina propria is thin, elastic and completely encircled by smooth muscle in
a spiral manner – this arrangement permits contraction during expiration.
- The submucosa has less sero-mucus glands, they are rarely found in small
airways.
- The submucosa merges with the surrounding adventitia and with the lung
parenchyma.
- The cartilage framework is reduced to few irregular plates.
- BALT.

26. Bronchioles – general histology

- Bronchioles are the terminal segments of the conducting portion: intralobular

airways.
- Diameter is less than 1 mm.
- Have no cartilage support.
- The bronchiole supplies a pulmonary lobule.
- Mucosa
- Respiratory epithelium undergoes transition: pseudostratified to simple
ciliated columnar with only scattered goblet cells
- Lamina propria: the layer of smooth muscle is relatively thicker than in the
bronchi and under the control of autonomic NS + rich in elastic fibers.
- The smooth muscle layer is disposed in a spiral manner like that of the
bronchi.
- Glands, lymphatic nodules and cartilage are absent.
- The total cross-sectional area of all bronchioles combines is far greater than that of
the rest of the conducting passages combines, thus the tone of the bronchial smooth
muscle effectively controls resistance to airflow within the lungs.
- Instability of the bronchial smooth muscle leading to contraction and consequent
narrowing is a central feature of the disease, Asthma.

27. Terminal bronchioles – general histology

- The last segments of the conducting portion.

- The smallest diameter passages of the purely conducting portion of the respiratory
tree. Further bronchioles, beyond this, become increasingly involed in gaseous
exchange.
- Each terminal bronchiole divides to form short, thinner-walled branches called
respiratory bronchioles. Their walls contain a small number of single alveoli.
- Pulmonary acinus = 1 terminal bronchiole + all the respiratory bronchioles and
alveoli associated.

Epithelium
- Devoid of goblet cells
- Ciliated cuboidal cells
- Few non-ciliated cells = Clara cells

Clara cells
- Dome-shaped at the apical surface without cilia.
- Basally located nucleus with indentation.
- A few membrane-bound vesicles at the apical pole.

26
- Produce a mucus-poor, watery proteinaceous secretion, helping with clearance and
reduction of surface tension in small airways.

Lamina propria
- Thick layer of smooth muscle.
- Elastic fibers.

- Glands, lymphatic nodules and cartilage are absent

Drawing

28. Respiratory bronchioles – general histology

Bronchiolar function
- Respiratory bronchioles are the first part of the bronchial tree that allows gas
exchange.
- Respiratory bronchioles constitute a transitional zone in the respiratory system; they
are involved in both air conduction and gas exchange. They have a narrow diameter
and are lines by the cuboidal epithelium.
- The epithelium of the initial segments of the respiratory bronchioles contains both
ciliated cells and Clara cells.
- Distally, Clara cells predominate.
- Occasional brush cells and dense-core granule cells are also present along the length
of the respiratory bronchioles.
- Alveoli are the sites at which air leaves and enters the bronchiole to allow gas
exchange.

Alveoli are the site of gas exchange.

- The surface area available for gas exchange is increased by the lung alveoli.
- Alveoli are the terminal air spaces of the respiratory system and are the actual sites
of gas exchange between the air and the blood.
- Each alveolus is surrounded by a network of capillaries that brings blood into closed
proximity to inhaled air inside the alveolus.
- About 150-250 million alveoli are found in each adult lung; their combined internal
surface area is approximately 75 m2, roughly the size of a tennis court.
- Each alveolus is a thin-walled polyhedral chamber approximately 0.2 mm in
diameter that is confluent with an alveolar sac.

27
- Alveolar ducts: are elongated airways that have almost no walls, only alveoli, as
their peripheral boundary. Rings of smooth muscle are present in the knob-like inter-
alveolar septa.

- Alveolar sacs: are spaces surrounded by clusters of alveoli. The surrounding alveoli
open into these spaces.
- Alveolar sacs usually occur at the termination of an alveolar duct but may occur
anywhere along its length.
- Alveoli are surrounded and separated from one another by an exceedingly thin CT
layer that contains blood capillaries.
- The tissue between adjacent alveolar air spaces is called the alveolar septum or
septal wall.
- Alveolar epithelium is composed of type I and type II alveolar cells and occasional
brush cells.

29. The intra-alveolar septum

- Between the adjacent alveoli the wall or alveolar septum consists of the flattened
epithelial lining cells of each alveolus separated by capillaries and delicate collagen
fibers and elastin, which condenses around the opening of each alveolus, and merge
with those around the opening of adjacent alveoli to form a fine, 3-dimensional
supporting meshwork for the whole lung parenchyma.
- The alveolar septa contain small openings about 8 nm in diameter  alveolar pores,
which permit equalization of pressure between alveoli, and provide a collateral air
circulation should a bronchiole become obstructed.
- 2 layers of squamous epithelium.
- Interstitium: CT + collagen and elastic fibers + macrophages + fibroblasts + a rich
network of blood capillaries  All these structures comprises the inter-alveolar
septum.
- Alveolar pores have a diameter of 10-15 micrometer.

30. Blood-air barrier

- Thickness: 0,1-0,5 micrometer

- Composed of
- The cytoplasm of the alveolar cells (type I squamous)
- The fused basal lamina of the opposed alveolar and endothelial cells
- The cytoplasm of the endothelial wall.

Drawing

28
32. Alveolar cells

The cells of the intra-alveolar septum + alveolar cells

Endothelial cells
- Continuous and non-fenestrated
- very thin – efficient gas exchange
- The nucleus: small and elongated, and the organelles are clustered
- In the flattened portion of the cell, many pinocytotic vesicles can be found

Alveolar cells
- Type I (squamous) alveolar cells  Pneumocytes I
- Form the thin squamous epithelium of the alveoli
- Cover more than 90% of the alveolar surface
- Very thin – about 25 nm
- The organelles are grouped around the nucleus
- In the thin portion of the cell, many pinocytotic vesicles can be found
- Form the blood-air barrier
- Their tight junctions minimize the leakage of interstitial fluid into the
alveolar lumen
- Type II (great) alveolar cells  Pneumocytes II
- Cuboidal cells intermixed among the type I cells with tight and desmosomal
junctions.
- Usually found in groups of 2-3 at the point where the alveolar walls unite
- Cover only 5% of the alveolar surface
- Are capable of regeneration and replacement of type I cells after injury
- Resemble secretory cells: well developed RER + Golgi complex +
mitochondria

- Contain lamellar bodies:

- Diameter of 1-2 micrometer
- Their content appear as concentric lamellae
- Contain phospholipids + GAG + proteins
- Released at the apical pole providing an EC alveolar coating – pulmonary
surfactant

Interstitial cells
- Fibroblasts: synthesize GAG, elastic fibers, collagen I and III
- Contractile cells: bound to the basal surface of the alveolar epithelium, and contract
to reduce the volume of the alveolar lumen
- Mast cells

Alveolar macrophages
- Macrophages = dust cells
- Small percentage of the cells in alveoli, represent the main cellular host defense
mechanism
- Part of the mononuclear phagocyte system, and are derived from blood monocytes
- The only alveolar clearance mechanism for particulate material that has escaped the
tracheo-bronchial filters.
- To leave the lungs, these cells migrate to the nearest bronchiole and exit via the

29
muco-ciliary escalator:
- Release many factors including some that recruit neutrophils, and other,
which interact with T lymphocytes for cell-mediated immune response.
- AP = alveolar pore

Drawing

33. Pulmonary surfactant

- Formed by 2 layers:
- An aqueous protein-containing phase covered by
- Phospholipid film of dipalmitoyl-phosphatidyl-choline (DPPC)
- It is constantly being turned over
- Reduces the surface tension of the alveolar cells:
- Reduces the work of breathing
- Prevents the alveolar collapse during expiration
- Type II alveolar cells are responsible for surfactant production.
- Most of the type II Pneumocytes are surrounded by a basement membrane and only
a small portion of their surface is exposed directly to the alveolar space, where it
exhibits microvilli associated with surfactant secretion.
- The surfactant cell contains: RER + free ribosomes + moderate numbers of
elongated mitochondria
- The membrane bound lamellar bodies of Pneumocytes II are composed mainly of
PL, particularly DPPC. This is released by exocytosis, spreading out over the alveolar
surface where it combines with other carbohydrate and protein-containing secretory
products (some maybe derived from Clara cells), to form a tubular lattice of
lipoprotein  tubular myelin.
- In the event of 2 alveolar surfaces coming together, this overcomes the effect of
surface tension, which would otherwise cause them to adhere  this allows for
normal inflation of the alveoli at birth and for the re-inflation, which collapse after
airway obstruction.

30
ORAL CAVITY

34. The lining mucosa: localization, structure and function

Location
- Cheeks + lips + alveolar floor + ventral face of the tongue + soft palate

Mucosa
- Non-ker. str. sq. epith.
- Basal layer
- Intermediate layer
- Superficial layer
- Other cell types: melanocytes (basal layer) + Langerhan’s cells + Merkel cells +
intraepithelial lymphocytes

Lamina propria
- LCT: blood and lymph vessels + free nerve endings and Meissner corpuscles
- Papillae: rare and shallow

Submucosa
- LCT: collagen fibers + elastic fibers
- Minor salivary glands:
- cheeks + tongue + lips + soft palate
- tubulo-acinary + serous + mucous + mixed
- Blood vessels + nerves
- Isolated sebaceous glands (Fox-Fordyce?)
- Is absent on the ventral face of the tongue.

Function
- Forms an important protective barrier between external environment of the oral
cavity and internal environment of the surrounding tissues.
- Resistant to pathogenic organisms that enter oral cavity and to indigenous
microorganisms residing there as microbial flora.
- Epithelial cells + migratory neutrophils and saliva  contribute to maintaining the
health of the oral cavity and protecting the oral mucosa from bacterial, fungal and
viral infections.
- These protective mechanisms includes: several salivary antimicrobial peptides + the
defensins expressed in the epithelial + the defensins expressed in neutrophils + the
secretory IgA.
- If a person has immunodeficiency or undergoing antibiotic therapy, in which the
balance between microorganisms and protective mechanisms is disrupted: oral
infections are rather common.

35. The masticatory mucosa: localization, structure and function

- Location: gums and hard palate

Mucosa
- Keratinizing or para-keratinizing str. sq. epith.
1) Basal layer

31
2) Sinous layer
3) Granular layer
4) Superficial layer

Lamina propria
- Papillary layer
- Frequent and deep papillae
- Blood vessels and nerve endings
- Reticular layer
- DICT
- Gums: collagen fibers insert into the alveolar bone periosteum.

Submucosa
- Only in the hard palate
- Anterior: adipose tissue
- Posterior: minor salivary glands, which is continuous with the submucosal layer of
the soft palate.

36. Lips and cheeks: general structure

This topic includes both lips + cheek (transition part)

Has 2 surfaces:
- Outer: keratinized, hair follicles, sebaceous glands
- Inner: non-keratinized, oral surface (few salivary glands, ducts into surface
epithelium), DICT + LCT, blood vessels (which give the red color)

- Muscle: striated in one direction, no adipocytes or glands, but may have many blood
vessels.

Found between the 2 surfaces:

- Muscle: orbicularis oris muscle  lip
- Link between internal + external surfaces  the lip it-self.
- If no link: might be cheek or lip, hard to tell (in microscopic slides)

Vermillion border
- The transmission of keratinization (so, border between lip and adjacent normal
skin), which represents the change in epidermis.
- Going from highly keratinized external skin to less keratinized internal skin.
- There are never hair follicles present, but some sweat glands may be present.
- Blood vessels are close to surface (visible because of the red color)

37. Hard and soft palate: general structure

Hard palate

- Is a thin, horizontal bony plate of the skull, located in the roof of the mouth.
- Formed by palatine process of the maxilla and horizontal plate of palatine bone.
- It forms a partition between the nasal passages and the mouth. The anterior portion
of the roof of the hard palate is the ruggae, which are the irregular ridges in the
mucous membrane that help facilitate the movement of food backwards to the

32
pharynx.
- This partitioning is continued deeper into the mouth by a fleshy extension called the
soft palate.
- Important in feeding and speech. The interaction between tongue and hard palate is
essential in the formation of certain speech.

Soft palate

- Also known as the muscular plate. It is the soft tissue constituting the back of the
roof of the mouth.
- The palate is distinguished from the hard palate at the front of the mouth in that it
doesn’t contain bone.
- Soft palate is moveable, consisting of muscle fibers sheathed in mucous membrane.
- It is responsible for closing off the nasal passages during the act of swallowing, and
also for closing off the airway.
- During sneezing, it protects the nasal passages by diverting a portion of the excreted
substance to the mouth.
- The uvula hangs from the end of the soft palate (which is not actually involved in
snoring processes).
- A speech sound made with the middle part of the tongue (dorsum) touching the soft
palate is known as the velar consonant.
- It is possible for the soft palate to retract and elevate speech to stearate the oral
cavity (mouth) from the nasal cavity in order to produce the oral speech sounds.
- If this separation is incomplete, air escapes through the nose, causing speech to be
perceived as nasal.

38. The tongue: general structure, innervation

- Parenchymous structure with 2 surfaces: ventral (downwards) + dorsal (upwards).

- Also has tip + 2 edges + root (base)

Muscular core
- Striated muscle fibers with perpendicular orientation.
- Belongs to extrinsic muscles: genioglossus, hyoglossus, and, intrinsic: lingual.
- Interspersed minor salivary glands + adipose cells + numerous blood vessels and
nerve fibers

Ventral face
- Lining the oral mucosa

Dorsal face
- Specialized mucosa
- Lingual papillae

- The tongue is a muscular, parenchymous organ covered by oral mucosa which is

specialized for manipulating food, general sensory reception and the special sensory
function of taste.
- A V-shaped groove, the sulcus terminalis, demarcates the anterior 2/3 (body + tip)
of the tongue from the posterior 1/3 (base).
- The mucosa of the anterior 2/3 is formed into papillae of 4 types, the most

33
numerous, the filiform papillae.
- Among them are scattered the small red globular fungiform papillae.
- 12-20 large circumvallate papillae form a row immediately anterior to the sulcus
terminalis and these papillae contain most of the taste buds and foliate papillae.
- The lingual papillae are projections of the tongue surface with a CT core on the
dorsal surface.

Function
- Taste perception: sweet + sour + bitter + salty
- Mastication + movements + speech

- The body of the tongue consists of a mass of intercalating bundles of skeletal muscle
fibers, which permit an extensive range of tongue movements.
- The mucous membrane covering the tongue is firmly bound to the underlying
muscle by a dense, collagenous lamina propria, which is continuous with the
epimysium of the tongue muscle.
- The base of the tongue (posterior):
- Non-ker. str. sq. epith.
- Crypts present
- Lingual tonsils: diffuse and nodular lymphoid tissue
- Prominent.
- Nerve supply:
- Motor: XII
- General sensitivity:
- Anterior 2/3: V
- Posterior 1/3: IX
- Sensory:
- Anterior 2/3: VII
- Posterior 1/3: IX

Sensory innervation
- VII and IX
- Subgemmal + perigemmal + intragemmal nerve plexuses.

39. The specialized mucosa: localization, structure and function

- Numerous mucosal irregularities and elevations: lingual papillae, cover dorsal

surface of the tongue, anterior to the sulcus terminalis.
- Lingual papillae and their associated taste buds constitue the specialized mucosa of
the oral cavity. There are 4 types:

Papillae
- Filiform papillae:
- Numerous, smallest, conical.
- Elongated projections of CT that are covered by ker. str. sq. epith.
- No taste buds.
- Serve only a mechanical role.
- Distributed over entire anterior dorsal surface with their tips pointing
backward.
- Appear to form rows that diverge to the left and right from the midline, and

34
 that parallel the arms of the sulcus terminalis.
- Fungiform papillae:
- Mushroom-shaped projections, isolated, spread among filiform papillae.
- CT with abundant blood vessels.
- Rare taste buds, but they are present in the epithelium.
- Located on the dorsal surface of the tongue.
- Only visible to the unaided eye as small spots.
- Tend to be more numerous at the tip of the tongue.
- Foliate papillae:
- Consist of parallel rows ridges separated by deep mucosal clefts Aligned at
right edges to the long axis of the tongue. They occur in the lateral edge of the
tongue.
- CT core + blood vessels.
- Contain taste buds, most frequent in young people.
- In aged individuals, they may not be recognized, but are easily found in
young individuals, on the posterior lateral surface of the tongue, where many
taste buds are present in the epithelium of the facing walls of neighboring
papillae.
- Small serous glands empty into the clefts.
- Circumvallate papillae:
- Large, dome-shaped, located in mucosa just anterior to the sulcus terminalis
- 8-12, diameter: 0,01-0,2 cm
- Each papilla is surrounded by a deep cleft (Vallum) that contains numerous
taste buds.
- Ducts of the lingual salivary glands: von Ebner. They empty their serous
secretion into the base of the clefts. This secretion flushes material from the
cleft to enable the taste buds to respond rapidly to changing stimuli.
- Very frequent taste buds

40. The taste buds: localization, structure and function

- Present on fungiform (about 250/papilla), foliate and circumvallate papillae.

- Can also be present on soft palate + glosso-pharyngeal arches + posterior wall of
pharynx + face of epiglottis.
- Oval (80x50 micrometers), pale staining bodies that extend through the thickness of
the epithelium.
- A small opening onto the epithelial surface at the apex of the taste bud: taste pore.

There are 3 different types of taste buds:

Sensory (neuroepithelial cells)

- Most numerous cells in the taste bud.
- Elongated cells extend from the basal lamina of the epithelium to the taste pore,
through which in the apical surface of each cell, microvilli extend.
- Near apical surface they are connected to neighboring neuroepithelial or supporting
cells by tight junction.
- At base, they form synapse with the process of afferent sensory neurons of the facial
(VII), glossopharyngeal (IX) or vagus (X) nerves.
- The turnover time of neuroepithelial cells is about 10 days.

35
Support cells
- Less numerous.
- Also elongated cells, those extend from the basal lamina to the taste pore.
- Like neuroepithelial cells they contain microvilli on their apical surface and possess
tight junctions, but they do not synapse with the nerve cells.
- The turnover time of supporting cells is also about 10 days.

Basal cells.
- Small cells located in the basal portion of the taste bud, near basal lamina.
- They are stem cells for the other 2 cell types.

Function
- Taste perception: sweet + sour + bitter + salty

41. Dental enamel: general structure

- The hardest substance in the body: 96-98% calcium hydroxyapatite, which is the
mineral part.
- Acellular mineralized tissue that covers the crown of the tooth; once destroyed it
cannot be replaced.
- A mineralized material derived from epithelium: more mineralized and harder than
any other mineralized tissue in the body because of the high percentage of calcium
hydroxyapatite.
- Enamel that is exposed and visible above gum line: clinical crown.
- The anatomical crown describes the entire tooth that’s is covered by enamel, some
of which is below the gum line.
- Enamel varies in thickness over the crown and may be as thick as 2,5 mm on the
cusps (biting and grinding surfaces) of some teeth.
- Enamel layer ends at the neck or cervix of the tooth at the cemento-enamel junction.
The root of the tooth is covered by cementum, a bone-like material.
- Enamel is composed of rods that span the entire thickness of the enamel layer. The
non-stoichiometric carbonated calcium hydroxyapatite enamel crystals that form the
enamel are arranged as rods and are 4 mm wide and 8 micrometers high  represents
the entire layer from the dentino-enamel junction to the enamel surface.
- Enamel crystals are primarily oriented parallel to the long axis of the rod within the
head, and in the tail more obliquely.
- The limited spaces between rods are also filled with enamel crystals.
- Striations observed on enamel rods (contour lines of Retzius) may present evidence
of rhythmic growth of the enamel in the developing tooth.
- The substance in saliva that affect teeth include: digestive enzymes, secreted AB and
a variety of inorganic components.
- Enamel is produced by ameloblasts (before tooth eruption: because once erupted
you cant restore it and make the blasts produce enamel again) of the enamel organ.
Dentin is produced by neural crest derived odontoblasts of the adjacent mesenchyme.
- Odontoblasts: cylindrical cells, reparative function.
- It is formed by enamel prisms and inter-prismatic substance.
- Mineralization defects may occur: enamel tufts, spindles or lamellae.

- Inorganic component, 98%.

- Calcium hydoxyapatite crystals (the mineral part)

36
 - Hardest substance of the body.
- Composed of enamel rods (formerly called prisms) and inter-rod enamel.
- Striae of Retzius – series of lines, having a brown appearance. They are
produced by air in the interprismatic spaces.
- Organic compound, 2%, ECM:
- Enamel specific proteins: amelogenins, ameloblastins (developing enamel) +
enemalins and tuftelins + protease.
- Produced by ameloblasts during tooth histogenesis.

42. Amelogenesis

- By ameloblasts – cells of ectodermic origin, that cover the dentin during crown
formation.
- Columnar, polarized cells.
- Synthesis organelle: RER, Golgi complex and mitochondria
- Secretory granules that store proteins form enamel matrix.
- Apical extensions – adamantine prism around them and determine the orientation of
hydroxyapatite crystals

1) Secretory step
- Protein synthesis  organic matrix (amelogenins, enameline, ameloblastins)

2) Maturation step (matrix mineralization)

- Massive influx of calcium and phosphate
- Water and protein resorption (especially amelogenins).

- Ameloblasts secrete enamel only during tooth development.

- Enamel doesn’t regenerate after eruption, but ion exchanges between enamel and
oral environment exist.

43. Dentin: general structure

- Calcified material forms most of the tooth substance.

- Lies deep to the enamel and cementum. Contains less hydroxyapatite than enamel
but more than is found in bone and cementum.
- Dentin may be primary, secondary or tertiary.

Odontoblasts

- Produce and secrete Predentin – organic matrix of the dentin.

- 1 cell layer that lines the tooth pulp. Cells establish tight junctions.
- Large columnar cells arranged in epithelial sheet, along the junction between dentin
and pulp, all the way down to the root apex.
- Rich in ER and Golgi apparatus, especially during primary dentin formation, to give
it a high secretory capacity. (First collagenous matrix to form predentin, then mineral
to form the complete dentin)
- Apical odontoblasts processes with microtubules, microfilaments and secretory
granules.

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Inorganic component 70%
- Calcium hydroxyapatite crystals
- Growth lines von Ebner glands
- Dentin tubules (Tomes canaliculus)
- Interglobulary spaces Germak.
Organic compound 30%
- ECM  collagen + GAG + odontoblasts

Contains 2 unique proteins:

- Dentin phosphoprotein (DPP)
- Rich in aspartic acid and phosphoserine
- Binds large amounts of calcium
- Involved in initiation of mineralization and control of mineral size and shape
- Dentin sialoprotein (DSP)
- Rich in aspartic and glutamic acid, serine, glycine, chondroitin 6-sulfate
- Also involved in mineralization process

It has: dental pulp + dentinal tubules + dentinal matrix + odontoblasts + dentin + cell-
free zone + cell-rich zone + predentin + odontoblasts (both inactived + activated):

Drawing

44. Odontoblasts and dentin formation

- Dentin is produced by odontoblasts.

- Dentin is the first mineralized component of the tooth.
- Outermost dentin: mantle dentin, which is formed by subondontoblastic cells. They
produce bundles of collagen fibers (von Korff’s fibers).
- Odontoblasts differentiate from cells at the periphery of the dental papilla.
- Progenitor cells have the appearance of typical mesenchymal cells (i.e. do not
contain little cytoplasm).
- During differentiation into odontoblasts, the cytoplasmic volume and organelles
characteristic of collagen-producing cells increase.
- Cells form a layer at the periphery of the dental papilla and secrete organic matrix of
dentin (or predentin), at their apical end (away from the dental papilla).
- Predentin thickens and odontoblasts move or are displaced centrally.

38
- A wave of mineralization follows the receding odontoblasts, which makes up the
dentin.
- As cells move centrally, odontoblastic processes elongate. The longest are
surrounded by mineralized dentin.
- With time, dentin immediately surrounding the dentinal tubule becomes more highly
mineralized. This is the more mineralized sheath, called the peritubular dentin.
- Remainder of dentin is called the intertubular dentin.

45. Cementum: general structure

- Cementum covers the root of the tooth

- 2 types of cementum:
- Cellular: usually forming the outer layer
- Acellular: usually forming the inner layer
- Root is the part of the tooth that fits into its alveolus/socket in maxilla of mandible.
- Cementum = thin layer of bone-like material, secreted by cementocytes, cells that
closely resemble osteocytes  65% mineral (like bone).
- Cellular cementum: Lacunae/canaliculi in cementum contain cementocytes and their
processes, respectively. They resemble those structures in bone that contain
osteocytes and osteocyte processes.
- Unlike bone, cementum is avascular. Canaliculi in cementum don’t form an
interconnecting network. A layer of cementoblasts is seen on outer surface of
cementum, adjacent to periodontal ligament.
- Collagen fibers (Sharpey’s fibers), those project out of the matrix of cementum and
embed in the bony matrix of the socket wall form the bulk of the periodontal
ligament.
- Elastic fibers are also a component of the periodontal ligament.
- This mode of attachment of the tooth in its socket allows slight movement of the
tooth to occur naturally and forms basis of orthodontic procedures used to straighten
teeth and reduce malocclusion of the biting and grinding surfaces of maxillary and
mandibular teeth.
- During corrective tooth movements, the alveolar bone of the socket is resorbed and
resynthesized, but the cementum is not.

46. Dental pulp

- Young CT, mesenchymal, originating from the dental papilla.

- Stellate cells, with long branching processes.
- Lymphocytes + plasma cells + macrophages + eosinophils.
- Ground substance (jelly like).
- Blood vessels + nn.
- Weil space: area without cells, with von Korff collagen fibers that extend into the
dentin.
- Odontoblasts.

- Dental pulp cavity is a CT compartment bounded by tooth dentin.

- Central pulp cavity is a space within a tooth that is occupied by dental pulp, a LCT
that is richly vascularized and supplied by abundant nn.
- Pulp cavity takes a general shape of the tooth: blood vessels + nn, enter the pulp
cavity at the tip (apex) of root at apical foramen.

39
- Blood vessels and nn extend to the crown of the tooth. Here, they form vascular and
neural networks beneath and within the layer of odontoblasts.
- Some bare nerve fibers also enter the proximal portions of the dentinal tubules and
contact odontoblasts processes.
- Odontoblast processes are believed to serve a transducer function in transmitting
stimuli from the tooth surface to the nn in the dentinal pulp.
- In teeth with more than one cusp, pulpal horns extend into the cusps, which contain
large numbers of nerve fibers.
- More of these fibers extend into dentinal tubules at other sites.
- Because dentin continues to be secreted throughout life, the pulp cavity decreases in
volume with age.

47. Periodontium: components, structure and function

- Formed by all tooth supporting tissues: alveolar bone + cementum + gingiva +

periodontal ligament.
- The alveolar processes of maxilla and mandible contain sockets or alveoli for the
roots of the teeth.
- Alveolar bone proper: A thin layer of compact bone, which forms the wall of the
alveolus and is the bone to which the periodontal ligament is attached. The rest of the
alveolar process consists of supporting bone.
- Surface alveolar bone usually shows regions of bone resorption and bone deposition,
particularly when a tooth is being moved.
- Peridontal disease usually leads to loos of alveolar bone, as does the absence of
functional occlusion of a tooth with its normal opposing tooth.
-The periodontal ligament is fibrous CT joining tooth to its surrounding bone. This
ligament is also called the periodontal membrane, which provide tooth attachment
(fixation) + tooth support + bone remodeling (during movement of a tooth) +
proprioception + tooth eruption.

Histological sections show both DCT + LCT.

DCT:
- Contains collagen fibers, fibroblasts (elongated parallel to the long axis of
the collagen fibers).
- Fibroblasts also contain internalized collagen fibrils that show that they
produce collagen fibrils and resorb collagen fibrils, thereby adjusting
continuously to the demands of tooth stress and movement.
LCT:
- Contains blood vessels + nerve endings.
- In addition to fibroblasts and thin collagenous fibers, the periodontal
ligament also contains thin, longitudinally disposed oxytalan fibers.
- They are attached to bone/cementum at each end. Some appear to be
associated with adventitia of blood vessels.

- Gingiva is a specialized part of oral mucosa, the mucus membrane part, called gums,
which is located around the neck of the tooth.
- Firmly attached to the teeth and no underlying alveolar bony tissue.
- Composed of 2 parts:
- Gingival mucosa: synonymous with the masticatory mucosa
- Junctional epithelium/attachment epithelium: adheres firmly to the tooth.

40
- A basal lamina-like material is secreted by the junctional epithelium and adheres
firmly to the tooth surface.
- The cells then attach to this material via hemidesmosomes.
- Basal lamina and hemidesmosomes  form epithelial attachment.
- In young individuals, this attachment is to the enamel. In older individuals where
passive tooth eruption and gingival recession expose the roots, the attachment is to the
cementum.
- Above attachment of epithelium to the tooth is a shallow crevice, the gingival
sulcus, which is lined with crevicular epithelium that is continuous with the
attachment epithelium.
- Periodontium refers to all tissues involved in attachment of a tooth to the mandible
and maxilla  crevicular + junctional epithelium, cementum, periodontal ligament
and alveolar bone.

41
DIGESTIVE SYSTEM

48. General histological structure of the alimentary canal

- Portion of alimentary canal extending from proximal part of esophagus to distal part
of anal canal. A hollow tube of varying diameter.
- The tract is essentially a muscular tube lined by a mucous membrane.
- The arrangement of the major muscular component remains relatively constant
throughout the tract whereas the mucosa shows marked variations in the different
regions of the tract.

The tube has the same basic structural organization throughout its length, with 4
distinct functional layers:

Mucosa
- Lining epithelium, underlying lamina propria, chorion, thin smooth muscle layer,
muscularis mucosa, which produces local movement and folding of the mucosa.
- At 4 points along the tract the mucosa undergoes abrupt transition from 1 form to
another:
- The esophageo-gastric junction
- The gastro-duodenal junction
- The ileo-caecal junction
- The recto-anal junction

Submucosa
- This layer of loose collagenous tissue supports the mucous and contains the larger
blood vessels, lymphatics, nn, Meissner nervous plexus, sometimes glands, DICT

Muscularis propria
- The muscular wall proper consists of smooth muscle which is usually organized as
an inner circular layer and an outer longitudinal layer.
- The action of the 2 layers, at right angle to one another, is the basis of peristaltic
contraction.
- The 2 layers are separated by CT, containing Auerbach myenteric plexus.
- Cajal cells
- Circular layer thickens to form sphincter.

Adventitia
- This outer layer of LCT conducts the major vessels and nn. In obese individuals it
contains a large amount of adipose tissue.
- The gut lies within the abdominal cavity (peritoneal cavity).
- Serous membrane of simple sq. epith., the mesothelium and a small amount of
underlying CT.
- An adventitia consisting only of CT is found where the wall of the tube is directly
attached/fixed to adjoining structures (i.e. body wall and certain retro-peritoneal
organs).

Muscularis externa = muscularis propria + adventitia

-  Cajal cells
- Elongated cell processes.

42
- Located intra-pleural, between smooth muscle fibers or in perimysium.
- Connected with nerve endings and smooth muscle fibers.
- Diagnosed based o morphological and ultrastructure criteria.

Functions:
- Passage
- Lubricate
- Digest
- Signal and communicate
- Protect

Mucosal forms:
- Protective:
- In the oral cavity, pharynx, esophagus and anal canal.
- Surface epithelium: Str. sq. epith. (may be keratinized in people with
coarse diet).
- Secretory:
- Only in the stomach
- Consists of long, closely packed tubular glands
- Absorptive:
- The entire small intestine
- The mucosa is arranged into finger-like projections called villi with
intervening short glands, crypts.
- In the duodenum, some crypts extend through the muscularis mucosa
to form submucosal mucus glands.
- Absorptive + protective
- In the large intestine
- The mucosa is arranged into closely packed straight tubular glands,
consist of cells specialized for water absorption and mucus secreting
goblet cells which lubricate the passage of feces.

49. The histological particularities of the esophageal duct

- The esophagus is the most muscular segment of the GIT.

- Length: about 25 cm.
- Courses through neck, mediastinum, where it’s attached to adjacent structures by
CT. When it enters abdominal cavity, it is free for 1-2 cm and then enters stomach.
- Lumen normally collapsed by tonus of muscularis externa, throwing mucosa into
longitudinal folds.
- Conforms to typical 4-layered alimentary tube structure.
- Non-ker. str. sq. epith. protects against abrasion.
- Esophageal glands of submucosa produce mucus that, with saliva, lubricates the
surface.
- Esophageal cardiac glands of lamina propria near stomach, secreting neutral mucus
to protect against gastric acid reflux.
- Muscularis externa is thick with striated muscle in upper portion to propel food
rapidly (peristalsis).

Modification of subendothelial layers

- Muscularis mucosa

43
 - Unique, single longitudinal layer, sparse superiorly but thickest of
GIT dorsally.
- Muscularis externa
- Upper 1/3 striated muscle fibers
- Lower 1/3 smooth muscle fibers
- Middle 1/3 mixed muscle fibers
- Outer CT layer
- Adventitia above diaphragm
- Serosa below diaphragm

Mucosa: epithelium, lamina propria, muscularis mucosa, cardiac glands

Submucosa: submucosal glands, Meissner nervous plexus
Muscularis externa: Auerbach nervous plexus
Adventitia/serosa

- Esophageal varicosities, submucosal vv form porto-caval anastomoses.

- Portal hypertension  highly induces esophageal varicosities. Rupture 
hemorrhage.
- Esophageal strictures
- Achalasia: lack of relaxation of smooth esophageal muscle
- Neoplasic infiltration
- Extended sclerosis

50. The general histological structure of the stomach

Functions
- Dilated part of GIT, serving as a reservoir for the accumulation of a meal, received
as bolus via esophagus.
- Moiling and partial digestion forms chyme, which is passed in controlled amounts
into the duodenum.
- Generally not absorptive, but some water and salts are absorbed (alcohol and aspirin
via damaging mucus sheet and surface epithelium).
- Simple columnar epithelium, underlying lamina propria, which connects to the
glands at the base, which are simple tubular branched glands.
- Histologically it is divided into 3 regions, but in gross anatomy it is divided into 4
regions: cardia, fundus, body and pylorus.
- Histologically:
- Cardiac region (cardia) – part of the esophageal orifice, which contains
cardiac glands.
- Pyloric region (pylorus) – part proximal to pyloric sphincter, which contains
pyloric glands
- Fundic region (fundus) – largest part of stomach, situated between cardia and
pylorus, and contains fundic and gastric glands.

Mucosa
- Glandular epithelia, lamina propria
- Appears pale, glistering and greyish-pink, thrown into ruggae when empty.
- Covered with a continuous sheet of visible mucus: lubricates and protects against
acid.
- The mucosa of the entire stomach has a tubular glandular form but there are 3

44
distinctly different histological zones:
- The cardia, is a small area of predominantly mucus-secreting glands,
surrounding the entrance of the esophagus.
- The mucosa of the fundus and the body consists of glands that secrete acid-
peptic gastric juices and protective mucus.
- The glands of the pylorus secrete mucus, and associated endocrine cells
secrete the hormone gastrin.
- Muscularis mucosa

Submucosa
- Relatively loose and distensible, contains blood vessels

Muscularis externa
- Inner oblique muscle fibers
- Middle circular muscle fibers
- Outer longitudinal muscle fibers

Serosa
- Thin, peritoneal surface
- Glands of the gastric mucosa:
- Open into bottom of gastric pits: cardiac glands + fundic glands + pyloric
glands
- Lie within lamina propria, fully occupying it except for occasional lymph
nodes.

51. The fundic (gastric) gland – structure, function

- Most abundant (15 million), occupy most of gastric mucosa.

- Simple columnar epithelium goes down to lamina propria and at the base the glands
begin that are present throughout gastric mucosa.
- 4 cell types within glands produce nearly all gastric enzymes (and some mucus) and
then secreted into the stomach.
- Straight, simple, branched, tubular glands, which have a wavy appearance, have
relatively long necks, and, shorter, wider bases. The base divides into 2-3 branches
and become a little coiled near the muscularis mucosa.
- Cells of gastric glands produce about 2L of gastric juice every day.
- Several open into a single gastric pit.
- Gastric pit is shorter, glands are longer. Pit/gland ratio  1:4 or 1:3 ratio.
- Chief cells (peptic cells), mucus cells, parietal (oxyntic) cells (between mucus and
zymogen cells) and APUD cells.

Gland
- Gastric pit: surface mucus cells
- Neck: parietal, mucus neck cells, APUD
- Base: chief cells, parietal cells, APUD
 synthesize pepsin: the pepsinogen remains inactive until it reaches the stomach
lumen where it is activated by the gastric juices.

- Chief peptic cells:

- Basally located nucleus

45
 - Granular and basophillic cytoplasm, with RER, ribosomes
- Secrete pepsinogen, renin and weak lipase
- Parietal cells:
- Round, large, central nucleus
- Eosinophillic (pink) cytoplasm
- Numerous mitochondria – highly metabolically active
- Secrete hydrochloric acid and intrinsic factor.
- Mucus neck cells
- Secrete soluble mucus
- Enteroendocrine cells (APUD)
- GIT hormones into lamina propria
- Stem cells
- Give rise to mature cells, replacing old ones

52. Types of cells in gastric mucosa

1) Mucosal neck cells

- In the necks of the glands, interspersed with parietal cells.
- Shorter with less mucus and longer liver (about 1 week) than surface mucosal cells.
- Vagal stimulation causes secretion of acidic soluble mucus only during stomach
activity.

2) Mucus secreting cells

- Cover the laminal surface of the stomach and line the gastric pits into which the
gastric glands open.

3) Parietal oxyntic cells

- Secreted hydrochloric acid and intrinsic factor.
- Interspersed among glands of neck and base.
- Bulging and unique staining give glandular epithelium a beaded appearance.
- Most numerous of the middle portion of the gland’s neck.
- Eosinophillic cytoplasm with a large, central, round, bi-nucleated cells, which
appear triangular in cross sections with apex toward lumen of gland and base resting
on basal lamina.
- In electron microscope, you can see an extensive IC canalicular system that
communicates with lumen of gland. Numerous microvilli of surface of canaliculi.

4) Chief (zymogenic) cells

- Typical protein secreting cells.
- Cuboidal or low columnar cells.
- Located in deepest part (base) of fundic glands.
- Condensed, basally located nuclei.
- Strongly basophillic, granular cytoplasm in the basal area (large content of RER and
ribosomes).
- Apical cytoplasm is eosinophillic with zymogen granules, which contain enzyme
precursors.
- You can easily differentiate between apical and basal poles in H&E stain.
- Secrete pepsinogen (pepsin precursor).

5) Enteroendocrine cells (APUD, G cells)

46
- Occur at the level of fundic glands, but most common at base.
- Small cells, resting on basal lamina, often not reaching gland lumen, or sending a
slender extension to reach it.
- Cytoplasm appears clear in H&E stain.
- Secrete products into either lamina propria or underlying blood vessels. Found at
every level of fundic gland.
- Produce gastrin, secretin, cholecystokinin (CCK) and GTP.
- Amine precursor uptake decarboxylation APUD.
- APUD cells are rich in specific secretory granules.

6) Stem cells
- 1 stem cell gives rise to all phenotypes of glandular cells.
- Produce new crypts, repairs entire crypt, give rise to gastric carcinoma.

53. The general histological structure of the small intestine segments

- The SI comprising the duodenum, jejunum and ileus is the principal site for
absorption of digestion products from the GIT.
- Simple columnar epithelium, which make protrusions that are covered by villae.
- Duodenum: first, shortest and widest part. Begins at pylorus of stomach and ends at
duodeno-jejunal junction.
- Jejunum: 6 m long, begin at duodeno-jejunal junction, constitutes the upper 2/5 of
SI. Gradually changes morphologic characteristics to become ileum.
- Ileum: about 4 m, continuation of jejunum, constitutes the lower 3/5 of SI. It ends at
ileo-cecal junction, the union of distal ileum and cecum.
- 4 factors combine to provide an enormous surface area:
- The SI is extremely long (> 6 m in humans)
- The mucosa and submucosa are thrown into circulatory arranged folds called
Plicae circulares or Valves of Kerckring which are particularly numerous in
the jejunum.
- The mucosal surface is made up of numerous finger-like projections called
villi, where the mucosa between the bases of the villi is formed into crypts,
called crypts of Lieberkuhn.
- The muscularis mucosa lies immediately beneath the mucosal crypts and separated
the mucosa from the submucosa.
- The vascular submucosa extends into, and forms the core of the Valves of
Kerckring.
- Inner circular and outer longitudinal layers of the muscularis are responsible for
continuous peristaltic activity of the SI.
- The peritoneal aspect of the muscularis is invested by the loose collagen serosa,
which is lines on its peritoneal surface by mesothelium. A prominent feature of the SI
are 200 or so lymphoid aggregations known as Peyer’s patches within the lamina
propria  positive diagnosis for ileum.

Mucosa
- Highly modified.
- Laminal surface covered with finger-like villi.
- Enterocytes paneth cells.
- Enteroendocrine cells, M cells and Goblet cells.
- Lamina propria = LCT + Lieberkuhn glands + muscularis mucosa.

47
Submucosa
- LCT, blood vessels, lymphatic vessels, lymph nodules and maybe some adipose
cells in duodenum and jejunum.
- Protrusions into lumen form valves: Valves of Kerckring (=mucosa + submucosa,
make up the valves from protrusions).
- Duodenum is distinguished by presence of Brunner’s gland, occupying most of the
submucosa.

Muscularis externa
- Inner circular smooth muscle fibers for mixing.
- Outer longitudinal for peristalsis, and, also Auerbach nervous plexus.

Serosa
- The peritoneum, outermost layer, because the SI is intraperitoneal.

GALT
- = gastric tract associated lymphoid tissue
- In lamina propria of SI, most obvious in ileum because of Peyer’s patches.
- Peyer’s patches  immune-competent lymphoid nodules with T and B lymphocytes
and suppressor cells.
- The Peyer’s patches is an important site for the induction of the primary mucosal
immune response in the gut.

- The immune protection in the SI is insured mainly by IgA secreting plasmocytes.

- Submucosa of SI
- Duodenum Brunner’s glands – branched tubular glands with alkaline
secretion, to protect against hydrochloric acid.
- buffer for acidic gastric chyme
- Insure the optimum pH for pancreatic enzyme activation
- Muscularis externa
- Inner circular muscle layer – segmentation contractions – mix the chyme and
favor absorption
- Outer longitudinal muscle layer – for peristaltic movement.

- Duodenum jejunum  ileum

- Circular folds diminish
- Villi change from ridge/leaf like to finger-like
- Goblet cells increase in number
- Lymphoid tissue increases
- Peyer’s patches (aggregate follicles) in lamina propria of ileum, with
overlying microfold cells.

54. Specialized structures of intestinal mucosa and submucosa, involved in

increasing the absorptive surface

- Histological elements:
- Kerckring valves
- Villi
- Microvilli

48
Kerckring valves
- They are circular folds.
- Mucosa and submucosa thrown into cresentic folds, which project into lumen.
- Not obliterated by distension (like ruggae are).
- Begin about 5-6 cm distal to pylorus, reach maximal size and density distal to the
major duodenal papilla.
- Large and numerous in jejunum, diminishing almost completely over length of
ileum.
- Increase the luminal surface area 3x.

Villi
- Cover entire mucosal surface, 10-40/mm2.
- Large and numerous in jejunum, smaller and fewer in ileum.
- Vary in shape from broad and ridge like (proximal duodenum) to leaf-like (distal
duodenum and proximal jejunum) to finger-like (distal jejunum and ileum).
- Increase the luminal surface area 8-10x.

Microvilli (striated border)

- Evident by electron microscope on luminal surfaces of enterocytes covering villi,
and, give the apical pole a brush border.
- Remarkably uniform with a density of about 200/mm2.
- Increase luminal surface area 20x, an area sufficient to absorb 9-14 L/day.
- The smallest augmenting feature is the most effective in increasing absorptive area.

- Structure of microvilli is centered by a core of actin filaments.

- Core of actin filaments stabilized by ABP (fimbrin and fascin).
- Attached to cell membrane by myosin-solidar movement.
- Extended in cytoplasm – terminal web.
- A helical arrangement of myosin molecules binds the actin bundle to the inner
surface of the filament.

55. The general structure of a villus

- Epithelium: simple columnar, consisting of: enterocytes 90%, goblet cells 9,7% and
enteroendocrine cells 0,3%.
- Core of villus is an extension of the lamina propria, containing fibroblasts, smooth
muscle cells, lymphocytes, plasma cells eosinophils, macrophages, and netweork of
fenestrated blood capillaries located just beneath the epithelial basal lamina.
- Villi = a core of LCT covered by simple columnar epithelium.

Villus vs. crypts:

Villus:
- Function: absorption and secretion
- Vascularity: more vascular, fenestrated capillaries
Crypts:
- Function: cell production and secretion
- Vascularity: less vascular, non-fenestrated capillaries

49
Drawing

- The intestinal villi are lines by simple columnar epithelium, which is continuous
with that of the crypts.
- The predominant cell type: enterocytes – tall columnar, basally located nucleus,
involved in membrane digestion and absorption.
- Mucus secreting goblet cells are scattered.
- Mitotic activity of stem cells, at the base of crypts produces a continuous supply of
new cells which progress up the villi where they mature before degenerating  the
entire epithelial lining is replaced every 3rd day.
- At the base of the crypts – clusters of paneth cells (exocrine protein secreting cells).
- The lamina propria extends between the crypts and into the core of each villus, and
contains a rich vascular and lymphatic netweork, into which digestive products are
absorbed.
- Muscularis mucosa  beneath the base of the crypts.

56. The general structure of a Lieberkuhn gland

- The Lieberkuhn gland (intestinal crypt) are simple tubular glands within lamina
propria in SI and colon.
- They descend from villus base to muscularis mucosa, further increasing epithelial
surface (but not necessarily area available for absorption).
- Single layer of epithelial cells lines crypts and covers villi  a continuous sheet,
constantly renewed (every 3rd day).
- Renewal start in crypt and ends at villus tip, where cells enters lumen.
- 17 billion cells/day are lost.

Epithelium
- Simple columnar epithelium consisting of:
- Undifferentiated stem and intermediate cells
- Stem cells in the base of crypt, capable of cell division.
- Differentiate (via intermediate forms) into 4 cell types:
1) Enterocytes
2) Goblet cells  proceed to villus
3) Enteroendocrine cells

50
 4) Paneth cells, protein secreting
Has eosinophillic, cytoplasmic granules  remain in crypt

- The enterocytes contain digestive enzymes, which digest specific food while they
are being absorbed through epithelium. Enzymes: sucrose, peptidases maltase, lactase
and intestinal lipase.
- Also, new epithelium is formed here, which is important because the cells at this site
are continuously worn away by passing food. The basal portion of the crypt contains
multipotent stem cells.
- During mitosis, one of the 2 daughter cells remains in the crypt as an stem cell,
while the other differentiates and migrates up the side of the crypt and into the villus.
- Goblet cells are also produces in this fashion.

Lamina propria
- Mainly in which glands are embedded.
- Lymphatic nodules (major part of GALT).
- Aggregation nodules of ileum  Peyer’s patches

Muscularis mucosa
- Lies immediately beneath the base of the crypts.

Drawing

57. Types of cells in intestinal mucosa

At lest 5 different types of cells are found in the intestinal mucosal lining. Mature
cells of intestinal epithelium are found in both intestinal glands and surface of villi.

Enterocytes
- Columnar absorptive cells with microvilli.
- Glycocalyx
- Covers microvilli
- Made of glycoprotein enzymes secreted by enterocytes (for example

51
 enterokinase) for terminal digestion of protein and sugars at the site of their
absorption.
- Junctional complexes bind adjacent cells (prevent direct access of luminal contents
into the intercellular space).
- Mitochondria are abundant within enterocytes reflecting the high-energy demands of
the process of absorption (direct passage of low molecular weight digestion products
across the luminal plasma membrane).
- Between the bases of the enterocytes are intercellular clefts into which chylomicrons
are first passed to the lacteals (lymph).
- Lymphocytes are commonly found in the intercellular clefts between enterocytes
where they play an important part in the immunological defense of the tract.
- Close proximity of blood capillaries to enterocyte basement membrane.
- The Glycocalyx of the enterocyte microvilli is unusually prominent. It provides
protection against auto digestion and acts as the site for absorption of pancreatic
digestive enzymes.
- Endocytic vesicles are often seen between the bases of microvilli and membranous
vesicles are common in the superficial cytoplasm.
- The main feature of the basal enterocytic cytoplasm is numerous free ribosomes,
SER, mitochondria, and membranous vesicles, containing lipoprotein droplets for
exocytosis into the intercellular cleft.

Goblet cells
- Unicellular glands interspersed among absorptive cells.
- Cell organelles located basally (stem), stored mucigen droplets apically.
- Secrete layer of mucous covering Glycocalyx.
- Lubricates and is a barrier to noxious agents.

Paneth cells
- Located in the base of the crypts.
- Involved in antibacterial protection:
- Digest cell walls of certain bacteria and also phagocytize.
- Appear to regulate normal bacterial flora of small intestine
- L-defensins, which is involved in cytotoxic lymphocytic defense.

Enteroendocrine DNES cells

- Protein secreting cells.
- Concentrated in lower portion of crypts but migrate onto villi.
- Release hormones to coordinate functions of the gut, liver and pancreas.
- Pancreatic and gallbladder activity (CCK and secretin).
- Gastric secretion and mobility (motilin).
- GIP – stimulates insulin secretion.
- Somatostatin and histamine – paracrine activity (local effect in bloodstream).
- Several peptides secreted by nerve cells located in the submucosa and
muscularis externa: neurocrine hormones, represented by VIP, bombesin and
enkephalins.

Microfold (M) cells

- Convey microorganisms and other macromolecules from intestinal lumen to Peyer’s
patches.
- Modified enterocytes (epithelial cells) covering Peyer’s patches.

52
- Have microfolds rather than microvilli on the apical surface. They take up
microorganisms and macromolecules from lumen in endocytic vesicles.
- M cells are AG- transporting cells. Vesicles are transported to the baso-lateral
membrane, where they are being discharged into epithelial intercellular space in the
vicinity of CD4 T-lymphocytes.
- Substances that gain access to the body from intestinal lumen via M cells come into
contact with cells of the immune system as they reach the baso-lateral surface. AG
that reaches lymphocytes in this manner, stimulate a response in the GALT.

Stem cells
- At the base of the Lieberkuhn crypt.
- Capable of cell division into the other 4 cell types.

Intermediate cells
- Constitue most of the cells found within intestinal stem cell (located in lower half of
intestinal gland). They are capable of cell division and usually undergo 1-2 divisions
before they become committed to differentiation into either absorptive or goblet cells.
- They have short, irregular microvilli with long core filaments extending deep into
apical cytoplasm, numerous macular (desmosomal) junctions with adjacent cells.
- Small mucin-like secretory granules form a column in center of cytoplasm.
- Intermediate cells that are committed to becoming goblet cells develop a small,
rounded collection of secretory granules just beneath apical plasma membrane.
- Intermediate cells that are committed to becoming absorptive cells lose the secretory
granules and begin to show concentrations of mitochondria, RER and ribosomes in
apical cytoplasm.

58. General histological structure of colonic wall

- Comprises cecum with its projecting vermiform appendix, colon, rectum and anal
canal.
- Colon is further subdivided on the basis of its anatomical location into ascending,
transverse, descending and sigmoid colon.
- 4 layers characteristic of the alimentary canal are present throughout. However,
several distinctive features exist at the gross level:

- The principal functions of the LI are the recovery of water from the liquid residue of
the contents of the SI and the propulsion of increasingly solid feces to the rectum
prior to defecation.
- The muscular wall is consequently thick and capable of powerful peristaltic activity.
It has inner circular muscle layer and outer longitudinal muscle layer.
- In the rectum, the longitudinal layer doesn’t completely surround the tract. It forms
3 separate longitudinal bands called Teniae coli.
- In the colon and cecum (longitudinal layer of muscle cells concentrated in to teniae,
which divides wall in-between into Haustra coli).
- Omental appendices are small, fatty projections of serosa, found on outer surface of
colon.
- In the mucosa, neither valves of Kerckring (plicae circulares) nor villi are present.
- Consistent with its functions of water absorption and fecal lubricating, the mucosa
consists of absorptive cells and mucus secreting goblet cells.
- The goblet cells are arranged into closely packed straight tubular glands, an

53
arrangement which enhances the functional surface area. These glands are analogous
with crypts of Lieberkuhn.
- The epithelium undergoes continual turnover at the luminal surface, the cells being
replaced by mitosis at the base of the glands.
- The thick glandular mucosa is folded in the non-distended state (not plicae
circulares).
- Immediately above the anal valves, the mucosa forms longitudinal folds: Columns of
Moragni.
- Muscularis mucosa – prominent feature of LI mucosa.
- The colonic wall contains numerous leukocytes, including lymphocytes, as a
protection from ingress of microorganisms.
- Glands are covered by simple columnar epithelium, and goes into lamina propria.
Beneath is the corion (where Lieberkuhn glans are located). Beneath the corion is he
muscularis mucosa.
- Crypts of Lieberkuhn – simple tubular glands with simple columnar surface
epithelium.
- Absorptive cells + goblet cells + stem and intermediate cells.
- The submucosa, patho-physiologically: diverticulosis, polyposis.

59. The histological structure of the appendix

- Cecum forms blind pouch just distal to ileo-cecal valve.

- Appendix is a thin, finger-like extension of this pouch.
- Cecum looks like the rest of the colon, appendix differs.
- Appendix uniform layer of longitudinal muscle in the muscularis externa.
- Most important feature of appendix: large number of lymphatic nodules, which
extend into submucosa.
- Large amounts of lymphoid tissue (nodules) in mucosa/submucosa decreases with
age.
- Mucosal glands are much less closely packed than in LI.
- The lymphoid tissue form follicles often containing germinal centers. These follicles
bulge into the lumen and like the follicles of Peyer’s patches are invested by simple
epithelium of M cells, which presumably facilitate sampling of AG in the
appendicular lumen.
- The appendix contains GALT.
- No teniae (longitudinal layer is continuous).
- Patho-physiology:
- Normally, appendix is lost and the appendage is filled with scar tissue.
Blockage of opening between appendix and cecum (usually due to scarring)
build up of appendicis (inflammation of appendix).
- Appendix is also a common site for carcinoid (type of tumor originating
form enteroendocrine cells lining mucosa).

54
Drawing

55
LIVER, PANCREAS AND SALIVARY GLANDS

60. The Glisson capsule and the portal space

- The liver is an encapsulated organ – Glisson’s capsule.

- It’s a thin, but tough, collagenous capsule, which is invested in the external surface
of the liver, a single layer of mesothelial cells.
- When you feel pain in upper right quadrant, this capsule swells.
- Fine connective septas form lobules.
- Intralobular, fine network of reticular fibers, which at the periphery become
continuous with the Glisson’s capsule.

- The portal space is at the periphery of the classical hepatic lobule. It contains the
portal triad, which includes:
- Interlobular vein
- Interlobular artery
- Interlobular bile duct

- 1 or more lymphatic vessel

- Non-myelinated nervous fibers.
- The portal lobule has a triangular shape and a portal space in the center, with a
central vein in each angle.

Drawing

61. Connective tissue of liver

- Small amount
- Found in:
- Glisson’s capsule
- Liver hilum
- Connective septa (organ compartmentalization)
- Surrounds blood vessels, nn and bile ducts
- In the lobule you find reticular fibers, which sustain the parenchyma and
maintain sinusoid capillaries open.

- Hepatocytes regeneration:
- Great power regeneration  cellular hyperplasia and hypertrophy
- When aggression repeats:
- Hepatocytes regeneration
- High production of CT  results in hepatic fibrosis, first in portal

56
 spaces. The CT produces forms as irregular connective septa, which
will lead to loss of normal organ architecture.

62. Liver vascularization and innervation

- The liver vascularization is important because it constitutes 25% of the heart flow.
- It has a double vascularization:
- Functional vascularization  portal vein:
- 75% of the hepatic blood volume.
- Carries to the liver: nutrients and toxic substances absorbed through
the GIT + hemoglobin degrading products from spleen + pancreatic
endocrine secretion.
- Nutritive vascularization  hepatic artery
- 25% of the hepatic blood volume.
- Brings the oxygenated blood to the liver.

Hepatic artery vs. Portal vein

- Capillaries of hepatic artery - Capillaries of portal vein
(portal space) (sinusoids) (intralobular)

- The hepatic portal vein and hepatic artery branch repeatedly within the liver, their
terminal branches running within the portal tracts.
- Blood from both systems then runs between the branching plates of hepatocytes in
the sinusoids, which converge to drain into a terminal hepatic (centrilobular) venule.
- These drain to intercalated vv and hence to the hepatic vein, which drains into the
inferior vena cava.

- Innervation: sympathetic – hepatic plexus (from coeliac plexus), and,

parasympathetic – anterior posterior vagal trunks.
- Lymphatic vascularization: There are no lymph capillaries in the lobule, but they are
well developed in extralobular spaces.

63. Architectural units of the liver parenchyma

- Formed of hepatocytes – 75%

- 20-30 micrometers in diameter
- 1-2 nuclei
- Acidophillic cytoplasm
- Glycogen or lipid inclusions.
- Other types f cells in the liver: Ito cells + pit cells + oval cells.
- The arrangement of hepatocytes within the liver parenchyma:
- They form flat, anastomosing plates usually only one cell thick between
which blood passes towards the terminal hepatic venule.
- The sinusoids are lined by a discontinuous layer of cells, which do not rest on
basement membrane and which are separated from the hepatocytes by a narrow space,
the Space of Disse. This drains into the lymphatics of the portal triad.

Space of Disse
- 150-200 A.

57
 - Contains: microvilli of the hepatocyte + reticular fiber bundles + Ito cells +
Pit cells + hematopoietic cells (numerous in fetal life, rare in adults).

Ito cells – fat storing cells

- 1/20-25 hepatocytes .
- Star-shape, rare organelles, numerous lipid inclusions.
- Roles: collagen type III secretion + deposits exogenous A vitamin + possible
hematopoietic role in fetal life.
- Phenotype modification in pathological conditions: adipocytes, fibroblasts,
and hematopoietic cells.

Pit cells
- Rare in humans.
- Cytoplasm granules of 300 nanometer in diameter.
- Endocrine function + variety of circulating lymphocytes + NK cells.

64. The hepatocyte – structure, ultrastructure and functions

- 80% of the liver’s cells are hepatocytes

- Life span: 150 days
- 20-30 micrometer in diameter
- Polyhedral shape  3 types of surfaces:
- Sinusoidal surface – vascular pole
- Canalicular surface – bile pole
- Intercellular surface

In LM:
- Nucleus: central, euchromatic, frequently polypoid, 25% of cells are binucleated and
the number increases by age, regeneration process
- Cytoplasm: eosinophillic, Berg basophillic bodies, numerous inclusions

In EM:
- RER: towards the vascular pole, continuous synthesis of export proteins, various
plasmatic proteins (albumins, coagulation factors, globulins, fibronectin).
- Polyribosomes: synthesis of endogenous proteins
- SER: dispersed
roles: metabolization of glycogen + cholesterol synthesis + detoxification +
inactivation + bile synthesis
- Mitochondria: dispersed, number and dimension varies with localization
- Golgi complex: Perinuclear, 50/cell, roles: protein excretion + VLDL formation +
lysosome formation.
- Lysosomes: towards the bile pole, Catabolization of exogenous substances and old
organelles, deposit of ions – increase in hemochromatosis and hemosiderosis
- Peroxisomes (dense bodies): towards the bile pole, H2O2 metabolism,
gluconeogenesis, purines metabolism – uric acid, alcohol metabolism, beta-oxidation
of long chain fatty acids, formation of acetylaldehyde
- Glycogen inclusions: vary with nutrition, period of the day
- Lipid inclusions: towards the vascular pole, transitory, alcoholism – fatty liver
- Plasma membrane - specialized domains:
- vascular pole:

58
 - 75% of the membrane surface
- Microvilli, increases surface G folds
- Separated from the wall of the sinusoidal capillary by the
Perisinusoidal space of Disse
- bile pole
- 15% membrane surface
- Adjacent membranes:
- Microvilli: enzyme activity: ATPase, alkaline phosphatase,
and specific glycoproteins
- Actin filaments: in cytosol close to the canaliculi
- Tight junctions: above and beneath canaliculi

- The classical hepatic lobule

- Form polyhedral prism (2mm/0,7 micrometer)
- Plates of hepatocytes in a radial disposition, perforated, ramified,
anastomosed and separated by anastomosed sinusoidal capillaries
- Central vein

65. Perisinusoidal cells: structure, ultrastructure and function

- Present in the Perisinusoidal space of Disse.

- Ito cells + Pit cells + hematopoietic cells (numerous in fetal life, rare in adults –
except chronical anemia).

Ito cells
- Fat storing cells
- 1/20-25 hepatocytes
- Star shape, rare organelles, and numerous lipid inclusions.
- Roles:
- Collagen type III secretion
- Deposits exogenous A vitamin
- Possible hematopoietic role in fetal life
- Phenotype modification in pathological conditions:
- Adipocytes + fibroblasts + hematopoietic cells

Pit cells
- Rare in humans
- EM – granules of 30 nm in diameter
- Role:
- Endocrine function
- Variety of circulating lymphocyte – NK cells
- Occasional fibroblasts with the capacity to store lipids are found in the space of
Disse between the sinusoidal lining cells and the hepatocytes

Endothelial cells
- Nucleus: flat with nucleolus bulging in lumen
- Enzymes with transport role: ATP-ases + alkaline phosphatase
In EM:
- Few cellular organelles
- Many grouped fenestrae without diaphragm

59
 - Many pinocytosis vesicles
- Gap junction

Kupffer cells
- Components of the mononuclear phagocytic system
- Found at the junction of 2 sinusoid capillaries
- Star shaped, bulging into lumen, capable of division
- In LM: may see them with vital dyes (Tryptan blue)
- In EM: rich in mitochondria, RER, lysosomes, residual bodies, phagolysosomes
- Role: export protein synthesis (5%) + immunity (surface receptors of Ig, interleukin,
cytokine, TNF secretion, phagocytic activity)

66. Liver sinusoids and sinusoidal cells: structure, ultrastructure and function

- The sinusoid capillaries are rich intralobular net.

- They contain a mixture of arterial and venous blood  hepatocytes never have a
completely oxygenated blood (from the arterial blood)
- Blood flow direction: lobule periphery  lobule center
- Sinous shape, lumen diameter: 9-12 micrometers.
- Wall: discontinuous endothelia with endothelial cells + Kupffer cells, and, a basal
lamina with reticular fibers.

Endothelial cells
- Flat, with nucleus bulging in lumen.
- EM: few cellular organelles, many grouped fenestrae without diaphragm, many
cytosis vesicles and gap junctions.
- Enzymes with transport role: ATPase, alkaline phosphatase and Kupffer cells.
- Components of the mononuclear phagocytic system.
- Found at the junction of 2 sinusoid capillaries.
- Star-shaped, bulging in lumen.
- Capable of division.
- LM: with vital dyes, Tryptan blue
- EM: rich in mitochondria, RER, lysosomes, residual bodies, phagolysosomes.
- Role:
- Export protein synthesis (5%)
- Immunity: surface receptors for IgG, interleukin, cytokine, TNF secretion,
phagocytic activity (increase of spleen resection amplifies and becomes essential).
- With the spleen, Kupffer cells participate in the removal of spleen erythrocytes and
other particulate debris from the circulation.

67. Bile canaliculi: structure, ultrastructure and function

- Bile: liver exocrine secretion product.

- Produced by hepatocytes + Kupffer cells.
- Bile flow direction: center of hepatic lobule  periphery of lobule.
- The bile canaliculi form an anastomosing network within the plates of hepatocytes.
- The canaliculi have no discrete structure of their own but consist merely of fine
channels formed by the plasma membranes of adjacent hepatocytes.
- Bile canaliculi of adjacent hepatocyte plates merge to form canals of Hering before
draining into the bile ductules of the portal tracts.

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- The hepatocyte plasma membranes forming the walls of the canaliculi contain the
enzyme ATPase which suggests that bile secretion is an energy-dependent process.
- Within each hepatocyte plate, the canaliculi form a regular hexagonal network
reminiscent of chicken wire, each hexagon endorsing a single hepatocyte.

Bile canaliculus
- Diameter: 0.5-1.5 micrometer.
- Initial segment of bile duct system.
- They don’t have their own wall  space delimited by membranes of 2 hepatocytes.
- Form a net between hepatocytes.

Hering canaliculus
- Diameter: <15 micrometer.
- In close relations with hepatocytes in terminal plate.
- They have their own walls
- Simple cuboidal / simple squamous epithelia.
- Reticulin fibers.

68. Bile ducts: structure, ultrastructure and function

Intrahepatic bile ducts

- Intralobular ducts
- Bile canaliculus
- Hering canaliculus
 Initial segment of the bile duct. They don’t have their own wall but spaces,
which are delimited by membrane of 2 hepatocytes.
- Extralobular ducts
- Perilobular bile ducts
- Interlobular bile ducts
- Lobar hepatic ducts
 In LM: small cavities between neighboring hepatocytes, where they form a
net between these hepatocytes.
 Found in portal spaces
 Structure: simple cuboidal /columnar epithelia with microvilli and basal
membrane, with a CT rich in elastic fibers.
- Hering bodies:
- Diameter: <15 micrometers
- In close relationship with their own wall: simple cuboidal/squamous
epithelia with reticular fibers.

Extrahepatic bile ducts

- Common hepatic duct
- Cystic duct
- Choledocus duct

- Extrahepatic bile ducts

- Structure:
1) Mucosa
- Simple columnar epithelia with mucus cells.

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 - Chorion rich in: elastic fibers + lymphatic infiltrates + mucus tubulo-
acinar glands.
- Particularities:
Cystic duct  spiral folds with muscular axis (Heister spiral
valve).
Choledocus duct  endocrine cells (somatostatin).
2) Muscularis layer
- Initially a discontinuous layer.
- Particularities: in choledocus duct the layer becomes thick, forming
Oddi sphincter.
3) Serosa

69. The gall bladder: structure, ultrastructure and function

- Mucosa
- Fold with LCT from lamina propria, pseudoglandular aspect.
- Simple columnar epithelium, with mucus secreting cells and cells involved
in ion transport.
- Loose submucosa  elastic fibers + blood and lymph vessels.
- Lamina propria: LCT, many elastic fibers, and rich capillary network.
- Tunica muscularis: fine, smooth muscle fibers in various directions.
- Serosa/Adventitia: thick collagenous tissue, conveying larger lymphatic and blood
vessels.
- Gallbladder seen in EM):
- The microvilli on the surface of the cell and the secretory granules
containing mucus.
- The epithelial cells transport NaCl through lumen to adjacent CT.
- Water flows passively, causing the bile to become concentrated.

- The gallbladder is a pear-shaped, distensible, muscular sac, which has a capacity to

store about 50 ml in humans. It is attached to the visceral surface of the liver.
- It is a blind pouch that leads via a neck to the cystic duct. It stores and concentrates
bile. It can store and remove around 90% of the water from the incoming bile, which
results in an increase of bile salts, cholesterol and bilirubin concentrations up to 10-
fold.
- Microvilli on surface of the cell and secretory granules containing mucus are present
in the gallbladder.
- The presence of lipid in the duodenum promotes the secretion of CCK by endocrine
cells of duodenal mucosa stimulating contraction of the gallbladder and forcing bile
into the duodenum.
- Bile is an emulsifying agent facilitating the hydrolysis of dietary lipids by pancreatic
lipases.
- In the neck of the gallbladder, mucus glands are often found in the submucosa.
- Mucus may provide a protective surface film for the biliary tract.

70. Exocrine pancreas: structure, ultrastructure and function

- Exocrine portion (acini): contain secretory cells with basophilic cytoplasm

- Endocrine portion (islet of Langerhans): different types of endocrine cells are seen
in the islet.

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- N: surrounded by numerous cisternae or RER near the base of the cell
- Golgi complex: situated at apical pole of nucleus + associated with several
condensing vacuoles and numerous mature secretory (zymogen) granules
- The lumen contains proteins recently released from the cell by exocytosis.

- Each serous acinus is made up of an irregular cluster of pyramid-shaped secretory

cells, the apices of which surround a narrow lumen, which represents the terminal end
of the duct system. It also has a very broad basal surface.
- The smallest of the tributaries are known as intercalated ducts.
- Adjacent acini are separated by inconspicuous CT containing numerous capillaries.
- The intercalated ducts drain into interlobular ducts in the septa of the gland.
- The intercalated ducts are lined by simple cuboidal epithelium, which become
stratified cuboidal in the larger ducts.
- With increasing size, the ducts are invested by a progressively thicker layer of often
collagenous CT.
Serous secretory cells of acinus produce digestive enzyme precursors secreted by the
pancreas.
Acinar cells are characterized by basophilia in basal cytoplasm + acidophilic zymogen
granules in apical cytoplasm.
Zymogen granules*: most abundant.
The squamous centroacinar cells lack both ergastplasm + secretory granules stain
very lightly with eosin: helps to ID them in sections.
- The wall of the main pancreatic duct contains smooth muscle.
- Secretory cells:
- The nucleus is surrounded by numerous cisternae of RER near the base.
- The Golgi complex: is situated at the apical pole of the nucleus + associated
with several condensing vacuoles and numerous mature secretory zymogen
granules.
- The lumen contains proteins recently released from the cell by exocytosis.
- Cells similar to those are between the intercalated ducts and interlobular ducts.
- Cells lining the intercalated ducts are responsible for elaborating the water and the
component of pancreatic secretion.

*Zymogen granules contain a variety of digestive enzymes in an inactive form get

activated once they enter lumen of small intestine:
- Pancreatic enzymes can digest most food substances. The inactive
enzymes/proenzymes:
- Proteolytic endopeptidase and proteolytic exopeptidase (digest and
cleaving proteins into a.a.) + amylolytic enzymes (digest and cleaving
carbohydrates into glycogen) + lipases (digest and cleaving lipids
giving FA) + nucleolytic enzymes (digest nucleic acids producing
mononucleotides).

71. Salivary glands: structure, ultrastructure and function

- Saliva is produced by 3 pairs of major salivary glands: the parotic + submandibular

+ sublingual + numerous minor accessory glands scattered throughout the oral
mucosa (lingual + labial + buccal + molar + palatine glands).
- The minor salivary glands secrete continuously and are in general under local

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control, whereas the major glands mainly secrete in response to parasympathetic
activity, which is induced by physical, chemical and physiological stimuli.

- The glands are divided into numerous lobules.

- Each lobule contains many secretory units.
- General organization:
- Capsule: DICT + septa of CT divides into lobes + nn + blood vessels.
- In lobes: parenchyma (made of adenomers)  secreting part.
- The excretory ducts have a stratified cuboidal epithelial lining.
- The secretory lobules contain:
- Serous cells: stains strongly with H&E
- Mucus cells: almost unstained.

Adenomers
- Round structures, with tubular acinus
Serous cells

- N: basal, round, euchromatic
- C: double-stained: basophilic (basal pole) + acidophilic (apical pole)
- Form serous acini or serous demilunes
Mucus cells
- N: flattened, heterochromatic (dark N), located at base
- C: very pale (light pink), vacuolar
- Form acini
Myoepithelial cells
- Contact adenomers

Parotid gland
- Is almost solely composed of serous secretory acini, giving it a strongly stained
appearance in H&E stain.
- Produces a thin watery secretion rich in enzymes and ABs.

Submandibular gland
- Contains both serous and mucus secretory cells and produces a secretion of
intermediate consistency.

Sublingual gland
- Predominantly mucus secretory cells and produces viscous secretion.

Salivary secretory unit

- Consists of a terminal branched tubulo-acinar structure composed exclusively of
either serous or mucus secretory cells or a mixture of both.
- In mixed secretory units where mucus cells predominate serous cells often form
semilunar caps called Serous demilunes, surrounding the terminal part of mucus
acini.
- Myoepithelial cells embrace the secretory units, their contraction helping to expel
the secretory product.
- The terminal secretory units merge to form large intercalated discs, which are also
lined by secretory cells.
- The intercalated discs drain into striated ducts (large cuboidal cells).

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- Serous cells secretion
- Salivary proteins.
- Watery fluid containing inorganic ions.
- Isotonic with plasma.
- In the striated ducts, the ionic content of the secretion is modified by active
reabsorption and further secretion of ions to produce saliva, which is hypotonic with
respect to plasma.
- the ionic composition of saliva varies of different flow rates, but are generally: Na
and Cl in saliva < plasma, and, K and HCO3- in in saliva > plasma.
- Transport process in the striated ducts is facilitated by large surface area offered by
basal infoldings of lining cells and fueled by numerous associated mitochondria.

Drawing:

65
ENDOCRINE SYSTEM

72. Histological structure of the hypophysis

- = pituitary gland.
- Is a small, slightly elongated organ, approximately 1 cm in diameter, lying
immediately between the 3rd ventricle in a bony cavity in the base of the skull.
- Its hormonal secretions have as target organs other endocrine glands.
- It arises form and different embryonic rudiments:
- One is a depression in the floor of the forming brain – Neurohypophysis.
- The other is an evagination of the dorsal surface of the forming gut –
Rathke’s pouch – Adenohypophysis.
- Consequently, in the finished state, this organ has 2 parts that are distinctly different
in appearance and in nature.
- The pituitary gland is lodged in a pocket of the sphenoid bone.
- It’s surrounded by a CT capsule from dura mater  septa  lobes.
- It’s the physical and physiological ‘’meeting place’’ of the body’s 2 great systems
for responding to the environment:
- The endocrine system and the nervous system.
- The hypothalamus links the NS to the endocrine system via pituitary gland.

General histological structure:

- CT capsule – divides by this septa the gland into lobes/lobules.
- Parenchyma – groups of cells surrounded by fenestrated/sinusoid capillaries.
- CT stroma – reticular fibers and cells.
- Blood vessels
- Autonomic nerve fibers around blood vessels and secretory cells.

Drawing

73. Adenohypophysis

- Anterior pituitary
- Arises as an epithelial upgrowth from the roof of the primitive oral cavity, known as
Rathke’s pouch and comes from the gut epithelia.
- This glandular epithelium is wrapped around the anterior aspect of the posterior
pituitary.
- Several distinct parts:
- Pars distalis
- Pars intermedia

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 - Pars tuberalis  that comes to form a sort of sleeve-like covering of the
stalk.
- An opening or gap between the pars distalis and the pars intermedia: Rathke’s pouch
is the vestigial remnant of the lumen of the gut.
- The anterior pituitary has the typical structure of epithelial-derived endocrine glands
elsewhere in the body.
- It secretes both trophic and direct-action hormones:
- Trophic hormones:
- Thyroid stimulating hormone (TSH)
- Follicle stimulating hormone (FSH)
- Adenocorticotrophic hormone (ACTH)
- Luteinizing hormone (LH)
- Direct action hormones:
- Growth hormone (GH)
- Prolactin
- Hypothalamic control of anterior pituitary secretion is mediated by specific
hypothalamic releasing hormones, for example TSH-RH. An exception is prolactin
secretion, which is under the inhibitory control of dopamine.
- These releasing hormones are conducted from the median hypothalamic eminence to
anterior pituitary by a unique system of portal veins.
- The pars intermedia synthesizes and secretes melanocyte-stimulating hormone in
humans, the importance of MSH and the control of its secretion is poorly understood.

Portal circulation and the Adenohypophysis

- The Adenohypophysis receives blood from branches of the internal carotid artery.
- Hypophysial aa end in capillary beds.
- The blood in the portal circulation goes first to the median eminence of the brain,
where it feeds an extensive capillary plexus.
- Form small venules, they drain into the blood sinusoids of the Adenohypophysis.
- Transports hypophysial peptides from the hypothalamus to the hypophysis.
- Portal system: one in which the drainage from a capillary bed is immediately put
into a 2nd capillary bed.
- Functional significance: hypothalamus itself produces hormone-releasing factors,
which have as their target cells of pars distalis.

Drawing

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Pars distalis
- The most prominent area.
- Consisting of a uniform mass of cell-cords of functional cells.
- Irregularly shaped sinusoids between the cords.
- Granular cells:
- Chromophils:
- Acidophillic, produce GH and prolactin
- Basophillic, produce TSH, ACTH, FSH and LH.
- Chromophobes:
- Probably basophils that have discharged their hormones.
- Agranular cells:
- Folliculo-stellate cells which are basophillic
- Stem cells, which are chromophobes.

Cells of the anterior pituitary

- Acidophils:
- Somatotrophs: Cells responsible for GH secretion, and are the most
numerous making up almost ½ of the bulk of anterior pituitary.
- Mammotrophs, lactotrophs, prolactin secreting cells.
- Basophils:
- Corticotrophs: secrete ACTH, 20% of the anterior pituitary mass.
- Thyrotrophs: secrete TSH, 5% of the anterior pituitary mass.
- Gonadotrophs: secrete FSH and LH, 5% of the anterior pituitary mass. Has 2
distinctive cell types for each one of the gonadotrophs.

Pars intermedia
- Pressed closely up against the pars nervosa.
- Grades into the pars tuberalis without a definite boundary.
- Cells form cords between irregularly shaped sinusoids.
- Normally no acidophillic cells, only basophillic ones.
- Secretes pro-opio-melanocortin POMC – beta lipotrophin and MSH
- Remnant of the embryonic Rathke’s pouch may persist as a few small follicles.

Parts tuberalis
- Secretes gonadotrophs and corticotrophs.
- Forms ‘’sleeve’’ around the stalk of the pars nervosa itself.
- Similar to pars intermedia – small, basophillic cells.

74. Hypothalamic secretory neurons: secretion of posthypophysis and

hypophysiotropic peptides

- Functionally there are 2 types of neurons:

- Peptidergic neurons
- Neurons that secrete hypophysial peptides.

Peptidergic neurons
- Large neurons (25 micrometers)
- Cell bodies located in the paraventricular and supraoptic nuclei.
- Contain large secretory granules (100-200 nanometers).
- Secrete peptides transported to the posterior pituitary along the unmyelinated axons:

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ADH (vasopressin) + oxytocin.
- They end up in a neurovascular connection.
- The secretory granules are stored in a dilution along the axon – Herring bodies.
- Part of the axons do not reach the posterior hypophysis and discharge their secretory
products in the capillary plexus of the median eminence.

Neurons that secrete hypophysial peptides

- Small (15 micrometers).
- Contain small secretory granules (100-110 nanometers).
- Axons end up in a neurovascular connection.
- The peptides synthesized here control the secretory activity of the anterior pituitary.
- Arcuate nucleus – GH-RH + GH-IH + dopamine (for prolactin) + Gn-RH.
- Ventro-medial nucleus – Gn-RH and TRH
- Periventricular nucleus – CRH and GH-IH
- Paraventricular nucleus – TRH, CRH, Gn-RH and GH-IH
 Secretion is controlled by negative feedback – concentration of the hormone
synthesized by the endocrine gland.

75. Neurohypophysis

- Posterior pituitary = pars nervosa (derived from the brain)

- Is derived from a down-growth of nervous tissue from the hypothalamus to which it
remains joined by the pituitary stalk.
- The posterior pituitary secretes 2 hormones: ADH (vasopressin) + oxytocin (acts on
non-endocrine tissue).
- ADH is synthesized in the neuron cell bodies of the supraoptic nucleus. Oxytocin is
synthesized in those of the paraventricular nucleus of the hypothalamus.
- Bund to glycoproteins the hormones pass down the axons of the hypothalamus –
pituitary tract through the pituitary stalk to the posterior pituitary where they are
stored in the distended terminal parts of the axons.
- Release of the these hormones is controlled by nervous impulses passing down the
axons from the hypothalamus, this process is called neurosecretion.
- The Neurohypophysis consists mainly of unmyelinated nerve fibers with associated
glial elements  Pituicytes (supportive cells for the neurosecretory axons):
- Reticular fibers network
- Fenestrated capillaries
- Non-myelinated axons of neurosecretory cells, the cell bodies of which are
located in the hypothalamus.
- The stalk is hollow, and at the top it communicates with the 3rd ventricle of the
brain:
- Lined by the same glial elements – the ependymal cells
- Filled with CSF
- At the bottom it ends blindly inside the pars nervosa
- The pars nervosa and its stalk  form neurohypophysis.

Pars nervosa
- Arises as a ventral outpouching of the floor of the brain.
- It retains its connection with the brain.
- It’s a neural tissue.
- Consists of:

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 - Highly branched glial cells – Pituicytes – resident astrocytes
- Microglia
- Unmyelinated nerve fibers – axons coming from neurons located in the
hypothalamus.
- they don’t form synapses with other neurons.
- They end in contact with blood capillaries.
- Dilations along the axon known as the Herring bodies.
- The 2 hormones released are: oxytocin (synthesized in
paraventricular nucleus) + ADH (synthesized in the supraoptic nucleus).
- Damage to the supraoptic nucleus will result in Diabetes insipidus.

Pituitary adenoma
- A tumor will lead to hypersecretion – the most common cells that hypersecrete are:
- GH: leads to Giantism (childhood) or Acromegali (adulthood)
- Prolactin: hyperprolactinemia leads to infertility
- ACTH: secondary Cushing’s syndrome type symptoms
- Tunnel vision and blindness can result with large tumors because of proximity to
optic chiasma.

76. Pineal gland

- Small cone-shaped structure in the midline of the brain, projecting from the roof of
the diencephalon, post part of the roof of 3rd ventricle.
- Resemble to a pine tree, or in latin ‘’pinus’’.
- Included in the DNES
- The pineal gland is connected to the brain via a short stalk containing man nerve
fibers, many of which communicate with the hypothalamus.
- Capsule  pia mater  septa  incomplete lobules.
. The cells are arranged in groups/cords.
- The pineal gland is very well vascularized.
- Innervation: unmyelinated sympathetic nerve fibers.

Cells:
- 95% are pinealocytes – paraneurons.
When stimulated they synthesize and secrete chemical messengers: amine and small
polypeptides.
- Large, round euchromatic nucleus
- Cytoplasm slightly basophillic in H&E
- Cell projections end in dilation near blood vessels.
- Secrete:
- Melatonin
- Peptides: arginine, vasotocin, angiotensin I
- 5% astrocytes, which cannot be seen on a H&E stained slide. Completely surround
the capillaries and pinealocytes.

- With age, the CT becomes more obvious and the brain sand appears. The presence
of the acervuli cerebri (=brain sand), serial deposits of Ca, PO4 and CO3. Their
mineral composition makes them radio opaque.
- The pineal gland receives input from nerve fibers that inform it on the level of light
outside via sympathetic nerve fibers connected with retina. This coordinates the

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circadian rhythm of the body – melatonin is maximal at night.
- Production of melatonin by the pineal gland is inhibited by light and permitted by
darkness.
- Melatonin has systemic effects:
- Synchronizes of the biological clock – treatment of circadian disorder.
- Inhibits SCN – induces sleep
- Supplemental melatonin users have reported an increase in the vivid or
frequency of dreams.
- Inhibits LH secretion and the ovulation – involved in some form of sterility
- Maintains the body temperature

77. Thyroid: histological structure

- The thyroid gland is a lobulated endocrine gland lying in the neck in front of the
trachea.
- It is unique among the human endocrine glands in that it stores large amounts of
hormone in an inactive form within EC compartments called follicles. In contrast,
other endocrine glands store only small quantities of hormones in IC sites.
- The main bulk of the gland develops from an epithelial down-growth from the fetal
tongue whereas the calcitonin secreting cells are derived from the ultimobranchial
element of the 4th brachial pouch.  Origin: endodermal.
- The functional units of the thyroid gland are the thyroid follicles, irregular spherical
structures composed of a single layer of cuboidal epithelial cells bounded by a
basement membrane.
- The thyroid gland is enveloped by an outer capsule of LCT and an inner capsule of
fibro-elastic tissue.
- From the inner capsule, fine collagenous septa extend into the gland dividing the
gland into lobules and conveying a rich blood supply together with lymphatics.
- During histological preparation, the lobules tend to shrink leaving spaces in the
septal plane.
- The thyroid gland is organized into follicles – hollow balls of cells, each with a wall
composed of simple cuboidal epithelium, follicular cells.
- An amorphous material is present inside the follicle – colloid storage form of
hormones, could last for 2-3 minutes.
- Between the follicles: CT of the septa with fenestrated capillaries + C cells or
parafollicular cells.
- In activity secreting thyroid, the follicles tend to be small and the among of colloid
diminished, the cuboidal lining are relatively tall, reflecting synthesis. Conversely, the
follicles of less active gland are distended by stored colloid and the lining cells appear
flattened against the follicular basement membrane.

Thyroid gland produces hormones of 2 types:

- Iodine-containing hormones: tri-iodothyronine (T3) + thyroxin (T4).
- T4 is converted to T3 in the general circulation by removal of 1
iodo-thyronine unit, although a small amount of T3 is secreted directly.
- T3 is much more potent than T4 and appears to be in a metabolically
active form of the hormone.
- These thyroid hormones regulate the basal metabolic rate and have an
important influence on growth and maturation, particularly of nervous
tissue.

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 - They stimulate mitochondrial respiration and oxidative
phosphorylation. So, more ATP is produced faster.
- Secretion is regulated by TSH – from anterior pituitary gland.
- The polypeptide hormone calcitonin:
- It regulated blood calcium levels in conjunction with parathyroid
- It lowers blood calcium levels, by inhibiting the rate of
decalcification of bone by osteoclastic resorption and by stimulating
osteoblastic activity.
- Control of calcitonin secretion is dependent only on blood calcium
levels and is independent of pituitary and parathyroid hormone levels.

Biosynthesis of thyroid hormones:

- Follicular cells concentrate inside from the blood by means of iodide pump
in the basal plasma membrane.
- The import of iodide is stimulated by TSH
- Depends on ATP-dependent pump. The iodide is pumped in with Na+ by a
co-transporter (active transport is required since the concentration of iodide is
>50 folds inside).
- iodide is converted into iodine by the enzyme thyroid peroxidase.
- Iodine is transported to the follicular plasma membrane, where it is released into the
follicular lumen , the colloid. Iodine is essentially for 2-3 tyrosine to fuse, to form
thyroid hormones.
- The glycoprotein thyroglobulin is synthesized in the RER, glycosylated and
packed by the Golgi apparatus, then released to the lumen by exocytosis.
- In the lumen, iodine combines with tyrosine residues of thyroglobulin to
form T3 and T4. TSH stimulated enzymatic degradation of thyroglobulin to
effect release of the thyroid hormones.

- Secretion of these hormones involves engulfment of thyroglobulin – hormone

component to form cytoplasmic vacuoles.
- The vacuoles then fuse with lysosomes of the follicular cell cytoplasm and
hydrolytic enzymes cleave the hormone to form the thyroglobulin (phagolysosome).
- The hormones are rebased in the basal cytoplasm  bloodstream.
- T4 is formed exclusively in the thyroid and secreted in contrast, 80% of T3 found
circulating in the blood is derived from metabolism of T4 in peripheral tissues,
especially the liver and kidney.
- T4 is the most common form, less potent than T3.
- T4 is converted into T3 in the blood stream.
- Thyroid-hormone-binding globulin (THBG) – carries thyroid hormones in blood.
- At any given time it has bound over 99.9% of T3 and T4 in the blood.

Reabsorption/mobilization:
- TSH promotes the endocytosis and breakdown of the colloid.
- TSH works by a G-protein/cAMP second messenger system.
- Thyroglobulin is then endocytosed into the follicular cell, and those
endosomes merge with internal lysosomes to form phagolysosomes.
- Phagolysosomes then degrade the big thyroglobulin molecules into
individual amino acids, and T3 + T4.
- The globulin components are re-secreted back into the colloid lumen.
- T3 and T4 are lipophilic and thus simply diffuse into the blood.

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Goiter  iodine deficiency:
- Leads to constant stimulation of the thyroid by TSH because of no T4 feedback at
the pituitary.
- Colloid is almost completely gone, as it is constantly being mobilized.
- No thyroxin is being made because there is no iodide.
- Follicular cells hypertrophy  Goiter thyroid gland.

Hashimoto’s thyroiditis
- ABs are found to thyroid peroxidase with the new discovery of the iodide
transporter, the search is on for ABs to the transporter which may be implicated in
various forms of thyroid disease.

78. Thyroid cells: structure, ultrastructure, functions

Parafollicular cells
- Groups between the follicles/between the follicular cells and the basement
membrane:
- Oval-shaped, larger and more lightly stained (clear C-cells) than the
follicular cells.
- The C cells do not produce colloid.
- They produce calcitonin.
- Large, euchromatic nucleus.
- RER, Golgi apparatus, round granules with calcitonin.
- They have different embryonic origin from the follicular cells, and in some
species constitue a discrete endocrine organ called the ultimo-branchial body.

Thyrocytes (follicular cells)

- Surround a lumen containing the colloid thyroglobulin.
- The thyroglobulin is a glycoprotein complex which stores the thyroid hormones
prior to secretion.
- Cuboidal epithelia.
- Basophillic cytoplasm.
- Round, centrally located nucleus.
- RER dilated cistern.
- Golgi apparatus located at the basal part of the cell when it rests, and in the upper
when active.
- Mitochondria are present.
- Microvilli at the apical pole, occasionally pseudopodia.
- Lysosomes/phagolysosomes at the apical pole.
- Apical vesicles.
- TSH receptors at the basal pole.
- Function: synthesis, secretion, resorption and protein digestion.

79. The adrenal cortex: structure and function

- The adrenal gland is surrounded by a distinct CT capsule, which sends a few septa
into the parenchyma (dense fibrous tissue capsule).
- Has a distinct cortex and medulla, each of different embryologic origin and function.
- Extensive vascularization of both parts.

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- The cells form cords and sinusoids, which facilitates contact between the cells and
the blood.
- Synthesizes steroid hormones.
- Have a foamy appearance: because of the extensive lipid material in them +
numerous SER and Golgi profiles in their cytoplasm.

The adrenal cortex:

- Arises from embryonic mesoderm, and is essential to life.
- 3 layers, 3 differentiation stages of the same cells:
- Zona glomerulosa (15%)
The layers of acidophillic cells form arcades or small arches of cells. Produces
aldosterone (acts on resorption of Na+ in the kidney). Influences by
angiotensin, not ACTH.
- Zona fasciculata (75%)
Has a foamy appearance. The large polygonal cells form regular parallel rows.
Produces cortisol: low protein synthesis + enhances gluconeogenesis, and has
significant anti-inflammatory properties. It is controlled by ACTH.
- Zona reticulate (7%)
Closest to the medulla, which represents the dark zone. Cells may contain
lipofuchsin and are organized to form network-like anastomosing cords.
Separating the rows and cords – sinusoids. Produces dehydro-epiandrosterone
– anabolic. Controlled by ACTH.

- The proportion of the 3 zones are different in different moments of life:

- In uteri: zona reticularis dominates, zona glomerulosa is absent.
- Until puberty: zona fasciculata dominates, zona glomerulosa appears.
- Adult: zona fasciculata is largest.
- Old people: zona glomerulosa and reticularis involutes.
- During stress: zona fasciculata dominates.

Structure and ultrastructure

Zona glomerulosa
- The secretory cells are arranged in irregular ovoid clumps separated by delicate
trabeculae containing wide diameter capillaries.
- The collagen of the capsule and trabeculae – stain blue with AZAN stain.
- The secretory cells:
- Round strongly stained nuclei
- Little cytoplasm (poorly stained)
- SER, mitochondria (numerous)
- Triglyceride droplets – the basic structure for steroids synthesis
- Secretes mineralocorticoids hormones, principally aldosterone. Aldosterone
regulates body Na+ and K+ levels by stimulating Na pump, particularly in the renal
tubules, increasing the resorption of Na, increasing blood volume (which means
increasing BP).
- Aldosterone secretion is independent of ACTH (renin-angiotensin-aldosterone)

Zona fasciculata
- Broadest of the 3 types.
- Consists of narrow cords of secretory cells, often only 1 cell thick, separated by fine

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strands of CT containing wide capillaries.
- Large secretory cells, abundant poorly stained cytoplasm.
- Cytoplasm – rich in lipid droplets and SER  foamy look.
- Secretes glucocorticoid hormones, principally cortisol (high blood glucose, high
synthesis of glycogen).
- Control of cortisol is maintained by the hypothalamus via the anterior pituitary
hormone ACTH.
- This is also the site of secretion of small amounts of androgenic sex hormones.

Zona reticularis
- Thin innermost zone.
- Consists of an irregular network of branching cords. Clumps of glandular cells
separated by numerous wide capillaries.
- The glandular cells are much smaller than those of zona fasciculata:
- Cytoplasm stains more strongly – few lipid droplets.
- In H&E: brown wear and tear pigment lipofuchsin.
- Secretes small quantities of androgens and glucocorticoids.

Steroid synthesis
- Whether you get aldosterone or cortisol depends on the final enzyme in the pathway
which is specific to either glomerulosa (aldosterone) or fasciculata (cortisol) cells.
- LDL (low density lipoprotein) is endocytosed into the glomerulosa cells.
- Cholesterol ester first hydrolyzes the cholesterol. Cholesterol ester hydrolase is
stimulated by ACTH  cAMP  Protein kinase A.
- The rest of synthesis requires shuffling back and forth between SER and
mitochondria.
- Inner mitochondrial membrane: cholesterol  pregnenolone.
- SER: pregnenolone  17-hydroxypregnenolone.
- Inner mitochondrial membrane: 17-pregnenolone  11-deoxycortisol (or
deoxyaldosterone).
- SER: 11-deoxycortisol  cortisol.

Blood supply of adrenal gland

- Suprarenal aa  capsular plexus
- The medullary aa run straight through the cortex, and ramify into the sinusoids of
the medulla.
- The cortex is supplied by cortical aa, which discharge their blood into the sinusoid
of the zona glomerulosa.
- Venous outflow from the cortex is mixed with that of the medulla, and carries
secretions from both parts.

80. The adrenal medulla: structure and function

- Origin: neural crest, belongs to the DNES.

- It is a sympathetic paraganglion.
- Stimulated by direct neural signals – axons of preganglionic sympathetic neurons 
secretes catecholamines.
- Epinephrine, the ‘’fight or flight’’ hormone, rebased from adrenal medulla
under conditions of stress.
- Norepinephrine.

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- Has its own arterial blood supply, isolated from the supply to the cortex.
- Cords of anastomosing cells form network with capillaries and post-capillary
venules.

- The adrenal medulla is composed of closely packed clumps of secretory cells

supported by a fine collagenous network containing numerous wide diameter
capillaries.
- Many venous channels draining blood from the sinusoids of the cortex pass through
the medulla towards the central medullary vein.
- The secretory cells:
- Large granular nuclei
- Extensive strongly basophillic cytoplasm (intensive synthesis activity).

Chromaffin cells
- Adrenal medullary hormones are not secreted continuously but are stored in
cytoplasm granules and released in response to nervous stimulation.
- When fixed in chrome salsa, the catecholamines granules are oxidized to a brown
color  Chromaffin reaction.
- Granules in the cytoplasm: adrenalin/noradrenalin, ATP, chromogranins, dopamine-
beta-hydroxylase.
- No axons/dendrites.
- 95% adrenergic smaller, less electro dense granules, content fills the granule. 5%
noradrenergic larger, electro dense granules, electron-lucent layer beneath the
membrane.
- Noradrenaline-secreting cells exhibit much more strongly positive reaction than
adrenalin-secreting cells.
- Secretion in small amounts are less stimulated.
- Vasoconstriction increases BP, and, secretion prepares body to react to stress.

Addison’s disease
- Primary adrenal insufficiency
- Etiology: 80% of these cases are autoimmune, most of the rest is by tuberculosis.
- Both cortisol and aldosterone will be affected.

Secondary deficiency
- Giving a patient too much glucocorticoids therapy can result in secondary
deficiency. Suppressed ACTH when the therapy is stopped.
- Doesn’t affect aldosterone, because it’s not stimulated by ACTH.

Cushing’s syndrome
- Too much cortisol.
- Either inherit or by drugs, or by a pituitary tumor secreting excessive ACTH.

Pheochromocytoma
- Adrenal medulla hyper functions.
- From a benign tumor, which can lead to hypertension and hyperglycemia.

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81. Synthesis and secretion of catecholamines

Drawing

82. Parathyroids

- 4 small oval bodies associated with the thyroid gland.

- History: complete removal of the thyroid gland was noted to cause death because of
spasms of the laryngeal and thoracic muscles that prevented breathing  tetany.
- The parathyroid gland has a thin fibrous capsule.
- It is not lobulated.
- Well vascularized.
- The thin capsule gives rise to septa, which divide the parenchyma into dense cord-
like masses of secretory cells (which are prone to shrinkage).
- The septa carry blood vessels, lymphatics and nerves.
- 2 types of secretory cells:
- Chief cells
- Most abundant
- Round, euchromatic nucleus
- Weakly stained, acidophillic cytoplasm (the staining intensity is
according to the degree of secretory activity)
- Actively secreting cells contain little RER, stains poorly
- The chief cells produce parathyroid hormone (or parathormone PTH)
 which causes increase in resorption of bone through osteoclasts
activity, increasing serum calcium.
- EM: protein synthesis organelles, storage granules, lipid and
glycogen deposits.
- Oxphil cells
- Larger and less numerous, tend to occur in clumps
- Not present at birth, but in high age.
- No known function – degenerated cells.
- Abundant acidophillic cytoplasm
- Small dark nucleus
- EM: many mitochondria, few protein synthesis organelles

Post-thyroid hormones increase serum calcium levels in 3 ways:

1) Direct action on bone, increasing the rate of osteoclastic resorption, promoting
breakdown of the bone matrix.

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2) Direct action on the kidney, increasing renal tubular reabsorption of calcium and
inhibiting the resorption of phosphate ions from the glomerular filtrate.
3) Promotion of the absorption of calcium from the small intestine. This effect
involves vitamin D.

- Secretion of parathyroid hormone is stimulated by a decrease in blood calcium.

- In conjunction with calcitonin secreted by the parafollicular cells of the thyroid
gland, blood calcium levels are maintained within narrow limits.
- PTH is the most important regulator of blood calcium levels and is essential to life
whereas calcitonin appears to provide a complementary mechanism for fine
adjustment and is not essential to life.

83. Endocrine pancreas: structure and function

- Distributed through the mass of the organ as ‘’islands’’ of lighter staining material –
Island of Langerhans.
- 200 000 to 2 millions/pancreas.
- Set off from the surrounding exocrine tissue by a thin capsule of reticular fibers.
- Extensively vascularized – capillary beds surrounded by secretory cells.
- Represents 1.5% of the pancreatic volume.
- 30-300 micrometer in diameter.
- Each islet contains hundreds of cells.
- The islets of Langerhans are composed of clumps of secretory cells supported by a
fine collagenous network containing numerous fenestrae capillaries.
- A delicate capsule surrounds each islet.

Endocrine cells:

B cells:
- Make insulin
- 70% of the islet cells
- Located in the center of the islet
- An antagonistic hormone that is vital to normal carbohydrate metabolism
Alpha cells
- Make glucagon
- 20% of the islet cells
- Located in the periphery of the islet
- An antagonistic hormone that is vital to normal carbohydrate metabolism
D cells
- Secrete somatostatin
- 5-10% of the islets cells
- Located at the periphery of the islet.
- Paracrine action – inhibit the secretion of insulin and glucagon
PP or F cells
- Secrete the pancreatic polypeptide
- 1-2% of the islet cells
- Located at the periphery of the islet

- Each islet is supplied by as many as 3 arterioles, which ramify into branched

capillaries. The islet is drained by about 6 venules passing between the exocrine acini

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to interlobular veins.

84. The diffuse neuroendocrine system: definition, examples of component cells.

- Widely separated cells present either in classic endocrine organs or dispersed

throughout the body, whose function was to act as a diffuse NE system.
- All cells share a common embryonic origin: neural crest.
- In all the cells – the presence of neural markers: neuron specific enolase.
- Usually, the cells are located between epithelial cells.

DNES is composed by:

Endocrine cells
- that resembles neurons, the stimulus promotes electrical activity.
- Classical endocrine cells – under stimulation, the cells synthesize and store chemical
messengers, amine or peptides.
- More than 40 types of cells of amine precursor uptake and decarboxylate (APUD)
series.
APUD cells
- They produce more than 35 physiologically active peptides and a small number of
equally active amines.
- 17 of these peptides have been identifies born in endocrine cells and neuronal cells.
- Sharing a neural and an endocrine location and sited of production – they are called
common peptides.
- The DNES is 3rd subdivision of the NS, whose products suppress, amplify or
modulate the activities of the other 2 divisions.

Classification of DNES cells

- Cells that are located in the endocrine glands: anterior pituitary gland + thyroid
gland + parathyroid gland + adrenal medulla + pineal gland
- Cells from other tissues and organs:
- Digestive tract: in the mucosa and submucosa
- Skin
- Respiratory system
- Urogenital tract
- Mammary gland
- The DNES cells should possess synaptic vesicle-like structure or neurosecretory
type granules.
- The cells exhibit receptor and secretory functions.
- The cells should be of neuro-endodermal origin.

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MALE GENITAL APPARATUS

85. Components of the male reproductive system – enumerate

- Testes (male gonad), paired organs lying in the scrotal sac, produce:
- Male gametes: spermatozoa
- Male sex hormones: testosterone
- Genital ducts: ductuli efferents, epididymis, ductus deferens and ejaculatory duct.
Storage and transport of spermatozoa.
- Accessory glands: the paired seminal vesicles and single prostate gland. Secretion of
seminal fluid happens here.
- Penis
- Organ of copulation
- The bulbourethral glands of paired small accessory glands: secrete a fluid
which lubricates the urethra for the passage of semen during ejaculation.

Seminiferous tubules  rete  efferent  epididymis  deferent duct 

ejaculatory duct

86. General structure of the testes

- Developed in the abdominal cavity.

- During embryological development, each testis with the first part of its duct system,
blood vessels, lymphatics and nerves, descend along a tortuous path from the wall of
the peritoneal cavity to the scrotum.
- During migration, the testis carries with it an investing layer of peritoneum so that in
the scrotum the testis is almost completely surrounded by a serous space, which
represents an extension of the peritoneal cavity.
- The space around the testis becomes isolated from the peritoneum, its serosal lining
being known as the tunica vaginalis. The tunica vaginalis secretes a small amount of
lubricant fluid and protects the testis by allowing it to move freely in the scrotal sac.
- Descensus testis, 3rd month.
- Scrotal sac: 7th month.
- it’s a paired organ and has an ovoid shape.
- Dimensions: high – 5 cm, width – 2.5 cm and anterior-posterior – 3 cm.
- Weight: about 14 g (usually between 9-21 g).
- Cryptorchidism  infertility.
- 27 degrees Celsius inhibits spermatogenesis but not testosterone synthesis.

Structure

Tunica vaginalis
- From peritoneum = mesothelium
- Parietal layer
- Visceral layer

Tunica albuginea
- A fibrous, inextensible capsule, dense regular CT, elastin fibers, smooth muscular
cells (may/may not be present).
- Mediastinum testis  collagenous septa  250 testicular lobules.

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- Within each lobule are 1-4 highly convolutes tubes, the seminiferous tubules, in
which spermatozoa are produced.
- The seminiferous tubules converge upon a plexus of spaces, the rete testis  15-20
small ductuli efferents – conduct spermatozoa to the extremely tortuous 1st part of the
ductus deferens – epididymis.

Tunica vasculosa
- Blood vessels , lymphatic vessels, nn.
- Smooth CT

87. Lobuli testis – general

- Number: 250/testis.
- Shape: pyramidal
- Base: albuginea
- Top: mediastinum (efferent, rete)
- Face: collagenous septa
- Content: Seminiferous tubules 1-4, highly convolutes tubes. In both endings you
will find mediastinum. One ‘’blind’’ end, whereas the other is the testis.
- Interstitial tissue.

Drawing

88. The interstitial tissue of the testis

- 35% of the testis volume.

- Components:
- LCT: collagen fibers + reticulin + fibroblasts + macrophages
- Small blood vessels  fenestrated capillaries with diaphragm
- Lymphatics
- Nerves
- Interstitial cells of Leydig.

89. The cell of Leydig

- Shape: polygonal.
- Diameter: 15-20 micrometers.
- Location: between the seminiferous tubules
- Single/clumps
- In LM:
- Nucleus: round, euchromatic, eccentrically

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 - Cytoplasm: eosinophillic, spongy (lipidic vacuoles). Lipochrome pigment
(which increases with age) may or may not be present.
- In EM, characteristics of steroid-secreting cells:
- SER
- Golgi app.
- Mitochondria (tubular cristae)
- Lipid vacuoles
- Lipochrome pigment
- Elongated crystals of Reinke
- Protein nature (function), only in human adults
- In fetus, in week 6, they are fully differentiated, and can secrete testosterone.
Between months 4-8, they have a progressive regression.
- At birth, it’s not active (cannot be distinguished from the fibroblast)
- At puberty, a new differentiation occurs, secretion will resume, and 95% of
testosterone (5% in adrenal gland). Secretory activity controlled by LH (ICSH)
interstitial cell stimulating hormone.

Testosterone
- Synthesis: 6-7 mg/day
- Synthesis varies along the day. In the morning it’s 30% higher, and, in evenings it’s
lower.
- Synthesis decrease with age (30-40 and older)
- Testosterone in blood (circulating testosterone), may be found.
- Testosterone in germinal epithelium, is essential for the proliferation and
differentiation of germ cells.
- 200x concentrated  circulating testosterone.
- Sertoli cells secretes androgen binding protein, which combines and transport
testosterone.

90. The seminiferous tubules – general feature

- Number: 400-600/tubule
- Length: 250 m/tubule
- Highly concentrated and lined by a stratified epithelium which consists of 2 distinct
population of cells:
- Cells in various stages of spermatogenesis and spermatogenesis are
collectively referred to as the spermatogenic series.
- Non-spermatogenic cells called Sertolli cell, support and nourish the
developing spermatozoa.
- Length: 30-60 cm, diameter: 200-300 micrometers.
- Lumen narrows  continues to a straight tubule.
- In the interstitial spaces between the tubules, endocrine cells called Leydig cells are
found either singly or in groups in the supporting tissue.

Structure
- Tunica propria (external)  basal lamina (middle)  seminiferous epithelium
(inner).
- Tunica propria: 2-3 layers of fibroblasts/myolid cells. If they thicken, this will cause
infertility.
- Basal lamina.

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- Seminiferous (germinal) epithelium: 2 types of cells
- Supporting Sertolli cells
- Spermatogenic lineage
 4-8 layers of stacked cells.

91. The spermatogenic lineage

1) 1Type A spermatogonium
2) 2 type B spermatogonium
3) 4 primary spermatocytes
4) 8 secondary spermatocyte
5) 16 spermatids
6) 16 spermatozoa
 This process takes 64 days.

Spermatogonium  type a spermatogonia  type B spermatogonia  primary

spermatocyte  secondary spermatocyte  spermatid, then through spermatogenesis,
the spermatozoa will be the result.

92. The spermatogonium

- Origin: primordial germ cell

- Location: basal compartment epithelium, just above the basal lamina. It’s present in
testes before puberty. At puberty, they will undergo mitosis.
- Shape: round, with a diameter of 12 micrometers.
- Type:
- A spermatogonium (Ad/Ap): dark/pale
- B spermatogonium

Spermatogonium (Ad - dark)

- Nucleus: oval/round + fine, granular chromatic which stains intensely + 1-2 nucleoli
- Reserve stem cell (differentiated)
- Replicate by mitosis only to maintain the germ cell pool  spermatogonium.

Spermatogonium (Ap – pale)

- Nucleus: round + fine, granular chromatin which has a pale staining + 2 nuclei
develop attached to nuclear envelope.
- Reserve stem cell
- Replicate by mitosis several times  reservoir of stem cells + spermatogonium
Ap/Ap/Ap/B.

Spermatogonium B
- Nucleus: round + intensely granular chromatin (peripheral) + 1 nucleolus
- Differentiated committed germ cell
- Replicates by mitosis once  produce 2 primary spermatocytes.

- The primitive germ cells of the male, the spermatogonia, are present only in small
numbers in the male gonads before sexual maturity. After puberty, spermatogonia
undergo multiple mitosis to provide a supply of cells which then undergo meiosis to
form male gametes.

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93. The primary spermatocyte

- 46 chromosomes (44+XY) (2n, 2c)

- Shortly after their formation  DNA replication  1st meiotic division.
- Prophase takes 22 days.
- Anaphase  telophase, quickly into  secondary spermatocytes.

94. Secondary spermatocyte

- Location: medial, just under the spermatids

- Diameter: 9 micrometer, difficult to observe
- 23 chromosomes (22 + XY) (1n, 2c)
- Short-lived cell, no S-shape, no DNA synthesis
- They will quickly enter the 2nd meiotic division
- Prophase takes about 8 hours, and this results in 2 spermatids.

95. The spermatids and spermiogenesis

- Spermatids
- Location: superior
- Origin: division from spermatocyte II
- 23 chromosomes (n, c), haploid cells
- Aspect/dimension vary very much
- 1 spermatid results in 1 spermatozoon
- Spermiogenesis is the process by which spermatids, the gametes produced by
meiotic division, are transformed into motile mature spermatozoa.

This involves the following steps:

1) The Golgi apparatus elaborates a large vesicle, the acrosomal vesicle, which
accumulates carbohydrates and hydrolytic enzymes. The formed acrosome: Golgi 
vesicle  head cap.
2) The acrosomal vesicle becomes applied to one pole of the progressively elongating
nucleus to form a structure known as the acrosomal head cap.
3) Meanwhile, both centrioles migrate to the end of the cell opposite to the acrosomal
head cap. The centriole aligned parallel to the long axis of the nucleus elongates to
form a flagellum, which has a basic structure similar to that of cilium.
4) As flagellum elongates, 9 coarse fibrils, which may contain contractile proteins
become arranged longitudinally around the core of the flagellum. Further rib-like
fibrils then become disposed circumferentially around the whole flagellum.
5) The cytoplasm migrates to surround the 1st part of the flagellum with the remainder
of the flagellum appearing to project from the cell but in fact remaining surrounded
by plasma membrane. This migration of cytoplasm thus concentrates mitochondria in
the flagellar region.
6) As the flagellum elongates, excess cytoplasm is phagocytosed by the enveloping
Sertolli cell prior to release of the spermatid into the lumen. The mitochondria
become arranged in a helical manner around the fibrils, which surround the 1st part of
the flagellum.

- Forming acrosome: Golgi  vesicle  head cap

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- Forming Flagellum: centrioles  axoneme   
- Changes in nucleus: chromatin  shape  position
- Excess cytoplasm: removal of residual bodies of Reynaud.

- Throughout the entire process from spermatogonia to spermatozoa, hundreds of

spermatids remain connected to one another by narrow cytoplasmic bridges which
only break down upon release of spermatozoa into the lumen of the seminiferous
tubule. This explains the synchronous development of spermatozoa at any lumen of
the tubule.

Drawing

96. The Sertolli cell: LM, EM, functions

- Elongated: base – basal lamina + apical – lumen

- Lateral outlines poorly defined (surround spermatogenic cells)
- Forming a continuous layer beyond together by junctions.
- Junctional (Sertolli-Sertolli), has 2 compartments:
- Basal compartment (1 spermatogonium  spermatocyte)
- Adluminal compartment (1 spermatocyte  spermatids)
- Occluding junctions  blood-testes barrier
- Adluminal compartment:
- Haploid cells – protected from blood-born products
- Haploid cells – protected against autoimmune reaction
 recognized as foreign  destroyed.
- Only 1 formed spermatocyte passes the junctions!

- Spermatogenic cells depend upon the Sertolli cells to mediate exchange nutrients-
metabolites.
- Nucleus: oval/elongated/triangular(irregular, euchromatic, nucleolus with 2 mass
heterochromatin.
- Cytoplasm:
- Abundant, but poorly defined
- Lateral processes that surround germ cells
- SER (highly ordered; lipid synthesis), Golgi apparatus, elongated
mitochondria

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 - Lipidic, lysosomes
- Cytoskeleton – actin (apical)
- Junctions, gaps (S-S, S-Spermatids)
- Crystals (basal)
- Charcot-Botcher bodies

Functions
- Support (nutritional + protection) for germ cells
- Secretion fluid in seminiferous tubules (nutritional + transport)
- Secretes ABP (  FSH  concentrate testosterone). Inhibin – inhibits release of
FSH.
- Phagocytosis – residual bodies/degenerate germ cells. They degenerate spermatozoa
(about 50%)
- Release of spermatozoa (apical active movement + opening Sertolli  spermatid
junction)
- The secretory cells rest on the basement membrane of the seminiferous tubules and
their cytoplasm extends to the lumen of the tubule, filling the narrow spaces between
the cells of the spermatogenic series.
- The cytoplasmic outline of the Sertolli cells is thus highly irregular and constantly
changing to permit the progressive movement of developing spermatozoa towards the
luminal surface.
- Sertolli cells are bound to one another by junctional complexes containing extensive
tight junctions.
- The junctional complex is located towards the basal layer of the spermatogenic
epithelium so as to divide the tubule into basal and adluminal compartments.
- The adluminal compartment contains the spermatids which are thus isolated by a
blood-testes barrier, the Sertolli cells medicating all metabolic exchange with the
systemic compartment.
 The function of this barrier is to prevent exposure of gametes, which are
antigenically different from somatic cells to the immune system, thus preventing an
autoimmune response.
- Sertolli cells are postulated to act as ‘’nurse’’ cells providing structural and
metabolic support for the developing spermatogenic cells.
- During spermiogenesis, Sertolli cells phagocytose excess cytoplasm cast off by the
spermatids.

97. The tubuli recti and rete testis

- Seminiferous tubules end (only in Sertolli cells) as tubuli recti.

- Composed of:
- Simple cuboidal epithelium
- Dense connective sheath
- Seminiferous tubules (tubuli recti) converge upon the mediastinum testis, which
consists of a plexiform arrangement of spaces, the rete testis, surrounded by a highly
vascular collagenous CT containing myloid cells.
- It is a highly anastomotic network of channels:
- Lined by a single layer of cuboidal/columnar epithelia
- With surface microvilli and a single flagellum
- DCT + blood vessels
- Myloid cell contraction helps to mix the spermatozoa and move them towards the

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epididymis.
- The lining epithelium is though to secrete some constituents of seminal fluid.
- Flagellar activity is presumed to aid progress of spermatozoa, which do not become
motile until after maturation is completed in the epididymis.

98. The ductuli efferents

- = efferent duct
- The rete testis drains into the head of the epididymis via some 10-20 convoluted
ducts, the ductuli efferents.
- The ductuli are lined by a single layer of epithelial cells, some of which are tall
columnar and ciliated and others which are short (cuboidal) and non-ciliated, which
will have a ‘’saw’’ aspect.
- Both cell types often contain a brown pigment of unknown composition.
- Ciliary action in the ductuli propels the still non-motile spermatozoa towards the
epididymis.
- A thin band of circularly arranged smooth muscle surrounds each ductules and aids
propulsion of the spermatozoa towards the epididymis (1-2 layers of smooth muscle
cells).
- Intra – extra – testicular (head epididymis).

99. The ductus epididymis

- The epididymis is a long extremely convoluted duct extending down the posterior
aspect of the testis to the lower pole where it becomes the ductus deferens.
- The major function of the epididymis is the accumulation, storage and secretion of
spermatozoa. During this time the spermatozoa develop motility.
- Ductus epididymis = body and tail of epididymis.
(Ductuli efferents = head of epididymis)
- It’s a tube of smooth muscle lined by a pseudostratified epithelium.
- From the proximal to the distal end of the epididymis, the muscular wall increase
from a single circular layer to 3 layers organized in the same manner as in ductus
deferens (inner and outer longitudinal).
- Proximally, the smooth muscle exhibits slow rhythmic contractility, which gently
moves spermatozoa towards the ductus deferens.
- Distally, the smooth muscle is richly innervated by the sympathetic nervous system
which produces intense contractions of the lower part of the epididymis during
ejaculation  store spermatozoa for 12 days.
- The epithelial lining exhibits a gradual transition from a tall pseudostratified
columnar proximally, to, a shorter pseudostratified distally.
- The principal cells of the epididymal epithelium: tall columnar (40-80 micrometers)
with stereocilia (10-25 micrometers)
- Thought to be involved in absorption of excess fluids accompanying the
spermatozoa from the testis.
- The ultrastructure strongly suggests an additional secretory function –
glycoprotein
- Phagocytosis
- Basal cells are small and round.
- Occasional lymphocytes may be seen within the epithelium.

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100. The ductus deferens and ejaculatory duct

- The ductus (vas) deferens, which conducts spermatozoa from the epididymis to the
urethra, is a thick walled muscular tube consisting of inner and outer longitudinal
layers and a thick intermediate circular layer.
- Like the distal part of epididymis, the vas deferent is innervated by SNS, producing
strong peristaltic contractions to expel its content into the urethra during ejaculation.
- The vas deferens is lines by a pseudostratified epithelium.
- The epithelial lining and its supporting lamina propria are thrown into longitudinal
folds, which permit expansion of the duct during ejaculation.
- The dilated distal portion of each ductus deferens, the ampulla, receives a short duct
draining the seminal vesicle  thus forming the ejaculatory duct.
- The ejaculatory ducts converge to join the urethra as it passes through the prostate.

Mucosa (epithelium + lamina propria)

- Longitudinal folds, which project into the lumen
- Pseudostratified epithelium; columnar cells with stereocilia
- Lamina propria, with numerous elastic fibers

Muscularis
- Has 3 layers
- Longitudinal
- Circular
- Longitudinal

Adventitia
- Ampulla, expanded lumen (dilated distal portion)
- Ejaculatory duct
- Simple/pseudostratified columnar epithelium
- 2 ducts open in prostatic urethra
- No muscularis layer

 Ampulla and seminal vesicle = ejaculatory duct + urethra

101. The seminal vesicles

- The seminal vesicle is a complex glandular diverticulum of the associated vas

deferens.
- Between them the seminal vesicles secrete about ½ of the total volume of seminal
fluid, most of the rest being secreted by the prostate gland.
- A lumen of each vesicle is highly irregular, honeycombed appearance.
- The epithelial lining:
- Columnar/cuboidal pseudostratified
- Consists of secretory cells, which produce a yellowish viscid, alkaline fluid
containing fructose, fibrinogen, vitamin C and prostaglandin.
- RER, Golgi apparatus, secretory granules, lipofuchsin brown granules, lipid
droplets, Lipochrome pigment.

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- Lamina propria – LCT
- Muscularis – inner circular + outer longitudinal
- Adventitia

- Although not thought to store spermatozoa, seminal vesicle are often seen to contain
spermatozoa which have probably entered by reflux from the ampulla.
- During ejaculation, muscle contraction forces secretions from the seminal vesicles
into the urethra via the ampulla.

102. The prostate

- The prostate is a large gland, which surrounds the bladder neck and the 1st part of
the urethra in the midline.
- The wall of the prostatic urethra is formed by the substance of the gland.
- The ejaculatory ducts join the prostatic urethra just before its exit from the prostate
gland.
- 20 grams, it’s the largest accessory sex gland.
- Capsule – vascular, fibro-elastic:
- Broad septa (incomplete one), which makes up about 50 lobules.
- This CT contains numerous smooth muscle cells, which are innervated by
SNS, which stimulated powerful contraction during ejaculation.

- Glandular parenchyma:
- Compound tubulo-acinar glands (30-50 glands)
- Arranged concentrically around the urethra.
- 3 strata around urethra (mucosa, submucosa, principal glands)

- Periurehtral mucosal, submucosal: simple cuboidal/columnar epithelium,

secrete directly in urethra
- Principle glands: 30-50 glands, which makes up 15-30 ducts. They are
composed of simple/pseudostratified columnar epithelia.

- Fibro-muscular stroma: dense fibro-elastic tissue + smooth muscle

- Lamina may contain 0.2 – 2 mm of spherical lamellar bodies.
- Prostatic concretions: Condensation of secretory material  calcium.
- With age, the mucosal and submucosal glands and their supporting tissue tend to
become greatly enlarged leading to the condition of benign prostatic hyperplasia
which may cause urinary outflow obstruction.
- In contrast, it’s the main prostatic glands (mucosal and submucosal), which give rise
to prostatic cancer.

103. The bulbourethral glands

= Cowper glands – exocrine glands

- Location: in the bulb of urethra

- Diameter: 0.5-15 cm
- Duct: 3 cm
- It is a compound tubulo-acinar gland
- CT capsule, divides the gland into several lobules

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- Cuboidal/columnar unistratified epithelium
- Fibro-elastic stroma: elastic fibers + smooth skeletal muscle cells
- Secretes clear, viscous fluid, which lubricated urethra.
- The glands gradually diminish in size with increase in age.
- Homologous to Bartholin’s glands in female.

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FEMAL GENITAL APPARATUS

104. The ovary – general structure

- Paired female gonads (primary reproductive organs) are the ovaries.

- Function:
- They produce the female gamete or ovum.
- Also produce the female sex hormones: estrogens and progesterone
- The ovaries flank the uterus and each is held in place by several ligaments.
- Located in the ovarian fossa, a depression in the posterior pelvic wall.
- The ovaries are served by:
- Ovarian aa – branches of the abdominal aorta
- Ovarian branches of the uterine aa (enter the hilum of ovary)  helicine aa.
- The ovary is surrounded externally by a fibrous tunica albuginea.
- The tunica albuginea is covered externally by a layer of cuboidal epithelial cells
called the germinal epithelium.
- The ovary has
- An outer cortex which houses the forming gametes in follicles
- An inner medullary region containing large blood vessels and nn
- 3-5 cm long, flattened ovoid shape.
- The body of the ovary consists of spindle shaped cells, with fine collagen fibers and
a ground substance. These components together are called the ovarian stroma. The
stromal cells are mainly fibroblasts but also include bundles of smooth muscle cells.
- The human ovary is dominated by an active corpus luteum and several degenerating
corpura lutea and corpura albicantes.

Ovarian folic
- Embedded in the ovarian cortex are many tiny sac-like structures, the ovarian
follicles.
- Each follicle consists of an immature egg called an oocyte encased by one or more
layers of very different cells.
- The surrounding cells are called follicle cells if a single layer is present, and
granulosa cells when more than 1 layer is present.
- Follicles of different stages of maturation are distinguished by their structure
(primary, secondary, mature, ruptures follicles).

105. Follicular development

- During early fetal development, primordial germ cells called oogonia migrate into
the ovarian cortex where they multiply by mitosis.
- By 4th of 5th months of human fetal development, some oogonia enlarge and assume
the potential for development into mature gametes.
- At this stage, they become known as primary oocytes and commence the 1st stage of
meiotic division.
- By the end of 7th month of fetal development, the primary oocyte becomes
encapsulated by a single layer of flattened follicular cells of epithelial origin to form
primordial follicles of which there are some 400,000 in the human ovary at birth.
- This encapsulation arrests the 1st meiotic division and no further development of
primordial follicles then occurs until after the female reaches sexual maturity.
- The process of meiotic division is only completed during follicular maturation

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leading up to ovulation and fertilization. Thus, all the female germ cells are present at
birth but the process of meiotic division is only completed 15-50 years later.
- In contrast, in males, meiotic division of germ cells commences only after sexual
maturity and formation and maturation of spermatozoa is accomplished within 64
days.
- During each ovarian cycle, up to 20 primordial follicles is in some way activated to
begin the maturation process. Nevertheless, usually only 1 follicle reaches full
maturity and is ovulated whilst the remainder undergo atresia before this point.
- During maturation, however, the follicles have an endocrine function which may be
far behind the capacity of a single follicle and primary purpose of the other follicles
may be to act as an endocrine gland.
- Follicular maturation involves changes in the oocyte, the follicular cells and the
surrounding stromal tissue.
- Follicular maturation is stimulated by the FSH secreted by the anterior pituitary
gland.

Primordial follicle
- 1 layer of squamous follicle-like cells surrounds the oocyte.

Primary follicle
- Can be:
- Unilaminar: the oocyte is surrounded by a single layer of cuboidal cells
- Multilaminar: the oocyte is surrounded by a stratified cuboidal epithelium

Secondary follicle
- As the follicle grows follicular fluid accumulates between the cell.
- The cavities that contain this fluid coalesce and form a larger cavity, the antrum.

Developmental events
- Migration to ovarian cortex happens in 6th week of development.
- Multiplication by mitosis.
- Some oogonia develop the potential to become mature female gametes.
Encapsulation by follicular cells. First stage of meiotic division is arrested.
- Birth: No further follicular development until sexual maturity.
- Sexual maturity: Secretion of pituitary FSH and LH.
- Some primordial follicles develop towards maturity with each ovarian cycle
- Increasing secretion of estrogen progressively inhibits release of FSH and
promotes LH release.
- First meiotic division is completed.
- Second meiotic division commences.
- Increasing levels of estrogen inhibit FSH release and promotes large release of LH.
Ovulation: progesterone secretion by corpus luteum maintained by LH.
- Fertilization/Implantation: Corpus luteum in pregnancy is maintained by HCG
secreted by developing embryo.

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Drawing

106. Graafian follicle

- The most mature stage of follicle development.

- The follicle will actually bulge from the surface of the ovary.
- Each month in adult women, 1 of the ripening follicles ejects its oocyte from the
ovary, an event called ovulation.
- Follicles that aren’t selected for ovulation undergo a process of degeneration
called atresia.
- After ovulation, the ruptures follicle is transformed into a very different looking
structure called the corpus luteum, which eventually degenerates.

107. Follicular atresia

- The process of follicular atresia (degeneration) may occur at any stage in the
development of the ovum.
- By the 6th month of development, the fetal ovary contains several millions of
primordial follicles, yet by the time of birth less than ½ of a million remain.
- Atresia continues until puberty and thereafter through the reproductive years.
- In addition, with each ovarian cycle, about 20 follicles begin to mature, usually all
but 1 becoming atretic at some stage before complete maturity.
- The histological appearance of atretic follicles varies enormously, depending on the
stage of development reached and the progress of atresia.
- Secondary follicle in early atresia: The oocyte has degenerated and the granulosa
cells have begun to discharge.
- Advanced atresia is characterized by gross thickening of the basement membrane
between the granulosa cells and the theca interna forming the so-called glossy
membrane.
- Atretic follicles are ultimately replaced completely by collagenous tissue.

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108. Corpus luteum – functions and evolution

- Following ovulation, the ruptured follicle collapses and fills with a blood clot and
the layers of the follicular wall become re-organized to form a temporary gland, the
corpus luteum of menstruation.
- Size: 1.5-2.5 cm, that of the antecedent ovulatory follicle.
- under the influence of LH secreted by the anterior pituitary, the cells of the former
zona granulosa increase in size and begin secretion of progesterone.
- The cytoplasm of these cells contains a bright yellow pigment (lutein) which gives
rise to the name granulosa lutein cells and the name corpus luteum to the whole
structure.
- Progesterone promotes exocrine secretion by glands in the endometrium which have
by now greatly proliferated under the influence of the estrogens secreted by the
follicles before ovulation. This provides a suitable environment for the implantation
of a fertilized ovum.
- The cells of the former theca interna also increases in size but to a lesser extent.
Although interrupted by ovulation, these cells continue to secrete estrogens, which are
recessed to maintain the thickened uterine mucosa. These cells are called the theca
lutein cells.
- The blood clot, granulosa lutein and the theca lutein layers are invaded by capillaries
and larger vessels from the former theca externa to form a rich vascular network
characteristic of endocrine glands.
- The corpus luteum is dependent on the secretion of LH from the anterior pituitary.
However, increased levels of progesterone inhibit LH secretion. Without the
continuing stimulus of LH, the corpus luteum cannot be maintained and in days 12-14
after ovulation it regress ultimately forming a functionless corpus albicans.
- Once the corpus luteum regresses, secretion of both estrogen and progesterone
ceases. Without these hormones, the endometrial lining of the uterus collapses
resulting in the onset of menstruation.
- Implantation of a fertilized ovum in the uterine wall interrupts the integrated ovarian
and menstrual cycles.
- After implantation, a hormone called HCG (human chorionic gonadotropin) is
secreted into the maternal circulation by the developing placenta.
- HCG has an analogous function to that of LH and maintains the function of the
corpus luteum in secreting estrogen and progesterone until about the 12th week of
pregnancy.
- After this time, the corpus luteum of pregnancy slowly regress to form a functionless
corpus albicans and the placenta takes over the major role of estrogen and
progesterone secretion until parturition.
- The corpus luteum of pregnancy is a much larger structure than the corpus luteum of
menstruation but has a similar basic organization.

109. The uterine tubes – general structure and function

- Also known as the Fallopian tubes or oviducts.

- Extends from the region of an ovary to the uterus.
- The proximal portion of the tube – that, which enters the uterus is the isthmus.
- The curved middle portion is the ampulla (where fertilization occurs).
- The distal portion is the infundibulum, which is an open funnel-shaped structure

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bearing ciliated finger-like projections called fimbriae that drape over an ovary.
- An ovulated oocyte is expelled into the peritoneal cavity.
- The cilia on the fimbriae generate a current of peritoneal fluid that sucks the ovary
into the uterine tube.
- The uterine tube wall contains lots of smooth muscle.
- The mucosa contains ciliated and non-ciliated cells. The non-ciliated cells produce a
secretion that keeps the oocyte (and only sperm present) nourished.
- An ectopic pregnancy may occur when an ovum is fertilized in the peritoneal cavity
and begins developing there. Such pregnancies naturally abort often with substantial
bleeding.
- Also, pathogens in the reproductive tract can sometimes spread into the peritoneal
cavity causing an extremely severe inflammation called pelvic inflammation disease.
- The uterine tubes conduct the ovum from the surface of the ovaries to the peritoneal
cavity and are also the site of fertilization by spermatozoa.
- The infundibulum moves so as to overlie the site of rupture of the Graafian follicle
at ovulation.
- Movement of the ovum down the tube is mediated by gentle peristaltic action of the
longitudinal and circular smooth muscle layers of the oviduct wall. This is aided by
the current of fluid propelled by the action of the ciliated epithelia.

110. The oviduct epithelium

- The mucosal lining of the oviduct is thrown into a labyrinth of branching,

longitudinal folds which provide a suitable environment for fertilization This is most
prominent in the ampulla.
- The epithelium is a simple columnar…
- Ciliated
- Non-ciliated: the produce a secretion which is propelled towards the uterus
by the numerous ciliated cells carrying with it, the ovum.
- The secretion probably also has a role in the nutrition and protection of the ovum.
- The ration of ciliated/non-ciliated cells and the height of the cells undergo
cylindrical variation under the influence of ovarian hormones.
- The ciliated cells are generally shorter than the secretory cells making the epithelial
surface somewhat irregular in outline.
- Has a lamina propria + muscularis layer + serosal layer (continuous with the broad
ligament).

111. The general structure of the uterus

- The uterus is located anterior to the rectum and posterior to the bladder.
- It is a hollow, thick-walled organ that functions to receive, retain and nourish a
fertilized egg.
- The major portion of it is the body.
- In the region superior to the oviduct entrance is the fundus.
- Slightly narrow region between the body and the cervix (most inferiorly) is the
isthmus.

Cervix
- The cervix is the narrow neck of the uterus that projects into the vagina inferiorly.
- The cavity of the cervix is the cervical canal, which connects with the vagina at the

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external os and connects with the cavity of the uterine body via the internal os.
- There are cervical glands in the mucosa that secrete a mucus that fills the cervical
canal and covers the external os, presumably to block the movement of bacteria from
the vagina to the uterus.  An exception occurs at the mid-cycle when the cervical
mucus becomes less viscous so as to allow sperm passage.

Uterine wall
- Has 3 layers: perimetrium (outer), myometrium (middle) and endometrium (inner).
- The perimetrium, the outermost serous layer is the visceral peritoneum.
- The myometrium is the bulky middle layer made of smooth muscle, which contracts
rhythmically altering parturition.
- The endometrium is the mucosal lining of the uterine cavity. It’s where the embryo
implants and resides during development. It has 2 chief layers, which is made of
simple columnar ciliated epithelium:
- The stratum functionalis is the superficial layer and it undergoes cyclic
changes in response to blood vessels of ovarian hormones and is shed during
menstruation.
- The stratum basalis forms a new functionalis after menstruation ends. It’s
unresponsive to ovarian hormones.
- The endometrium has numerous uterine glands that change in length as the
endometrial thickness changes.

Blood supply
- The uterine aa arise from the internal iliacs in the pelvis and sends branches into the
uterine wall. These branches break up into several arcuate aa within the myometrium.
- The arcuate aa send radial branches into the endometrium where they give off
straight aa to the stratum basalis and spiral aa to the stratum functionalis.
- The spiral aa undergo repeated degeneration and regeneration and its their spasms
that actually cause the functionalis layer to be shed during menstruation.

- The endometrial lining of the uterine cavity consists of a simple columnar ciliated
epithelium supported by a cellular stroma containing numerous simple tubular glands.
- Under the influence of estrogen and progesterone secreted by follicles during the
ovarian cycle, the endometrium undergoes regular cyclic changes.
- For successful implantation, the fertilized ovum requires an easily penetrable, highly
vascular tissue and an abundant supply of glycogen for nutrition.

112. The menstrual cycle

- A series of cyclic changes that the uterine endometrium goes through each month as
it responds to changing plasma levels of ovarian hormones: estrogen and
progesterone.

Menstrual cycle
- Days 1-5
- The uterus sheds all but the deepest portion of the endometrium.
- Stratus functionalis is detached from stratus basalis and sloughed off through the
vagina.
- In day 1, FSH levels are just starting to rise.
- In day 5, estrogen production is beginning.

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Drawing:

Proliferative phase
- Days 6-14 are the proliferative phase.
- Under the influence of the rising estrogen levels, the stratum basalis generates a new
stratum functionalis.
- As the new layer thickens, its glands enlarge and its spiral aa increase in length.
- The simple tubular glands proliferate to form numerous glands, which begin
secretion coincident with ovulation.

Secretory phase
- Days 15-27.
- Progesterone from the corpus luteum acts on the endometrium causing the spiral aa
to elaborate and coil more tightly and converts the stratum functionalis to a secretory
mucosa.
- The uterine glands enlarge, coil and begin to secrete nutritious glycoproteins into the
uterine cavity  this is also stimulated by progesterone.
- When progesterone levels fall (i.e. if implantation doesn’t occur), spiral aa spasm.
This denies the endometrial cells O2 and nutrients causing them to die.
- Spiral aa constrict one last time and then suddenly relax and open wide. Blood
rushes into the capillary beds and bursts them causing them to slough off and the
uterine cycle is back to day 1.

113. The squamo-columnar junction of the uterine cervix

- The uterine cervix protrudes into the upper portion of the vagina and contains the
endocervical canal linking the uttering cavity with the vagina.
- The function of the cervix is to admit spermatozoa to the genital tract at the time
when fertilization is possible, i.e. around the time of ovulation, but at other times,
including pregnancy, to protect the uterus and upper tract from bacterial invasion.
- In addition, the cervix must be capable of great dilation to permit the passage of the
fetal head during parturition.
- The endocervical canal is lined by a single layer of tall columnar mucus-secreting
cells.

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- Where the cervix is exposed to the more hostile environment of the vagina, it is
lined by the thick stratified squamous epithelium as in the rest of the vagina.
- The cells of ectocervix often have clear cytoplasm due to their high glycogen
content.
- The junction between the vaginal and endocervical epithelium is quite abrupt and is
normally located at the external os, the point at which the endocervical canal opens
into the vagina.
- The main bulk of the cervix is composed of tough, collagenous tissue containing
relatively little smooth muscle.
- Beneath the squamo-columnar junction, the cervical stroma is often infiltrated with
leukocytes forming part of the defense against ingress of microorganisms.

114. The vagina – general structure

- Thin-walled tube lining between the bladder and the rectum and extending from the
cervix to the body exterior.
- The urethra is embedded in its anterior wall.
- Provides a passageway for the delivery of an infant, menstrual flow and a
passageway for semen.
- The wall of the vagina consists of 3 coats: an outer adventitia + a smooth muscle
muscularis + a mucosa.
- Epithelium is stratified squamous non-keratinized.
- The vaginal mucosa has no glands. The cervical mucus glands and Bartholin’s
glands lubricate it.
- Vaginal epithelial cells release large amounts of glycogen, which is anaerobically
metabolized to lactic acid by the resident vaginal flora. This creates an acidic
environment that is harmful to sperm and to pathogenic microorganisms.
- In the relaxed state, the vaginal wall collapses to obliterate the lumen and the
vaginal epithelium is thrown up into folds.
- The dense lamina propria, contains many elastic fibers, has a rich plexus of small vv
and is isolated by glands.
- The smooth muscle bundles of the muscular layer are arranged in circular and
longitudinal layers. The long layers predominate especially externally.
- The combination of a muscular layer and a highly elastic lamina propria permits the
gross distention, which occurs during parturition.
- Conversely, after coitus, involuntary contraction of the smooth muscle layers
ensures that a pool of semen remains in the cervical region. Thick elastic fibers in the
outer adventitial layer also facilitate these functions.

115. Inactive mammary gland and active mammary gland in lactation

- The morphology of the secretory portion of the mammary gland varies with
menstrual cycle.

Inactive mammary gland

- The glandular component is sparse and consists of chiefly of duct elements. During
the menstrual cycle, the inactive breast undergoes slight cyclic changes. Early during
the follicular phase, the intralobular stroma is less dense, and terminal ductules appear
as cords formed by the cuboidal-shaped epithelial cells with little or no lumen.
- During luteal phase, the epithelial cells increase in height, and lumina appear in the

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ducts as small amounts of secretion accumulate.
- Also, fluid accumulated in the CT, which is followed by abrupt involution and
apoptosis during the last few days of menstrual cycle before onset of menstruation.

Mammary glands undergo dramatic proliferation and development during pregnancy.

- The mammary glands exhibit a number of changes in preparation for lactation.

These can be examined by the trimester of pregnancy.
- First trimester is characterized by elongation and branching of the terminal ductules.
The lining epithelial and Myoepithelial cells proliferate and differentiate from breast
progenitor cells found in epithelium of terminal ductules. Myoepithelial cells
proliferate between the base of the epithelial cells and the basal lamina in both the
alveolar and ductal portions of the gland.
- Second trimester is characterized by differentiation of alveoli from the growing ends
of the terminal ductules. The development of the glandular tissue is not uniform, and
variation in the degree of development is seen even within a single lobule. The cells
vary in shape from flattened to low columnar. Plasma cells, lymphocytes and
eosinophils infiltrate the intralobular CT stroma as the breast develops.
- At this stage, amount of glandular tissue and mass of the breast increases mainly due
to the growth of the alveoli.
- Third semester commences maturation of the alveoli. The epithelial glandular cells
become cuboidal with nuclei positioned at the basal cell surface. They develop an
extensive RER; secretory vesicles and lipid droplets appear in the cytoplasm.
- The actual proliferation of the interlobular stromal cells declines and subsequent
enlargement of the breast occurs through hypertrophy of the secretory cells and
accumulation of secretory product in the alveoli.
- The changes in glandular tissue during pregnancy are accompanied by a decrease in
the amount of CT and adipose tissue.

116. Placenta at term – general structure

- The developing fetus is maintained by the placenta, which develops from fetal and
maternal tissues.
- The placenta consist of a fetal portion, formed by the chorion, and a maternal
portion, formed by the decidual basalis.
- The 2 parts are involved in physiologic exchange of substances between the
maternal and fetal circulation.
- The utero-placental circulatory system begins to develop around day 9, with
development of vascular spaces called trophoblastic lacunae within the
syncytiotrophoblast.
- Maternal sinusoids, which develop from capillaries of the maternal side, anastomose
with the trophoblastic lacunae.
- The differential pressure between the arterial and venous channels that communicate
with the lacunae established directional flow from the aa into the vv, thereby
establishing a primitive utero-placental circulation.
- Numerous pinocytotic vesicles present in the syncytiotrophoblast indicate the
transfer of nutrients from the maternal vessels to the embryo.
- Proliferation of the cytotrophoblast, growth of chorionic mesoderm, and blood
vessel development give rise to the following:

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- Primary chorionic villi are formed by the rapidly proliferating cytotrophoblast. They
send cords or masses of cells into the blood-filled trophoblast lacunae in the
syncytiotrophoblast. The primary villi appear between days 11 and 13 of
development.
- The secondary chorionic villi are composed of a central core of mesenchyme by an
inner layer of cytotrophoblast and an outer layer of syncytiotrophoblast. They develop
at about day 16 when the primary chorionic villi become invaded by LCT from
chorionic mesenchyme. The secondary villi cover the entire surface of the chorionic
sac.
- The tertiary chorionic villi are formed by the end of 3rd week as the secondary villi
become vascularized by blood vessels that have developed in their CT cores.

117. Placenta tertiary villus

- The tertiary chorionic villi are formed by the end of 3rd week as the secondary villi
become vascularized by blood vessels that have developed in their CT cores.

- As the tertiary villi are forming, cytotrophoblastic cells in the villi continue to grow
out through the syncytiotrophoblast. When they meet the maternal endometrium, they
grow laterally and meet similar processes growing from neighboring villi.
- This, a thin layer of cytotrophoblast cells called the trophoblastic shell is formed
around the syncytiotrophoblast.
- The trophoblastic shell is interrupted only at sites where maternal vessels
communicate with the intervillous spaces. Future growth of the placenta is
accomplished by interstitial growth of the trophoblastic shell.
- Several types of cells are recognized in the CT stroma of the villi: mesenchymal
cells, reticular cells, fibroblasts, myofibroblasts, smooth muscle cells, macrophages
and fetal placental AG-presenting cells, historically also known as Hofbauer cells.
- Fetal placental AG-presenting cells are the specific villous macrophages of fetal
origin that participate in the placental innate immune reactions. In response to AG,
they proliferate and up-regulate specific surface receptors that recognize and bind to a
variety of pathogens.
- Like other AG-presenting cells, if stimulated, they increase the number of MCH II
molecules on their surfaces. They are more common in the early placenta.
- The vacuoles in these cells contain lipids, GAGs and glycoproteins.
- Recent studies of HIV-infected placentas indicate the HIV is primarily localized
within the fetal placental AG-presenting cells and in the syncytiotrophoblast.

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SKIN

118. General functions of the skin

Protection
- Chemical barrier
- Skin secretions:
- At low pH, the sebum slow down bacterial growth
- Human defensin is a natural antibiotic
- Cathelicidins proteins that prevent Strep A infections in wounded
skin
- Melanin:
- Chemical pigment that prevents UV damage
- Biological barrier
- Langerhan’s cells in epidermis present AGs to lymphocytes.
- Dermal macrophages (2nd line of defense).
- Physical/mechanical barriers
- Continuity prevents bacterial invasion.
- Glycolipids prevent diffusion of H2O and H20-soluble substances between
cells.
- Substances that are able to penetrate the skin:
- Lipid-soluble substances like O2, CO2, steroids and fat-soluble
vitamins.
- Organic solvents like acetone, dry cleaning fluid and paint chemicals
- Salts of heavy metals like mercury and nickel.

Body temperature regulation

- Production of sweat-dissipate heat-
- Constriction of dermal blood vessels – retain heat.

Cutaneous sensation – cutaneous sensory receptors

- Meissner’s corpuscle and Merkel cells – defect changes in pressure.
- Pacinian receptor – detect deep pressure contacts.
- Hair follicle receptors – movement across the surface of the skin.
- Nerve endings – detect painful stimuli.

Metabolic functions
- Synthesis of vitamin D – increasing calcium absorption in the body.
- Chemical conversion of many substances.

Blood reservoir
- Preferential shunting of blood as needed.

Excretion
- Elimination of nitrogen-containing wastes like salt and H2O.

119. Types of skin

- Thick skin, restricted to:

- The palms of the hands (0.88 mm) and soles of the feet (1.4 mm)

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 - Lacks hair
- Has abundant sweat glands
- Thin skin:
- Has hair
- Covers the rest of the body
- 0.12 to 0.17 mm

The skin consists of:

- 2 distinct but tightly attached layers:
- Epidermis
- Dermis
 Between them, you can find the dermal-epidermal junction
 Underlain by the hypodermis
- Structures associated with the skin:
- Glands (sebaceous and sweat glands)
- Hair
- Nails

120. Epidermal layers

- The epidermis is the outer layer of the skin.

- Compromised of keratinized stratified squamous epithelium.
- It is derived from the ectoderm.
- Lacks blood vessels, but has innervation: un-encapsulated free nerve endings.
- The epidermal layer is further divided into 5 strata:
- Stratum corneum
- Stratum lucidum (only in thick skin)
- Stratum granulosum
- Stratum spinosum
- Stratum basale
- The epidermis contains all populations specialized for specific functions:
- 2 major populations: keratinocytes and melanocytes
- 2 minor populations: Langerhan’s and Merkel’s cells.

Stratum basale (stratum germinativum)

- Cell types present: keratinocytes + Merkel cells + melanocytes
- A layer of columnar basophillic keratinocytes.
- Divides continuously and gives rise to the keratinocytes in all other layers.
- Desmosomes to their neighbors and hemidesmosomes to the basal lamina.
- Have melanin granules.
- Cytokeratin intermediate filaments (tonofilaments) are important components both
junctions.
- The cytokeratin content increases as these cells approach the stratum corneum,
where it constitutes about 50% of their total protein.

Stratum spinosum
- Several layers of large keratinocytes.
- Cuboidal or polygonal in the deeper layers and slightly flattened in the upper layer.
- Cytoplasm
- Tonofilaments:

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 - Fill the cytoplasm; extend into the numerous cell processes
responsible for the cells spiny appearance.
- Insert into the desmosomes that attach the tips of these processes to
those of adjacent cells.
- Lamellar bodies
- Melanin granules
- The mitotic rate is lower.
- Mitosis occurs only in the malphigian layer, which includes the stratum basale and
stratum spinosum.
- Langerhan’s cells are found in the stratum spinosum.
- Stratum basale + stratum spinosum  Malphigian layer (corpul malphigian).

Stratum granulosum
- Lies above the stratum spinosum.
- Few layers of flattened cells.
- Cytoplasm:
- Tonofibrils (tonofilaments bundles)
- Keratohyalin granules – the intense basophilia of these granules is caused by
their content of a phosphorylated histidine  rich precursor of the protein
filaggrin.
- Lamellar bodies – release their contents (GAG and PL) into the intercellular
spaces: Sealing the deeper layer from the external environment and protection
from dehydration.
- Produces vitamin D (cholecalcified) – requires UV irradiation of precursor molecule
(7-dehydrocholesterol).

Stratum lucidum
- Overlies stratum granulosum.
- Is apparent only in thick skin.
- It’s narrow, acidophillic, and translucent band of flattened keratinocytes.
- The nuclei, organelles and intercellular borders are no longer visible.
- Cytoplasm:
- Tonofilaments bundles embedded in an amorphous electron-dense matrix
derived from the keratohyalin granules: immature keratin.
- Insoluble involucrin.

Stratum corneum
- The outermost layer.
- Many layers of dead flattened enucleated keratinocytes with thickened plasma
membranes.
- The final stage of keratinization filled with mature keratin, a refringent scleroprotein
higher molecule volume of the polypeptides of mature keratin.
- Dead cells are continuously exfoliated from the surface and replaced by cells from
the deeper waves.

121. The keratinocytes

- Make up most of the epidermis.

- They participate in the continuous turnover (renewal) of the skin surface by passing
through 4 overlapping processes:

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 - cell removal, or mitosis
- Differentiation, or keratinization
- Cell death and exfoliation
- The entire process takes 15-30 days and occurs in waves.
- A cell layer produced by a mitotic wave in the basal layer undergoes keratinization
in synchrony.
- Each wave pushes the cell layers produced in earlier waves toward the surface.

122. The melanocytes

- Derives from the neural crest.

- 10-25% from the cells of basal layer but do not participate in keratinization.
- Round cell bodies
- Central nuclei
- Long cytoplasmic processes that pass between the cells of the stratum basale and
spinosum.
- End in small indentations on the keratinocyte surfaces.
- The cytoplasm contains many mitochondria + a well developed Golgi complex +
RER + special membrane-bound organelles (melanosomes).
- There is no difference in the number of melanocytes per unit area in the skin of
dark- and light-skinned races.
- Rather, differences in skin color reflect differences in the rates of melanin synthesis,
accumulation and degradation.

123. Melanin synthesis

- Tyrosine (with tyrosinase)  dopa  dopamine  melanin

Tyrosinase is synthesized by ribosomes of the RER and transported to the Golgi
complex. Membrane limited tyrosinase-filled vesicle called melanosomes pinch off
from the Golgi complex accumulate in the Golgi region and develop through 4 stages
to become mature melanin granules.

Faith of mature melanin granules:

- Mature granules move into the tips of the melanocytes processes.
- They are ‘’injected’’ into the keratinocytes of the basale and spiny layer, cytokine
secretion.
- They accumulate over the nuclei of the dividing keratinocytes, protecting the DNA
from the damaging effects of the sun’s rays.
- During keratinization, the granules, along with the nuclei and the organelles, are
digested by lysosomes.

Factors affecting melanin synthesis:

- Increased exposure to UV rays both darkens existing melanin and speeds tyrosinase
synthesis.
- Pituitary ACTH contains a peptide sequence identical to MSH that is known to
influence human pigmentation.
(Addison’s disease involves underproduction of cortisol by the adrenal cortex. The
pituitary gland releases excess ACTH to stimulate the adrenals. The resulting
stimulation of tyrosine activity in melanocytes causes the hyperpigmentation that
accompanies Addison’s disease.)

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- Albinism is caused by genetic defect in tyrosine synthesis and a consequent absence
of tyrosinase activity.

- Melanocytes of affected individuals typically contain only stage II melanosomes.

124. The melanosomes

- They are special membrane-bound organelles in melanocytes.

Stage I
- They are round vesicles with tyrosinase activity associated with fine-granular-to-
filamentous material in the vesicle periphery.

Stage II
-They are ovoid and contain parallel filaments.
- The associated tyrosinase activity triggers melanin deposition on the filaments.

Stage III
- They have the same structure as in stage II, but continued melanin deposition has
partly obscured the filaments.

Stage IV
- Mature melanin granules are 1 micrometer long, 0.4 micrometer wide, and so
completely filled with melanin that their ultrastructure is no longer visible.

125. Melanin functions

- Certain sun’s rays break from highly reactively free radicals.

- Ionizing radiation or free radicals can alter DNA structure causing cell death or
neoplastic transformation.
- The DNA of the dividing cells in the Malphigian layer is most susceptible to these
effects.
- Melanin’s dark color allows it to absorb some rays and free radicals.

Melanin
- Contributes to skin, eye and hair color.
- Include the:
- Dark brown pigment eumelanin, found in the epidermis, iris and brown and
black hair.
- The cysteine-rich pigment pheomelanin, found in red hair.

126. The pigmentation system

Skin color is conferred mainly by the:

- Pigments melanin and carotene.
- The thickness of the epidermis.
- The number of dermal blood vessels.
- The color of the blood in these vessels.

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127. Langerhan’s and Merkel’s cells

Langerhan’s cells
- Cells of the mesodermal origin, they arise in bone marrow and many belong to
mononuclear phagocyte system.
- AG-presenting cells.
- Found in stratum spinosum.
- Star-shaped, lack tonofilaments.
- They stain selectively with fold chloride.
- Contain numerous rod-like cytoplasmic granules, Birbeck granules.

Merkel’s cells
- Scattered in stratum basale.
- Most numerous in thick skin.
- They resemble basal keratinocytes but have a clearer cytoplasm containing many
small dense granules.
- Free nerve endings form a disk-like expansion, Merkel’s disk that covers the basal
surface of each Merkel’s cell.
- Suggest that the cells function as sensory mechanoreceptors.

128. Dermis – structural organization

- Contains: hair follicle (found in only thin skin) + sebaceous and sweat glands.
- Consists of 2 layers of vascular CT that blend at their common border: papillary
layer + reticular layer.

Papillary layer
- LCT, rich in reticular fibers.
- Beneath the epidermal basement membrane.
- Anchoring fibrils, expand into the epidermal basal lamina to reinforce dermal-
epidermal junction. Contains:
- Immunoprotective cells
- A capillary network
- Abundant free nerve endings, some of which penetrate the epidermis
- Tips of many dermal papillae, which contain encapsulated touch receptors,
the Meissner corpuscle.

Reticular layer
- Beneath the papillary layer
- DICT
- Richly vascularized
- Contain many arterio-venous anastomoses or shunts which control the amount of
blood reaching the papillary capillaries and thus aid in regulating hear loss.
- Contain a rich supply of nn in both free and encapsulated endings, the Pacinian
corpuscle.

Dermal-epidermal junction
- The stratum basale is underlain by a basement membrane connecting the epidermis
and dermis.
- The junction has the appearance of zigzagging interdigitations between upward

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projections of the dermis – dermal papillae, and downward projections of the
epidermis – epidermal ridges.

129. The hair follicle – structural organization

- Hair grows only in the thin skin.

- It’s size, shape and distribution vary according to race, age, sex and body region.
- Hair follicles are structures in skin that form hairs and maintain their growth.
- They extend from the surface deep into the dermis or hypodermis. The hair bulb –
consists of a cap of rapidly dividing epithelial cells (germinal matrix) overlying a
dermal papilla – with nerve and blood supply. Cells from germinal matrix keratinize
forming the concentric layers of the hair shaft as they move toward the surface.

Germinal matrix
- A cluster of epithelial cells capping the dermal papilla.
- Can be divided into 4 indistinct zones concentrically arranged around the papilla.
- The zone closest to the papilla resembles stratum basale of the epidermis in both
structure and function.
- It contains both columnar epidermal cells and melanocytes responsible for hair
color.
- Central cells produce large, vacuolated, moderately keratinized cells that form the
medulla of the hair.
- Cells that produce the cortex of the hair are located laterally.
- Cells forming the hair cuticle originate in the next layer.
- Peripheral epithelial cells develop into the internal and external root sheaths.
- The external root sheath surrounds the entire hair follicles and is continuous with the
epidermis, with the basal layer.
- In the internal root sheath, the cells disappear at the level of the opening of
sebaceous gland ducts.
- The most peripheral layer of the germinal matrix forms the poorly keratinized cells
of the internal root sheath.

130. The hair shaft

Has 3 concentric layers formed by germinal matrix:

Medulla
- Forms the thin shafts in the central core.
- Composed of poorly keratinized, often vacuolated cells.

Cortex
- Surrounds the medulla and is composed of several layers of fully keratinized
polygonal cells.

Cuticle
- The shafts outermost layer.
- Within the bulb, the cells are cuboidal.
- Further up become columnar, filled with keratin.
- Then they finally become flattened, highly keratinized cells, which will form the
hard cuticle that covers the hairs outer surface.

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131. Hair follicle associated structures

Internal root sheaths:

- Layer closest to hair shaft.
- Extends from the bulb to the level of sebaceous glands.
- Form 3 layers:
- Cuticle: is a layer of flat cells separated from the hair cuticle only by a
follicular canal.
- Huxley’s layer: composing 3 layers of low cuboidal cells.
- Outermost layer is: Henle’s layer, a translucent layer of flattened to cuboidal
cells resembling the epidermal stratum lucidum.

Sebaceous gland:
- Found near the neck of the root sheath.
- Deliver the secretions via a short duct into the follicular canal.

Arrector pill mm:

- Small bundles of smooth muscle fibers that originate in the papillary dermis and
extend obliquely toward the hair follicle.
- Insert into the follicles CT sheath below the sebaceous glands.
- When they contract, cause the hairs to stand upright, giving the appearance of
gooseflesh and compress the sebaceous glands.

External root sheath:

- Surrounds the internal root sheath and is continuous with the epidermis.
- Above the level of the sebaceous glands, it includes all the epidermal layers.
- Below the level, it retains only the granulosum, spinosum and basale.
- The granulosum is also lost near the follicle’s base, where the spinosum and basale
become continuous with the layers of the germinal matrix.

Glossy membrane:
- This is the thickened basal lamina underlying the stratum basale of the external root
sheath.

Connective tissue sheath:

- A layer of condensed CT that surrounds the entire follicle, including the bulb. It
extends along the follicle to the surface where it blends into the looser papillary
dermis.

132. The nail

- The nail is a plate of highly keratinized cells, which are analogous to, but harder
than the stratum corneum.
- The nail plate consists of 2 parts:
- Nail root (the part hidden in the nail groove)
- The nail body (the visible part of the nail)
- Free end
- The nail and its supporting structure are surrounded by papillary dermis, the nail
matrix:

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 - A thickened region of epidermis containing: proliferating cells in the layer
that directly contacts the dermis + keratinizing cells between this basal layer
and the nail plate.
- The nail bed:
- Lies beneath the nail body, distal to the nail matrix.
- Consists of only the deeper epidermal layers, for which nail serves as a
stratum corneum.
- The eponychium (cuticle):
- Is a thick keratinized layer extending from the upper surface of the nail
groove over the most proximal part of the nail body.
- The hyponchium:
- Is a local thickening of the stratum corneum underlying the free (distal) end
of the nail plate.
- The lunula:
- Is the whitish, opaque, crescent-shaped region on the proximal nail body,
adjacent to the nail groove.
- Its distal border corresponds roughly to the underlying nail matrix.

133. The sebaceous gland

Structure and localization:

- Exocrine gland
- Occur in all thin skin areas
- Most often in association with hair follicles where their ducts open
- Most numerous in the skin of the face, forehead and scalp.
- In hairless skin, they open directly into the surface.
- Their acinar secretory portions contain many large lipid-filled cells that appear pale
staining and foamy.

Functions:
- The acinar cells fill with lipid droplets containing a mixture of triglycerides, waxes,
squalene and cholesterol and its esters.
- Their nuclei become pyknotic and the cells eventually burst, releasing their contents
and other cell debris into the ducts, in a holocrine secretion.
- The oily sebum moves through the ducts and into the hair follicle, where it covers
the hair and moves out onto the surface.
- Lubricates the skin and may have some antibacterial or antifungal effect.
- The secretory activity of these glands, which begin functioning at puberty is
continuous and is increasing by androgens.

134. The eccrine (merocrine) sweat gland

Sweat gland:
- 2 types of sweat glands: eccrine (or merocrine) + apocrine.
- Both develop as epidermal invaginations into the dermis, and they differ mainly in
their size, distribution and secretory products.
Secretory portions:
- Highly coiled parts of the sweat glands.
- Located in the deep reticular dermis or shallow hypodermis.
- Surrounding CT condenses to form a sheath around the basal lamina.

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- There are numerous Myoepithelial cells between the basal lamina and the secretory
cells.
- The secretions are released via exocytosis.
- Secretory cells are larger and stain lighter than the duct lining cells.
- 2 secretory cell types are seen:
- Dark (mucoid) cells – pyramidal and line most of the glands secretory
portion. Their bases do not reach the basal lamina and they contain dark
granules.
- Clear cells – pyramidal. They lack secretory granules, contain abundant
glycogen and surround the inner layer of dark cells. Their basal pole (ion and
H2O transport), which contacts the basal lamina, is highly infolded.

Eccrine sweat gland:

- The most numerous sweat glands in humans.
- About 3 000 000 per individual
- They occur over most of the body, except for the glans penis, glans clitoris and the
vermillion border or the lips.
- They are most abundant in thick skin, such as the palms, where you can find about
3000 per inch.
- They are simple coiled tubular glands with coiled ducts.
- The coiled ducts are:
- Lined with simple to stratified cuboidal epithelium.
- Cells are smaller than those in the secretory portion and stain darker.
- Each duct opens directly onto the skin surface.

Secretory product:
- A watery secretion: NaCl, urea, ammonia and uric acid.
- Excreting products of protein metabolism.
- Evaporation of H2O from the skin surface decreases body temperature by cooling
the blood in the papillary capillaries.

135. The apocrine sweat gland

Sweat gland:
- 2 types of sweat glands: eccrine (or merocrine) + apocrine.
- Both develop as epidermal invaginations into the dermis, and they differ mainly in
their size, distribution and secretory products.
Secretory portions:
- Highly coiled parts of the sweat glands.
- Located in the deep reticular dermis or shallow hypodermis.
- Surrounding CT condenses to form a sheath around the basal lamina.
- There are numerous Myoepithelial cells between the basal lamina and the secretory
cells.
- The secretions are released via exocytosis.
- Secretory cells are larger and stain lighter than the duct lining cells.
- 2 secretory cell types are seen:
- Dark (mucoid) cells – pyramidal and line most of the glands secretory
portion. Their bases do not reach the basal lamina and they contain dark
granules.
- Clear cells – pyramidal. They lack secretory granules, contain abundant

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 glycogen and surround the inner layer of dark cells. Their basal pole (ion and
H2O transport), which contacts the basal lamina, is highly infolded.

Apocrine gland:
- Less numerous than merocrine glands.
- Occur mainly in the axilla, pubic and oral regions, and the areolae of the breasts.
- Structure:
- Simple coiled tubular large glands.
- The coiled ducts are lined with cuboidal epithelium and open into hair
follicles.
- Secretory portions:
- Coiled and embedded in the dermis.
- Wide lumen lined by cuboidal to columnar cells.
- Myoepithelial cells are present between the secretory cells and the basal
lamina.

Secretory product:
- It is a viscous, odorless fluid that acquires a distinctive odor as a result of bacterial
degeneration.
- The secretory cells of these glands released their apical cytoplasm along with the
secretory product.

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URINARY APPARATUS

136. Kidney lobes and lobules

- Location: on either side of the spinal column in the retroperitoneal space of the
posterior abdominal cavity. They extend from the 12th thoracic to the 3rd lumbar
vertebrae. The left kidney position is slightly higher.
- Shape: bean-shaped organs.
- Size: 10 cm long x 6.5 cm wide x 3 cm thick
- Renal capsule: collagen fibers that cover outer surface of the organ.
- Adipose capsule: layer of adipose tissue that surrounds and protects the kidney
against trauma.
- Renal fascia: CT that anchors the kidney to surrounding structures.

Lobes and lobules

- Medullary pyramid
- Associated cortical tissue
- Cortical columns
- Number of lobes = number of medullary pyramids
 These structures constitute one lobe.

- Medullary ray
- Surrounding cortical material
- Lobule consists of a collecting duct + all the nephrons that it drains
 These structures constitute one lobule.

137. The nephron – general structure

- Structural and functional unit of the kidney

- Renal corpuscle of Malpighi
- Uriniferous tubule: Proximal tubule + loop of Henle + distal tubule
- Types of nephrons:
- Subcapsular or cortical nephrons:
- Renal corpuscles in the outer part of the cortex.
- Short loops of Henle
- Juxtamedullary nephrons
- Renal corpuscles in the inner part of the cortex
- Long loops of Henle
- Intermediate or mid-cortical nephrons
- Renal corpuscles in the mid-region of the cortex.

Functions:
- Blood filtration in renal corpuscle
- Resorption in PCT and DCT
- Urine concentration in Henle’s loop and DCT
- Secretion in PCT and DCT

138. The renal corpuscle

- The renal corpuscle is responsible for the filtration of plasma and is a combination

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of 2 structures, Bowman’s capsule and the glomerulus.
- Bowman’s capsule consists of a single layer of flattened cells resting on a basement
membrane. It forms the distended blind end of renal tubule.
- The glomerulus is a globular network of densely packed anastomosing capillaries,
which invaginates Bowman’s capsule.
- Within the capsule, the glomerulus is invested by a layer of epithelial cells
called podocytes, which constitute the visceral layer of the capsule.
- The visceral layer is reflected around the vascular stalk of the glomerulus to
become continuous with the parietal layer, which constitute Bowman’s
capsule proper.
- The space between the visceral and parietal layer us Bowman’s space and is
continuous with the lumen of the renal tubule.
- The parietal epithelium of the capsule is continuous with the epithelium lining the
renal tubule.
- The renal corpuscle of Malpighi has:
- A vascular pole: afferent and efferent arterioles.
- A urinary pole: entrance of renal tubule.

Drawing

- Parietal layer:
- Simple squamous epithelium
- Basal lamina
- Visceral layer:
- Specialized cells – podocytes / visceral epithelial cells.

139. Renal circulation

- Some aspects of the blood supply of the kidney have been described in relation to
specific functions (i.e. glomerular filtration, control of BP and countercurrent
exchange). It remains, however, to provide an overall description of the blood supply
of the kidney.
- Each kidney receives a large branch from the abdominal aorta, the renal artery. The
renal artery branches within the renal sinus and sends interlobular arteries into the
substance of the kidney.
- These aa travel between the pyramids as far as the cortex and then turn to follow an

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arched course along the base of the pyramid between the medulla and the cortex.
- Thus, these interlobular aa are designated actuate aa. They branch from the arcuate
aa and ascend through the cortex toward the capsule. Although the boundaries
between the lobules are not distinct, the interlobular aa, when included in a section cut
perpendicular to the vessel, are located midway between adjacent medullary rays,
travelling in the cortical labyrinth.
- As the traverse the cortex toward the capsule, the interlobular aa give off branches,
the afferent arterioles, on to each glomerulus. A single afferent arteriole may spring
directly from the interlobular artery, or a common stem from the interlobular artery
may branch to form several afferent arterioles.
- Some interlobular aa terminate near the periphery of the cortex, whereas others enter
the kidney capsule to provide its arterial supply.
- Afferent arterioles give rise to the capillaries that form the glomerulus. The
glomerular capillaries reunite to form an efferent arteriole that, in turn, give rise to a
second network of capillaries, the peritubular capillaries. The arrangement of these
capillaries differs according to whether they originate from cortical or juxtamedullary
glomeruli.

- Efferent arterioles from cortical glomeruli lead into a peritubular capillary network
that surround the local uriniferous tubules.
- Efferent arterioles from juxtamedullar glomeruli descend into the medulla alongside
the loop of Henle; they break up into smaller vessels that continue toward the apex of
the pyramid but make hairpin runs at various levels to return as straight vessels
toward the base of the pyramid.
- Thus the efferent arterioles from the juxtamedullary glomeruli give rise to vasa recta
involved in the countercurrent exchange system and their peritubular capillary
network.

Generally, venous flow in the kidney follows a reverse course to arterial flow, with
the veins running in parallel with the corresponding aa.
- Thus, peritubular cortical capillaries drain into interlobular vv, which in turn drain
into arcuate vv, interlobular vv and the renal vein.
- The medullar vascular network drains into arcuate vv and so forth.
- The peritubular capillaries near the kidney surface and capillaries of the capsule
drain into stellate vv (so called for their pattern of distribution when viewed from the
kidney surface), which drain into interlobular vv, and so forth.

Lymphatic vessels:
- The kidneys contain 2 major networks of lymphatic vessels. They are not usually
visible in routine histologic sections but can be demonstrated by experimental
methods.
- One network is located in the outer regions of the cortex and drains into larger
lymphatic vessels in the capsule.
- The other network is located more deeply in the substance of the kidney and drains
into large lymphatic vessels in the renal sinus. There are numerous anastomoses
between the 2 lymphatic networks.

Nerve supply:
- The fiber that form the renal plexus are derived mostly from the sympathetic
division of the autonomic nervous system. They cause contraction of vascular smooth

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muscle and consequent vasoconstriction.
- Constriction of the afferent arterioles to the glomeruli reduces the filtration rate and
decreases the production of urine.
- Constriction of the efferent arterioles from the glomeruli increase the filtration rate
and increases the production of urine.
- loss of sympathetic innervation leads to increased urinary output.
 It is evident, however, that the extrinsic nerve supply isn’t necessary for normal
renal function. Although the nerve fibers to the kidney are cut during renal
transplantation, transplanted kidneys subsequently function normally.

140. Ultrafiltration barrier (membrane)

Filtration apparatus of the kidney:

1) Endothelium of the glomerular capillaries
2) Glomerular basement membrane (GBM)
3) Visceral layer of Bowman’s capsule (contains podocytes)

GBM:
- Principal component of filtration barrier.
- Acts as physical barrier and an ion-selective filter.
- Components:
- Lamina rara externa: adjacent to podocytes processes
- Lamina densa: contains type IV collagen
- Lamina rara interna: adjacent to capillary endothelium

Functions of ultrafiltration barrier:

- Endothelial fenestrate: barrier for cells and thrombocytes.
- Basement membrane: physical barrier.
- Filtration slits: allow the ultrafiltrate from the blood to the center, Bowman’s space.

Drawing

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141. Mesangium and renal interstitium

Mesangium
- Mesos=middle, angeion=vessel, cells and their extracellular matrix=Mesangium

- Mesangial cells:
- Positioned much the same as pericytes
- Located in glomerulus, between capillary loops, surrounded by basement
membrane
- Are concentric and have receptors for angiotensin II
- Mesangial matrix
- Mesangium functions:
- Phagocytosis:
- Mesangial cells remove trapped residues and aggregated proteins
from GBM.
- Structural support:
- Mesangial cells provide support for the podocytes in the areas where
the epithelial basement membrane is absent or incomplete.
- Secretion:
- Synthesize and secrete IL-1 and PDGF

Renal interstitium
- The CT of kidney parenchyma, surrounds the nephrons, ducts, blood and lymphatic
vessels.
- Cortical interstitium (constitutes approximately 7% of the cortex volume).
- Medullary interstitium (constitutes more than 20% of the medullar volume.

142. Uriniferous tubes

Proximal tubule
- Has 2 segments:
- A convoluted segment, PCT, in the renal cortex
- A Straight segment, pars recta
- The PCT is the longest, most convoluted section of the tubule. It’s responsible for
the reabsorption of about 75% of the glomerular filtrate.
- The pars recta descend towards the medulla before becoming the loop of Henle.
- The proximal convoluted tubule is lined by simple cuboidal epithelium. It has a
basement membrane and some surface specializations: microvilli + a junctional
complex + plicae or folds + extensive interdigitations of basal processes + basal
striations, consisting of elongated mitochondria.
- Functions:
- Reabsorption:
- Passive, for H2O.
- Active, for glucose, amino acids, proteins and ions.
- Secretion.

Henle’s loop
- Located in the renal cortex and medulla.

- Thick descending limb – very similar in structure to the DCT

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- Think descending limb – simple squamous epithelium, completely permeable to
H2O and ions.
- Thin ascending limb – simple squamous epithelium, impermeable to H2O,
permeable to salts.
- Thick ascending limb, simple cuboidal epithelium.

- The function of the loop of Henle is to produce an increasing osmotic gradient from
the cortex to he tip of the renal papilla by the counter current multiplier mechanisms.
This involves the active transport of Na+ and Cl- into the medullary interstitium by
the ascending thin limb, which is impermeable to H2O.
- The increasing osmotic pressure in the medullary ECF provides the mechanism by
which urine later undergoes concentration in the CTs and ducts under the influence of
ADH.

Distal tubule
- Straight tubule:
- Located in the cortex and medulla.
- Simple cuboidal epithelium.
- Transports ion from tubular lumen to interstitium.
- Convolutes tubule:
- Located in the cortex.
- Simple cuboidal epithelium.
- Establishes contact with vascular pole of renal corpuscle (macula densa).
- Responds to aldosterone by resorbing Na+ and Cl- from lumen.
- Ca2+ resorption.
- This activity is essential for maintenance of acid-base balance in the blood.

Collecting ducts
- Located in cortex and medulla.
- Several nephrons are drained by a single collecting tubule.
- Multiple collecting tubules join in the deeper aspect of medulla to form larger ducts
of Berllini  perforate the renal papilla at the area cribrosa.
- The collecting ducts are lined by simple cuboidal epithelium (which becomes taller
distally, to columnar) with 2 types of cells:
1) Principal cells – light cells
- Are principal cells of the system
- Few short microvilli, small mitochondria
- Na+ and H2O resorption (passes an abundance of ADH)
- K+ secretion

2) Intercalated cells – dark cells

- Many mitochondria
- Cytoplasm appears denser
- Cytoplasmic folds, microplicae
- Microvilli are present on apical surface
- Secretion of H+ or HCO3-  support acid-base balance

- The collecting tubules and ducts concentrate urine by passive resorption of H2O into
the medullary interstitium following the osmotic gradient created by the
countercurrent multiplier system of the loop of Henle.

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- The process is known as the countercurrent exchange system and is controlled by
ADH. ADH increases the permeability to H2O of the CTs and ducts, which will result
in retention of H2O by the body and the production of hypertonic urine.
- Conversely, ADH secretion is inhibited by H2O overloading and an increasing
volume of hypotonic urine is thus produced.

Nephron functions:
- Blood filtration in renal corpuscle.
- Reabsorption in PCT and DCT.
- Urine concentration in Henle’s loop and DCT.
- Secretion in PCT and DCT.

143. Juxtaglomerular apparatus

- The JGA is a specialization of the glomerular afferent arteriole and the DCT of the
corresponding nephron and is involved in the regulation of systemic blood pressure
via the renin-angiotensin-aldosterone mechanism.
- The JGA includes:

Macula densa
- On returning to the cortex from the renal medulla, the ascending thick limb of the
loop of Henle becomes the first part of the distal convoluted tubule (DCT) and comes
to lie in the angle between the afferent and efferent arterioles at the vascular pole of
the glomerulus.
- The macula densa is an area of closely packed, specialized cells lining the DCT
where it abuts onto the glomerular vascular pole.
- Compared with other DCT lining cells, the cells of the macula densa are taller and
have longer more prominent nuclei, which are situated towards the luminal surface,
the basal cytoplasm being crammed with mitochondria.
- The basement membrane between the macula and underlying cells is extremely thin.
- The cells of the macula densa are thought to be sensitive to the concentration of Na+
in the fluid within the DCT.
- A decrease in the systemic blood pressure, results in a decrease in production of
glomerular filtrate, which in turn results in a decreased concentration of Na+ in the
distal tubular fluid.

Juxtaglomerular cells
- Juxtaglomerular cells are specialized smooth muscle cells of the wall of the afferent
arteriole forming a cluster around it just before it enters the glomerulus.
- Their cytoplasm containing immature and mature membrane bound granules of the
enzyme renin.

Extraglomerular mesangial cells (= Goodmaghtigh/Lactic cells)

- Form a conical mass, the apex of which is continuous with the Mesangium of the
glomerulus.
- Laterally it is bounded by the afferent and efferent arterioles and its base abuts onto
the macula densa.
- the lactic cells are flat and elongated.
- They have an extensive fine cytoplasmic process extending from their ends and are
surrounded by a network ‘’laeis’’ of mesangial material.

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- Their function is unknown.

Functions of JGA:
- Acts on both baroreceptor and chemoreceptor controlling systemic blood pressure
by secretion of renin by the JG cells.
- Regulated blood pressure by activating the renin-angiotensin-aldosterone system:
- Maintaining Na+ homeostasis and renal hemodynamics.

144. Ureters

- About 25-30 cm long.

- Diameter of 3-4 mm.
- Conducts urine from the renal pelvis to urinary bladder.
- Intraperitoneal.
- Urothelium lines the luminal surface of ureter wall.
- Mucosa:
- Urothelium + thick lamina propria + CT and collagen fibers.
- Muscularis:
- 3 layers (in upper 2/3, 2 layers) (in lower 1/3, 3 layers) of smooth
muscle (inner and outer – longitudinal, middle – circular)
- Adventitia:
- Adipose tissue + collagen fibers
- Vessels and nn + lymphatics

- The lumen of the ureter is lined by transitional epithelium, which is thrown up into
folds in the relaxed state allowing the ureter to dilate during the passage of a bolus of
urine.

145. Urinary bladder

- Mucosa: urothelium + lamina propria

- Muscularis: 3 layers of smooth muscle (detrusor muscle)
- Thin inner and outer longitudinal layer
- Thick middle circular layer
- Adventitia: dense, irregular, collagenous type of CT and numerous elastic fibers.

Urothelium (stratified):
- 3-6 layers of cells.
- Transitional epithelium cells:
- The superficial cells are rounded and bulge into the lumen
- Frequently are binucleated
- Acidophillic cytoplasm
- Impermeable barrier: prevents H2O from being drawn through the
epithelium into hypertonic urine.
- The number of layers being greatest when the epithelium is least distended at the
time of fixation.
- The cells of the basal layer are compact and cuboidal or columnar in form, those of
the intermediate layers are more polygonal whilst the surface cells are tall columnar
with large, round nuclei with prominent nucleolus.
- The surface outline has a fuzzy superficial cytoplasm, more intensely stained.

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- The surface plasma membrane consists of thickened inflexible plaques with narrow
zones of normal membrane between acting as ‘’hinges’’, allowing sections of the
membrane to fold, forming deep clefts and stacks of flattened fusiform vesicles. This
structure renders the urothelium impermeable to urine, which is potentially toxic.

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