Knowledge Co-op 2004 Presents:
The Histology Final
Review Packet
Disclaimer: Although the Histo Final Packet is a highly
acclaimed study aide, and we have been extremely
careful to make it accurate and complete (thanks to all
the lecturers for editing these notes!), we still can’t
promise perfection.
Good luck on the test!!
Your coordinators: Genie Bang (bang0076) and Kathryn
Berkseth (berk0095)
**Don’t forget, this packet along with the Exam
Explained for the 2003 Final will be posted on the K-Coop
website.
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Cardiovascular System
Dr. Erlandsen
K-coop writer: Thuy Nguyen
Capillaries
Composition
Size
Blood Capillaries
1. simple squamous epithelium
(endothelium)
2. basement membrane
Uniformly about 8 μm in diameter
Lymph Capillaries
1. simple squamous epithelium
2. incomplete basement
membrane
Variable
Things Found in Capillaries:
1. interdigitations (finger-like junctions) of adjacent cell membranes jointed by tight junctions
between
cells of the endothelium
a. fluid exchange occurs here
2. some capillaries have pores with or without diaphragm coverings (see chart on capillaries)
3. pericytes:
a. mesenchyme-like cells
b. found intermittently around capillaries
c. surrounded by capillary basement membranes
d. thought to be contractile
e. may function as mixed macrophages
d. may augment basement membrane production
f. capable of transforming into vascular smooth muscle cells (repair of injury)
4. pinocytotic vesicles
a. size: 50-70 nm in diameter
b. invaginations of the cell membrane on both inner & outer surfaces of the capillary
c. function as transportation of high molecular weight molecules across the endothelium
5. diffusion across the wall:
a. transports: water & ions between the capillary lumen & extracellular space
b. rate depends on: blood & colloid osmotic pressure
6. diapedesis: the fancy term for amoeboid migration of white blood cells through the
endothelium and into
the extracellular space
Vessel Tunics
Tunica Intima: the innermost layer composed of
1. a single layer of squamous endothelial cells
2. basement membrane
3. subendothelial layer that lies beneath the endothelial cells composed of longitudinally
arranged:
a. loose connective tissue
b. fibroblasts
c. scattered muscle cells
4. internal elastic lamina (especially well developed in muscular arteries) composed of:
a. fenestrated layer of elastic fibers
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Tunica Media: the intermediate layer composed of circumferentially arranged
1. smooth muscle cells
2. interspersed within the smooth muscles are:
a. elastic fibers
b. type III collagen
These fibrous elements form lamellae within the
ground substance secreted by smooth muscle cells.
c. proteoglycans
3. external elastic lamina
c. well developed in larger muscular arteries
b. usually more delicate than the internal elastic lamina
c. separates the tunica media from the overlying tunica adventitia
Tunica Adventitia: outermost layer composed of longitudinally arranged:
1. fibroblasts
Dense connective tissue
2. type I collagen fibers
3. elastic fibers
4. becomes continuous with the connective tissue elements surrounding the vessel
Basic Arteries Info:
1. tunic media is the most well-developed tunic in all arteries
2. inner elastic lamina is nearly always present
3. an external elastic lamina is present in LARGE arteries
Specializations of Arteries:
1. vasa vasorum: tiny nutrients arteries supply the walls of elastic arteries (little holes in the aortic wall)
2. nerves:
a. efferent: vasomotor fibers from the autonomic system terminate on arterial smooth muscles
b. afferent fibers are also present, sending back information to the nervous system
3. carotid body: a mass of epitheloid cells & nerve endings found at the bifurcation of the common carotid
artery.
It is responsible for stimulation of respiration in response to lowered blood CO2
4. carotid sinus: a dilatation of the internal carotid artery containing nerve endings sensitive to:
blood pressure change
Veins
1. Their structure is highly variable and depends on the physiological stress to which they are subjected.
2. For the rest of the information on veins look in the chart
Valves of Veins:
1. found in many medium-sized veins
2. they are composed of:
a. paired invaginations of the tunica intima (the core)
b. free edges (2 leaflets) point in the direction of blood flow (so that when blood happens to flow
backward,
the pressure from the backward flow would force the leaflets to move down and prevent
backflow)
c. lined by endothelium on either side of the leaflet
d. reinforced by collagen & elastic fibers
e. they lack circular smooth muscles
3. valves are absent in the portal system
4. valves aid movement of blood under low pressure back to the heart
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Comparison of Arteries vs. Veins
Lumen
Wall thickness
Wall Content
Special things
Arteries
Smaller
Thicker
More smooth muscle
More elastic fiber
Inner elastic lamina
Veins
Larger
Thinner
More collagen than
smooth muscle
May have valves
The Heart
I. The 3 tunics of the blood vessels are continued in the heart but now they’re given different names (to
complicate
our lives of course):
A. Endocardium:
1. continuous with the intima of the vessels
2. composed of:
i. endothelium
ii. basement membrane
iii. subendothelial connective tissue (occasionally may have some smooth muscle)
a. responsible for binding endocardium to myocardium
b. composed of loose connective tissue w/collagen, elastic fibers, & fat
iv. subendocardial connective tissue
c. the impulse conducting system passes through this layer in the ventricles
B. Myocardium
1.. thick bundles of cardiac muscle in ventricles & thinner in atria
2. sheets of cardiac muscle spiral around the heart
3. thin collagen, elastic, & reticular networks separate muscle bundles
4. capillaries & nerves also pass between the muscle bundles
C. Epicardium
1. visceral layer of the pericardium
2. visceral & parietal pericardia together form the mesothelium lined fluid filled pericardial
sac
3. a thin layer of loose connective tissue (subepicardium) that connects the mesothelium to the
myocardium and carries:
i. coronary arteries
ii.cardiac veins
iii. nerves
iv. ganglia
4. fat is found in the epicardium especially surrounding the arteries & veins of the heart
5. epicardium is distinguished from the endocardium by a large amount of fat accumulation
II. Cardiac Skeleton
1. fibrous ring: dense connective tissue surrounding the atrioventricular, aortic & pulmonary
valves (heart)
2. composed of:
i. large amount of collagen
ii. elastic fibers
iii. chondroid-like connective tisse may be found
3. provides support for attachment of cardiac muscle & valves
4. fibrous trigones = thickened areas of dense fibrous connective tissue:
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i. between the right & left atrioventricular canals
ii. aortic valve
5. membranous part of the atrioventricular septum
III. Cardiac Valves
1. composed of evaginations of endocardium (at the fibrous rings):
i. into the right & left atrioventricular canals
ii. at the origins of the aorta
iii. at the origins of the pulmonary trunk
2. each valve is covered on both sides by endothelium
3. core of collagen & elastic fibers
IV. Impulse Conducting System of the Heart
A. Purkinje fibers: specialized cardiac muscle fibers
1. consists of poorly striated (due to loss of myofibrils) cardiac muscle fibers
2. important in coordinating the heart beat
3. cells have a high content of glycogen
B. Sino-atrial (SA) node:
1. composed of specialized myofibers at the junction of the superior vena cava & the right
atrium
2. the origin of the stimulus for atrial contraction
C. Atrioventricular (AV) node:
1. composed of conducting myofibers in the interatrial septum (in between the 2 atria) near the
opening of
the coronary sinus
2. receives stimulation from the contractile wave that passes through the atrial muscle fibers
(although it
can also act as an autonomic pacemaker)
3. sends out an impulse via the AV bundle branches through the heart skeleton to stimulate
contraction of
the ventricular muscles
V. Other Things to Remember About the Heart:
1. sympathetic autonomic nervous system: stimulates myocardial activity
2. parasympathetic autonomic nervous system (vagal): inhibits myocardial activity
3. regeneration of cardiac muscle is negligible = take care of your heart!
4. tissue injured by wounding or disease is replaced by fibrous connective tissue (something that will be
nailed in your brain from pathology next year)
Sample Exam Questions:
1. Which one of the followings is TRUE about vascular capillaries?
a. all vascular capillaries have fenestrations
b. sinusoidal capillaries have thin diaphragms covering their fenestrations
c. diffusion of water and ions to and from the capillary lumen occurs mainly by diffusion
d. pinocytosis is the main route for transporting high molecular weight compounds and is only
seen at the
inner surface of the capillaries (i.e. dumping stuff into the lumen of the capillaries)
e. diapedesis is a term describing the migration of red blood cells across the capillary wall into the
extracellular space
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2. Which of the followings are FALSE regarding arteries?
a. vasa vasorum are found in the walls of large arteries (e.g. aorta)
b. the tunica media of arterioles contain 1-5 layers of smooth muscle cells
c. autonomic nervous control of smooth muscle in the muscular arteries regulates distribution of
blood flow
d. the external elastic lamina is well developed in arterioles
e. the tunica adventitia is thinner than the tunica media in large arteries
3. Which of the followings are TRUE of veins?
a. valve leaflets are positioned so that their free edges are facing away from the blood flow
b. the tunica media is the most well developed layer compared to the tunica intima and adventitia
c. the walls of veins are thicker than their accompanying arteries
d. veins contain more collagen than smooth muscles
e. veins functioning in the portal system (e.g. hepatic portal) have many valves
4. Which of the followings are NOT TRUE about the heart?
a. Purkinje fibers have a high content of glycogen
b. the core of the cardiac valves contains collagen and elastic fibers
c. endocardium is continuous with the tunica intima of the blood vessels
d. regeneration of cardiac muscle occurs but is negligible
e. all of the above are true
Answers: 1. c; 2. d; 3. d; 4. e
Good Luck on your exams!
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8
Lymphoid System
I know this seems long and a ton of material was covered in lecture, but don’t get too stressed out. Just know that
you will learn this all again in Micro in the spring. If you have questions I’ll try to answer them!
Anne Pylkas, Pylk0010@umn.edu
I.
Protective Mechanisms are either:
a. Innate Immunity
i. Non specific, No diversity, No lag time, No memory
ii. Mechanical Barriers-skin, mucous membranes
iii. Secretions- muscous, epithelial cells secrete FAs- acidic, protective
iv. Competition- pathogens must compete with normal nonpathogenic bacteria
v. Fever- makes it more difficult for bacteria to thrive, also causes bacteria to require more iron
that the body attempt to make unavailable
vi. Soluble factors- Dnase, Rnase, lysozyme present in blood and lymph. Complement produces
transmembrane channels in gram negative bacteria
vii. Inflammation- attracts cellular responses to the area
viii. Mononuclear phagocyte system
b. Adaptive Immunity
i. Specific- recognition of a specific foreign substance (an epitope as part of an antigen)
ii. Large diversity of responses
iii. Several days lag time and memory, acquired immunity
iv. Lymphoid system mediates adaptive immune response
1. Cellular immunity- short distance, T cells
2. Humoral immunity- long distance, B cells
II. Lymphoid System
a. Lymphocytes
i. B Cells- Humoral immunity- antibody secreting plasma cells, antibodies travel in the blood
stream
ii. T Cells- Cellular immunity- defends against transformed cells, must come in contact with target
iii. Stages of Lymphocytes
1. Naïve Cells- Have never encountered an antigen- small 8-10μm in diameter, basophilic
nucleus, heterochromatin
2. Lymphoblasts- Formed in response to antigen encounter- large, actively synthesizing
protein- Antigen required for viability
3. Effector cells- Produced in response to antigen- Active, antigens required for viability
a. B lymphocyte effectors- Plasma cells
b. T lymphocyte effector- Cytotoxic T cells (Tc), T Helper cell (Th)
4. Memory Cells- Formed in response to antigen- similar to naïve cells, inactive, survive
for many years, antigens NOT required for viability, upon second exposure to antigen
that they were first activated by they change into an effector cell
b.
Humoral Immunity- B-Cells
i. Destroy bacteria and foreign substances, long distance
ii. B-cells develop and become immunocompetent in bone marrow, then either circulate in the
blood and migrate to other areas and stay there
iii. Found in lymph nodules, cortex of lymph nodes, peripheral white pulp of spleen
iv. B cells surface receptors- membrane bound antibodies, IgM and IgD, both recognize the same
epitope (an epitope is the specific sequence on the antigen molecule that combines with the
antibody)
v. Usually require Th cells for function (some antigens can activate B cells without T-helper cells)
1. B cell comes in contact to with the antigen that it recognizes, it internalizes the antigen
and combines it with MHCII
2. It then presents the antigen-MHCII complex on its surface to every Th cell it
encounters
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c.
3. If the Th cell recognizes the same epitope it becomes activated and secretes a bunch of
cytokines
4. The B cells is activate and changes into a plasma cell, which produces antibodies and
secretes them into blood stream, antibodies secreted by plasma cells have same
specificity for antigen as surface antibodies of the B cell it came from, secreted
antibodies mark bacteria for destruction by macrophages. Plasma cells live 10-20 days
and rarely divide, memory cells are also produced
vi. Antibodies- Y shaped
1. IgM and IgD are on the surface of the B cell, when activated the B cell becomes a
plasma cell and secretes primarily IgM. Plasma cells formed later in the response will
secrete other antibody isotypes, primarily IgG, in a process called isotype switching.
Memory cells arise after this switch has occurred
a. Primary Immune response, first exposure to an antigen, IgM secreted
first, other isotypes later in the response
b. Secondary Immune response, second exposure to antigen, IgG secreted
at beginning of response.
2. Antibodies can also neutralize viruses/bacteria by binding to them
3. Agglutination/Aggregation- Form large Ab/Ag complexes
a. All antibodies have two receptor sites and all can bind two epitopes.
Some antibodies are dimmers (IgA) and some are pentamers (IgM) and
can therefore bind multiple epitopes. IgA and IgM are therefore more
efficient in aggregation of antigens
4. Complement Activation- IgG or IgM bound antigens trigger complement
5. Antibodies can also induce inflammation
6. 5 Isotypesa. IgA- Secretory Aby- tears, saliva, gut lumen, milk
b. IgD- Antigen receptor on B cells
c. IgE- Allergic responses, host defense against parasites
d. IgG- Most abundant, crosses placenta, secondary immune response
e. IgM- First isotype produced in the primary immune response, antigen receptors
on B cells (monomer), present in blood and tissues (pentamer), most effective at
agglutination
Cell-Mediated Immunity- T-Cells
i. Recognize and destroy intracellular microbes or transformed cells, short distances
ii. T-cells- develop in bone marrow, become immunocompetent (begin expressing surface T cell
receptors ) in thymus
iii. The T cell receptor (TCR) recognizes the antigen, CD4 surface molecules (T-helper) recognize
‘self’ protein MHCII, CD8 surface molecules (CTLs) recognize a “self” protein MHC I (look
ahead for an explanation for what MHC is). Basically the T-cells must be able to recognize that
the presenting cell is “self” via the MHC and that the antigen is “non-self”
iv. So the antigen must be bound to an MHC molecule on another cell for Tcell to recognize it
v. 80% of lymphocytes in blood, 90% of lymphocytes in lymph
vi. Effector cells
1. T helper cells- CD4+
a. These are the cells that HIV infects and inactivates
b. When a B cell (or other antigen presenting cell) binds an antigen to a surface
receptor, the antigen is internalized, combined with and MHCII molecule, and
presented on the surface for all the Th cells to see. If a Th cell recognizes the
antigen it is activated and begins secreting lymphokines or cytokines, which
activates the presenting cell (the B cell or other APCs) and the immune response
begins.
c. So in general T-helper cells assist in the activation of other lymphoid cells (B
cells, macrophages, other T-cells).
2. T cytotoxic cells- CD8+
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d.
e.
f.
g.
a. Epitopes from proteins already inside ANY cell in the body (including viral,
normal, abnormal host proteins) can be presented on that cell’s surface in
association with a MHCI molecule.
b. If a Tc cell recognizes the protein then is becomes activated (with the help of Thelper cells) and tells the presenting cell (ANY cell in the body) to DIE.
Remember that Tcell are exposed to self proteins in the thymus and if they
reacted to them, the T cells were killed, so if they are reacting to these proteins,
they are NON self
c. The Tc cells kill the cells by a lethal hit, T cells release:
i. Perforins (glycoproteins)- insert into membrane of target cells and
form hydrophilic pores
ii. Granzymes- enter pores and drive cells to apoptosis
MHC (Major Histocompatibility Complex)- integral membrane proteins on surface of most cells
i. CD8 molecules on Tc cells recognize MHCI molecules
1. Peptide fragments are continuously degraded within the cell and combined with MHCI
and transported to the cell surface
2. Tc cells recognize as “self” or “non-self”
3. If “non-self” then Tc cells are activated
ii. CD4 molecules on Th cells recognize MHCII molecules, which are found on Antigen
Presenting Cells (APCs)
1. APCs endocytose and degrade exogenous antigens
2. Peptide fragments combine with MHCII molecules to cell surface, if fragment
recognized as foreign, Th cells are activated
APCs
i. Monocyte derived APCs- mononuclear phagocytic system
1. Macrophages- dust cells (lung), macrophages, kupfer cells (liver), engulf and destroy
foreign antigens
2. Myeloid Dendritic cells- spine-like projections used to capture antigens
a. Langerhan cell- epithelia of skin, GI, respiratory tracts
b. Interdigitating dendritic cells found in T cell regions of lymph nodes and spleen
ii. Non Monocyte derived APCs
1. Epithelial reticular cells- present “self” antigens to developing T cells in thymus
2. B cells- Present MHCII-Ag complex to Th cells and activate them
Lymphocyte recirculation and lymphocyte homing/recruitment
i. Lymphocyte recirculation- naïve lymphocytes continuously move, via blood and lymph, from
one peripheral lymphoid tissue to another. This ensures contact between limited number of
specific lymphocytes and the antigens they recognize. They enter lymph nodes and MALT
through high endothelial venules (HEVs) and exit tissues via lymphatic vessels to reenter
circulation
ii. Lymphocyte homing/recruitment- subsets of lymphocytes migrate to particular tissue sites.
Regulated by selective expression of:
1. Homing receptors- adhesion molecules on lymphocytes
2. Addressins- endothelial ligands for homing receptors
Natural Killer (NK) Cells- A third type of lymphocyte that doesn’t possess the surface molecules or
either T or B cells, kill transformed or virally altered cells via perforins and granzymes, but they act
non-specifically, they never enter the thymus to become immunocompetent, preferentially kill cells
coated with antibodies
III. Central (Primary) Lymphoid Organs
a. Functions
i. Antigen Independent Proliferation- these organs are where lymphocytes develop from stem
cells and divide to form a clone (all share specificity to same antigen) and acquire surface
receptors
ii. Where self-tolerance is acquired- ability of immune system to distinguish “self” from “non-self”
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1. Clonal Deletion- Lymphocytes that recognize self are destroyed in central lymphoid
organs
b.
Organs
i. Bone Marrow- B and T lymphocytes develop from stem cells, B cells become
immunocompetent (acquire surface receptors)
ii. Thymus- Fully formed and functional at birth, most active in childhood, atrophies after puberty
but continues to produce T cells throughout adulthood at a reduced rate
1. Structure- 2 lobes
a. Capsule- dense irregular connective tissue surround thymus and has trabecula
that extends into cortex and medulla to make lobules
b. Cortex- Outer portion of lobules, very basophilic, where T cells mature and
become immunocompetent, contains high concentration of rapidly developing
lymphocytes (thymocytes)
c. Medulla- less basophilic, fewer lymphocytes
2. Blood Supply- Small arteries enter capsule and travel within trabeculae- arterioles
leave trabeculae and penetrate parenchyma along cortex/medulla border and feed
capillaries in cortex and medulla, post capillary venules in medulla
3. Cytoreticulum- In parenchyma, stellate shaped Epithelial Reticular Cells- long
cytoplasmic arms linked by desmosomes, form a meshwork for T cells, also produce
hormones necessary for T cell maturation and display “self” antigens to T cells
4. Cortex- T cell maturation
a. First rapid T cell division- Antigen Independent
b. Begin to express Tell receptors under the influence of epithelial reticular cells,
adrenal gland, thyroid, and pituitary
c. Epithelial reticular cells present “self” antigens to T cellsi. Positive Selection- T cell must recognize MHCI or II
ii. Negative Selection- T cell must not recognize any other antigens
present in the thymus- only self antigens are presented so only self
reacting cells are destroyed
d. Foreign Antigens excluded from the Cortex by:
i. Sheaths of epithelial cells held together by occluding junctions
separate cortex from medulla, capsule, trabeculae, and blood
capillaries
ii. No afferent lymph vessels into thymus
iii. Only blood supply to cortex is via capillaries
iv. Blood-Thymic Barrier surrounds capillaries
1. Non-fenestrated endothelium
2. Basal Lamina of endothelial cells
3. Thin perivascular connective tissue sheath with macrophages
4. Basal lamina of epithelial reticular cells
5. Epithelial reticular cells with occluding junctions
5. Medulla
a. Fewer Lymphocytes
b. No Blood-Thymus Barrier
c. Hassal’s Corpuscles- masses of tightly packed epithelial reticular cells- function
unknown, increase with age
d. Mature T cells leave the thymus via blood vessels in medulla
IV. Peripheral (Secondary) Lymphoid Tissues
a. Basicsi. Non encapsulated or incompletely encapsulated collections of lymphoid cells
ii. Lymphoid cells and foreign antigens are brought in close contact to facilitate an immune
response (Antigen-Dependent Proliferation)
iii. Contains Reticular Tissue- found in all lymphoid tissues and organs except thymus, facilitates
interaction between antigens, lymphocytes, and APCs
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1. Matrix of branched reticular fibers, in some regions the fibers are ensheathed by
cytoplasmic processs of reticular cells
2. Macrophages and dendritic cells along reticular fiber network endocytose invading
organism and present antigens to nearby lymphocytes
iv. Lymph Nodules- NON-encapsulated, B cells (a few peripheral T cells)
1. Corona (Mantle)- Tightly packed small lymphocytes, activated B cells migrate out of
follicle, interact with Th cells and migrate back to form germinal center
2. Germinal Center- Lymphocytes arisen from one (or a few) antigen specific B cells
a. Dark zone – rapidly dividing activated B cells. Hypermutation of genes
coding for receptors.
b. Light zone – Affinity maturation occurs. B cells with higher affinity receptors
(bind antigen more efficiently) are selected for and B cells with lower affinity
receptors die. Higher affinity B cells go on to produce plasma cells.
v. Types:
1. Diffuse infiltration- isolated or small accumulation of lymphoid tissue in epithelium or
connective tissue (except in CNS)
2. Non-encapsulated- Concentrated accumulation of lymphocytes with APCs and
reticular tissue- close proximity to “outside”
3. Partially encapsulated- tonsils
4. Encapsulated- lymph nodes, spleen
b. Examples of Peripheral Lymphoid Tissues
i. MALT- Mucosal Associated Lymphoid Tissue- Non encapsulated
1. Lymphoid tissue in lamina propria of muscous membranes of GI (GALT, peyer’s
patches in ileum), respiratory (BALT), urinary, reproductive tracts
ii. Tonsils- Aggregates of lymph nodes guarding entrance to oral and nasal pharynx
1. Palatine- Large, paired, between fauces, multiples crypts, covered by stratified
squamous non-keratinized epithelium
2. Lingual- Smaller, more numerous nodules at base of tongue, 1 crypt, covered by
stratified squamous non-keratinized epithelium
3. Pharyngeal (adenoids)- single mass in nasopharynx, no crypts, respiratory epith
iii. Skin-Specialized immune system- lymphocytes and accessory cells
1. Langerhans Cells- Immature dendritic cells in suprabasal portion of epidermis, forms
almost continuous network that captures antigens and delivers to lymph node
V. Peripheral (Secondary) Lymphoid Organs
a. Lymphatic System
i. Lymph- Ultrafiltrate of blood produced at arterial end of capillaries
1. Some returns to blood via venous capillaries
2. Some returns to blood via lymph system
ii. Lymph Vessels- small capillaries converge to form larger vessels and drain into veins at base of
neck
1. Unidirectional flow- tissues heart
2. No pump, very low pressure
3. Movement driven by compression of vessels by adjacent skeletal muscles, pulsations
of nearby arteries, contractions of muscular tunica intima, normal movements of limbs
4. Lymph Capillaries- highly permeable, closed ended, irregular lumen size, permeable to
proteins, bacteria, viruses, and, cancer cells. Walls have few intercellular junctions,
lack continuous basal lamina, edges of adjacent cells overlap forming mini valves,
anchoring filaments made of collagen attach endothelial cells to surrounding
connective tissue
5. Lymph Collecting Vessels- Like veins, but thinner walls with lymph nodes scattered
along filter lymph, valves prevent backflow
6. Collecting vessels lead to five lymph trunks which lead to two lymph ducts- Right
drains to upper right quarter of body, Left drains the other ¾ of body
b. Lymph Nodes- About 500 in the human body
i. Function
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1. Filter and remove micro organisms and foreign particles from lymph before returned to
circulation, lymph must cross at least 1 node before returning to blood
2. Activates B and T cells- as lymph passes through node, antigens are trapped and
brought to lymphocytes and APCs, recognition leads to immune response
ii. Structure
1. Convex surface- Afferent lymph vessels enter here
2. Concave surface (hilum)-Arteries and veins enter and exit, efferent lymph vessels leave
3. Capsule- gives rise to trabeculae which extend into parenchyma
4. Subcapsular sinus- beneath capsule
5. Cortex- beneath subcapsular sinus
a. Outer cortex contains reticular tissue, nodules, primarily B cells
b. Paracortex- Reticular tissue, No nodules, mostly T cells, lymphocytes enter
node from blood via High Endothelial Vessel
c. Paratrabecular Sinuses- Run parallel to trabecula and connect subcapsular
sinus to medullary sinuses
d. Medulla- Medullary cords (branched clusters of reticular tissue with
lymphocytes, plasma cells, and macrophages) and sinuses (contains lymph)
c.
iii. Filtration of Lymph- Lymph vessels pierce capsule at convex surface, lymph flows to
subcapsular sinus to paratrabecular sinuses to medullary sinuses to efferent lymph vessels
1. Sinuses are lined with endothelium, which is continuous when adjacent to connective
tissue but discontinuous when adjacent to parenchyma- allows exchange of lymph and
cells between sinuses and parenchyma
2. Lumens of sinuses filled with mesh of reticular cells and fibers- aids in removal of
antigens
a. Retards flow of lymph through node and increase chance for interaction to occur
between antigens and cells
b. Mechanical filter
c. Structure for attachment of macrophages
iv. Responses of Lymph node to Antigen1. Antigen enters and is phagocytosed by macrophage, macrophage displaying the antigen
migrates to paracortex and activates Th cells
2. Th cells migrate to:
a. Cortex and trigger B cell response, plasma cells move to medullary cords
i. 90% go to sinuses then to bone marrow and release antibodies to
blood
ii. 10% remain in cords and release antibodies to sinuses
b. Medullary sinuses and leave lymph node and proceed to area of antigenic
activity, inflamed site
Spleen
i. Structure
1. Capsule- dense irregular fibroelastic connective tissue
2. At hilum the capsule thickens and gives rise to trabecula that carries arteries and nerves
in and lymph vessels out of the pulp
3. Islands of White- white pulp- high concentration of lymphocytes- basophilic,
lymphocytes activated here
a. Periarterial lymphatic sheaths (PALs)- sleeves of lymphoid tissue around
central arteries, mainly T cells and APCs (dendritic). Thymic dependent
region (T cells) that surrounds the central arteries
b. Lymphoid nodules- At intervals along PALS, mainly B cells
4. Sea of Red- red pulp- high concentration of RBCs
a. Red pulp cords- splenic cords of billroth (reticular tissue with RBCs and
macrophages)
b. Splenic Sinusoids (between the cords)- walls made of long endothelial cells
separated by slits to allow for fluid and cellular exchange, reticular fibers form
a discontinuous basal lamina
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5. Marginal Zone
a. Border between red and white pulp, major activation site- loose lymphoid tissue
with macrophages, interdigitating dendritic cells, lymphocytes, small blood
filled spaces with little or no endothelial lining
ii. Flow of Blood
1. Splenic artery  trabecular arteries  branches of trabecular arteries enter
parenchyma (central arteries)  Central Arteries- lose PALS and branch to several
short parallel branches, pencillar arteries- 3 segments:
a. Pulp arteriole right after branching from central artery
b. Sheathed arteriole surrounded by macrophages
c. Terminal arterial capillaries to red pulp, opens into splenic cords (irregular
sheets of reticular tissue with RBCs and macrophages)
2. Open circulation in cords veins in red pulp  trabecular veins splenic vein
iii. Functions
1. Filters blood, removes micro organisms, foreign particles, old RBCs
2. Activates T and B cells
3. Stores platelets
4. Hemopoesis in fetus and adult if bone marrow is non functional
INTEGUMENT = Skin and its appendages (sweat glands, sebaceous glands, hair, nails)
Functions of the skin:
 Protection (injury, bacteria, desiccation)
 Regulation of body temperature
 Reception (sensations from the environment – touch, temperature, pain)
 Excretion (from sweat glands)
 Absorption of UV radiation (for the synthesis of vitamin D)
General Information:
 Skin is the largest organ in the body
 Skin is composed of an epidermis and the dermis
Epidermis
Stratified squamous keratinized epithelium
Derived from Ectoderm
Dermis
Dense, irregular collagenous connective tissue
Derived from Mesoderm
 The dermal/epidermal interface:
Formed below by raised ridges of the dermis: dermal ridges/ papillae
Formed above by invaginations of the epidermis: epidermal ridges
Together these two types of ridges are called the rete apparatus
 You should also be familiar with the hypodermis – loose connective tissue (containing various amounts
of fat) underneath the skin. The hypodermis is not part of the skin, it is part of the superficial fascia (you
should remember seeing this in gross anatomy!).
15
Classification of skin:
I. Thin skin
A. The epidermis is 70-150 m thick
B. Lacks a defined stratum lucidum and stratum granulosum (see below)
B. Almost everywhere on the body
C. Contains hair follicles, arrector pili, sebaceous and sweat glands
II. Thick skin
A. The epidermis is 400-600 m thick
B. The epidermis contains all five layers – see below
C. Located on the plantar and palmar surfaces
D. No hair follicles, arrector pili muscles, and sebaceous glands
E. Contains many sweat glands
Epidermis
Types of Cells:
I. Keratinocytes
A. Largest population of cells in the epidermis
B. Five layers (see table below)
C. Continually renewed (mitosis in the basal layer)
2. As the cells travel toward the surface they differentiate in the layers and accumulate
keratin filaments.
3. Near the surface the cells die and are sloughed off - the whole process takes 15-20 days
Layer
Characteristics
Stratum Basale/
Stratum Germinativum
Stratum Spinosum
Stratum Granulosum
Stratum Lucidum
Stratum Corneum
Deepest layer
Single layer of cuboidal/low columnar cells:
 Cells attached to each other by desmosomes
 Cells attached to basal lamina by hemidesmosomes
Mitotically active (mitotic figures – present at night when the
keratinocytes are dividing)
 The keratinocytes have receptors for epidermal growth factor and respond
to this hormone.
 keratinocytes contain cytokeratins (intermediate filaments)
 Polymorphous cells – polyhedral to flattened cells
 Also mitotically active – together with the stratum basale we call the
mitotic layers the malphighian layer which is responsible for the turnover
of keratinocytes
 numerous desmosomes (give the cells a “spiny cell” appearance)
 tight contact between cells = resistant to shearing forces.
 bundles of tonofilaments (intermediate filaments) extend from
desmosomes.
 Most superficial layer where the cells still have nuclei
 Cells have predominately keratohyalin granules (full of fillagrin, which
binds cytokeratin into tonofilaments) and lamellar, membrane-coated
granules (full of glycol-lipid for waterproofing seal)
 No nuclei or organelles
 Most apparent in thick skin
 Cytoplasm is predominately dense filaments
 Many dead, flat keratinized cells – known as squames/horny cells
16
 No nuclei or organelles
 Desquamation is the final process of removing the outer epidermal layer.
II. Specialized cells
Melanocytes
A. Function = Protection from UV light
1. Produce eumelanin pigment (brown-black) or pheomelanin in redheads (reddishyellow) from tyrosine.
2. The total number and distribution of melanocytes is nearly the same for all skin
tones.
3. UV radiation increases the size and activity of the melanocyte
B. Derivation = Neural crest cells
C. Location = stratum basale
D. one melanocyte is associated with a number of keratinocytes.
E. melanocytes have no desmosomes, only hemidesmosomes to attach to the basement
membrane.
Langerhans cells (Dendritic cells)
A. Function = Antigen presenting cells
1. Part of the mononuclear phagocyte system
2. Have surface Fc (antibody) and C3 (complement) receptors
B. Derivation = precursors in the bone marrow
C. Location = Mostly found among cells of the stratum spinosum but may
be seen in the dermis and in the stratified squamous epithelia of the oral cavity, esophagus,
and vagina. May be as dense as 800 per square millimeter
D. Distinguishing Feature = Birbeck granules (vermiform granules)
1. Look like pingpong paddles
Merkel cells
A. Function = Mechanoreception
1. Unmyelinated sensory nerves traverse the basal lamina to reach
the Merkel cells
2. Neurosensory unit
B. Derivation = Differentiated epithelial cells of early fetal epidermis
C. Location = stratum basale
D. Distinguishing feature = Electron- dense secretion granules in the perinuclear zone
and in the cell processes. Structure suggests it is a neuroendocrine
cell.
Dermis
General Information:
 Nutrient support to the epidermis
 Temperature regulation
 Contains hair follicles, glands, nerves
 Consists of two layers
Layers of the Dermis:
17
I. Papillary Layer
A. Most superficial layer of the dermis
B. Anchors the epidermis
1. Interdigitates with the epidermis via papillae
2. Separated from the epidermis by the basement membrane
a. Anchoring fibers (type VII collagen) extend from the basal
lamina into this layer to bind the epidermis to the dermis.
C. Composition and Contents:
1. Type III collagen fibers (reticular fibers)
2. Elastic fibers
3. Fibroblasts, macrophages, plasma cells, mast cells
4. Capillary loops
a. Nourish the epidermis (avascular)
b. Regulate body temperature
5. Meissner corpuscles
a. Mechanoreceptors
b. Locate in areas sensitive to tactile stimulation
II. Reticular Layer
A. Continuous with the papillary layer
B. Composition and Contents:
1. Type I collagen
2. Thick elastic fibers
3. Proteoglycans – rich in dermatan sulfate
4. Epidermally derived structures
a. Sweat glands
b. Hair follicles
c. Sebaceous glands
5. Fibroblasts, mast cells, lymphocytes, macrophages, fat cells
6. Encapsulated mechanoreceptors
a. Pacinian corpuscles – pressure and vibration
b. Ruffini corpuscles – tensile forces
EXOCRINE GLANDS = Secrete products via ducts onto the external or internal epithelial surface
from which they originated.
Examples are:
 Mucous Glands – secrete mucinogens (large glycosylated proteins that upon hydrated swell to
become known as mucin (a component of mucous))
 Serous Glands – secrete an enzyme rich watery fluid (e.g. pancreas)
 Mixed Glands – contain acini that produce mucous secretions and acini that produce serous
secretions (sublingual and submandibular glands)
18
Cells of exocrine glands exhibit three mechanisms for releasing their secretory products:
1. Merocrine – release of secretory product occurs by exocytosis (e.g. parotid gland)
2. Apocrine – a small portion of the apical cytoplasm is released along with the
secretory product (e.g. lactating mammary gland)
3. Holocrine – as a secretory cells matures and dies it becomes the secretory product (e.g.
sebaceous gland)
Ducts:
I. Intralobular (intercalated)
A. The first duct leaving the acinus
B. Squamous to cuboidal epithelium
II. Intralobular (striated)
A. Transition to tall columnar epithelium
B. Basal striations/Eosinophilia
III. Interlobular (Excretory)
A. Tall columnar to stratified columnar epithelium
B. Mainly a conduit
IV. Main Excretory Duct
A. Like the interlobular duct
B. Pseudostratified columnar, stratified cuboidal, or stratified columnar
Epithelium
Glands of the Skin
Location
Method of
Secretion
Product
Type of
Gland
Other
Features
Eccrine Sweat Glands
Apocrine Sweat Glands
Throughout the skin deep in Only in the axilla, areola of the
the dermis or hypodermis
nipple, and anal region in the
deep dermal and hypodermal
areas
Merocrine
Merocrine (despite the name –
however some claim the
apocrine method of secretion)
Sweat – up to 10 L per day Viscous odorless product that
in extreme conditions
presents a distinctive odor
when metabolized by bacteria
Simple coiled tubular gland Duct opens into canals of the
Duct opens to sweat pore
hair follicles superficial to the
on sikin surface
entry of the sebaceous gland
ducts
 Innervation by
postganglionic sympathetic
fibers
 Dark cells – line lumen of
the secretory unit and
secrete a mucus-rich
substance
 Clear cells – release a
watery secretion
 Modified apocrine sweat
glands constitute the
ceruminous glands of the
external auditory canal and the
glands of Moll in the eyelids
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Sebaceous Glands
Throughout the body (except
for palms and soles) in the
dermis and hypodermis
Holocrine
Sebum (an oily substance that
maintains suppleness of the
skin)
Lobular
Duct opens into the hair
follicular canal (or onto the
skin surface in areas without
hair)
 Acne is a chronic
inflammatory disease
involving the sebaceous
glands and hair follicles
 Myoepithelial cells –
contractions help expel
fluid from the gland
Salivary Glands
Parotid
Submandibular
Sublingual
Secretions
Serous
Features
Other
Fat is a common feature
Produces 30% of the saliva
Serous (major)
Mucous (minor)
Fat may be present but is sparse
Produces 60% of the saliva
Mucous (major)
Serous (minor)
Little or no fat
Produces 5% of the saliva
Saliva:
Primary – secreted by the acini (isotonic)
Secondary – modified by the striate ducts (hypotonic – Na+ reabsorbed
and K+ is excreted)
Enzymes – alpha amylase, maltase, lysozyme, lactoferrin
Other constituents – IgA, glycoproteins, water, electrolytes, protein
Control of secretion – sympathetic (viscous, high organic content)
- parasympathetic (copious, thin, low organic content)
Pancreas
The pancreas is both an exocrine gland (digestive juices) and an endocrine gland (hormones).
Exocrine Pancreas
The largest exocrine organ in the body
Produces digestive enzymes:
Pancreatic amylase
Pancreatic lipase
Ribonuclease
Deoxyribonuclease
Trypsinogen
Chymotrypsinogen
Procarboxypeptidase
Elastase
Controlled release of pancreatic enzymes:
Cholecystokinin (from DNES cells of the small intestine)
Acetylcholine (parasympathetic control)
Controlled release of bicarbonate rich fluid (to neutralize acidic chyme):
Secretin (from enteroendocrine cells of the small intestine)
Acinar cells (Pyramidal shape)
Base on basement membrane (basophilic) – has receptors
for cholecystokinin and acetylcholine
Apex toward the lumen of the acinus (acidophilic) - filled with
secretory granules (zymogen granules)
Duct system:
20
Center of acinus  intercalated ducts (centroacinar cells)  Intralobular
ducts  interlobular ducts  Main pancreatic duct  Common bile duct
 Papilla of Vater
Endocrine Pancreas - Islets of Langerhans (round, light staining islands)
Cell types:
 Cells – purple, secrete insulin (for glucose uptake)
 Cells – unstained, secrete glucagon (glucose production)
 Cells – secrete somatostatin (inhibits  and  locally)
PP Cells – produce pancreatic polypeptide (inhibits exocrine secretion)
G gells – secrete gastrin (release of HCl)
Islets of Langerhans
1. Derived from endoderm
A. Proliferates during childhood
B. Sudden expansion of islet volume during pregnancy
2. 1% of the pancreatic mass
3. Gap junctions
A. Between islet cells
B. There is increased cell communication under conditions of enhanced
insulin secretory activity
4. Blood supply
A. Islets receive a disproportionately large amount of blood flow to the
Pancreas
B. Blood flows from B cells to A cells to D cells (think BAD)
5. Islet-Acinar Axis
A. Efferent blood from the islet enters a second capillary network
supplying the acinar pancreas
B. The blood is rich in insulin and has a trophic and secretory stimulation
effect on acinar cells
6. Nerve supply
A. Sympathetic – NE inhibits insulin secretion and increases glucagon
Secretion
B. Parasympathetic nerves
7. Insulin Synthesis
A. Start with Pre-proinsulin
B. Cleaved to proinsulin
C. In the Golgi the peptide folds and forms disulfide bridges between
the A and B chains
D. The C peptide is cleaved to produce insulin
8. Islet Pathology
A. Type I Diabetes – autoimmune disease that destroys islet B cells
B. Type II Diabetes – Islet B cells are intact but their function is altered
21
ENDOCRINE SYSTEM
I.
The endocrine system consists of ductless glands that secrete specific
hormones into the blood that have effects throughout the body. There are three
subclasses of endocrine glands:
A. Endocrine-secrete hormone into capillaries, which is then transported to the target organ by
blood.
B. Neuroendocrine- specialized nerve cells; secrete product into capillaries, which are then
transported to the target organ by blood.
C. Paracrine-specialized endocrine cells, secrete their products into the interstitium and the
hormone has local action on neighboring cells.
II.
Features of endocrine glands
A. Target organs can be endocrine glands or other organs.
B. All endocrine glands are islands of endocrine secretory cells highly vascular with fenestrated
capillaries.
C. Cells are supported by reticular fibers.
III.
Three classes of hormones:
Tyrosine Derivatives
(catecholamines and thyroid
hormones)
Ex: norepinephrine, epi,
thyroxine
Water soluble
Ectodermally derived
Ex: insulin, glucagon, FSH, ADH
Ex: aldosterone, estrogen
Water soluble
Ecto or endodermally derived
Lipid soluble
Mesodermally derived
Processed in RER/golgi
Stored in secretory granules
Processed in RER/golgi
Stored in secretory granules
Many mitochondria and SER
Cholesterol precursors stored in
lipid droplets, no stored secretory
product
IV.
Proteins and
Polypeptides
Steroids and fatty acid
derivatives
Classes of endocrine receptors
A. Catecholamine and peptide hormone receptors- located on the cell membrane.
1. G-protein coupled receptors-hormone bindsATP converted to cAMP (2nd
messenger)influences metabolism and nuclear functions.
2. Phospholipase C linked receptors- 2nd messengers include diacylglycerol and inositol1,4,5-triphosphase (IP3).
3. Tyrosine kinase coupled receptors.
B. Steroid receptors-located in the nucleus.
1. Hormone binds to receptor-hormone receptor complex binds directly to DNA.
2. Stimulates transcription.
22
Specific Glands
VI.
PITUITARY GLAND – integrates nervous and endocrine systems
Regulates: growth, reproduction, & metabolism
Controlled by: hypothalamus (the brain center of homeostasis)
A. Pituitary is composed of 2 Parts
1. Anterior Pituitary (Adenohypophysis or pars distalis, intermedia, & tuberalis)
a. Derived from upward evagination (Rathke's pouch) of oral ectoderm.
b. Contains glandular epithelium.
2. Posterior Pituitary (Neurohypophysis or Pars Nervosa)
a. Derived from downward projection of the diencephalon (hypothalamus) of neural
ectoderm.
b. Contains neural secretory tissue.
B. Blood Supply
1. Superior hypophyseal arteries.
2. Inferior hypophyseal arteries.
3.Portal system- carries regulatory hormones from hypothalamus to anterior
pituitary.
a. Blood enters median eminence via inferior and superior hypophyseal arteries and
distribute in a capillary bed.
b. The effluent from this capillary bed collects into veins, which in turn enter into a
second capillary bed, which supplies the anterior pituitary. The venous blood leaves
the pituitary via hypophyseal veins.
C. Control of secretion
1. Pituitary cells are under influence of hypothalamus, which releases regulatory hormones in the
Median Eminence (posterior pituitary), which are transported to the Anterior Pituitary via the
hypothalamic-hypophyseal portal circulation and increase or decrease anterior pituitary
release of hormones.
2. Regulatory hormones secreted by hypothalamus:
a. GHRH (Growth Hormone Releasing Hormone)
b. GHIH (Growth Hormone Inhibiting Hormone, Somatostatin, SRIF)
23
c. PIH (Prolactin Inhibiting Hormone) (Dopamine)
d. PRH (Prolactin Releasing Hormone)
e. TRH (Thyroid Releasing Hormone)
f. CRH (Corticotropin Releasing Hormone)
g. FSHRH/LHRH
D. ANTERIOR PITUITARY (Adenohypophysis), 3 parts:
1. Pars tuberalis- surrounds infundibulum, highly vascular, doesn't secrete hormones
contain FSH & LH. Cuboidal/low columnar basophiilic cells w/small
but may
granules
2. Pars Intermedia- between pars distalis and pars nervosa (post. pit.), cuboidal, cell-
lined
cysts (Rathke's cysts). Small to non-existent in humans.
3. Pars distalis- the main secretory part, covered by fibrous capsule of parenchymal
cells
surrounded by reticular fibers.
E. Parenchymal Cells (secretory cells)
1. Chromophobes: (50%)-cells stain poorly- little or no protein & secretion granules in cyto.
a. Now regarded as resting stage cells- become acidophils/basophils when active.
b. Also include Follicular cells: non-secreting supportive and phagocytic cells
2. Chromophils: (50%) - stain well- contain numerous electron dense secretion granules.
a. Acidophils (40%) PAS (-) stain pink/orange w/ eosin
i.
Somatotropes - Secretes Growth Hormone (GH)- Affects epiphyseal cartilage,
stimulates growth indirectly via stimulation of liver and kidney to produce
somatomedins which manifest GH effects. Also has direct effects on other cells.
a) Hypersecretion (acidophil tumors): results in gigantism, acromegaly, and
diabetes.
b) Hyposecretion (hypopituitary): results in dwarfism.
ii. Mammotrophs - Secretes Prolactin (PRL) - Stimulates mammary
gland
development in preparation for lactation. Enlarge during pregnancy under influence
of estrogen "Pregnancy Cells.” Also regulate glucose sensitivity of islet B-cells and
may have a role in immune function.
b. Basophils (10%) [PAS (+) due to glycoprotein nature] stain blue w/hematoxylin.
i.
Corticotrophs (melanotrophs)- Secretes several hormones:
(a) ACTH (Adrenocorticotropic Hormone): Stimulates adrenal secretion of
corticosteroid hormones. Hypersecretion: Addison's disease (adrenal cortical
24
insufficiency) & Cushing's disease (adrenocortical hyperplasia &
hypercorticolism).
(b) MSH (Melanocyte Stimulating Hormone): large doses cause
hyperpigmentation.
(c) Lipotropin: Mobilizes fat in some species but function unknown in humans.
(d) Proopiomelanocortin (POMC): precursor molecule for secretory products of
the corticotrophs (ACTH, MSH, and lipoprotein).
ii. Gonadotrophs - Secrete 2 hormones:
(a) Follicle Stimulation Hormone (FSH): Female: Follicular development, Male:
Gametogenesis. Castration leads to hypertrophy "Castration cell.”
(b) Luteinizing Hormone (LH)/Interstitial Cell Secreting Hormone (ICSH):
Female: Maturation of the Graafian Follicle, development of the Corpus
Luteum and Progesterone secretion. Male:
Stimulates androgen
(testosterone) secretion.
iii. Thyrotrophs –
Secretes: Thyroid Stimulating Hormone (TSH)- Stimulates the thyroid gland to
synthesize and secrete thyroid hormones. Become hypertrophic and hyperplastic in
hypothyroidism or thyroidectomy.
F. POSTERIOR PITUITARY (Neurohypophysis)
An extension of the BRAIN (Hypothalamus). 3 parts:
1. Median eminence
2. Infundibulum- connects the pituitary to the hypothalamus.
3. Pars Nervosa- receives distal terminals of the Hypothalamic-hypophyseal tract, made up of
100,000 neurons from the Supraoptic and Paraventricular nuclei.
a. Supported by Pituicytes (glial cells)- 25 % volume of Pars Nervosa.
b. Neurosecretory cells are specialized neurons, which secrete into capillaries.
c. The neurons terminate as many branches, called palisades, on capillaries and are dilated
and filled with neuro-secretion granules stored in large dilatations (herring bodies).
d. Granule Content:
i.
Vasopressin (ADH antidiuretic hormone)- regulates amt. of H20 released by the
kidney. In large doses, acts as a vasoconstrictor to increase BP. Low ADH results
in diabetes insipidus where there is a large volume of hypotonic urine (i.e. the
distal tubule is impermeable to H20).
25
ii.
Oxytocin- targets the uterus and mammary gland to stimulate uterine contraction
and lactation.
iii.
Neurophysins: precursors for the above that are clipped to form a mature
hormone. (Neurophysin I  Vasopressin; Neurophysin II  Oxytocin)
V.
THYROID GLAND
A. 15-30 gm, two lobes are connected by an isthmus.
B. From: endoderm that migrated from the base of the tongue; remains attached to the tongue
by way of a thyroglossal duct to the foramen caecum.
C. Receives autonomic innervation.
D. Two cell types:
1. Follicular Cells - Continuous layer of cuboidal epithelium surrounding a central mass of
colloid. Microvillus border w/ well developed RER, Golgi, lysosomes, junctional
complexes and lateral interdigitations, and no secretion granules.
a. Thyroglobulin: PAS (+) glycoprotein. Synthesized in the RER and mannose is
added. Galactose and Fructose added in the Golgi apparatus; Un-iodinated
thyroglobulin is transported by vesicles to the follicular lumen. Thyroglobulin is then
secreted into the colloid in the lumen of the follicle where it is iodinated by
peroxidase and stored.
b. Pathway
TRH (hypothalamus)  TSH (pituitary)  follicular cell receptors 
increased cAMP  Thyroglobulin uptake and release of T3 and T4
c. More T4 > T3 is released. T4 is converted into T3 by the liver.
d. T3 & T4 Effects:
i.
Negative feedback on hypothalamus and pituitary.
i.
Increase mitochondrial metabolism.
ii.
Increase # of cristae.
iii.
Increase Basal Metabolic Rate (Carbo metabolism and lipid metabolism).
iv.
Acceleration of catabolic reactions of glycolysis, Krebs cycle, and oxidative
phosphorylation.
v.
Body growth promoter.
vi.
Stimulates development of nervous system.
e. Pathway
TRH (hypothalamus)  TSH (pituitary)  follicular cell receptors  increased
cAMP  Thyroglobulin uptake and release of T3 and T4
26
f. Disorders:
i.
 Iodine leads to Iodine deficiency goiter =  colloid & hyperplasia of
follicular cells.
ii.
Hyposecretion hypothyroidismLeads to Myxedema in adults and Cretinism in children.
iii.
Hypersecretion hyperthyroidismMost common is Graves Disease:
In this autoimmune disease. There is a
circulating gamma globulin, which binds to the follicular cell and mimics
TSH. Therefore, the gland is constantly stimulated in an unregulated manner.
2. Parafollicular cells –
a. Secretes: calcitonin - which functions to lower blood Ca2+ and PO4 by inhibiting
osteoclast activity. Secretion regulated by blood Ca2+ levels
b. Appearance: Large ovoid cells with poorly staining cytoplasm.
c. Derived from: Neural Crest cells
d. Location: Scattered throughout the thyroid gland. May also be located between
follicles.
VII. PARATHYROID GLAND
A. Appearance: Four small glands (5-10 mm) found on the thyroid gland.
B. Derived from: 3rd and 4th branchial pouches.
C. MAIN FUNCTION: secrete Parathyroid Hormone (PTH)-  blood Ca2+.
1. Counteracts the effect of Calcitonin. Hypercalcemia suppresses PTH secretion while
hypocalcemia promotes secretion.
2. Promotes Ca2+ absorption from the gut.
3. Increases resorption of Ca2+ from bone by binding to osteoblasts, which secrete a cytokine,
which affects osteoclast activity.
4. Increases PO4 excretion by the kidney.
5. Decreases Ca2+ excretion by the kidney indirectly (by promoting vitamin D uptake and
metabolism.)
6. Hyperparathyroidism leads to increased serum calcium levels, bone loss and renal calculi.
D. 3 Cell Types.
1. Chief cell (most) the only cell type seen until adolescence. Dark staining w/
granules. Secretes PTH.
27
2. Wasserhelle cells- inactive chief cells w/ clear cytoplasm and few granules.
3. Oxyphils- same as acidophils- eosinophilic due to lots of mitochondria. No granules,
function unknown.
E. Calcium Summary: Regulation is by parathyroid hormone, vitamin D and calcitonin. Calcitonin
acts on bone to inhibit calcium resorption. Parathyroid Hormone promotes calcium release from
bone and inhibits its secretion by the kidneys. Vitamin D acts largely to promote calcium uptake
from the gut.
VIII. ADRENAL GLAND
2 Parts:
CORTEX
MEDULLA ("middle")
90 %
10 %
Mesoderm
Neuroectoderm
Steroids
Catecholamines
Carb/protein metabolism &
HR, smooth muscle function, & carb/lipid
electrolyte distribution
metabolism
Pituitary gland (ACTH) &
Sympathetic division of ANS
Derived from
Secretes
Affects
Regulated by
Kidney (Renin)
A. Innervation: Preganglionic sympathetic nerve fibers synapse on adrenal medullary cells
(Chromaffin cells).
B. Blood Supply: Rich vasculature (Sup. Mid. and Inf. Suprarenal arteries) with three intraglandular
vascular routes:
1. Capsular Arteries.
2. Cortical Arteries (Arise from capsular arteries, branch as sinusoids in cortex, converge at
inner cortex and empty into medullar vascular bed bringing high concentrations of steroid
hormones into contact with the medullary cells.
3. Medullary Arteries: Penetrate cortex to go directly to medulla. Therefore, the medulla has
two blood supplies.
4. Veins coalesce in medulla to form a large central vein.
C. ADRENAL CORTEX consists of three concentric layers.
1. Zona Reticularis (7%) - Thin mantle, little lipid, eosinophilic, extensive
lipofuscin pigment, produces weak androgens
(Dehydroepiandrosterone)- forms both androstenedione & testosterone.
28
2. Zona Fasciculata (78%) - Long radially arranged cords. One or two cells thick with an
interspersed capillary network. May reach from capsule to medulla.
a.
Produces glucocorticoids (Cortisol)-effects:
i. Decreases protein synthesis, glucose uptake, & insulin production.
ii. Increases lipolysis, amino acid uptake by liver, glucose synthesis,
glycogenesis, blood glucose, protein breakdown (wasting).
b. NET RESULTS: Increase Blood Glucose, increase Urinary Nitrogen Excretion,
increase Fat Loss.
c. Also has anti-inflammatory and anti-mitotic properties.
d. Overproduction of cortisol (Cushing's syndrome)- results in: Diabetes Mellitus,
muscle wasting, easily bruised skin, osteoporotic bones, central obesity ('moon face'
and 'buffalo hump'), susceptibility to infection, gastric ulcer, hypertension.
3. Zona Glomerulosa (15%) -Spherical to columnar cells.
a. Produces mineral corticoids (aldosterone).
b. Plasma sodium deficiency  + release of Renin converts angiotensinogen into
angiotensin I & II Glomerulosa activityAldosterone.
c. Result: sodium resorption in the proximal convoluted tubule of the kidney
which causes an increase in H20 resorption =  blood pressure.
D. ADRENAL MEDULLA see above chart for general info.
1. Made of Adrenal medullary cells (Chromaffin cells)- secrete catecholaminesepinephrine (80%), Norepinephrine, enkephalin, & DOPA. Also contain ATP and
acetylcholine (from sympathetics).
2.
Synthesis of catecholamines: tyrosine  DOPA  Dopamine  Norepinephrine (via
DOPA beta hydroxylase)  epinephrine (conversion stimulated by glucocorticoids).
3. Effects of Epinephrine:
a.  glycogenolysis.
b. Fatty acid mobilization.
c.  heart rate.
d.  blood pressure.
e. Vasoconstriction of skin and G.I. vasculature.
f. Vasodilation of coronary and skeletal muscle vasculature.
g.  alertness- via the brain stem Reticular Activating System(RAS).
29
h.  blood glucose via Glucagon secretion and  insulin secretion
E. Effects of Enkephalin- (Opioid peptide.) - Stress induced analgesia.
IX. PANCREAS (Islets of Langerhans) see Endocrine Pancreas section of the Skin and Exocrine lecture
above.
Gastrointestinal System
Blatantly plagiarized from last year’s K-coop. Any questions email Ted Honebrink @
hone0020@tc.umn.edu.
I. Hollow organs have 4 mail layers (Tunics)
Mucosa
1. Epithelial lining
a. major portal into the body
b. protective
c. secretory
c. absorption--surface amplifications
e. stratified or simple
2. Basement membrane
a. still is type IV collagen
b. still has laminin
c. may vary from the basement membrane in other tissues in the body
2. Lamina propria
a. loose connective tissue
a. contains vessels, lymphs, and glands
b. formed by epithelial invaginations
d. lymphoid tendencies (common tendency of GI tract which increases from the
stomach all the way to the colon; lots of lymphocytes and phagocytes)
3. Muscularis mucosa
a. thin circular and outer longitudinal smooth muscle layers
b. separates mucosa from submucosa, permitting movement of the former with
respect to the latter
Submucosa
1. Dense irregular connective tissue with blood and lymph vessels
2. Contains glands in the esophagus and duodenum (called Brunner’s glands in the
duodenum); there is no other place in the GI tract that contains glands in the
submucosal layer
3. Also contains Meissner’s plexus--parasympathetic nervus plexus
30
Muscularis externa
1. Has smooth muscle cells spirally orientated and divided into two sublayers
a. internal (circular)
b. external (longitudinal)
c. Auerbach’s nerve plexus (autonomic nerves, parasympathetic division) & vessels
located in between these layers but is associated with the internal layer
2. Responsible for peristalsis, tone
Serosa and/or Adventitia
1. Thin layer of dense connective tissue covered with peritoneum (serosa)
2. Large vessels and nerves found here
II. General Principles of the GI Tract
A. Overview
1. Epithelial lining of the tract arises from endoderm
2. Connective tissue and smooth muscle are derived from splanchnic or visceral
mesoderm
3. Key changes as tract progresses caudally
a. lumen widens
b. surface area of lumen increases and changes from invaginations to crypts and villi
c. increased number of layers involved in forming macroscopic folds
d. increased number of mucous secreting cells and goblet cells–only in small and
large intestine
e. increased lymphatic infiltration of the connective tissue
4. General function of the GI tract
a. selectively permeable barrier
b. transports and digests food
c. absorbs nutrients, produces hormones that modify activity of the gut
d. Abundant lymphoid tissue, secretory IgA, and lysozyme protect gut from bacteria
B. Esophagus
1. Muscular tube that transports food to stomach–warms or cools food
2. Has same layers as rest of digestive tract
3. Mucosa of oral cavity, pharynx, and esophagus lined with non-keratinized stratified
squamous epithelium
4. Lower third of esophagus is only smooth muscle in muscularis externa
5. Upper third has only skeletal muscle in muscularis externa
6. The two mix as they approach each other
7. Has serosa when it runs into peritoneum
8. Submucosa has mucus secreting glands (esophageal glands)–glands switch their
location to lamina propria (cardiac glands) at the esophageal-stomach junction
C. Stomach
1. Kill bacteria with acid
2. Begin protein breakdown and form chyme
31
3. Mucosa and submucosa have rugae in all regions
4. Mucosa has simple columnar epithelium that invaginates to form gastric pits which
contain 5-7 gastric glands each (total of 35 million glands)–in lamina propria
5. Lamina propria in spaces between gastric glands and pits; contains vascular supply
6. Muscularis Externa has 3 layers of smooth muscle–(1) incomplete, oblique inner layer
(2) continuous, circular middle layer (3) longitudinal outer layer, continuous with
esophagus
7. No goblet cells in stomach wall
8. 3 regions of stomach
a. cardiac stomach
i. Near esophageal opening
ii. Lamina propria contains simple or branched tubular glands–extend into 1/4
depth of mucosa
iii. Secretory cells produce mucus and lysozyme
iv. Few parietal cells
b. fundus/body
i. Mainly branched tubular gastric glands
ii. 3-7 open into each gastric pit–extend 1/4 to 1/3 into mucosa
iii. At the base of the gland are: (1) parietal cells (2) chief cells (3)
enteroendocrine cells
iv. At the neck: (1) mucus neck cells (2) undifferentiated cells
c. pyloric/pylorus
i. Long pits–extend ½ depth of mucosa, and short glands found at distal third of
stomach near opening to small intestine
ii. Glands secrete mucins (Muc6) and lysozyme
iii. Enterochromaffin cells commonly found in pyloric glands & proximal part of
duodenum (1) secrete somatostatin (2) secrete serotonin (vasoconstrictor) (3)
gastrin, etc.
9. Gastric gland cells
a. surface mucous cells
i. Appear empty or foamy
ii. Tall columnar cells cover entire surface and line gastric pits
iii. Secrete neutral mcuus
b. mucous neck cells
i. At neck of gastric pits
ii. Flattened basal nuclei; apical granules and microvilli
iii. Secrete acid mucus (Muc6)
c. undifferentiated (regenerative) stem cells
i. Base of gastric pits and neck of gastric glands
ii. Renewal of surface epithelium (turnover every 4-5 days) and glandular cells
d. parietal cells
i. Large
ii. Round or triangular
iii. Dark cells
iv. Central nuclei
v. Pink cytoplasm
32
vi. Tubular vesicles in cytoplasm for activation
vii. Microvilli and intracellular canaliculi
viii. Main function = ion transport (e.g. acidify the stomach’s contents)
ix. Forms gastric barrier–Carbonic anhydrase & sodium bicarb to protect stomach
cells
x. Produces Hcl
xi. Secretes intrinsic factor required for absorption of vitamin B1
e. chief (Zymogen) cells
i. Located at base of gastric pit
ii. Pale staining cells wit oval nuclei; basal mitochondria
iii. Large, apical secretion granules
iv. Microvilli
v. Lots of RER
vi. Produce (1) Pepsin (digestion of proteins) (2) Rennin (curdles milk) (3) Lipase
(fat digestion)
f. enterochromaffin cells
i. Between chief cells and basement membrane
ii. Secrete enteric hormones (1) Glucagons (2) Gastrin (3) Somatostatin (4)
Serotonin
iii. Secretion granules toward basement membrane
D. Small Intestine
1. Functions
a. absorption
i. Circular folds (plicae circulares) of entire mucosa with a core of submucosa
that projects into the lumen; maximum development in the distal duodenum
and proximal jejunum
ii. Villi–projections of the mucous membrane with a core of lamina propria into
lumen; tall in duodenum, tongue-like in jejunum, broad and short in ileum;
DISTINGUISHING FEATURE of small intestine; epithelium of villi replaced
every 3-5 days by upward migration of cells from crypts of Lieberkuhn
(remember that the crypts of Lieberkuhn are in between villi); villi increase
surface area for absorption
iii. Microvilli-cytoplasmic projections of the cell surface that form the STRIATE
BORDER
b. digestion
i. Exocrine glands (pancreas and liver)
ii. Submucosal glands (duodenal Brunner glands)
iii. Intestinal crypts (invaginations of epithelium into lamina propria)
2. Layers
a. epithelium - simple columnar, with many other cell types (know these cell types
and their functions-absorptive, goblet–Muc 2 and 3, enteroendocrine–hormones,
columnar crypt cells–secretory IgA, paneth cells–lysozyme, M cells–antigen
transport and pathogen binding, stem cells, intraepithelial leukocytes–T cells)
b. lamina propria - loose CT (connective tissue), large numbers of plasma cells
making secretory IgA, lacteals–drain fat
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c. submucosa - projects into the plicae circulares in duodenum and jejunum;
infiltrated with lymphocytes in Payer’s patch regions
d. muscularis externa
e. serosa - duodenum has a serosa only on its anterior surface, the posterior
duodenum is retroperitoneal
3. Other testable details
a. the duodenum is characterized by Brunner’s glands in its submucosa, which secrete an
alkaline mucus (neutralized stomach acid)
b. goblet cell population increases as you go down small intestine–few in duodenum,
many in ileum
E. Large Intestine
1. Features
a. no folds or villi, no Paneth cells
b. simple columnar epithelium with microvilli
c. many goblet cells
d. some absorptive cells
e. some enteroendocrine cells
f. lamina propria has marked lymphoi tissue forming nodules
g. presence of plicae semilunares–form haustra
2. Functions
a. absorbs water passively
b. actively transports sodium out
3. Regions of the large intestine
a. ileocecal junction - a slit like junction where the ileum meets the large intestine
b. cecum - small blind pouch of large intestine, structurally identical to colon
c. appendix - blind diverticulum, no villi, often contains debris, lymphoid tissue in
lamina propria, often immune cells in lamina propria and submucosa
d. colon and rectum - teniae coli–>incomplete outer longitudinal layer of muscularis
esterna; epiploic appendices–>adipose tissue sacs on serosa
e. Rectoanal junction - shows a decrease and finally a complete loss of intestinal
crypts, mucous membrane folded longitudinally to form the rectal columns, simple
columnar epithelium abruptly changes to stratified squamous nonkeratinized
epithelium, circumanal glands under epithelium, internal layer of the muscularis
externa thickens to form the INTERNAL SPHINCTER OF THE ANUS; the
external sphincter is formed by skeletal muscle surrounding the anal canal
34
Liver
I tried to make this liver and gallbladder stuff as to the point as possible (and hopefully less
painful in the process). Good luck - email me if you have questions.
--Tara (kend0057)
A QUICK and GENERAL Overview of the LIVER:
 The largest gland in the body, it secretes both endocrine and exocrine products.
 Receives dual blood supply: 75% of its blood is nutrient rich from the portal vein and
25% is oxygen rich from the right and left hepatic arteries.
 Receives about 20-25% of the cardiac output.
 Displays counter current flow: blood flows toward the center and bile flows toward the
periphery of a classic hepatic lobule.
 Has the capacity to regenerate – the differentiated cells are able to divide!
 All nutrients absorbed in the alimentary canal (except for chylomicrons) are transported
directly to the liver through the portal vein.
 Takes up digested nutrients such as lipids, amino acids, CHOs and vitamins.
 Stores and releases triglycerides, glucose, and vitamins.
 Synthesizes albumin, prothrombin & fibrinogen, globulins, glucose, triglycerides,
phospholipids, cholesterol and lipoproteins.
 Metabolizes lipids (has receptors for LDL) – endocytoses, acidifies, and frees the
particles from the receptors (which are recycled out to surface). LDL is then degraded in
lysosomal compartments to cholesterol, triglycerides, etc.
 Metabolizes iron (has receptors for transferrin) and stores it. Too much iron in the liver
results in a granular appearance = hemosiderin deposits (hemosiderosis).
 Hemoglobin is broken down in the spleen; bilirubin binds to albumin and is brought to
the liver where glucuronic acid is added to make it water-soluble (NOTE: if you don’t
have a spleen, the liver can take over this function with its Kupffer cells).
 Deaminates amino acids and eliminates subsequent ammonia in the form of urea.
 Detoxifies drugs and other xenobiotics.
 Forms bile (750 ml/day) – 90% of bile is recirculating!
 Embryonic hematopoiesis
 Cirrhosis seen as extensive fibrotic tissue and the hepatocytes are filled with lipids (no
longer functional). This is caused by chronic alcoholism and is irreversible.
Now, on to the histology…
 Parenchyma
o Hepatocytes (60% of liver cells and 80% of liver volume – mean life span of 150 days)
 Are polar cells with blood vessel abutting the walls (sinusoids).
 There are 3 surfaces:
 Sinusoidal surface with microvilli for increased nutrient absorption
from the Space of Disse.
 Basolateral surface with tight junctions, desmosomes and gap
junctions.
35

o
Bile canaliculi (also located on basolateral side), quite extensive
with 15% of plasma membrane. Tight junctions prevent bile from
leaking.
Sinusoidal cells (blood flow from periphery to central lobule)
 Kuppfer cells, fenenstrated endothelial cells, fibroblasts and
lipocytes.
 The sinusoids themselves are 10um in diameter and are separated
from the hepatocytes by the Space of Disse (irregular space
between endothelial wall and hepatocyte containing many
reticular fibers), which is 1-2 um wide. This is major site of
absorption of nutrients and secretion of endocrine products.
Blood Flow Overview
Portal vein  Interlobar vein Interlobular vein  Terminal portal venules (perilobular
veins) inlet venule Sinusoids  Central vein Sublobular vein Collecting vein
Hepatic vein Inferior vena cava
**The Portal Triad = portal venule, hepatic arteriole, and bile duct BUT is actually a quartet
because it also contains a lymphatic vessel (derived from the space of Disse).
The stroma of the liver consists of:
 The dense connective tissue of Glisson’s Capsule, which enters the liver at the porta
hepatis.
 The central vein and portal triad conduits.
 Reticular fibers supporting the sinusoids
Liver Lobulation…this is an important concept!
 The Classic lobule
o Polygonal with the central vein in the center and portal triads at the periphery.
o Blood flows toward the center and bile flows toward the periphery.
o This model stresses the endocrine function of the hepatocyte: blood flows from
the periphery to the center as products such as fibrinogen, albumin and glucose
are secreted into it.
o Central lobular necrosis presents itself in this pattern.
o Shortcoming of model – connective tissue sheath that defines the lobule is not
well seen in humans (better in other species).
 The Portal lobule
o Triangular shape with the portal triad at its center and each of the three points
represented by a central vein.
o This model emphasizes the exocrine (bile secretion) function.
o No longer a very useful model.
 The Liver acinus (aka. Portal acinus, Rappaport’s lobule)
o Ovoid or diamond shaped.
o Models the gradient of metabolic activity and is useful in describing
regeneration, centrolobular necrosis and the development of cirrhosis.
o Separated into zones:
36


Zone 3 is closest to the central vein, receives blood with the lowest
nutrient content, and these are the first cells to die during any ischemic
process.
Zones 1 and 2 are closest to the portal triad, receive the most nutrient rich
blood, and are the last to die while being the first to regenerate (zone 1 has
the HIGHEST blood nutrients where as zone 2 receives intermediate
amounts).
Hepatocyte Cytology and Histophysiology
 Mitochondria: Hepatocytes are very mitochondria rich.
 Lysosomes: Break down undesired structures in the cell (contain about 50+ different
catabolic enzymes that are made in the RER and transported to the Golgi and then
targeted to the lysosome by mannose-6-P) and have an internal pH of 4-5. The absence
of certain lysosomal enzymes results in diseases such as Tay-Sachs (hexosaminidase A
deficiency) and Metachromatic Leukodystrophy (acid maltase deficiency).
 RER and Golgi: Plasma proteins (albumin, fibrinogen, prothrombin, etc.) are synthesized
in the RER and pass through the Golgi apparatus (but there are no storage or secretion
granules in the liver – so only make as much as needed to be released). VLDL particles
are synthesized in the RER, but also involve SER activity.
 SER: More abundant in zone 3 of the liver acinus. The SER works to synthesize
cholesterol and phospholipids, esterify free fatty acids to glycerol to form triglycerides
(which are secreted as VLDL), conjugate bilirubin, and biotransform xenobiotics and
metabolites. ALSO, dehalogenase converts T4 to T3 in the SER.
 Peroxisomes: These are bound to the membrane. They use hydrogen peroxide to oxidize
products, while also playing a role in beta-oxidation of fatty acids and purine catabolism
(in which end product is uric acid).
 Glycogen: stored in rosettes and viewed with PAS stain (a fasted liver will have less
glycogen and less rosettes – via glucagon regulation).
Other Sinusoidal cells
 Kupffer cells: These are fixed hepatic macrophages with Fc and complement receptors
that are active in phagocytosis and antigen processing and presentation. They bind and
breakdown hemoglobin and myoglobin to bilirubin so they are able to take over RBC
degradation from the spleen, if necessary (stain very dark blue).
 Stellate cell (aka. Ito cell): Contains type III collagen and lipid droplets with vitamin A (so
have a role in hepatic fibrosis).
 Endothelial cells: Fenestrated, have indistinct basal lamina, no pericytes.
 Fibroblasts: Most known for synthesis of type III collagen reticular fibers.
 Oval cells: Give rise to bile ducts and hepatocytes and only under unusual conditions are
activated.
The biliary space: bile goes opposite direction of blood flow!
 Bile canaliculus
o Is a 0.5-1.5um channel (boundary) between hepatocytes.
o Zonula occludens and desmosomes contribute to its formation and keep bile from
leaking out.
37



o Membrane bound ATPases are used to pump bile constituents into the
canaliculus.
Terminal ductules (aka. Intercalated Duct OR Canal of Hering)
o Considered the transformation from canaliculus to interlobular ducts.
o May modify bile by secreting bicarbonate.
Interlobular Bile Ducts
o Contain cuboidal to columnar epithelium.
o May modify bile by secreting bicarbonate.
Bile transport
o Extra hepatic bile ducts (right and left hepatic ducts) Cystic duct common
bile duct
GALLBLADDER
Some QUICK and GENERAL facts about the GALLBLADDER:
 Volume capacity 30-50cc
o The filled bladder surface is stretched evenly.
o Empty bladder has decussating folds or rugae.
 Mucosa
o The lumen is composed of simple columnar microvillus epithelium.
o Is capable of extracting water, inorganic salts & other electrolytes – works to
concentrates bile!
o Mucous glands are present at the neck of the gallbladder
o Rokintansky-Aschoff Crypts, or diverticula
 Invaginations of the surface epithelium
 Favor bacterial retention and inflammation
o Lamina propria
 Thin & consists of dense irregular connective tissue
 Numerous blood & lymphatic vessels occupy this area but are small & not seen
in typical preparations.
 No muscularis mucosa
o Tunica muscularis (muscularis externa) is a layer of smooth muscle w/ some collagen &
elastic fibers.
o Serosa is a thick layer of dense irregular connective tissue & contains an abundance of
arteries, veins, & lymphatics.
Secretory stimulation:
 Stimulation of the gall bladder is via gut enteroendocrine cells which secrete secretin, an inducer
of biliary bicarbonate & water secretion.
 These cells also secrete cholecystokinin (CCK) which causes gall bladder contraction.
38
Male Reproductive System
Lecture: Dr. Marker
K-Coop: Neil Shah (shah0115@umn.edu)
“All your bases are belong to us.”
There are a number of ways to approach writing a K-Coop – each with their own
advantages/disadvantages. Basically, last year’s K-Coop copied the notes packet (which are the
same for y’all this year). Since you have those, and presumably have studied them intently, I’ve
chosen to follow the tack of addressing the objectives listed in the course packet. So, with much
ado about nothing here goes…
1) Identify under LM (be sure you can do this, K-Coop just won’t do here) and give the function
of the testis, seminiferous tubules, conducting tubules and ducts, accessory glands including the
seminal vesicle and prostate, and the penis and male urethra.
Testis – makes sperm and sex hormones. Lose the testis and men lose their sex drive
(and sing all funny – eunuchs). Multiple sex-offenders often want to self-castrate – hopefully this
helps you remember what these things do…or helps you get a pie piece in trivial pursuit.
Seminiferous tubules – sperm are made here; many seminiferous tubules are found
within each testis. The voyage begins here!
Connecting tubules and ducts – these connect the seminiferous tubules to the outside
world. Within this system the sperm mature and are stored. This system has multiple
subdivisions (like renaming a road every 3 miles) all of which you need to know because they
are of functional significance – see 4A.
Accessory glands – the seminal vesicles and the prostate gland. The seminal vesicles
“produce and store mucoid secretions high in fructose” (sperm food) – these do NOT store sperm
(that’s the connecting tubule system, remember?). The prostate gland is a heart-shaped gland that
surrounds the urethra below the bladder. Why is this important? Well, if your prostate is huge it
constricts your urethra and you can’t urinate (one cause is benign prostatic hyperplasia). The
purpose of the prostate is to produce a secretion that is slightly acidic to neutralize the acidic
urethra and vagina (inhospitable to sperm!).
2) Spermatogenesis v. spermiogenesis. Ok, these are really close and easy to confuse, but
they’re really different: spermIOgenesis is the last step of spermATOgenesis. Here’s a helpful
graphic:
Here’s how the numbers work out: 1 type A 1 type B 2 primary 4 secondary 8
spermatids 8 sperm
39
Here it is with ploidy: 1x(2N)  1x(2N)  2x(4N)  4x(2N)  8x(1N)  8x(1N)
sperm
Remember, mitosis doubles the DNA before splitting and meiosis just splits the DNA.
The anomaly is primary spermatocytes which double their DNA before they begin meiosis. This
is really important to understand so draw and redraw it (with ploidy numbers and counts) until
you’re sure you have it.
Spermiogenesis, the transformation from spermatids to sperm, has four steps (low
yield): Golgi phase, cap phase, acrosomal phase (the tip), maturation phase.
3) Compare and contrast the following structures:
seminal vesicle v. prostate: the former makes sperm food (they do NOT make sperm –
do not miss a question about this), the latter makes a slightly acidic fluid that makes the very
acidic urethra and vagina more hospitable. Sperm McDonalds v. Sperm TUMS (antacid).
seminiferous tubule v. epididymis: sperm are made in the former and mature/conveyed
in the latter. Sperm Factory v. Sperm Subway. As a low-yield aside the epididymis is
comprised of the ductuli efferentes and the ductus epididymis.
sperm-spermatid v. spermatogonia: you know the first part right? Spermatids undergo
spermIOgenesis to form sperm with no ploidy change (1N1N). Spermatogonia are the germ
cells that give rise to all of the other cell types seen in spermATOgenesis. There are two types of
spermatogonia: Type A (which give rise to one Type A and one Type B) and Type B (which
came from a Type A, and go onto form two primary spermatocytes). Note how the Type A keep
perpetuating themselves while giving rise to one Type B which goes on to make sperm. Child v.
Parent.
stereocilia v. cilia: long v. short. Stereocilia are only found in two places in the body:
sensory hair cells in the inner ear and in the ductus epididymis. It is critical that you associate
stereocilia with the ductus epididymis because they help define this region from other portions of
the conducting tubule/duct system (which might have cilia). In fact, the ductuli efferentes, which
drain the rete testis INTO the ductus epididymis, have the only true cilia of the subway system.
Leydig v. Sertoli. AH-nold v. A nursery (that looks like a Christmas tree…seriously).
Testosterone is made from cholesterol in Leydig cells. Sertoli cells, on the other hand, hold all of
the germ cell  sperm stages and help nourish the developing sperm. And yes, they really do
look like Christmas trees…to me at least. Just picture Leydig as some ‘roided out baseball player
(Jason Giambi) and you’ll be OK.
4)
Trace the route of sperm from formation to the outside world:
Aight, here’s the subway system: Seminiferous tubules  Epididymis  Vas
Deferens  Ejaculatory Duct  Urethra  Penis  I’m FREE!!!
And here’s the famous mnemonic from anatomy: SEVEN-UP (forget the N). Note that
vas deferens = ductus deferens (old skool v. new skool). Also, note that there are a few
microsteps between the seminiferous tubules and the epididymis (low yield): seminiferous
tubules (Sertoli lives here)  tubuli recti  rete testis  ductuli efferentes (true cilia)  ductus
epididymis (STEREOCILIA!!!).
40
What role does the nervous system play in erection?
A big role. First, remember “Point and Shoot” from Dr. Roberts – parasympathetics
(from L4-S5) will cause erection while sympathetics (T1-L3) control ejaculation.
Circulatory system?
Blood rushes into the corpora cavernosa distending the helicine arteries (which go from
helices to straight) and cuts off venous outflow. Since the tunica albuginea doesn’t stretch the
penis has no choice but to harden in response (this is exactly how penile implants work – except
with saline…and balloons). Nervous system input controls smooth muscle cell relaxation (Viagra
works here!) which leads to blood in-flow.
How many sperm arise from a single…
Spermatid – 1
Secondary spermatocyte – 2
Primary spermatocyte – 4
Type B spermatogonia – 8
Type A spermatogonia – 0 or infinity. Remember, Type A cells become another Type A
and a Type B after MITOSIS.
How many X and Y sperm arise from each of the above cells?
Uhh…I don’t know exactly what this is asking for – but here’s what you need to know
about X and Y (according to me): Each sperm has EITHER an X OR a Y. X/Y separation occurs
at the secondary spermatocyte step.
Where are sperm stored in the body?
The epididymis stores sperm.
If a male lacked functional accessory glands would you expect him to be:
Fertile – YES. His sperm would be formed normally. The trouble would occur on the
way out. His sperm would have no McDonalds and no TUMS – they’d die of starvation or be
burned by the acidic urethra and vagina. IVF would work for this guy.
Impotent – NO. He can still ‘get it up’ because his vasculature and nerves are intact.
There may not be much ejaculate, however, since the absent prostate usually makes up the bulk
of the ejaculate with its prostatic secretion. Also, upon erotic stimulation he would not produce
any mucoid secretion from the absent Cowper’s glands.
Feminized – NO. His AH-hold (Leydig) cells are still pumping out testosterone from
within the seminiferous tubules.
So he’s a fertile, manly man who is capable of sexual intercourse and ejaculation (low volume)
but whose sperm are undernourished and unprotected in the harsh outside world.
Would the same effects be expected if he only lacked functional interstitial cells?
Interstitial cell = Leydig cell. This guy will NOT be like AH-nold. In fact, he’s not much
of a man at all. He will be INFERTILE and FEMINIZED. Spermatogenesis requires
testosterone (and FSH) so no sperm will be formed. He will have significantly reduced sex drive
41
(if any) so whether or not he’s impotent is of question. Functionally, though, intact vasculature
and nerves would theoretically allow for erection/ejaculation. If he were to ejaculate it would
appear to be of normal volume because the accessory glands would still be producing prostatic
fluid/nutrients/mucoid fluid.
5) Describe Sertoli cells and discuss their function with regard to the development of
sperm.
These irregularly shaped (Christmas tree!) “nursing” cells extend from the basal surface
of the seminiferous tubule to the lumen. All stages of spermatogenesis take place within the
Sertoli cell (Type A/B cells are found near the basal surface and spermatid/sperm are found on
the apical surface with all of the other types in-between). Sertoli cells exist to nourish,
mechanically support and protect developing spermatids. One final note of import: sertoli cells
form occludens junctions between themselves to create a blood-testis barrier.
Well, that about wraps things up. If you have any questions feel free to contact me and I’ll do my
best to help you out. I hope that you found some of this information useful as it is pretty
important stuff (esp. if you want to go into any specialty where you might deal with men).
Good luck on the test!
Female Reproductive System
Kcoop was due before you guys had this lecture, so I just copied last year’s notes.
rung0015@umn.edu
OVARIES
The Basics: The ovaries are two, almond shaped structures responsible for production of the
germ cell and (acting as an endocrine gland) producing estrogens and testosterone.
The Histology: Think layers.
The outermost layer is the germinal epithelium and is simple cuboidal
epithelium.
Next up is the tunica albuginea. It’s a tough, irregular connective capsule,
analogous to the male tunica albuginea.
The cortex is the outer part of the parenchyma (i.e. the functional part!) and is the
site of oocyte development. Remember this! It will come back to haunt you…Not
surprisingly, you can find ovarian follicles in all stages of development and
degeneration in the cortex.
Last, but certainly not least, is the medulla. It contains lots of collagen, nerves,
blood and lymph vessels.
42
Oogenesis: This is the process by which germ cells develop (remember, that’s one of the two
functions of the ovaries).
1. Diploid primordial germ cells originate in the yolk sac and then cruise on out to the
genital ridges by the 6th week of embryonic development.
2. In the fetal ovary, the primordial germ cells divide and form oogonia (2n 2c). Between 57 million oogonia are produced in the fetal ovaries. Alas, most die in a process called
atresia.
3. At approximately 5 months of gestation, oogonia enter meiosis I and arrest in prophase
for as long as 55 years as primary oocytes (2n 4c)! At birth, female babies have
approximately one million primary oocytes but 600,000 become atretic before menarche.
***All the oocytes in the follicles are primary oocytes except the most mature, which just
before ovulation becomes a secondary oocyte.
4. Know this…Just prior to ovulation, a primary oocyte resumes meiosis and forms a
secondary oocyte and first polar body. The secondary oocyte enters meiosis II and
arrests in metaphase. These secondary oocytes are released from the ovary at ovulation.
5. During fertilization, the secondary oocyte completes meiosis II and becomes the ovum,
the mature germ cell. The second polar body is also formed.
6. Fusion of the ovum and spermatozoa pronuclei result in a zygote.
Ovarian Follicles
As mentioned earlier, ovarian follicles are found in the cortex. The follicles are comprised of a
primary oocyte + one or more layers of follicular cells and can be divided into 4 categories:
1. Primordial follicles: A primary oocyte and a single layer of flattened cells. These are the
most primitive.
2. Primary (preantral) follicles: A primary oocyte surrounded by one or more layers of
cuboidal follicular cells and a basal lamina. The surrounding cells = granulosa cells.
Between the oocyte and granulosa cells, look for a layer of glycoproteins called the zona
pellucida1.
a. There are two classes of primary follicles: unilaminar and multilaminar.
i. Unilaminar have (surprise!) only one layer of granulosa cells.
ii. Multilaminar have several layers of granulosa cells that multiply in
response to FSH, are connected by gap junctions, and are avascular.
b. ***At this point, the ovarian stroma organizes around the follicle to form a highly
vascular area called the theca folliculi
3. Secondary (antral) follicles: These are the sources of estrogen in the ovary.
Characterized by the presence of an antrum (fluid filled chamber between granulosa
cells) filled with liquor folliculi2. As the granulose cells continue to multiply in response
to FSH, a small group of them project out into the antrum and surround the oocyte – this
is the cumulus oophorus. Essentially, a cloud around the oocyte. The cells surrounding
1
The zona pellucida functions in fertilization and protection of the oocyte.
Liquor folliculi is a plasma exudates containing proteins secreted by the granulosa cells and hormones. As more
fluid is produced, these spaces coalesce to form a single, fluid-filled chamber called the antrum.
2
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the oocyte make up the corona radiate, a layer that is retained at ovulation and is key for
transporting the ova.
Recall the theca folliculi3 – at this stage, the TF differentiates into the theca interna, a
richly vascularized, endocrine producing cellular layer. The cells of the theca interna
produce androgens in response to LH, and the androgens are then converted to
estradiol by the granulosa cells when stimulated by FSH.
4. Mature (Graafian) follicles: Here, the granulose cells continue to proliferate, with the
ones forming the wall of the follicle known as the membrane granulosa. Add in a little
FSH and estrogen, and these cells spit out receptors for LH.
The Ovarian Cycle
There are three phases to the ovarian cycle.
A. Follicular Phase
Preantral phase: Levels of FSH start to rise, causing a limited number of primary
follicles to grow. In other words, this is the beginning of folliculogenesis.
Antral phase: Follicles continue to grow and form estrogen-producing secondary
follicles4. At some point, the most mature follicle becomes the dominant follicle. Now,
the dominant follicle is selfish little creature that is NOT dependent upon FSH for further
development. It doesn’t want any competition, so it secretes inhibin to suppress further
release of FSH (causing less mature, FSH dependent follicles to atrophy and die). At the
end of this phase, estrogen reaches a critical level  LH surge that triggers
ovulation.
Preovulatory phase: In response to the LH surge, the dominant follicle becomes a
secondary oocyte and first polar body, arresting in metaphase. The cumulus mass (2°
oocyte + corona radiate) breaks free and the region on the ovary surface where the
follicle is becomes avascular, known as the stigma. Basically, this is all happening to
prepare for the release of the cumulus mass.5
3
Recall: the theca folliculi is the vascular organization of the stroma around the follicle.
Three functions of estrogen – inhibition of FSH production and development of other follicles, stimulation of LH
production by the pituitary, and stimulation of the proliferative phase of the uterine cycle.
4
5
Remember, we talked earlier about the corona radiate (part of the cumulus mass) being important for transport of
the ova through the oviduct!
44
B. Ovulation:
The big one. The follicle ruptures and its fluid flows out, carrying with it the cumulus
mass to be picked up by the fimbriae.
C.
Luteal Phase:
The ruptured graafian follicle fills with blood, forming a clot, also known as the corpus
hemorrhagicus. Macrophages eventually remove this clot and the structure is invaded by
blood vessels, becoming a temporary endocrine organ called the corpus luteum. The
corpus luteum makes and releases hormones to support the uterine endometrium…but, it
needs continued stimulation by LH or hCG (in the case of pregnancy, hCG is secreted by
the placenta) to maintain its endocrine function.
There are two kinds of cells in the corpus luteum you need to know about:
1. Theca-lutein cells that express LH receptors and produce androgens and
progesterone when stimulated.
2. Granulosa-lutein cells also express LH receptors and produce progesterone and
convert androgens to estrogens.
What does the body do with these hormones? Well, the progesterone prepares the uterine
mucosa for implantation and inhibits LH secretion by the pituitary. Estrogen is a little easier
– it inhibits FSH.

No pregnancy the absence of LH leads to luteolysis.6 In response to decreased
estrogen and progesterone, menstruation occurs.

Pregnancy The placenta secretes hCG to maintain the corpus luteum of
pregnancy for three months. Once the CL ceases to function, it degrades to a
tissue scar called the corpus albicans.
Out of the ovaries and into the oviducts….
The oviducts function as the site of fertilization of the oocyte. They are paired, muscular
structures with walls comprised of three layers: Mucosa, muscularis, and serosa.
1. Mucosa
Has many longitudinal folds. Lumen of simple columnar epithelium with two cell types:
peg cells (aka secretory cells) and ciliated cells. The peg cells function to create a nice,
cozy environment for the spermatozoa/ovum/embryo. They are most active in the middle
of the menstrual cycle. The ciliated cells beat in waves toward the uterus to move things
along.
6
Degeneration of the corpus luteum to form the corpus luteum of menstruation.
45
2. Muscularis
Peristalsis is the main mechanism of propelling the oocyte or fertilized ovum toward the
uterus
3. Serosa
Covers the organ
The anatomy of the oviducts are fair game for the test so know this: Starting at their open end
and moving toward the uterus, the smooth muscle gets thicker and the mucosal lining becomes
less folded. The lumen gets smaller.
 Infundibulum: At the open end are the fimbriae that capture the ovulated oocyte.
The infundibulum is funnel shaped.
 Ampulla: The longest part and the site of fertilization.
 Isthmus: Often the site of ectopic pregnancy.
 Intramural region: passes through the uterine wall.
The Uterus
As you already know, the uterus is the site of embryonic and fetal development. It’s a thick,
pear-shaped organ comprised of a body, fundus, and cervix.
The body and fundus are similar in structure (finally! A 2-for-1!). The wall of the uterus has a
thick, muscular layer called the myometrium. The myometrium has 3 layers, the most important
of which is the highly vascular middle layer called the stratum vasculare. You find the arcuate
arteries in this layer.
The size and number of myometrial cells relates to estrogen levels:
 When estrogen is high (ie. Pregnancy), muscle cells are largest and most numerous.
 When estrogen is low (i.e. end of menstruation), muscle cells are the smallest.
 Conclusion? Absence of estrogen  myometrial atrophy.
As the uterus narrows toward the cervix, the myometrium is replaced by fibrous connective
tissue.
The myometrium contracts during parturition (childbirth) due to stimulation by prostaglandins
and oxytocin.
The mucosa layer of the uterus is the endometrium. It is composed of two cell types: nonciliated secretory cells and ciliated cells. Invaginations of the epithelium form uterine glands to
secrete nutrients to nourish the conceptus before placenta formation. The endometrium has 2
layers:

Functionalis: Formed under the influence of estrogen (during proliferative phase)
and progesterone (during the secretory phase) and vascularized by coiled helical
arteries. This is the layer that is sloughed at menstruation.
46

Basalis: A source for regeneration of the functionalis during proliferative phase.
Vascularized with coiled and straight arteries.
The uterine (menstrual) cycle
Three phases, lasting 28 days.
1. Menstrual Phase (Days 1-4)
Initiated by the drop in progesterone and estrogen in the absence of pregnancy. The
coiled arteries constrict, depriving the functionalis of blood. When the arteries dilate
again, they rupture due to their weakened state and disgorged blood removes functionalis
causing hemorrhagic discharge (menses). The entire functional layer is lost. This
occurs on day one.
2. Proliferative Phase (Days 5-14)
Initiated by a rise in estrogen due to the developing follicles. Begins when menstrual flow
ceases. The entire functionalis is regenerated from portions of the basalis.
3. Secretory Phase (Days 15-28)
Initiated by progesterone from the corpus luteum; begins after ovulation and lasts until
menstrual flow begins.
The Cervix
The cervix is the terminal end of the uterus that protrudes into the vagina. It is structurally
different from the body and the fundus. Its function is to link the uterine cavity with the vagina,
allowing for admittance of spermatozoa when fertilization is possible, protecting the uterus from
bacterial invasion, and permitting passage of the newborn during childbirth.
Structure:
1. Mucosa
NOT shed during menstruation. Comprised of endocervix and exocervix.
The endocervix is lined by mucus secreting simple columnar epithelium arranged in deep
palmate folds. It also contains branched cervical glands that secrete mucus under the
influence of hormones. During proliferative phase, the mucus is thin and watery,
facilitating the entry of spermatozoa. During the secretory phase, the mucus is viscous
and forms a plug to inhibit microbes and spermatozoa. The exocervix is the part that
protrudes into the vagina and is lined by stratified nonkeratinized epithelium. This
portion of the cervix does NOT have glands.
The junction of the endocervix and exocervix is quite abrupt and is frequently the site of
pre-cancers and cancers.
47
2. Cervical Wall
Contains little smooth muscle. Lots of dense CT. During parturition, the hormone relaxin
induces lysis of collagen in the cervical walls.
Pregnancy
During fertilization the oocyte and its corona radiate are picked up by the fimbriae and pushed
toward the ampulla while being nourished by the peg cells. Spermatozoa from the vagina pass
through the cervix, uterus, and oviduct where they travel to the ampulla and fertilize away.
Contact between sperm proteins and the zona pellucida triggers the acrosome reaction that
digests the ZP and permits sperm to enter the perivitelline space. Sperm comes into contact with
the oocyte, triggering the cortical reaction to prevent polyspermy. There are two components to
the cortical reaction that you should know:
1. Fast component: The membrane potential of the oocyte plasma membrane is altered to
prevent contact between the oocyte and another sperm. This lasts only a few minutes.
2. Slow component: The contents of the cortical granules in the oocyte’s cytoplasm are
released to hydrolyze the sperm receptor molecules of the ZP.
At this point, the secondary oocyte completes meiosis, forming the ovum and the second polar
body. The pronucleus of the ovum fuses with the pronucleus of the spermatozoa to form the
diploid zygote. The zygote undergoes cleavage in the oviduct, producing the blastomeres.
Continued division results in the morula. At the center of the cell mass the blastocyst develops.
It has two layers: the trophoblasts (these give rise to the embryonic portion of the placenta and
amniotic sac) and embryoblasts (give rise to the embryo proper).
Implantation occurs when the blastocyst enters the uterus and contacts the secretory
endometrium. This contact stimulates the stromal cells to transform into decidual cells which
will eventually form the maternal placenta. Now the trophoblasts proliferate and differentiate
into two layers: cytotrophoblast and syncytiotrophoblast. Vacuoles form within the
synctiotrophoblast and coalesce into large spaces, lacunae.
The placenta develops at the site of implantation and has a few important functions:
 Transfer of nutrients from mother to fetus
 Transfer of waste products from fetus to mother
 Endocrine organ
It is composed of the chorion (the fetal part) and the deciduas basalis (maternal).
Decidua basalis is divided into 3 regions:
-decidua basalis- between embryo & myometrium
-decidua capsularis- between embryo & uterus lumen
-decidua parietalis- remainder of deciduas
48
Chorion that comes in contact with deciduas basalis forms chorionic plate → chorionic plate
forms 1º villi (composed of cytorophoblasts with syncytiotrophoblast covering) →
extraembryonic mesenchyme invades this to form 2º villi → capillary beds form 3º villi
Placental barrier (6 layers):
-fetal capillary endothelium
-endothelium basal lamina
-villus mesenchyme
-trophoblast basal lamina
-cytotrophoblast
-syncytiotrophoblast
The Vagina
The vagina functions as a birth canal and as a source of protection for the uterus from
bacterial invasion. Again, it has three layers: mucosa, muscularis, and adventitia.
The mucosa does not have glands. It is marked by transverse folds to allow for expansion during
childbirth. The lumen is lined with stratified squamous nonkeratinized epithelium (same as the
exocervix), with the thickness depending on estrogen levels. ** Know that estrogen stimulation
leads to the storage of glycogen in the epithelial cells. As the epithelial cells are sloughed, the
glycogen is released into the lumen where it is metabolized to lactic acid, lowering the pH in
the lumen and providing protection against pathogens and sperm.
The muscularis is mostly longitudinal smooth muscle. The adventitia is mostly connective
tissue.
The Breast
The two main functions of the breast are to provide nourishment for the newborn and
antibodies for immunological protection of the newborn. They are comprised of a
parenchyma of 15-25 mammary glands. These are compound tubuloalveolar glands. Before
puberty, the glands have limited ducts. At puberty, estrogen and progesterone stimulate the
accumulation of adipose tissue and growth of the ducts. Unless the glands are stimulated by high
levels of hormones (during pregnancy) they do not develop beyond puberty. At menopause,
estrogen levels drop and mammary glands involute. They are replaced by adipose tissue.
The mammary glands:
 Lobes
15-25 per breast, separated by interlobar CT, each lobe drained by a single large
lactiferous duct into the nipple where they dilate to form the lactiferous sinuses.
 Lobules
15-25 per lobe, separated by interlobular CT and contain aggregates of loose
49
intralobular CT. Branches of the lactiferous ducts lead directly into each lobule and are
called terminal ducts.
Resting/Pregnant/Lactating Mammary glands:
 Resting: mostly CT, with ductules at the end of tubular structures
 Pregnant: estrogen and progesterone surges from the corpus luteum and placenta as
well as chorionic somatomammotrophin from the placenta activate the glands so that
they increase in size and form numerous alveoli. Late in pregnancy the glands secrete
colostrum, which is rich in IgA and is secreted the first 2-3 days after birth to give
immunity to newborns.
 Lactating: milk secretion by the alveolar cells is controlled by prolactin and is both
merocrine and apocrine. The suckling reflex is the response of the glands to the
mechanical stimulation of breast-feeding and involves inhibiting the release of
prolacting inhibiting factor and stimulating the release of oxytocin and results in milk
letdown.
The Urinary Sytem
12/6/04
Tina Byun (byun0009@umn.edu)
Here’s a couple of websites I found with some nice labeled H&E pictures of the various parts of
the urinary system (scroll past the text to find pictures):
1. University of Western Australia
http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Urinary/Urinary.htm#Kidney
2. University of Kansas
http://www.kumc.edu/instruction/medicine/anatomy/histoweb/urinary/urinary.htm
Functions of the urinary system (basically everything deals with maintaining homeostasis):
1. Eliminate wastes and toxic compounds
2. Regulate plasma volume, osmolarity, and acid-base equilibrium.
3. Endocrine function (the secretion of renin which you will learn about in physiology).
4. Regulation of red blood cell development (via erythropoietin – again, physiology).
5. Conversion of Vitamin D to its active form.
Kidney
In a nutshell, the kidney filters blood (removes a lot of the liquid and small soluble molecules)
thru the glomerulus to form an ultrafiltrate. Then, in the various parts of the tubule, ions, water,
small proteins, metabolites, other molecules (like glucose) are reabsorbed or secreted into the
ultrafiltrate to form urine (the fluid that exits the kidney via the ureter). Of course, this an
oversimplified view of things, but I think it’s important to have a grasp of what’s happening
functionally so you can anticipate the changes in types of epithelium that occur along the length
of a nephron.
50
Grossly, the kidney is surrounded by a stroma of thin connective tissue capsule of reticular fibers
covering the renal parenchyma (remember that reticular fibers are type III collagen that is most
easily visualized with silver stains). The concave part of the kidney through which the renal
pelvis, nerves, vessels, and lymphatics pass is called the hilum.
You should know all of the structures labeled on the following diagram:
a. Cortex – outermost layer of kidney beneath stroma
b. Medullary pyramid – 6-12 per kidney
c. Lobe = Medullary pyramid plus overlying cortex
d. Cortical (renal) Column – located between medullary pyramids
e. Medullary Rays = ascending/descending limbs of Loops of Henle and collecting ducts,
subdivisions of pyramids
f. Major Calyx
g. Minor Calyx – coalesce to form major calyx
h. Renal Pelvis = expanded proximal end of ureters
i. Papilla – apex of pyramid, inserts into minor calyx
j. Lobule – the renal corpuscles/nephrons that drain into a common collecting duct
k. Ureter
b&e
Cortical
(renal)
d
column
Major Calyxf
iP apilla
h
a
j
k
gMinor Calyx
c
Lobe
Adapted from: http://webanatomy.net/histology/urinary/kidney.jpg
51
If we’re going to make an ultrafiltrate of blood in the kidney, blood supply must be pretty
important. The path of blood through the kidney is as follows:
Abdominal Aorta
Inferior Vena Cava
Renal artery
Renal vein
Segmental artery
Segmental vein
Interlobar artery (between pyramids)
Arcuate vein
Arcuate artery = intralobar artery
Interlobular veins
Interlobular artery
P eritubular capillaries or Vasa Recta
Afferent arterioles
Efferent arterioles
Glomerular capillaries
Random anatomical notes:
The arcuate arteries and veins are located at the junction between the cortex and the medulla.
The interlobular arteries and veins are located in the cortical (renal) columns.
Next, we need to consider the nephron – a.k.a. the functional unit of the kidney (1.3 million per
kidney). A lot of blood goes through these things (180 LITERS of ultrafiltrate are produced
each day, but don’t worry, 178 L are reabsorbed so that we only make 1.5 L of urine).
There are 2 types of nephrons:
1. Cortical – shorter, 85%
2. Juxtamedullary – longer, 15%, respond to Anti-Diuretic Hormone
The first step in the nephron is to form ultrafiltrate. There are 3 layers through which blood is
filtered (be able to identify these components on EM):
1. Fenestrated capillaries – prevents passage of cells, platelets, and chylomicrons
2. Glomerular basement membrane (be able to identify the layers on EM) = fused basal
lamina
a. Lamina rara interna – next to capillary endothelium; composed of laminin,
fibronectin, heparin sulfate (negative charge repels negatively charged particles)
b. Lamina densa – central electron dense layer; composed of type IV collagen (only
particles <69 kD can pass through, albumin CANNOT pass through)
c. Lamina rara externa – next to epithelial cell; same composition as lamina rara interna
3. Podocytes with diaphragms on filtration slits between foot processes
The following molecules can pass through the filter freely: water, electrolytes, some hormones,
small proteins (<5200 MW, although some larger proteins also get through), toxins, and other
small molecules. If the filter becomes clogged, mesangial cells come in and unclog/phagocytose.
52
Now that ultrafiltrate is in the nephron, here’s where it goes…
Flow through the Nephron
Renal Corpuscle/G lomerulus
Proximal Convoluted Tubule
Simple cuboidal/columnar
epithelium w/long microvilli
Thick Descending Limb/Proximal Straight Tubule
Thin Limb
Simple squamous
epithelium w/cilium
Thick Ascending Limb/Distal Straight Tubule
Distal Convoluted Tubule
Collecting Tubule/Duct
Simple low cuboidal epithelium
w/basal infoldings, lots of
mitochondria and short microvilli
Simple cuboidal epithelium w/lighter (principal)
and darker (intercalated) staining cells
Simple cuboidal/columnar
epithelium
Now, let’s talk a little bit about the Countercurrent Multiplier System. (By the way, the
physiology of this is not really needed to pass histology, but you’re going to have to learn it
somewhere down the line anyway.) This system is essential to allow for the concentration of
urine (so we can get rid of wastes without having to drink a couple hundred liters of water per
day). (*Thanks to Dr. Shawlot for providing the following summary!)
The loop of Henle creates a gradient of hypertonicity in the medulla that influences the
concentration of urine as it flows in the collecting duct. The descending part of the loop of
Henle is quite permeable to water, Na+ and Cl-. Since the interstitial fluid of the kidney
space of the medulla is hypertonic, sodium and chloride enter the ultrafiltrate and water
leaves in the descending portion of the loop. The ascending portion is impermeable to water
and actively pumps out Cl- ions (Na follows). This is directly responsible for the
hypertonicity of the interstitial fluid of the medullary region. The system of repetitive
transfer of small amount of chloride along the length of the loop (passively in the descending
loop and actively in the ascending loop) is called the countercurrent system. The filtrate that
reaches the distal convoluted tubule is hypotonic. The distal convoluted tubule leads to the
collecting duct. The hypotonic urine present in the collecting duct will lose water into the
interstitium as it descend in the medulla if antidiuretic hormone (ADH) is present and
hypertonic urine will be formed. If ADH is not present, the collecting duct walls are
impermeable to water and the kidney forms abundant hypotonic urine. The vasa recta system
allows the recovery of the components placed in the interstitial space (maintains osmotic
gradient). The limbs of the vasa recta are completely permeable to water and salts. The
arterial limb loses water and gains salts as it descend into the medulla and the ascending
venous limb gains water and loses salts (countercurrent exchange). Because the lumen of the
venous limb is larger than the arterial limb, a larger fluid volume is recovered (returned to
blood).
53
The minor calyx (transitional epithelium – 2-3 cells thick) and papillae (columnar epithelium)
while located next to each other can be distinguished by the type of epithelium.
Here’s the big chart that summarizes the various components of the nephron both from a
microscopic standpoint and function…lots to memorize here…
STRUCTURE
Glomerulus
Bowman’s Capsule
Proximal Convoluted
Tubule
CELL COMPOSITION
Endothelial Cells
 Comprise fenestrated capillaries
Mesangial Cells
 Phagocytosis
 Regulation of flow
 Support capillaries
 Contractile in response to Ang II
2 Cell Layers
 Simple Squamous Epithelium
(parietal/outer layer)
 Podocytes = foot processes wrap
around capillaries (visceral layer)
Simple cuboidal/columnar epithelium
w/extensive microvillus brush border
and basolateral interdigitations
(makes borders between cells appear
unclear microscopically), lots of basal
mitochondria (for active pumping of
sodium)
Thick Descending Limb
(Proximal Straight Tubule)
Thin Descending Limb
Simple cuboidal/columnar epithelium
w/long microvilli, eosinophilic
Simple squamous epithelium w/cilium
Thin Ascending Limb
Simple squamous epithelium w/cilium
Thick Ascending Limb
(Distal Straight Tubule)
Simple low cuboidal epithelium
w/short microvilli, basal infoldings
(w/mitochondria), lateral
interdigitations, basophilic
Simple cuboidal epithelium w/lighter
(principal) and darker/no microvilli
(intercalated) staining cells
Distal Convoluted Tubule
Collecting Duct
Simple cuboidal epithelium w/lighter
(principal) and darker/no microvilli
(intercalated) staining cells
54
FUNCTION
Tuft of capillaries in the renal corpuscle
supplied by the afferent arteriole,
recombine to form efferent arteriole.
Found within Bowman’s Capsule.
Receives ultrafiltrate/entrance into
nephron tubules.
Reabsorption of
 100% protein (pinocytosis)
 100% amino acids, glucose (active)
 60-85% Na+ (active), water (passive)
 Ca2+, Cl-, HCO3-, K+, PO4Secretion of
 H+, NH4+
 Other compounds (penicillin)
Fluid leaving this area has the same
osmolarity as plasma
Reabsorption of
 Water
Freely permeable
 Water out
 Urea and Na+ in
Forms countercurrent multiplier
Fluid leaving this area is hypertonic
Impermeable to water
Na+ out (follows Cl- which is pumped)
Forms countercurrent multiplier
Fluid leaving this area is hypotonic
Impermeable to water
Reabsorption of
 Na+ (active)
Impermeable to water (w/o aldosterone)
In the presence of aldosterone
 K+ secretion (principal)
 H+ secretion (intercalated)
 Na+ reabsorption
 Water reabsorption
Same as Distal Convoluted tubule in
cortical nephrons.
Medullary nephrons respond to ADH
 w/o ADH: impermeable to water 
copious hypotonic urine
 w/ADH: resorption of remaining 1% of
Na+, passive reabsorption of 10-20% of
remaining water  low volume,
concentrated/hypertonic urine
There’s also an important structure located where the distal convoluted tubule meets the afferent
arteriole. It is called the Juxtaglomerular apparatus.
1. Macula Densa cells of the distal convoluted tubule – skinnier/columnar cells with nuclei
that appear more tightly packed than in other tubule regions; detect levels of NaCl and
communicate the state of these ions to the lacis cells (see #2)
2. Extraglomerular mesangial (lacis) cells – release prostaglandins/vasoconstrictors in
response to signals from macula densa cells to regulate vascular flow through glomerulus
3. Juxtaglomerular cells of the afferent arteriole – muscle cells which secrete renin to
control aldosterone levels (these cells are packed with renin granules)
The renin-angiotensingen-angiotensin system was covered in our lecture. It’s not really in the
notes, but here it is in case it will be covered in your lecture.
Macula Densa senses low [Na+]
MD sends signal to arterial juxtaglomerular cells to release renin into bloodstream
Renin converts angiotensinogen (present in blood) into angiotensin I (mild vasoconstrictor)
Angiotensin Converting Enzyme in lungs and kidney convert angiotensin I
into angiotensin II (potent vasoconstrictor)
Angiotensin II stimulates aldosterone release fro m the adrenal cortex
Aldosterone stimulates increased reabsorption of NaCl in the distal convoluted tubule
Clinical Correlation (again covered in our lecture, not in the notes): Polycystic kidney disease
results from an autosomal dominant mutation of the PKD1 and 2 genes which affects
transmembrane proteins. This mutation causes the renal tubules to form cysts which leads to
renal failure.
Ureter
Microscopic features: stellate lumen, transitional epithelium, lamina propria between epithelium
and smooth muscle.
Transitional epithelium:
 Several cell layers (4-5) thick
 Umbrella/dome cells protrude into lumen
 Discoid vesicles found in the apical cytoplasm allow for the surface area of the epithelium to
be increased when the ureter is stretched
Smooth muscle layers:
 Inner – longitudinal
 Middle – circular
55
 Outer – longitudinal, exists only in the portion of the ureter nearest the bladder
* Look alikes: The ureter is a hollow structure approximately the size of a pencil eraser in
diameter (like the appendix, oviducts, and vas deferens). The ureter has a transitional
epithelium and inner and outer longitudinal muscle layers. The appendix has gastric pits
and a thin muscle layer. Oviduts have simple columnar epithelium (ciliated and nonciliated peg cells), inner circular and outer longitudinal muscle layers, folded mucosa,
and a simple squamous outer covering. The vas deferens has pseudostratified epithelium
over 3 layers of muscle (longitudinal-circular-longitudinal), and a star-shaped lumen.
Urinary Bladder
Microscopic features: transitional epithelium (6-8 cells thick), lamina propria, thick smooth
muscle (detrusor) layer bundles are not well organized in particular directions, nerves and
blood vessels run in connective tissue septa between muscle bundles
* Look alikes: The fact that the muscle is not organized into distinct layers and has transitional
epithelium but no glands is what distinguishes the bladder from other structures with
thick muscular layers (stomach, esophagus, uterus, colon).
Urethra
Microscopic features: transitional epithelium in proximal urethra  pseudostratified 
stratified squamous near external orifice, stellate lumen, connective tissue contains elastin
(see with special stains), external sphincter made of skeletal muscle
Take a look at the differences between male and female urethras in your course notes.
Respiratory System
Definitions:
Total Capacity – lungs expanded to maximum volume (6-7L)
Residual Volume – volume remaining in lungs at the end of a complete exhalation (1L)
Functional Residual Capacity –volume remaining in lungs after normal exhalation (2L)
Dead Space – air in conducting tubes that does not take part in gas exchange (150mL)
Respiratory Epithelium – ciliated pseudostratified columnar epithelium w/ goblet cells
Respiratory system can be divided into three parts, proximal to distal (note you only talked about
the first two this year):
I. Conduction Portion
A. Function
1. conduct air, remove dust particles, warm or cool and humidify air
2. dead space (no gas exchange)
B. Morphology
1. lined with respiratory epithelium (progressively becomes cuboidal)
2. has glands in lamina propria, smooth muscle, elastic fibers, cartilage
3. cilia, glands, and cartilage gradually decrease
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4. amount of smooth muscle and elastic fibers is constant so these are more
prominent in small airways
C. Components
1. Nasal Cavity
a. Vestibule
i. passageway for air
ii. lined with skin (stratified squamous keritinized
epithelium with hair follicles), progresses to respiratory
epithelium
b. Respiratory
i. respiratory epithelium with a thick basement membrane
on top of lamina propria (connective tissue) with
mixed (serous and mucous) glands and thin walled veins
ii. olfactory region
1. pseudostratified columnar epithelium (no goblet
cells), olfactory cells (bipolar neurons),
sustentacular cells and basal cells
2. Bowman’s glands (under epithelium) secrete
serous fluids that trap odorous particles
2. Nasopharynx
a. proximal portion lined with respiratory epithelium, distal
portion with stratified squamous non-keratinized epithelium that
continues to oropharynx
b. pharyngeal tonsils (adenoids)
3. Larnyx
a. connects pharynx and trachea
b. supported by hyaline and elastic cartilages.
c. Epiglottis
i. backbone of elastic cartilage
ii. anterior surface – stratified squamous non-keratinized
epithelium with taste buds
iii. posterior surface – respiratory epi w/ mixed
seromucous glands
d. True vocal cords
i. epi abruptly changes to stratified squamous nonkeratinized (no glands) over skeletal m.
ii. false cords have resp. epi
4. Trachea
a. hollow rigid tube formed by C shaped hyaline cartilage rings
b. respiratory epi over lamina propria (contains elastic
membrane) over submucosa (contains seromucous glands) over
cartilage and smooth m. rings .
(side note: the goblet cells in the trachea express the mucin gene:
MUC 1, 2, 4, 5AC)
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5. Primary/Main bronchi
a. trachea divides at carina into right and left branches
b. same histology as trachea except
i. cartilage plates instead of rings
ii. smooth m. encircles lumen
c. enters lung at hilus and branches
(lobar bronchi  bronchiole terminal bronchiole)
i. changes that accompany branching
1. epithelium changes from respiratory to simple
columnar with Clara cells (dome shaped, nonciliated) in smaller bronchioles
2. cartilage disappears (at bronchioles)
3. goblet cells disappear (at terminal bronchioles)
4. glands disappear
5. smooth muscle becomes prominent
6. elastic fibers become prominent
II. Respiratory Portion
A. Function
1. location of gas exchange between air and blood, a passive process
B. Components
1. Respiratory bronchioles (0.2mm diameter)
a. branches off of terminal bronchioles
b. have sack like outpouchings called alveoli
c. simple columnar/cuboidal epithelium with and without cilia that
becomes simple squamous in alveoli
2. Alveolar Duct
a. two or three branch off each respiratory bronchiole
b. lined with simple squamous epithelium, wall is composed of alveoli
3. Alveolar Sacs
a. alveolar duct terminates in two or three alveolar sacs
4. Alveolus (pl. alveoli) (75-300um diameter)
a. single outpouching structure which contains air
b. connected to adjacent alveoli by small slit-like openings called
alveolar pores (Kohn’s pores)
i. pores equalize alveolar pressure and permit the spread
of infection
c. gas exchange occurs here, there is a rich vascular supply
c. alveolar wall has five types of cells
i. Type I epithelium – squamous cell with attenuated
cytoplasm, flattened nucleus
1. forms blood/air barrier
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ii. Type II epithelium – large round cell that protrudes
into alveolus, cytoplasm ha
s lamellar bodies containing phospholipid
1. surfactant – secreted phospholipid that reduces
surface tension which prevents alveolar collapse
during expiration
iii. Endothelial cell – forms capillaries, most numerous
nuclei seen
iv. Fibroblast – produces connective tissue fibers
v. Smooth muscle – found at tip of alveolar sac
d. Alveolar macrophages
i. found in alveolar spaces, free of the wall
ii. arise from monocytes, phagocytosed material in
cytoplasm
III. Ventilatory mechanism – ribs, diaphragm, intrinsic muscles
(discussed in pathophysiology)
IV. Gas Exchange
A. Multilayer barrier between alveolar lumen and red blood cells (0.3-0.7um)
1. attenuated cytoplasm of Type I epithelial cell (0.05um)
2. basement membrane between Type I epithelial cell and capillary
endothelial cell (0.15um)
3. attenuated cytoplasm of capillary endothelial cell (0.25um)
B. Gas exchange is passive transport
C. Blood supply to lungs
1. right ventricle (venous blood)  pulmonary arteries  lung
(oxigenation)  pulmonary veins  left atrium
2. oxygenated blood needed by lung tissues is supplied by bronchial a.
V. Lung Defenses
A. Airway defenses – filtration, airway reflex (cough, sneeze), mucociliary
transport (carries particles up out of resp bronchioles and to larynx)
B. Alveolar defenses – surfactant, alveolar macrophages
C. Bloodstream and immunological defenses – humoral and cell-mediated mechs.
D. Respiratory diseases – result of damaged or abnormal defenses
1. Lung cancer from smoking, asbestos, etc.
2. Cystic fibrosis – thick mucus so hard for respiratory cilia to move
3. Kartagener’ syndrome – genetic disease, immotile cilia that lack
dynein arms, causes infertility, situs inversus, airway dilation and chronic
sinusitis
4. Asthma – problems in smooth m. contraction in smaller airways
5. Newborn Respiratory distress syndrome – insufficient surfactant made in type
II cells
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6. Pulmonary fibrosis – excess connective tissue fibers
7. Emphysema – α1-antitrypsin deficiency which allows elastase to degrade
elastin/elastic fibers
Some questions from the 1999 final:
Which of the following is/are TRUE?
1. Non-motile cilia form the olfactory sensory apparatus.
2. Motile cilia function in the embryological establishment of left-right body axis.
3. Motile cilia remove mucus-trapped debris from the airways.
4. Motile cilia transport surfactant in alveoli.
A. Only 1, 2 and 3 are correct.
B. Only 1 and 3 are correct.
C. Only 2 and 4 are correct.
D. Only 4 is correct.
E. All are correct.
Ans. A
Concerning the lung, which of the following statements is TRUE?
A. Alveolar pores serve as pathways for oxygen to cross the air-blood barrier.
B. Elastic fibers are important in the maintenance of the alveolar walls and nonforced
exhalation.
C. Interstitial cells regulate entry of air into the alveoli.
D. Asthma results from inflammation in the bronchiolar mucosa.
E. Respiratory bronchioles are covered with pseudostratified columnar epithelium.
Ans. B
Concerning the conduction portion of the respiratory tract, which of the following statements is
TRUE?
A. The nasal cavity is lined primarily by a simple columnar epithelium.
B. The larynx contains only elastic cartilage and fibrocartilage.
C. The false vocal cords contain skeletal muscle and lingual tonsils.
D. The trachea and primary bronchi contain C-shaped hyaline cartilages, but only
irregularly shaped cartilage plates are present in bronchioles.
E. Respiratory bronchioles contain no cartilage, no glands and no goblet cells.
Ans. E
Concerning the respiratory system, which of the following are false?
A. Type II pneumocytes produce surfactant.
B. The capillary endotheilial cells are fenestrated to maximize gas exchange.
C. Large numbers of macrophages enter the respiratory system each day.
D. Type I pneumocytes and endothelial cells form a single, fused basal lamina.
E. Clara cells are thought to regenerate the bronchiolar epithelium.
Ans. B
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