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UNIVERSITY OF MEDICINE AND PHARMACY TRGU MURE

DEPARTMENT OF MORPHOLOGICAL SCIENCES

HISTOLOGY OF THE ORGANS

LECTURE NOTES

Authors:

Professor Dr. Angela BORDA

Lecturer Dr. Simona MARCU

Junior Lecturer Dr. Cosmin MOLDOVAN

2012
The vascular system

The cardiovascular system


is specialized for transporting blood and lymph through
the body
may be divided into four major components:
the heart
the macrocirculation (arteries and veins - visible to the eye)
the microcirculation (capillaries network or capillary bed)
the lymph vascular system

1
General Structure of Blood Vessels

blood vessels have a common structural pattern


that can be seen in all vessels with the exception
of capillaries
their walls have three layers or tunics
the tunica intima
the tunica media
the tunica adventitia

2
General Structure of Blood Vessels
The tunica intima
delimits the vessel wall towards
the lumen
comprises 3 structures:
endothelium (simple squamous ep)
subendothelial connective tissue
the internal elastic lamina
which delimits the tunica intima from
the tunica media

General Structure of Blood Vessels


The tunica media
a layer of circumferential smooth
muscle and some elastic and type
III collagen fibers
the fibrous elements form lamellae
within the ground substance secreted
by the smooth muscle cells
the external elastic lamina
is more delicate than the internal elastic
lamina
delimits the tunica media from adventitia

3
General Structure of Blood Vessels
The tunica adventitia
the outermost layer which blends
with the connective tissue
surrounding the vessel
consists mainly of connective
tissue fibers - longitudinally
oriented
contains:
vasa vasorum which furnish a blood
supply
nerves - vasomotor innervation to
the smooth muscles of the tunica
media

General Structure of Blood Vessels

4
Endothelium
endothelial cells were once considered to be
simple lining cells with very few functional roles
recent research on endothelial cells has
revealed that they have amazing functional and
adaptive qualities
moreover, they are the key determinants of
health and disease in blood vessels and play a
major role in arterial disease

Endothelium - structure
endothelial cells are very flat
have a central nucleus
intercellular junctions - critical for the
integrity of the vessel
at the junctions between cells there
are overlapping regions which help
to seal the vessel
toxic substances, such as nicotine,
open up these junctions and allow
large molecules to pass through the
wall

5
Endothelium - structure

Endothelium - structure

6
Endothelium - structure
the cytoplasm is relatively simple:
few organelles, mostly in the
perinuclear zone
small vesicles (pinocytotic vesicles)
near to the cell membrane
mechanism for passing materials,
especially fluid, across the cells
gases simply diffuse through, very
rapidly (ex.lung capillaries)

Endothelium - function
selective filters which regulate the passage of gases, fluids and various
molecules
possess surface molecules which act as receptors and interaction sites
of important molecules (especially those that attract leukocytes)
leukocyte cell adhesion molecules - important in inflammation
angiotensin-converting enzyme (cleaves angiotensin I to angiotensin II)
synthesis function:
Factor VIII or von Willebrand's Factor - essential for blood clotting
(absent in haemophilia)
types II, IV, and V collagens, laminin
endothelin (constrict blood vessels and raise blood pressure)
nitric oxide or Endothelium-derived relaxing factor (induces smooth
muscle relaxation vasodilatation)

7
Endothelium - pathology
Endothelial cells play a crucial role in the initiation
(pathogenesis) of arterial disease
the most common form of disease is atherosclerosis
deposition of cholesterol in the sub-endothelial layer
endothelial cells become "injured" either physically by abrasion or by
toxic insult (such as from nicotine)
large molecules, which are normally confined to the blood, are
allowed to escape through the endothelium
macrophages also pass through, and accumulate fat (lipid and
cholesterol)
consequences: deposits known as "plaques", with consecutive
stenosis, thrombosis heart attacks, stroke

Micrograph of an artery that supplies the heart with significant


atherosclerosis and marked luminal narrowing. Masson's trichrome.

8
Arteries
Classification of Arteries
elastic arteries (conducting arteries)
muscular arteries (distributing arteries)
arterioles or resistance vessels (are precapillary arteries
with a diameter of less than 0.1 mm)

Elastic arteries

9
Muscular arteries

Arterioles
arteries with a diameter of
less than 0.1 mm
terminal arterial vessels that
regulate blood flow into the
capillary beds
structure
intima: thin layer
media: a single smooth muscle
cell layer
adventitia is scant

10
Capillaries
General Structure
are the smallest blood vessels (4-15 m)
have a very simple organization of the wall:
tunica intima (single layer of endothelial cells and BM)
an incomplete layer of pericytes:
cells with contractile properties regulate blood flow in
capillaries
involved in vascular remodeling and vascular repair they
can differentiate into endothelial and smooth muscle cells

Pericytes

11
Pericytes

Capillaries
Three types of capillaries can be distinguished based on
features of the endothelium

12
Capillaries

Capillaries
Sinusoid capillaries

13
Microcirculation
the circulation of blood in
arterioles (small arteries),
capillaries and venules (small
veins)
capillaries extend from structures
called precapillary sphincters
(PSs) and form the capillary bed
PSs control the blood flow between
the arteriole and capillaries
capillary bed allows fluid exchange
between capillaries and the tissues

14
Microcirculation
the PSs contain muscle fibers that
allow them to contract
when sphincters are open, blood
flows freely to the capillary bed
fluids, gases, nutrients, and waste pr.
are exchanged between the blood
and body cells
when the sphincters are closed,
blood is not allowed to flow through
the capillary bed
it must flow directly from the arteriole
to the venule through the
thoroughfare channel

Microcirculation
A thoroughfare channel
is a by-pass
allows blood to flow freely
between an arteriole and a
venule

15
Microcirculation
Important practical note
the blood is supplied to all parts of the body at all
times
but not all capillary beds contain blood at all
times: blood is diverted to the parts of the body
that need it most at a particular time
Example: when you eat a meal, blood is diverted from
other parts of your body to the digestive tract to aid
digestion and nutrient absorption

Veins
Veins originate from the capillary
network which comes together into
venules (the smallest venous vessels)
Characteristics
the walls of veins are thinner than the
walls of arteries
their diameter is larger
the tunica intima is very thin
internal and external elastic laminae are
absent or very thin
tunica media appears thinner than the
tunica adventitia, and the two layers
tend to blend into each other

16
Arteries and Veins

Elastic artery Muscular artery Vein

17
18
The Digestive System
Oral Cavity

The Lip

Top SSK
(thin skin)

Red Free
Margin

Bottom -
SSnonK

19
The Mucus Membrane of the Cheek
SSnon-K w/ mucus & serous glands in lamina propria

The Tongue at low mag

20
Filiform Papillae

21
Fungiform or Foliate Papillae

Vallate Papillae

22
Taste Bud
Diagram

Taste Bud

23
Diagram of
an adult
tooth

Developing Odontoblasts and Dentin

24
SEM of
dentin

Odontoblast
s colored
green

Developing Tooth
Ameleoblasts

Dentin

Odontoblasts

25
Ameleoblasts
Enamel

Dentin
Odontoblasts

The Digestive System


Digestive Tube
Esophagus to Stomach

26
Low mag Cross section through the Esophagus

Wall of the Esophagus

27
Esophagus

Esophageal
Mucus gland
(arrow)

Stomach Esophagus Junction

28
Stomach Diagram

Short Pits
(F)

Long
Glands
MM
muscularis
mucosa
(interna);
SM -
submucosa

29
Fundic Stomach with a
short pit

Surface mucus
secreting epithelium

Diagram of a
Fundic Gastric
Gland

30
Diagram of a Parietal Cell

Fundic
Gastric
Glands

Parietal
Cells

Neck Mucus
Cells

31
High mag Fundic Gastric Gland

N - neck mucus cells; P parietal cells

Cross section Fundic Gastric Gland

32
Pyloric Stomach

Long pits (P)

Short Glands

MM muscularis
mucosa (interna)

Pyloric Gastric Gland stained for Gastrin Cells

33
ALIMENTARY TRACT

Digestive system
Composed of:
the oral cavity
alimentary tract
associated glands (salivary gl, liver, pancreas)

34
Alimentary tract
is the tubular portion of the digestive tract
here the food is churned, liquefied and digested
its nutritional elements and water are absorbed
and the indigestible components are eliminated

it is about 9 meters long


is subdivided into morphologically recognizable regions:
the esophagus
the stomach
the small intestine (duodenum, jejunum and ileum)
the large intestine (caecum, colon, rectum, anal canal, and appendix)

General plan of organization of the


alimentary tract

35
Esophagus
is a muscular tube
of approximately 25 cm in
length
conveys the bolus
(masticated food) from the
oral pharynx to the stomach

Esophagus
the mucosa presents
numerous longitudinal
folds (along its entire
length)
allow distention
in distended esophagus the
folds disappear

36
Cross section through the Esophagus

Wall of the Esophagus

37
Esophagus
Mucosa
stratified squamous
nonkeratinized epithelium
lamina propria: unremarkable
esophageal cardiac glands - near
the junction with the stomach
houses occasional lymphoid
nodules - members of the MALT
system
muscularis mucosae

Esophagus
Submucosa
contains mucous glands known
as the esophageal glands
Muscularis Externa
is composed of both skeletal
and smooth muscle cells
Adventitia/serosa
E. is covered by an adventitia
until it pierces the diaphragm
after which it is covered by a
serosa

38
Clinical correlation
Barrett's syndrome
is probably a premalignant condition
initially due to gastroesophageal reflux
the stratified squamous nonkeratinized epithelium of
the esophagus, is replaced by a simple columnar
epithelium that resembles the lining of the stomach or
of the colon
the process is known as
METAPLASIA
the metaplastic area is reddish in color in endoscopy

Clinical correlation

Normal G-E junction Barrett esophagus

39
Stomach Esophagus Junction
(abrupt passage of the epithelium)

Stomach
the most dilated region of the alimentary canal
is responsible for the formation and processing
of the ingested food into a thick acidic fluid
known as chyme

40
Stomach
Anatomic regions
Cardia: a narrow region at the gastroesophageal junction (2 to 3
cm wide)
Fundus: a dome-shaped region to the left of the esophagus,
frequently filled with gas
Body (corpus): the largest portion, responsible for the formation
of chyme
Pylorus (pyloric antrum): a constricted portion
contains the pyloric sphincter that controls the intermittent release of
chyme into the duodenum
Histological regions (3): cardia, fundus and body have
the same structure, pylorus

Stomach
Mucosa
all the gastric regions display
rugae - longitudinal folds of the
mucosa and submucosa
permit expansion of the stomach
as it fills with food and gastric
juices
gastric pits (foveolae) -
invaginations of the epithelial
lining into the lamina propria,
increasing the surface area of
the gastric lining

41
Stomach Diagram

Fundic mucosa (structure)


the epithelial lining
is a simple columnar epithelium
secretes a visible mucus that:
adheres to, and protects the
stomach lining from digestion
the entrapped bicarbonate ions
in this mucus maintain a
relatively neutral pH at its
interface with the surface-lining
cell membrane, despite the low
(acidic) pH of the luminal
contents

42
Fundic mucosa (structure)
lamina propria
loose connective tissue, highly
vascularized
15 million closely packed
gastric glands
known as fundic (oxyntic) glands
extends from the gastric pits
base to the muscularis
mucosae
subdivided into three regions:
isthmus
neck
base

Fundic mucosa (structure)


the fundic glands are lined by a
simple columnar epithelium
composed of five cell types:
mucous neck cells
regenerative (stem) cells
parietal (oxyntic) cells
chief (zymogenic) cells
diffuse endocrine system (DES)
cells
also known as amine precursor
uptake and decarboxylation [APUD]
and enteroendocrine cells.

43
Fundic Stomach with a
short pit

Surface mucus
secreting epithelium

Cells of the fundic gland


Regenerative (stem) cells
relatively few
are interspersed among the
mucous neck cells
they proliferate to replace
all of the specialized cells
lining:
the fundic glands
gastric pits
luminal surface

44
Cells of the fundic gland
Mucous neck cells
produce soluble mucus
role: lubricates the chyme, reducing
friction as it moves along the
digestive tract

Fundic
Gastric
Glands

Parietal
Cells

Neck Mucus
Cells

45
Cells of the fundic gland
Parietal (oxyntic) cell
role: to produce
hydrochloric acid
gastric intrinsic factor
both products are released
into the lumen of the stomach

Cells of the fundic gland


Parietal (oxyntic) cell has:
round, basally located nuclei
eosinophilic cytoplasm
main characteristic:
the invaginations of their apical
plasmalemma to form deep
intracellular canaliculi lined by
microvilli
the cytoplasm bordering these
canaliculi contain the tubulovesicular
system (round and tubular vesicles)

46
Cells of the fundic gland
The number of microvilli and the abundance of
vesicles of the tubulovesicular system vary with
the HCl secretory activity of parietal cells
ex: during active HCl production, the number of
microvilli increases and the tubulovesicular system
decreases
the tubulovesicular system is probably used for
microvillar assembly, increasing the surface area of
the cell by four to five times in preparation for HCl
production

Mechanism of HCl formation


carbonic anhydrase
facilitates the production
of carbonic acid (H2CO3)
from water [H2O] and
carbon dioxide [CO2])
H2CO3 dissociates into
hydrogen ions (H+) and
bicarbonate (HCO3-)
within the cytoplasm of
the parietal cell

47
Mechanism of HCl formation
H+ is pumped out of the cell in
the intracellular canaliculus, and
the K + into the cell
then carrier proteins, utilizing
ATP as an energy source, pump
K+ and chloride ion (Cl-) out of
the cell
thus Cl- and H+ enter the lumen
of the intracellular canaliculus
separately, to combine as HCl

CLINICAL CORRELATIONS
Gastric intrinsic factor is necessary for vitamin B12
absorption from the ileum
absence of this factor results in deficiency of vitamin B12
consequence: development of pernicious anemia
because the liver stores high quantities of vitamin B12, a
deficiency of this vitamin may take several months to
develop an anemia, after the production of gastric
intrinsic factor ceases

48
Cells of the fundic gland
Chief (zymogenic) cells
produce and release enzymes into the
lumen of the stomach
pepsinogen
rennin
gastric lipase
histology:
columnar cells
basophilic cytoplasm
basally located nuclei
apically situated secretory granules that
house the proenzyme pepsinogen (and
other)

Cross section Fundic Gastric Gland

49
Cells of the fundic gland
DES Cells (APUD or
Enteroendocrine Cells)
members of the diffuse neuroendocrine
system cells
they secrete hormone-like substances
the target cells are in the immediate
vicinity of the signaling cell (paracrine
effect) or enter the circulation and
travel a distance to reach the target cell
(endocrine effect)

Enteroendocrine Cells

Gastrin Pancreatic polypeptide


stimulates HCl secretion, gastric (PP)
motility (especially contraction of stimulates the release of
the pyloric region and relaxation
enzymes by chief cells,
of pyloric sphincter to regulate
stomach emptying)
depresses the release of HCl
by parietal cells, etc
Serotonin, Substance P
Vasoactive intestinal
increases peristaltic peptide (PP)
movement
increases peristaltic action of
Histamine small and large intestines and
stimulates HCl secretion stimulates elimination of
water and ions by GI tract

50
Pyloric Gastric Gland stained for Gastrin Cells

Pyloric mucosa
deeper pits - extending
approximately halfway down
into the lamina propria
pyloric glands are highly
convoluted and tend to
branch
they contain the same cell
types
but the predominant cell type is
the mucous neck cell
in addition to producing mucus,
these cells secrete lysozyme,
a bactericidal enzyme

51
Pyloric Stomach

Long pits (P)

Short Glands

MM muscularis
mucosa (interna)

Muscularis Externa
muscularis externa of the stomach is composed
of three layers of smooth muscle:
the innermost oblique layer
middle circular layer
outer longitudinal layer

52
Gastric ulcer

Unique

Multiple (stress)

Gastric cancer

53
Alimentary tract
the esophagus
the stomach
the small intestine (duodenum, jejunum and ileum)
the large intestine (caecum, colon, rectum, anal canal,
and appendix)

Small intestine
Function:
digests food
absorbs end products of the digestive process
Digestion is facilitated by:
enzymes (from pancreas and glands of small intestine)
alkaline buffer (from pancreas, bile and glands of small
intestine )

54
Small intestine
muscular tube extending form the pyloric
sphincter to the ileocecal valve
has three regions
duodenum 25 cm
jejunum 2,5 m
ileum 3,5 m
these regions are histologically similar
they have minor differences which permit identification

Small intestine general structure


Main characteristic:
modifications to increase the
intestinal surface area:
plicae circulares or valves of
Kerckring
villi
microvilli
These 3 modification increase
the surface area 400 to 600 X

55
Valves of Kerckring
are permanent folds of the
submucosa and mucosa
form semicircular to helical
elevations
role:
increase 2-3 X the surface area
of the small intestine
decrease the velocity of the
movement of chyme along the
alimentary canal

Villi
are finger-like or leaf-like
structures formed by the
mucosa
covered by the lining epithelium
confer a velvety appearance to
the intestine surface
increase 10X the surface area
of the small intestine

56
Villi
contains:
capillary loops
lymphatic channel (lacteal)
few smooth muscle fibers
lymphoid cells
loose connective tissue

Microvilli
small projections of the
plasma membrane
found on absorptive cells
increase 20 X the surface
area of the small intestine

57
Intestinal Mucosa
the usual three layers
a simple columnar epithelium,
which covers
the villi
the intestinal glands (crypts of
Lieberkhn)
lamina propria
the muscularis mucosae

Intestinal Mucosa
Epithelium
absorptive cells
goblet cells
DES cells
stem cells
Paneth cells
M cells

58
Epithelium
Absorptive cells
tall columnar cells
involved in terminal digestion and
absorption of water and nutrients
lateral domain:
occluding junctions
lateral infoldings
the apical surface presents a brush
border
covered with a thick glycocalyx layer

Epithelium
Absorptive cells
role of glycocalyx
protection from autodigestion
involved in terminal digestion by its
content in enzyme (dipeptides and
disaccharides in their monomers)
US: abundant organelles
endosomes,
SER
RER, and Golgi apparatus
mitochondria

59
Epithelium
Role of absorptive cells
digestion
absorption
re-esterification of fatty acids into triglycerides
formation of chylomicrons

Epithelium
Goblet cells
the number increases from
duodenum toward the ileum
secrete mucus, a protective
layer lining the lumen

60
Epithelium
DES cells
produce paracrine and
endocrine hormones

Epithelium
M cells or microfold cells
in regions where
lymphoid nodules are
located
transport antigens
present in the intestinal
lumen to the
macrophages
B Lymphocytes

61
Epithelium
Paneth cells
located in crypts
visible in standard stains
due to the presence of large,
eosinophilic, apical secretory
granules
secrete
antibacterial agent lysozyme
defensive proteins (defensin)
tumor necrosis factor-

Epithelium
Stem cells regenerative cells
repopulate the epithelium of the
crypts
villi
located in crypts

62
Lamina propria

T lymphocytes Plasmocytes
present also in epithelium present only in lamina propria

Submucosa
Meissner's plexus
Brunner's glands
(duodenal glands).

63
Muscularis externa
composed of
inner circular layer
an outer longitudinal smooth
muscle layer
Auerbach's myenteric plexus
interstial cells of Cajal

Cajal cells CD117+ Schwann cells PS100 +

Regional Differences
Duodenum
the shortest segment
receives bile (liver) and digestive
juices (pancreas)
their ducts open into the
duodenum at the duodenal
papilla (of Vater)
contains Brunner's glands in its
submucosa (mucous glands)

64
Regional Differences
Jejunum
villi are narrower
increasing number of
goblet cells

Regional Differences
Ileum
lamina propria houses
permanent clusters of
lymphoid nodules - Peyer's
patches
in these regions villi are
reduced in height and may
even be absent

65
Patology gluten enteropathy
(nontropical sprue)

destroys the microvilli and even the villi


result from an allergic response to gluten

Large intestine - colon


is 1.5m long
divided into:
caecum, colon, rectum
the appendix small
outpouching of the caecum
all segments have the same
structure: colon
role: absorption of the
water and ions from the
chyme

66
Large intestine - colon
Characteristics:
colon has no villi
numerous crypts of Lieberkhn
crypts of Lieberkhn
similar to those of small intestine
do not have Paneth cells
more numerous goblet cells the
number is increasing towards the
end
fewer DES cells

Large intestine - colon


lamina propria
muscularis mucosae
submucosa of the colon
are similar with those of
the small intestine

The muscularis externa


is unusual
the outer longitudinal layer
forms three narrow ribbons
of muscle fascicles known
as taeniae coli

67
Vermiform appendix
a 5- to 6 cm long
diverticulum of the caecum
same structure as colon
numerous lymphoid nodules
adjoin the epithelium
inflammation of appendix:
appendicitis

68
Associated glands

Digestive system
Composed of:
the oral cavity

alimentary tract

associated glands
salivary gland
liver
pancreas

69
Major salivary glands
Three major glands
parotid
sublingual
submandibular
Minor salivary glands
situated in the connective tissue of the oral cavity
mucosa (including tongue)

Major salivary glands


Structure
are divided by connective tissue
septa into lobes and lobules
secretory units composed of:
acini
a duct system originating from
the acini
also participates in the secretory
process

70
Major salivary glands
Three types of secretory units

Acini
serous
mucous
mixt
and myoepitelial cells

71
Ducts
intercalated ducts (small ducts)
modify the composition of the
saliva
attached to the acini
composed of a single layer
of small cuboidal cells and
some myoepithelial cells
function
add bicarbonate ions to the
saliva (buffering function)
absorb chloride from the
saliva

Ducts
striated ducts
composed of a single layer of
cuboidal to low columnar cells
basolateral membranes -
plasma membrane infoldings,
containing mitochondria
role:
secretion of potassium
absorption of sodium

72
Ducts
terminal (principal) duct of
the gland delivers saliva into
the oral cavity
do not modify the composition
of the saliva

Properties of Individual Salivary Glands

Parotid Gland
physically is the largest
salivary gland,
it produces only about 30% of
the total salivary output
has a serous secretion

73
Properties of Individual Salivary Glands

Submandibular Gland
produces 60% of the total
salivary output
it manufactures a mixed saliva
the major portion is serous

Properties of Individual Salivary Glands

Sublingual Gland
is a very small gland
produces a mixed saliva
the major portion is mucous

74
The liver

The liver
the largest gland in the body
weight: 1500 g
located in the upper right quadrant of
the abdominal cavity, just inferior to the
diaphragm
subdivided into four lobes:
right
left
quadrate
caudate

75
The liver
Function
exocrine functions
responsible for the formation of bile
endocrine functions occupies a central position in
metabolism
synthesis of various proteins, etc
detoxification
converts toxic substances into nontoxic materials that are
excreted in the bile
elimination of defunct erythrocytes

The liver

Main topics
vascular supply
hepatocytes
intrahepatic bile ducts (bile
transport)

76
Vascular Supply
The liver has a dual blood supply:
the hepatic artery (25%) provides oxygenated blood
the portal vein (75%) brings nutrient-rich blood
all nutrients absorbed in the alimentary tract are transported
directly to the liver via the portal vein
the liver occupies a central position in metabolism
Blood leaves the liver through the hepatic veins

Hepatocytes
are arranged in hexagon-shaped lobules - the classical
lobules
in animals the lobules are clearly delimited by slender
connective tissue elements (the pig)
in humans the boundaries of the classical lobules can
only be approximated - scar connective tissue
the center of the classical lobule is occupied by the
central vein, the initial branch of the hepatic vein

77
Classical lobules

Pig liver Human liver

Hepatocytes
Hepatocytes radiate from the
central vein
they form plates of liver cells
they are separated from one
another by large vascular
spaces known as hepatic
sinusoids

78
Classical lobules
Where three classical lobules are in contact with each
other, the connective tissue elements are increased, and
these regions are known as portal areas
Portal areas house a triad and lymph vessels
slender branches of the hepatic artery - arterioles
branches of the portal vein - venules
interlobular bile ducts (recognized by their simple cuboidal
epithelium)
The portal areas are isolated from the liver parenchyma
by the limiting plate, a sleeve of modified hepatocytes

Classical lobules - portal areas

79
Vascular Supply
from the arterioles and venules
of the portal areas arise fine
branches:
distributing arterioles
distributing venules
they reach the periphery of the
classical hepatic lobule
empty in the hepatic sinusoids
central vein

Vascular Supply
Hepatic sinusoids
very simple structure
endothelial lining composed of
sinusoidal lining cells
discontinuous (fenestrated)
not always in contact with one
another
no BM
Kupffer cells - associated with
the sinusoidal lining cells

80
Perisinusoidal space of Disse
Between sinusoidal lining cells and the
hepatocytes a narrow space
the perisinusoidal space of Disse

Contains
a limited amount of type I and type IV
collagen fibers (BM is absent)
nonmyelinated nerve fibers
hepatic stellate cells (also known as Ito
cells or fat storing cells)
pit cells NK lymphocytes
microvilli of the hepatocytes

Perisinusoidal space of Disse Sinusoids and central vein

81
Patology Ito cell
Vitamin A excess
prominent Ito cells
vacuoles of fat in cytoplasm
Cirrhosis
secrets collagen fibers - fibrosis

Hepatocytes
are 5 - to 12 - sided polygonal
cells,
are closely packed together to
form anastomosing plates - one
cell in thickness
one hepatocyte comes in contact
with other hepatocytes but also
borders the space of Disse so
they have 2 domains
lateral domain
sinusoidal domain

82
Hepatocytes
LATERAL DOMAIN
hepatocytes contact each other
but also are responsible for bile
canaliculi formation
channels that conduct bile
between hepatocytes to the
periphery of the classical
lobules
the wall of this canaliculi is
formed by the hepatocyte cell
membrane
the membrane displays high
levels of Na+, K+-ATPase
activity

Hepatocytes
SINUSOIDAL DOMAINS
form microvilli that protrude into the
perisinusoidal space of Disse
they increase the surface area of the
sinusoidal domain 6 X
facilitate the exchange of material
between the hepatocyte and the blood
in the perisinusoidal space

83
Hepatocytes
are organelle-rich cells that
manufacture the bile and a large
number of endocrine secretions
RER, ribosomes
Golgi Apparatus
mitochondria (2000)
lisosomes
SER involved in detoxification

Hepatocytes
inclusions
lipid droplets are mostly very-low-density-
lipoproteins (VLDLs)
are especially prominent after the consumption of a fatty meal
glycogen the liver is a deposit of glycogen
is abundant subsequent to eating and lesser after fasting

84
Hepatocytes
Glycogen deposits

PAS staining Cytoplasmatic vacuoles

Three Concepts of Liver Lobules


the three types of liver lobules are:
the classical lobules
portal lobules
the hepatic acinus

85
Three Concepts of Liver Lobules
Classical lobule
was the first to be defined
it was defined histologically
because of the connective tissue
arrangement in the pig liver
in this concept
blood flows from the periphery,
to the center of the lobule into
the central vein

Three Concepts of Liver Lobules


Portal lobule
Definition: triangular region whose center is
the portal area
periphery is bounded by imaginary lines
connecting the three surrounding central
veins (that form the three apices of the
triangle)
History:
Bile enters the bile canaliculi and flows
to the periphery of the lobule to the
interlobular bile ducts of the portal areas
the concept of an exocrine secretion,
flowing to the periphery of a lobule was
not consistent with the situation in the
acini of most glands

86
Three Concepts of Liver Lobules
Hepatic acinus
is based on blood flow from the
distributing arteriole
in the order in which hepatocytes
degenerate, subsequent to toxic or
hypoxic insults
Three zones
zone 1 is the richest in oxygen
zone 3 is the most oxygen-poor

Liver functions
liver has 100 different functions, most of which are performed by the
hepatocytes
bile manufacture (bile is composed of water, bile salts, phospholipids,
cholesterol, bile pigments, and IgA)
lipid metabolism (hepatocytes remove chylomicrons from the space of
Disse and degrade them into fatty acids and glycerol)
carbohydrate and protein metabolism: maintenance of normal blood
glucose levels (deposit of glucose and neoglucogenesis) and the
synthesis of many blood proteins)
albumins, globulins (except Ig)
factors for coagulation (fibrinogen, prothrombin)
proteins that function in the transport of metabolites
all of the non-essential amino acids
vitamin storage: vitamin A
degradation of hormones and detoxification of drugs and toxins

87
Liver functions
Immune Function
IgA antibodies formed by plasma cells in the mucosa of the alimentary
canal enter the circulatory system and are transported to the liver
hepatocytes release the secretory IgA into the bile canaliculi
Kupffer cells accessory immunitar cells
the portal vein contains a considerable number of microorganisms that enter
the bloodstream from the lumen of the alimentary canal
these bacteria are opsonized in the lumen or mucosa of the gut or in the
bloodstream - Kupffer cells recognize and phagocytes them
also remove cellular debris and defunct erythrocytes from the blood
Liver regeneration the liver has a great ability to regenerate after a
hepatotoxic insult or even after a portion of the liver is excised

The pancreas

88
Pancreas
is both an exocrine gland that
produces digestive juices
a structure similar to a salivary
gland acini
and an endocrine gland that
produces hormones
endocrine components - islets of
Langerhans, are scattered among
the exocrine secretory acini

Exocrine pancreas
is a compound tubuloacinar gland
that produces daily about 1200 ml
of a bicarbonate-rich fluid
containing digestive proenzymes
round to oval acini
the lumen is occupied by three or
four centroacinar cells
a distinguishing characteristic
of this gland
the beginning of the duct
system of the pancreas
difficultly visible in HE

89
Exocrine pancreas

anti-trypsinogen IHC

Exocrine pancreas
Acini
RER, Golgi-Apparatus
secretory granules (zymogen
granules) fill the apical region
contain proenzymes whose number
diminishes after a meal
eliminated by exocytosis

90
Exocrine pancreas
Duct system
begins in the center of the acinus with the centroacinar
cells
it is the terminus of the intercalated ducts
they join each other to form larger intralobular ducts
which converge to form interlobular ducts
they deliver their contents into the main pancreatic duct
(Wirsung)
it joins the common bile duct before opening in the
duodenum at the papilla of Vater

Duct system

Intralobular pancreatic ducts Extralobular pancreatic ducts

91
Exocrine pancreas - function
the exocrine pancreas produces, stores, and releases a large
number of enzymes
pancreatic amylase
pancreatic lipase
proenzymes trypsinogen, chymotrypsinogen
also produces trypsin inhibitor, a protein that protects the cell from
accidental intracellular activation of trypsin
Release of the pancreatic enzymes is effected by:
cholecystokinin manufactured by DES cells of the small
intestine (especially of the duodenum)
acetylcholine released by the parasympathetic fibers

Endocrine pancreas
is composed of islets of
Langerhans, scattered among the
acini (about 1 million)
are spherical aggregates of
cells
greater numbers are present in
the tail

92
Endocrine pancreas
four main types of cells compose the
parenchyma of each islet of
Langerhans
beta () cells secrete insulin
alpha () cells secrete glucagon
delta () cells secrete somatostatin
PP (pancreatic polypeptide-
producing) cells secrete PP
these cells cannot be differentiated from
one another by routine histological
examination

Endocrine pancreas

Anti-insulin IHC Anti-glucagon IHC

93
Endocrine pancreas

Anti-somatostatin IHC Anti-PP IHC

Endocrine pancreas - histophisiology


Insulin
insulin binds to cell-surface insulin receptors on many cells,
especially skeletal muscle, liver and adipose cells
they take up glucose, thus decreasing blood glucose
Glucagon
acts mainly on hepatocytes, causing these cells to activate
glycogenolytic enzymes
these enzymes break down glycogen to glucose, which is
released into the bloodstream, increasing blood glucose

94
Endocrine pancreas - histophisiology
Somatostatin
paracrine effects are inhibition of the release of endocrine
hormones of cells and cells
endocrine effects are on smooth muscle cells of the alimentary
tract and gallbladder, reducing the motility of these organs
Pancreatic polypeptide
inhibits the exocrine secretions of the pancreas
stimulates the release of enzymes by the gastric chief cells
depresses the release of HCl by the parietal cells of the stomach

95
96
RESPIRATORY SYSTEM
Nasal cavities
Trachea
Bronchial tree
Lungs

Respiratory system

Resembles structurally
~branched tubuloacinar
gland
Consisting of

-airways
-two lungs + pleura
3 main portions

-air-conducting portion
-respiratory portion
-mechanism for ventilation

97
Respiratory system
The air-conducting portion
-provides a passage for inhaled and exhaled air in and out of
the respiratory portion

The respiratory portion


-main function is the exchange of gases between air and
blood

The ventilation mechanism involved in respiration


- inflow (inspiration) and outflow (expiration) of air

Respiratory system
composed in sequence of

Air-conducting portion Respiratory portion Ventilation mechanism

-nasal cavities and -respiratory -rib cage


associated sinuses bronchioles -intercostal muscles
-nasopharynx -alveolar ducts -diaphragm muscle
-oropharynx -alveolar sacs -elastic connective
-larynx -alveoli tissue of the lung
-trachea intrapulmonary
-bronchi
extrapulmonary
-bronchioles

98
Respiratory system
Airways consist of 4 main structural elements adapted to respiration:

-hyaline cartilage framework maintains open the airways

-mucosa ciliated cells (transport, cleaning of air),


rich in blood vessels (warming the air),
mucus secretion (protective mucus blanket, moistening air)

-elastic fibers, elements placed longitudinally assuring dilatation of


airways

-smooth muscles spiral arrangementto narrow the airways

Nasal cavities and paranasal


sinuses
provide an extensive surface area for
(1)warming and moistening air and
(2)filtering dust particles present in the inspired air
(3)the roof of each nasal cavity and part of the superior concha
contain the specialized olfactory mucosa

99
Nasal cavities
Organisation
-entrance nostril or naris -separated from another by the septum
-consisting of:
-the vestibul
-respiratory portion - regio respiratorica
-olfactory area - regio olfactoria

*-communications with:
-air-containing cavities within the bones of the skull - sinuses
maxillary, frontal, ethmoidal, and sphenoid
sinuses
communicate with the nasal cavity by openings
-posterior portion of the nasal cavities is the nasopharynx,
that at the level of the soft palate becomes the
oropharynx
-into the lateral walls of the oropharynx opens
the auditory tubes (eustachian tubes),
extending from the middle ear

*-abundant mucosa-associated lymphoid tissue is present


beneath the nasopharyngeal epithelium - Waldeyer's ring.
-at the posterior and upper regions of the nasopharynx - the
nasopharyngeal tonsils (adenoids)

100
Nasal cavities
1.Nostril - external surface is lined by keratinized squamous
epithelium
2.Vestibule - nonkeratinized squamous epithelium

3.Respiratory portion
-pseudostratified ciliated epithelium with goblet
cells
-supported by the lamina propria,
which consists of
-connective tissue
-seromucous glands
-a rich superficial venous plexus,
known as cavernous or erectile tissue.

Secretion of goblet cells + seromucous glands moistens the


mucosal surface and humidifies the inspired air
The venous plexus by blood warms up the incoming air

**The highly vascular nature of the nasal mucosa, accounts for


-common bleeding (epistaxis) after trauma or
acute inflammation (rhinitis).

Nasal cavities

101
Nasal cavities
The lamina propria is continuous with:
-the periosteum of bone
-perichondrium of cartilage,
forming the wall of the nasal cavities

From the lateral wall projecting into each nasal cavity


three curved plates of bone conchae (shell)
covered by a mucosa:
-superior
-middle
-inferior turbinate bones or conchae
which:
-cause airflow turbulence
-thus facilitating contact between the air and the
mucus blanket covering the respiratory region of each nasal
cavity
traps particulates in the air
transported posteriorly by ciliary action to
the nasopharynx
where they are swallowed with saliva

102
Nasal cavities

4.Olfactory area:
-olfactory epithelium three major
types of cells
-basal cells
-olfactory cells (bipolar
neurons)
-supporting or sustentacular
cells
-lamina propria
-continuos with the periosteum
-connective tissue layer
-olfactory serous glands -
glands of Bowman
-nerve bundles

Nasal cavities

103
Nasal cavities
Olfactory epithelium
-basal cells
-mitotically active stem cells
-producing daughter cells
-that differentiate first into
immature olfactory cells
and then into mature
olfactory cells

-supporting cells between


the olfactory cells
-apical pole microvili
-oval, dark stained, apically
placed nucleus
-they would have the role of glial
cells

-olfactory cells highly polarized


Nasal cavities -apical region,
-facing the surface of the
mucosa, dendrite
-forms a knoblike ending
olfactory vesicle or olfactory
knob
-with 10 to 20 modified cilia.
-basal region
-gives rise to an axon

Several axons
form small unmyelinated nerve
bundles (olfactory fila)
surounded by glial-like cells
olfactory nerve filaments
cross the cribriform plate of the
ethmoid bone
enters the olfactory bulb
establish appropriate synaptic
connections
with dendrites of mitral cells
(neurons)
axons olfactory tract

104
Olfactory serous glands - glands
of Bowman
-secrete a serous fluid in which
odoriferous substances are
dissolved
-contains the odorant-binding
protein (OBP) with high binding
affinity for a large number of
odorant molecules
-OBP carries odorants to receptors
present on the surface of the
modified cilia and removes
them after they have been
sensed.

-the secretory product of the glands


of Bowman contains protective
substances such as lysozyme
and IgA secreted by plasma cells

105
Trachea
-the major segment of the
conducting region

-continuation of the larynx

-branches to form the right and


left primary bronchi entering
the hilum of each lung
-tube like structure with:
-mucosa: epithelium+lamina
propria
-submucosa
-fibroelastic-cartilaginous
layerC-shaped cartilages
-adventitia

106
Trachea Epithelial liningrespiratory
epitheliumpseudostratified
columnar ciliated epithelium:

1.Columnar ciliated cells


-the predominant cell population
-250-300 cilia, in contact with the
lumen
2. Cells with microvili
-function as receptor cells
-in contact with nerve fibers
-serous secretion
3.Goblet cells
-abundant nonciliated cells, also in
contact with the lumen and the
basal lamina
-secreting mucus

Trachea
4.Basal cells
-rest on the basal lamina but do not
extend to the lumen
-undifferentiated cells function as
stem cell population

5.Cells of Kulchitsky
-neuroendocrine cells
-members of DES (diffuse endocrine
system)
-secrete peptide hormones such as
serotonin, calcitonin, antidiuretic
hormone (ADH) and
adrenocorticotropic hormone
(ACTH)
-in groups neuroepithelial bodies -
sensitive to O2

-origin of bronchial carcinoid tumours

107
Trachea

Lamina propria
loose connective tissue, with
-elastic fibers concentrated elastic
lamina,
-numerous cells lymphocytes,
plasma cells, mast cells,
eosinophils

Submucosa
mucous and serous glands (gl
tracheales)

Trachea

Cartilaginous layer
-15-20 C-shaped hyaline
cartilages, surrounded by a
fibroelastic layer,
-perichondrium,
-trachealis muscle - smooth
muscle fibers at the
posterior side

Adventitia-loose connective
tissue, adipocytes

108
Bronchi
They have two segments:
-extrapulmonary and
-intrapumonary
-arise from the trachea branches to form the right and left
primary bronchi entering the hilum of each lung

**the hilum - the region where the primary bronchus, pulmonary


artery, pulmonary vein, nerves, and lymphatics enter and
leave the lung.

Secondary divisions of the bronchi and accompanying connective


tissue septa divide each lung into lobes:
-the right lung has three lobes,
-whereas the left lung has two lobes.

Subsequent bronchial divisions further subdivide each lobe into


bronchopulmonary segments are the gross anatomic units
of the lung that can be removed surgically.

109
Bronchi bronchial tree
The primary bronchi or main right and left
-respiratory epithelium + lamina propria
irregular rings of hyaline cartilage
-two segments: extrapulmonary and intrapulmonary

After entering the lungs by the hillum:


-subdivide into lobar bronchi (3/2)
segmental bronchi (10/8)
primary bronchioles
terminal bronchioles
respiratory bronchioles
2-11 alveolar ducts
5-6 alveolar sacs
alveoli

Bronchi bronchial tree


The intrapulmonary segmentation results in the organization of a
pulmonary lobule and a pulmonary acinus

Pulmonary lobule
-the portion of the lung supplied by a terminal bronchiole
-includes the respiratory bronchioles, alveolar ducts, alveolar sacs,
and alveoli.

Pulmonary acinus
-the portion of the lung supplied by a respiratory bronchiole
-are subcomponents of a respiratory lobule.

110
-Bronchus: >1 mm
1.-mucosa: respiratory epitehlium + lamina propria (cells, elastic
fibers)
2. -muscle layer: smooth muscle bundles in a spiral arrangement
Reisseissen muscle
3. -submucosa: connective tissue, glands
4.-fibro-cartilaginous layer irregularly shaped cartilage
plates or islands
5.-adventitia

Bronchus

111
Bronchi

Bronchioles
-Bronchioles: <1 mm

Structure:
-pseudostratified columnar ciliated epithelium undergoes a
transition simple columnar ciliated epithelium

-thin lamina propria elastic fibers

-well developed layer of muscle bundles with circular or spiral


arrangement
-smooth muscle fibers
regulate the diameter of the bronchioles

- goblet cells, glands, cartilage islands


- adventitia

112
Bronchioles

Bronchioles
-Terminal bronchioles
-last part of the conducting
portionbranch into 2-10 smaller
segmentsthe smallest
bronchioles

Structure:
-simple cuboidal epithelium
1.-ciliated cells
2.-few - neuroendocrine cells
bombesin (muscle fibers,
epithelial cells, capillaries) +
3.cells with microvili
neuropithelial bodies
4.-cells with serous secretion

113
Bronchioles

5.-Clara-cellsnonciliated cell, en
dome, 80% of the cell population
Bronchioles -secretory granules surfactant
material two kind of proteins that
will attach to the surfactant (SP-A,
SP-D) act like opsonines (cover
the bacterium may be
phagocyted) + CCPdecrease
inflammation

-nonsticky, proteinaceous compound to


maintain the airway in the smallest
bronchioles
-produce enzymes that detoxify
substances dissolved in the
respiratory fluid
-regulate the transport of chloride ions

-Lamina propria thin, with few


elastic fibers

-Smooth muscle fibers with spiral


arrangement

114
Bronchioli
Respiratory bronchioles in
gas exchanges first
segment of the respiratory
portion
- <0,5 mm

-discontinuous wall

-ciliated unciliated simple


cuboidal epithelium

-connective tissue layer


collagen+reticular fibers
preventing bronchioles from
too large dilatation/expansion

-muscle layer

115
Bronchioli

Bronchioli
Bronchioles epithelium:

-nonciliated cells
-Clara cells
-isolated ciliated cells
-serous cells
-type II pneumocytes or
alveolar epithelial cells

116
Bronchioli branch to
form 2-11 alveolar
ducts branch to form
2 or more alveolar sacs

Alveolar ducts
-Ductus alveolaris
-2-11 alveolar ducts - tiny end ducts of the branching airways
that fill the lungs
-dilated structures
-interrupted wall alveolar sacs, alveoles
-simple squamous epitheliumalveolar epithelium
-fine network: collagen, reticular, elastic fibers
-few smooth muscle fibers - typical smooth muscle knobs
bulging into the lumen

117
Alveolar sacs
-Saccus alveolaris
-two or more centrally
placed structures
-interrupted wall
openings of several alveols

-formed from the


confluence openings of
several alveoli

-lined by the alveolar


epithelium
-surrounded by a
network of elastic and
reticular fibers
-smooth muscle fibers
does not longer exist

118
-Alveoli
Alveoli -polygonal respiratory chambers
- - 0,2-0,5 mm

-form a sponge-like arrangement of


gas filled spaces in lung tissue

-alveolar epithelium

-separated by interalveolar septa:


-capillaries (continuous
endothelial lining),

-collagen, reticular and elastic


fibers,
-elastic fibers allow the alveoli to
stretch as they fill with air when
breathing in
-they then spring back during
breathing out in order to expel the
carbon dioxide-rich air

-septal cells: fibroblast, alveolar


macrophag, pericytes, limfocytes,
plasma cells, mastocytes

119
Alveolar macrophages Alveoli
dust cells
-large cells, with a large oval
nucleus
-abundant lysosomes,
phagocyted vesicles (dust
cells)
-defend the alveolar wall
-monitor any inhaled dust or
bacteria that may have
escaped entrapment by the
mucous lining in the airway
-they are free cells migrating
over the luminal surface of
the alveolus

Located:
-intraseptally around
capillaries through Kohn
alveolar pores into the
alveolar epithelium
alveolar space coughing
or transported by ciliar action
into the upper airways
spitted it out or swallowed
with the saliva

Alveoli
Alveolar epithelium:

1.-type I pneumocyte type I


alveolar cell
-40% of the cell population 90%
-flattened squamous
-4-6 in diameter,
-few organelles,
-lateral extensions intervening in
passive gases exchange

120
Alveoli
2.-type II pneumocyte type II
alveolar cell
- 60% 10%
-secretory cells
-larger 8-12 great alveolar cells
-6-7 cells/alveolus
-pulmonary surfactant (after the
35. week of pregnancy)
multilamellar bodies

-maintenance and repair of the


alveolar epithelium when
injury occurs they may
increase in number and
differentiate into type I
pneumocytes

Alveoli
Pulmonary surfactant - surface-active lipoprotein complex
phospholipid and protein mixture that reduces surface tension in the thin
fluid coating within all alveoli
alveolar size regulation:
-helps all alveoli in the lungs expand at the same rate
-lowers the surface tension at the air-fluid interface and
thus reduces the tendency of the alveolus to collapse at the end of
expiration
nutritive function
helping in eliminating bacteria
help migration of macrophages

Surfactant deficiency
-respiratory distress syndrome
-hyaline membrane disease
-sudden infant/neonate death

121
122
123
Alveoli

-Each alveolus has


-a thin wall
-with capillaries
-lined by simple squamous
epithelial cells
-forming part of the air-blood
barrier

The air - blood barrier gas


exchange by passive diffusion

Alveoli
air - blood barrier:
1.-surfactant layer

2.-alveolar epithelium cytoplasmic extensions of type I alveolar


cells

3.-basal lamina synthesized by type I alveolar cells

4.inter-alveolar connective tissue sometimes it lacks


dual basal lamina

5.basal lamina - synthesized by endothelial cells

6.-endothelium of capillaries

124
125
Occlusion of main pulmonary arteries can kill the patient suddenly. Occlusion of
small pulmonary arteries has no major immediate effect. Occlusion of a
medium-sized branch of pulmonary artery can lead to a pulmonary infarction in
a person with compromised cardiac or respiratory status

126
This is the microscopic appearance of a pulmonary embolus (PE) in a
major pulmonary artery branch.

The rounded clear holes seen in the small pulmonary arterial branch in this
section of lung are characteristic for fat embolism. Fat embolism syndrome is
most often a consequence of trauma with long bone fractures. It can also be
seen with extensive soft tissue trauma, burn injuries, severe fatty liver, and very
rarely with orthopedic procedures

127
Patchy area of alveoli that are filled with inflammatory cells. The alveolar
structure is still maintained, which is why a pneumonia often resolves with
minimal residual destruction or damage to the lung.

Between the bronchial cartilage at the right and the bronchial lumen filled with
mucus at the left is a submucosa widened by smooth muscle hypertrophy,
edema, and inflammation (mainly eosinophils). These are changes of
bronchial asthma. The peripheral eosinophil count or the sputum eosinophils
can be increased during an asthmatic attack.

128
Disseminated intravascular coagulation (DIC) is a consequence of
widespread activation of the coagulation system through endothelial injury
and/or release of thromboplastic substances into the circulation. DIC can be
seen with severe infections, trauma, neoplasia, and obstetric complications,
among others. Small fibrin thrombi can form in small arteries of brain, heart,
lungs, kidneys, and other organs to produce ischemic tissue damage.

Both lymphatic and hematogenous spread of malignant neoplasms is possible


to distant sites. Here, a breast carcinoma has spread to a lymphatic within
the lung.

129
130
Urinary system

Urinary system
Function
removes toxic by-products of metabolism
from the bloodstream
removes urine from the body

131
Urinary system
Composed of:
two kidneys which:
remove the toxins from the bloodstream
conserve salts, glucose, proteins and water
help to regulate blood pressure, hemodynamics, and the acid-
base balance of the body
have an endocrine function: produce renin, erythropoietin
convert a precursor of vitamin D to the active vitamin
two ureters, urinary bladder and urethra which:
deliver the urine

Urinary system

132
Kidney
have a concave region - the
sinus
containing
fat
the hilum - where the kidney is
pierced by:
ureter
renal vein
renal artery
lymph vessels

Kidney
On a hemi-section the kidney
has two regions:
cortex: dark brown and granular
medulla: pale striated region
contains 6 to 12 renal pyramids
the base of each pyramid is oriented
toward the cortex constituting the
corticomedullary border
the apex points toward the hilum and
is known as the renal papilla

133
Renal papila
the apex is perforated
by about 20 openings
of the ducts of
Bellini
this region is known
as the area cribrosa

Kidney
the pyramids are separated from
each other by a material resembling
the cortex, the cortical columns (of
Bertin)
cortical continuations of material
located in the renal pyramids
constitute the medullary rays -
longitudinal striations
cortical labyrinth the renal
substance situated between 2
medullary rays
has a granular appearance renal
corpuscles

134
Kidney
a kidney lobe of the kidney
represents a renal pyramid,
with its associated cortical
substance
a kidney lobule is composed
of a medullary ray with part of
the cortical labyrinth
surrounding it

135
Kidney
The nephron is the
morphological and
functional unit of the kidney
composed of:
glomeruli
renal tube

The glomerulus
is a round structure, ~0.2 mm
in diameter
represents the beginning of the
nephron
it is invaginated by a tuft of
capillaries at the vascular pole
the opposite pole - the urinary
pole, continues with the
proximal renal tube

136
The glomerulus
Composed of:
a tuft of fenestrated
capillaries formed by
afferent glomerular
arteriole
and drained by the efferent
glomerular arteriole
thus the glomerulus is a
completely arterial capillary
bed

The glomerulus
the Bowman's capsule with 2
layers of epithelium
the outer or parietal layer - -
a simple squamous
epithelium
the inner layer, podocytes -
extremely complex in shape
in close apposition to the
capillaries
between them - the capsular
(urinary or Bowman) space

137
The glomerulus
The podocytes
give rise to small foot-like
processes,
primary - pedicles
secondary - pedicels
they form a fenestrated
epithelium around the
fenestrated capillaries of the
glomerulus
the openings between the
pedicles are called filtration
slits

The glomerulus
between the podocytes and
the endothelial cells of the
capillaries there is a thick BM
the glomerular BM
it can be subdivided into an
outer lamina rara externa,
a middle lamina densa
an inner lamina rara interna

138
The glomerulus
The glomerular filtration barrier
structure:
fenestrated endothelium
the glomerular BM
the podocytes
controls blood filtration
it prevents some large
molecules from entering the
capsular space
the fluid entering Bowman's
space is called the glomerular
ultrafiltrate

The glomerulus
The stroma
normal connective tissue cells are
replaced by a specialized cell type
known as intraglomerular
mesangial cells - pericyte like
cells
fuctions
support the capillary network
contractile cells - they have
receptors for vasoconstrictors
such as angiotensin II - reduce
blood flow through the glomerulus
phagocytic - resorption of the
basal lamina components

139
The renal tube
the proximal tubule has
two regions:
the proximal convoluted
tubule - located near renal
corpuscles
the pars recta of the
proximal tubule - which
descends in medullary rays
within the cortex and then
in the medulla
continues with the loop of
Henle

The renal tube


The proximal tubule
a simple cuboidal epithelium
with eosinophilic, granular-
appearing cytoplasm
has an elaborate striated
border
interwoven lateral cell
processes

140
The renal tube
The Henle's loop
Has 3 regions:
the descending thin limb
Henle's loop (hairpin-like)
the ascending thin limb
covered by simple
squamous epithelial cells

The renal tube


The distal tubule
has three regions:
the pars recta
the macula densa
the pars convoluta (the
distal convoluted tubule)
covered by low cuboidal
epithelial cells
few et short microvilli

141
The renal tube

Juxtaglomerular apparatus
has three components:
the macula densa of the distal
tubule
juxtaglomerular cells of the
afferent glomerular arteriole
extraglomerular mesangial
cells

142
Juxtaglomerular apparatus
The macula densa:
tall, narrow, pale cells
with centrally placed
nuclei
belongs to the distal
tube

Juxtaglomerular apparatus
Juxtaglomerular cells
modified smooth muscle cells
located in the tunica media of
afferent (occasionally on the
efferent) glomerular arterioles
contain specific granules
demonstrated to be the
proteolytic enzyme renin
also angiotensin-converting
enzyme (ACE) (also secreted by
the lung)

143
Juxtaglomerular apparatus
Extraglomerular mesangial
cells
occupy the space
bounded by the afferent
arteriole, macula densa,
efferent arteriole, and
vascular pole of the renal
corpuscle
are probably contiguous
with the intraglomerular
mesangial cells

Juxtaglomerular apparatus
Role
probably monitor the filtrate volume and sodium
concentration
if sodium concentration is below a specific threshold,
macula densa cells do two things:
they cause dilation of the afferent glomerular arterioles, thus
increasing blood flow into the glomerulus
they instruct juxtaglomerular cells to release the renin into
circulation (activation of the renin-angiotensin system and
consecutively the release of aldosterone, a hormone that acts on
cells of the distal convoluted tubules, increasing the resorption of
sodium and chloride ions.)

144
Collecting Tubules
the distal convoluted tubules
are connected to the
collecting tubule by a
connecting tubule
Role of CT: convey and
modify the ultrafiltrate from
the nephron to the minor
calyces of the kidney
are not part of the nephron

Collecting Tubules
are located in the medullary rays
and in the medulla
composed of a simple cuboidal
epithelium
are composed of two types of
cells
principal cells
intercalated cells
the end part of CT - papillary
collecting tubules (ducts of Bellini)

145
Excretory passages
the minor and major calyces
the pelvis
the ureter
the urinary bladder
the urethra

Excretory passages
Covered almost all
along by the urothelium
stratified epithelium
3 layers
impermeable
allows distension

146
Urether
deliver urine from the
kidneys to the urinary
bladder
structure 3 layers
mucosa, which lines the
lumen
urothelium
lamina propria
muscular coat (muscularis)
fibrous connective tissue
covering

Bladder
structure 3 layers
mucosa, which lines the
lumen
urothelium
lamina propria
muscular coat (muscularis)
longitudinal layer
circular layer
longitudinal layer
fibrous connective tissue
covering unremarkable

147
Bladder

148
Male Reproductive System

Male reproductive system

consists of:
two testes suspended in
the scrotum
a system of intratesticular
and extratesticular genital
ducts
associated glands
the penis, male copulatory
organ

149
Male Reproductive System

responsible for
the formation of the male gametes: spermatozoa
the synthesis, storage, and release of the male
sex hormone: testosterone

Testes
oval organ
size: 4 cm long, 2 to 3 cm
wide, and 3 cm thick
develop retroperitoneally on
the posterior wall of the
abdominal cavity
they descend into the scrotum
carry with them a portion of
the peritoneum it will
become tunica vaginalis

150
Testes
Tunica vaginalis
forms a serous cavity that
partially surrounds the testis
permits some degree of
mobility within the scrotum

Pathology - hydrocele of the testis

a large hydrocele of the testis


consists of: accumulation of clear fluid in the sac of tunica vaginalis
causes: inflammation, tumors

151
Clinical correlation
Cryptorchidism - permanent retention of testis
outside scrotum
associated with infertility and cancer
Hyperthermia has been identified as a factor in
male infertility, and it has been reported that males
who work with laptop computers held on their laps
for 1 hour/day exhibited an increase in scrotal
temperature by as much as 2.8 C
although these studies are not conclusive, it is suggested
that boys and young men must limit the use of computers
on their laps

Testes - structure
tunica albuginea - a capsule of
dense, irregular collagenous
connective tissue
posterior aspect is thickened
forms the mediastinum testis
gives rise to septa of connective
tissue
subdivide each testis into
approximately 250 pyramid-
shaped compartments known as
the lobuli testis

152
Testes
Each lobule has
1-4 blindly ending seminiferous
tubules
surrounded by a richly innervated
and highly vascularized loose
connective tissue which contains:
the interstitial cells (of Leydig)-
small aggregates of endocrine
cells

Seminiferous tubules
are composed of
a thick germinal epithelium
surrounded by the tunica
propria: a thin connective
tissue
contains myoid cells, similar
to smooth muscle cells
separated from each other
by a well-developed basal
lamina

153
Seminiferous tubules
the germinal epithelium is
several cell layers thick
composed of two types of
cells:
Sertoli cells
spermatogenic cells (in
various stages of maturation)

Seminiferous tubules

154
Seminiferous tubules
Sertoli cells
are tall, columnar cells

possess lateral cell membrane


infoldings
apical cell membranes are also
highly folded and project into
the lumina of the seminiferous
tubules
a nucleus with a large,
centrally positioned nucleolus,
basally located, clear, oval

Seminiferous tubules
Sertoli Cells roles
support, protect, and nourish
spermatogenic cells
phagocytose cytoplasmic
remnants of spermatids
secrete androgen-binding protein
macromolecule that facilitates an
increase in the concentration of
testosterone in the seminiferous
tubule
secrete hormones (inhibin)
inhibits the release of FSH by the
anterior pituitary
produce a nutritive medium
establish the blood-testis barrier

155
Seminiferous tubules Sertoli cells

crystalloids of Charcot-Bttcher

The blood-testis barrier


lateral cell membranes of adjacent Sertoli cells form
occluding junctions with each other
subdivide the lumen of the seminiferous tubule into
two isolated, concentric compartments
the basal compartment - narrower
the adluminal compartment wider
ROLE: to isolate the adluminal compartment from
the connective tissue, in order to protect the
developing gametes from the immune system
secondary spermatocytes have a different chromosome
number
they would be considered "foreign cells" by the immune
system

156
Seminiferous tubules
Spermatogenic Cells
spermatogenesis is the process whereby
spermatogonia give rise to spermatozoa
is divided into three phases:
spermatocytogenesis
meiosis
spermiogenesis

Seminiferous tubules
Spermatogenic Cells
are found in various stages of
maturation:
spermatogonia - located in the
basal compartment
primary spermatocytes

secondary spermatocytes

spermatids

spermatozoa
The last three located in the
adluminal compartment

157
Spermatogenesis
Spermatogonia are diploid cells that undergo mitotic
division to form
more spermatogonia
as well as primary spermatocytes
primary spermatocytes enter the first meiotic division
to form secondary spermatocytes
secondary spermatocytes undergo the second meiotic
division to form haploid cells known as spermatids
spermatids are transformed into spermatozoa (mature
sperm) through reducing much of their cytoplasm,
rearrangement of their organelles, and formation of
flagella

Spermatogenesis

158
Testes
Interstitial Cells of Leydig
small collections of
endocrine cells
secrete testosterone

Testes
Interstitial Cells of Leydig
polyhedral cells
have a single nucleus
crystallized proteins, the crystals
of Reinke (very characteristic)
they are typical steroid-producing
cells
mitochondria
a large accumulation of SER
a well-developed Golgi apparatus
some RER
lipid droplets
do contain no secretory vesicles
testosterone is probably released
as soon as its synthesis is
complete

159
Regulation of the testes function

Pathology testicular tumors

160
Genital ducts - intratesticular
The seminiferous tubules
continue with:
tubuli recti
that open into the rete testis (a
system of labyrinthine spaces
situated in the mediastinum
testes)
10 to 20 short tubules, the
ductuli efferentes

Genital ducts - extratesticular


epididymis
ductus deferens (vas
deferens)
ejaculatory duct
male urethra

161
Clinical correlation
Ductus deferens is easily perceptible
through the skin of the scrotum as a dense,
rolling tubule (has a muscular wall 1 mm
thick)
Vasectomy (surgical removal of a part of the
ductus deferens) is performed via a small slit
through the scrotal sac, thus sterilizing the
person

Epididymis
is a highly convoluted tubule
divided into a head, body, and
tail
is continuous with the ductus
deferens
the lumen is lined by a
pseudostratified epithelium
composed of two cell types
basal cells
principal cells

162
Ductus Deferens (Vas Deferens)
is a muscular tube
conveys spermatozoa from
the tail of the epididymis to
the ejaculatory duct

ACCESSORY
GENITAL GLANDS
Seminal vesicles
paired glands

secrete a viscous fluid that


constitutes about 70% of the
ejaculate
the lumen is lined by a
pseudostratified columnar
epithelium composed of
basal cells
low columnar cells

163
ACCESSORY
GENITAL GLANDS
Prostate Gland
surrounding a portion of
the urethra
3 glandular zones
peripheral
transitional
central
1 fibro-muscular zone

Prostate

164
Prostate - structure

compound tubuloalveolar glands


fibro-muscular stroma

165
IHC markers

P63 basal cells

PSA- secretory cells


Chro - endocrine cells

Pathology prostatic adenocarcinoma

166
Pathology prostatic adenocarcinoma

167
168
Female genital system

Female genital system


consists of:
internal reproductive organs
the paired ovaries
the oviducts
the uterus
the vagina
external reproductive organs
the clitoris
the labia majora, and the labia minora
mammary glands as their physiology and function are closely
associated with the reproductive system

169
Female genital system

Female genital system


Some notions
puberty - initiated by the secretion of gonadotropic hormones
(by the pituitary gland)
until then, the reproductive organs are incompletely developed and
remain in a state of rest
menarche - the first menstrual flow, occurring from about 9 to 15
years of age
the menstrual cycle - is repeated approximately each month (28
days) throughout the entire reproductive years
involves many hormonal, histological, and psychological changes
menopause - the end of her reproductive years
menstrual cycles become less regular as hormonal and neurological
signals begin to change

170
Ovary
covered by a simple cuboidal
epithelium (also called germinal
epithelium was thought to give
rise to germ cells)
tunica albuginea a poorly
vascularized, dense, irregular
connective tissue
ovary is divided into:
a cortex
a medulla

Germinal epithelium
and albuginea

171
Ovary
The cortex is composed of:
a stroma - connective tissue
ovarian follicles in various stages of development

Stroma

fibroblast-like stromal cells (also


known as interstitial cells)
fibers: reticular and few collagen
stroma is a hormonal-dependent
structure
can accumulate lipids in cytoplasm

172
Ovarian follicles
Before the onset of puberty, all the
follicles of the ovarian cortex are in the
primordial follicle stage
At puberty - onset of hormone secretion
gonadotropin-releasing hormone
(GnRH) produced by the neurosecretory
neurons of hypotalamus
pulsatile, release of gonadotropins
(follicle-stimulating hormone, FSH, and
luteinising hormone LH) from pituitary
As a result: begining of follicular
development and the onset of the
ovulatory cycle

Ovarian follicles

four developmental stages


primordial
primary
secondary
graafian
this development is dependent of FSH secretion

173
Ovarian follicles
Primordial follicles
composed of a single layer
of flattened follicular cells
the primary oocyte
separated from the ovarian
stroma by a basement
membrane

Ovarian follicles

Primary Follicles
two types of primary follicles, depending on
the number of layers of follicular cells that
surround the primary oocyte
unilaminar
follicular cells become cuboidal
primary oocyte grows to about 100- 150
multilaminar
follicular cells proliferate and stratify, forming
several layers of cells around the primary oocyte
follicular cells are more commonly referred to as
granulosa cells

174
Developing follicles

Developing follicles

175
Ovarian follicles
Secondary (Antral) Follicles
are similar to primary follicles
except for the presence of
accumulations of liquor folliculi
among the granulosa cells
this fluid is an exudate of plasma
contains glycosaminoglycans,
proteoglycans, steroid-binding
proteins produced by the granulosa
cells and some hormones
(progesterone, estradiol , inhibin)

Ovarian follicles
Secondary (Antral) Follicles
as more fluid is produced,
individual droplets of liquor
folliculi fuse to form a single,
fluid-filled chamber, the antrum

176
Ovarian follicles

Secondary (Antral) Follicles


during this stages:
developpment of zona pellucida - an
amorphous substance, separating the
oocyte from the surrounding follicular
cells
Stromal cells begin to be organized
around the follicle forming:
an inner theca interna, composed of a
richly vascularized cellular layer
an outer theca externa, composed
mostly of fibrous connective tissue

Ovarian follicles - secondary follicle

177
Ovarian follicles
Graafian (Mature) Follicles
may be as large as the entire
ovary
it is the follicle that undergoes
ovulation

Graafian (Mature) Follicle

178
Ovarian follicles
Graafian (Mature) Follicles
antrum
cumulus oophorus - a small group of
granulosa cells that project out from
the wall into the antrum
corona radiata - single layer of
granulosa cells, surrounds the oocyte
granulosa cells
theca interna - well developed
has the an endocrine appearance
secrets estrogens
theca externa

Graafian (Mature) Follicles

179
Ovulation
Ovulation
by the 14th day of the
menstrual cycle
the process of releasing the
oocyte from the graafian
follicle

Hormonal secretion during the ovulatory cycle

180
Corpus luteum
is formed from the remnants of
the graafian follicle
granulosa cells
thecal cells
is a temporary endocrine gland
that manufactures and releases
hormones that support the
endometrium
estrogens
progesterone

Corpus luteum
is a highly vascularized
structure
composed of:
granulosa-lutein cells (modified
granulosa cells)
secrets progesterone
theca-lutein cells (modified
theca interna cells)
secrets estrogens (small
amount)

181
Corpus luteum

Corpus luteum

182
Corpus luteum
Degeneration of corpus
luteum
occurs in the absence of
fertilization (pregnancy)
LH secretion
consists of fibrous connective
tissue
remnants persist as a scar on
the surface of the ovary

Atretic Follicles
follicles that undergo
degeneration are known as
atretic follicles
atresia is a continuous
process
unknown causes

183
Ovarian Medulla
is a richly vascularized
fibroelastic connective
tissue:
connective tissue cells
interstitial cells - secrete
estrogens
hilar cells - similar to Leydig
cells of the testes - secrete
androgens

Hystogenesis of ovarian tumors

184
Epithelial ovarian tumor

Mucinous Cystadenoma

Germinal ovarian tumors

Teratoma

185
Granulosa cell ovarian tumor

Oviducts (Fallopian or Uterine Tubes)


are conduit for:
spermatozoa to reach the
primary oocyte
to convey the fertilized egg to
the uterus
4 anatomical regions
intramural region
isthmus
ampulla is where fertilization
usually takes place
infundibulum whose open end
has projections called fimbriae

186
Uterine tubes
the walls are composed
of three layers:
Mucosa
many longitudinal folds
simple columnar epithelium
that lines the lumen
two different cell types
constitute this epithelium:
nonciliated peg cells
ciliated cells
Muscularis
Serosa

Ectopic pregnancy

Oviduct with an ectopic pregnancy Ruptured tubal pregnancy with


(tubal pregnancy) showing an approx 6-weeks-embryonic-age or
embryo of approx. 6-7 menstrual 8-weeks-gestational-age embryo,
weeks with intact amniotic sac

187
Uterus

Uterus
The uterus is a muscular
organ consisting of a:
fundus: rounded base
located superior to the exit
of the oviducts in the body
body: a broad portion into
which the oviducts open
cervix: narrow circular
portion that protrudes and
opens into the vagina

188
Uterus
The uterine wall of the body
and the fundus is composed
of:
endometrium
myometrium
adventitia or serosa

Endometrium
is the mucosal lining of the uterus,
consisting of 2 layers:
stratum functionale (the functionalis) - the
superficial layer
a thick, superficial layer that is sloughed at
menstruation
is vascularized by numerous coiled helical
arteries
stratum basale (the basalis) - the deeper
layer, closely attached to miometrium
narrow layer whose glands and
connective tissue elements proliferate and
thereby regenerate the functionalis during
each menstrual cycle

189
Endometrium
is composed of:
simple columnar epithelium
nonciliated secretory columnar cells
ciliated cells
lamina propria
cellular collagenous connective tissue:
star-shaped cells, macrophages,
leukocytes, and many reticular fibers
simple branched tubular glands made
of nonciliated secretory columnar cells

Endometrium

190
Endometrium functional histology
Menstrual Cycle: is a 28-day cycle
is divided into 3 phases
the menstrual
proliferative (follicular)
secretory (luteal) phases
under the control of different hormones, secreted by
the ovary

Endometrium functional histology

191
Endometrium
functional histology
Menstrual Phase (Days 1 to 4)
is characterized by the desquamation of the
functionalis layer of the endometrium
begins on the day that bleeding from the
uterus starts
occurs when fertilization does not take place
corpus luteum becomes nonfunctional thus
reducing the levels of progesterone and
estrogen

Endometrium
functional histology
Menstrual Phase (Days 1 to 4)
the coiled arteries become permanently
constricted, reducing the oxygen to the
functionalis layer
consequence: necrosis of the functionalis
rupture of the coiled arteries
menses: blood and patches of the
functionalis are eliminated

192
Endometrium functional histology
Proliferative (Follicular) Phase (Days 4 to 14)
is characterized by a reepithelialization of
the lining of the endometrium and renewal of
the functionalis
reconstruction of the glands, connective
tissue, and the coiled arteries of the lamina
propria from the residual basalis
the functional layer becomes much thicker
(up to 2 to 3 mm)
By the 14th day the functionalis layer has
been fully restored with a full complement of
epithelium, glands, stroma, and coiled
arteries

Endometrium
functional histology
Secretory (Luteal) Phase (Days 15
to 28)
is characterized by thickening of the
endometrium
as a result of edema and
accumulated glycogen secretions in
the highly coiled endometrial glands

193
Endometrium functional histology
The secretory products first
accumulate in the basal
region of the cytoplasm of
the cells constituting the
endometrial glands
at this point in the secretory
phase, the endometrium is
about 5 mm thick

Endometrium functional histology

Proliferative phase Secretory phase The basalis

194
Myometrium
is a thick smooth muscle layer,
composed of
inner longitudinal
middle circular
outer longitudinal layers
the size and number of the
myometrial muscle cells are related
to estrogen levels
when estrogen is absent, the
myometrial muscle atrophies, with
some cells succumbing to apoptosis

Myometrium
during pregnancy the increase in uterine size is
related to:
hypertrophy of the smooth muscle cells
and also to hyperplasia

195
Cervix
is the terminal end of the
uterus that protrudes into
the vagina

Cervix
the lumen of the cervix is lined by
a mucus-secreting simple
columnar epithelium
extending to the branched
cervical glands (false glands)
external surface, where the cervix
protrudes into the vagina, is
covered by a stratified squamous
nonkeratinized epithelium similar
to that of the vagina

196
Cervix

CLINICAL CORRELATION
Cervical carcinoma is one of the most common cancers in
women
the incidence increases in women with multiple sex partners
and herpes infections
etiology: infection with HPV
it develops from the stratified squamous nonkeratinized
epithelium of the cervix, where it is called carcinoma in situ
if detected by Pap smear in this stage, it can usually be
successfully treated with surgery
if not detected early, it may invade other areas and
metastasize, thus changing to invasive carcinoma, which
carries a poor prognosis

197
CLINICAL CORRELATION

CLINICAL CORRELATION

Babes-Papanicolaou ("Pap smear") technique is


a diagnostic tool for detecting cervical cancer
cells are scraped directly from the cervix

normal cells infected cells with HPV

198
Mammary glands
are compound tubuloalveolar
glands
consist of 15 to 20 lobes radiating
out from the nipple
they are separated from each
other by adipose and collagenous
connective tissue
each lobe is drained by its own
lactiferous duct leading directly
to the nipple
each of the ducts is dilated to
form a lactiferous sinus for milk
storage

Mammary glands

199
Mammary glands
Resting (Nonsecreting)
Mammary Glands
alveoli are not developed in
the resting mammary gland
structure:
secretory cells
myoepithelial cells

Mammary glands
Lactating (Active) Mammary
Glands
during pregnancy
the terminal portions of the ducts
branch and grow and develop
secretory units known as alveoli
the secretions of the alveolar
cells are of two kinds: lipids and
proteins

200
Mammary glands
Lipids are stored as droplets
within the cytoplasm
are released by the apocrine
mechanism
Proteins synthesized within
these secretory cells are
liberated from the cells by the
merocrine mechanism

Mammary glands
Areola and Nipple
areola is a circular, heavily
pigmented skin in the center
of the breast
in the center of the areola is
the nipple
a protuberance covered
by stratified squamous
epithelium containing the
terminal openings of the
lactiferous ducts

201
Mammary glands
The core of the nipple is
composed of:
dense collagenous connective
tissue
with abundant elastic fibers
connected to the surrounding
skin
a rich component of smooth
muscle cells

Clinical correlation: Brest cancer

202
THE ENDOCRINE SYSTEM

Introduction
Cell communication
Local
Surface molecules, gap junctions

Distant
Chemical messengers
Act on cell specific receptors

203
Types of secretion
Autocrine secretion
One cells chemical messenger acts upon its own
receptors
Local growth control - EGF (Epidermal Growth Factor)

Paracrine secretion
Chemical messengers act on adjacent cells
Diffuse neuro-endocrine system

Types of secretion
Endocrine secretion
Secretion of chemical messengers (hormones)
that act upon distant tissues after being
released in the blood stream
Synaptic secretion
Cell-to-cell synaptic communication

204
Endocrine secretion

Hormones
Distributed throughout the whole body
Act on target organs

Together with the nervous system, hormones


ensure the functionality and coordination of
all physiological systems within the organism

205
Endocrine cells
3 ways of grouping
Specialized organ endocrine gland
Adrenal glands, hypophysis, pineal gland
Distinct groups of cells within other organs
Ovary, testis, pancreas
Dispersed among other cells within epithelial
tissues
Digestive and respiratory systems
A part of the DNES

Endocrine glands

Generally composed of
Secretory cells of epithelial origin
Connective tissue
Rich in blood and lymph capillaies

Without excretory canal


Internal secretion glands

206
HYPOPHYSIS
(PITUITARY GLAND)

Ensures, together with the hypothalamus, the


endocrine and neuro-endocrine control of the
other endocrine glands

207
Anatomy and embryology

12x10x9 mm
0,5 - 1,5 g in adults
Within the sella turcica of the sphenoidal
bone
Connected to the hypothalamus by the
infundibular stem (pituitary stalk)

208
Anatomy and embryology
Adenohypophysis (anterior pituitary)
Glandular epithelial tissue
Pars distalis
The bulk of the anterior pituitary
Sometimes called anterior lobe
Pars intermedia
Rudimentary in humans
Between pars distalis and neurohypophysis
Pars tuberalis
Sheath of cells surrounding the pituitary stalk

Anatomy and embryology


Neurohypophysis (posterior pituitary)
Actually a prolongation of the hypothalamus
3 components
Neural lobe (pars nervosa)
Located behind the anterior pituitary
Pituitary stalk
Contains the axons of neurosecretory neurons
Median eminence
Some authors do not consider it a part of the pituitary

209
Differences
Anterior pituitary Posterior pituitary

Ectodermal
embryology embryology Nervous origin
origin

Glandular
structure structure nervous
endocrine

Storage for hormones


Secretes
role role secreted by the
hormones hypothalamus

Adenohypophysis

The master gland of the endocrine system


Regulates the activity of all other endocrine glands

Influenced by the hypothalamus


Stimulating and inhibiting hormones for the
hypophysial secretion

Secretes tropic hormones

210
Adenohypophysis
Cells arranged in islets and cords
Separated by sinusoid (fenestrated) capillaries

Acidophilic cells
Cytoplasm stained in red by acid dyes

Basophilic cells
Cytoplasm stained in blue by basic dyes

Chromophobic cells
Pale cytoplasm

211
Pars distalis
Somatotrope cells Secrete growth hormone (GH)
acidophilic
(somatotrophs)

Secrete prolactin (PRL)


Lactotrope cells acidophilic

Secrete adrenocorticotropic hormone (ACTH), -lipotropin ( -


LPH), -melanocytic stimulating hormone ( -MSH) i -
Corticotrope cells endorphin
basophilic

Secrete thyroid stimulating hormone (TSH)


Thyrotrope cells basophilic

Secrete gonadotropic hormones: follicle-stimulating hormone


Gonadotrope cells (FSH) and luteinizing hormone (LH)
basophilic

212
Somatotrophs
Approximately 50% of the cells in the anterior
pituitary
secrete growth hormone(GH)
No specific target organ
Acts upon all cells in the body
Increases protein synthesis
Favors growth and development
Deficit in childhood leads to dwarfism, and excess to
gigantism
Excess in adults leads to acromegaly

Lactotrophs
Approximately 25% of the anterior pituitary
Number and size increase during pregnancy and
lactation
Organelles involved in protein synthesis develop
Large secretion granules appear
secrete prolactin (PRL)
Initiates the development of the mammary gland
during pregnancy
Initiates and maintains lactate secretion after birth
Its secretion is stimulated by suckling

213
Thyrotrops

Large cells
5% of the anterior hypophysis
secretes thyroid stimulating hormone (TSH)
Stimulates follicular cells to secrete thyroid
hormones

Corticotrophs
Approximately 15-20% of the anterior hypophisis
Most contain unstained perinuclear vacuoles
enygmatic corpuscles
Derived from secondary lysosomes

secrete ACTH
Acts upon the zona fasciculata of the adrenal gland
Controls cortisole secretion

214
Gonadotrophs
Small cells

10% of the anterior pituitary

secrete FSH and LH


Both hormones are synthesized by the same cell

Pars intermedia
Between pars distalis and neurohypophysis
Underdeveloped in humans
contains
Basophilic cells
Chromofobe cells
Small vestigial cystic spaces filled with an eosinophilic substance
Secretes corticotrope hormones
Lipotrope hormones
Endorfins
-MSH
Does not secrete ACTH

215
Pars tuberalis
Richly vascularized
contains vessels pertaining to the hypothalamus-
hypophyseal portal system

Glandular cells
Mainly gonadotrophs
Arranged in cords and islets between blood
vessels

216
Pituitary adenomas
Benign tumors
Acidophil, basophil and/or chromophobe cell
proliferation
Generally they are functional
Secretion of hormones: PRL, STH, TSH, ACTH, LH
or FSH
Can also be non-secreting
May cause various endocrine syndromes

Neurohypophysis
Not an endocrine gland
Stores two hormones secreted by the
hypothalamus
Oxytocin
antidiuretic hormone (ADH, vasopressin)
Consists of
A network of non-myelinic axons
Glial cells - pituicytes

217
Neurohypophysis
Non-myelinic axons
Belong to neurons from the supraoptic and paraventricular
nuclei in the hypothalamus
End in the vicinity of fenestrated capillaries in the neural
lobe
Contain neurosecretory granules
Oxytocin
Vasopressin
Linked to neurophysin a tranport protein
ATP
Migrate along nervous terminations
Accumulate at the terminal end of axons neurosecretion
Sometimes spindle-like dilatations appear Herring bodies

218
Neurohypophysis
Pituicytes
Glial cells
Structure and function similar to those of astroglia in
CNS
Irregular shape
Numerous prolongations ending next to vessels
nuclei
round/oval, hypochromatic, conspicuous nucleolus
cytoplasm
Pale, with pygment granules

Function of the hypophysis

Controlled by releasing/inhibiting factors secreted


by the hypothalamus that reach the anterior
pituitary through the portal system

219
EPIPHYSIS CEREBRI
(PINEAL BODY, PINEAL GLAND)

Endocrine/neuroendocrine gland
Function in humans not clearly defined
Develops from the neuroectodermal plate
Cone-shaped
3-8 mm in diameter
100-200 mg
Covered by leptomeninges
Lobules separated by connective tissue septa that
contain non-myelinic nervous fibers and vessels

220
Pinealocytes
Highly modified neurons
Islets and cords separated by a rich network of
fenestrated capillaries
Round granular nucleus with large nucleolus
Pale cytoplasm
Numerous ramified processes in silver staining
Cytoplasmic ganulations
Melatonin
Serotonin

Glial cells
Between isles of pinealocytes
In contact with capillaries
Approximately 5% of the cells
Similar with astrocytes in CNS
Pale cytoplasm
Small hyperchromatic nucleus

Corpora arenacea
Brain sand
Calcified structures
Important CT and X-ray marker

221
Function of the epiphysis
Less known in humans
Secretes numerous neurotransmitters and
neuroendocrine regulating peptides
norepinephrine, dopamine, serotonin, histamine,
melatonin, somatostatin, TRF (Thyrotropin Releasing Factor)
Melatonin
Regulates the endocrine activity of the gonads e.g.
related to the menstrual cycle
Regulates reproductory function
Controls the onset of puberty
Regulates day/night and yearly cycles

222
THYROID

Introduction
Lobulated endocrine gland
In the anterior cervical region
Two lateral lobes connected by an isthmus
Normal weight 15-20 g
Average lobe size
40 x 15-20 x 20-40 mm
isthmus: 20 x 20 x 2-6 mm
Size and weight may vary greatly according to
Functional status
Gender
Hormonal status
Iodine intake

223
Architecture of the thyroid
Thyroid follicle

Morphologic and functional unit


Closed cavity delineated by a simple
epithelium
Variable shape: round-oval-polygonal
Average diameter 200 nm
May vary (50-500 nm)

Approximate count: 3 million

224
Follicular cell (thyreocyte)

Polarized cell
Apical pole towards the follicular lumen
Basal pole towards the basement membrane

Round/oval nucleus
Fine granular and/or coarse chromatin
Generally one nucleolus

Pale eosinophilic/amphophilic cytoplasm in HE

Follicular cell (thyreocyte)

Variable shape according to functional status


Flattened cells relatively inactive
Cuboidal cells secrete colloid into the follicular
lumen
May contain apical secretory vacuoles

Columnar cells re-absorb colloid

225
Follicular cell (thyreocyte)
Ultrastructure

Abundant rER
Well-developed Golgi apparatus
Above the nucleus
Location varies according to the phases of hormonal
synthesis

Numerous mitochondria
Size and location vary according to functional status

Numerous lysosomes at the apical pole

Follicular cell (thyreocyte)


Immunohistochemistry

Specific IHC marker: thyroglobulin


Mono-/polyclonal antibodies
Low molecular weight cytokeratins
Vimentin
-estrogen (not ) and progesteron receptors

226
C Cell
Discovered in the 19th century
Name derives from Calcitonin-Producing Cells
Difficult to identify on classically stained sections
Slightly larger and paler nuclei compared to follicular cells
Occasionally clear cytoplasm on formalin-fixated
preparations
Grimelius reaction
Fine cytoplasmic deposits of siver granules

227
C Cell

Always located within the follicle


Separated from the interstitial space by the
follicular basement membrane
The apical pole does have contact with the
colloid

C Cell
Ultrastructure
Variable number of secretion granules
60-550 nm
Type I granulations
280 nm
Moderately dense, finely granular content
Type II granules
130 nm
Higher density, pale halo undre the membrane

Type I granules are predominant


Both types contain calcitonin

228
C Cell
Immunohistochemistry

calcitonin
chromogranin A
serotonin
Neuron-specific enolase (NSE)
synaptophysin
Carcinoembrionar antigen (CEA)
LMWC

229
Thyroid hormone synthesis

Thyroid activity regulation


2 mechanisms:
Suprathyroidian: thyrotropin/thyroid stimulating
hormone (TSH)
Stimulates thyroid hypertrophy and hyperplasia
Accelerates intermediary metabolism
Increases nucleic acids and proteins synthesis
Stimulates thyroid hormone synthesis and secretion

Intrathyroidian: alterations of intraglandular iodine


levels
Regulates
Amino acid uptake
Glucose metabolism
Nucleic acid synthesis

230
Thyroid function
T3 and T4
Stimulate carbohydrate, lipid and protein
metabolism
Primary effect
Modulate the activity of ion pumps in cell membranes
regulate cell metabolite intake
Hormonal deficit during fetal development
Irreversible CNS lesions
Deficient myelination
Mental function impairment
Total lack of thyroid hormones endemic cretinism

Thyroid function
Calcitonin
Physiologic antagonist of parathormone (PTH)
Lowers calcium serum levels
Decreases bone resorption
Increases osteoid calcification
Secretion regulated by calcium levels
High alcium levels stimulate secretion
Low calcium levels inhibit secretion

231
PARATHYROID

Introduction
Adjacent to the thyroid
Oval shape
Several mm in diameter
Two pairs
2 superior
2 inferior

232
Development and structure
Inferior parathyroids and thymus from the third branchial
pouch
Superior parathyroids from the fourth branchial pouch
Thin capsule
Fine septa that delineate lobules
Within the septa adipose tissue
Adipose cells
Appear in puberty
Increase with age 60-70% of the glands mass
Secretor cells
Arranged in cords
Surrounded by a rich network of fenestrated and lymph
capillaries

Chief cells
approximately 8-10 m
Polygonal shape
Pale eosinophilic cytoplasm
Central round hypochromatic nuclei
Ultrastructure
Depends upon functional status
In synthesis abundant rER, active Golgi complex,
secretion granules containing PTH
Resting phase involuted organelles, secretion
granules still present

233
Oxyphilic cells
Without secretor function
Larger than chief cells (>10m)
Intnsely eosinophilic and granular cytoplasm
Small round hypechromatic nucleus
ultrastructure
Numerouse active, large mitochondria
Endoplasmatic reticulum and secretory granules are
unusual cells without endocrine activity
Rare before puberty
Numerous in young adults and elderly people

234
Function of parathyroid
Parathormone (PTH)
Regulates serum levels of calcium and phosphate ions
Increases calcium levels
Decreases phosphate levels
Feedback regulation
Low calcium levels stimulate secretion
High calcium levels inhibit secretion
Effects
Increases bone resorption through osteolysis
Diminishes renal excretion of calcium by stimulating tubular re-
absorption
Increases phosphate excretion
Increases calcium intestinal absorption

ADRENAL GLAND

235
Introduction
Adrenal cortex (cortical adrenal gland)
Approximately 90% of the gland
Same embryologic origin as gonads
Secretes steroid hormones (corticosteroids)
mineralocorticoids
glucocorticoids
Sexual hormones
Secretion is regulated by the ACTH
Adrenal medulla (medullar adrenal gland)
Derives from neural crests
secretes catecholamines
epinephrine (adrenalin)
norepinephrine (noradrenalin)
Belongs to the DNES
Secretion is regulated by the sympathetic and parasympathetic nervous
system

236
Adrenal cortex

Zona glomerulosa
Zona fasciculata
Zona reticularis

Zona glomerulosa
Peripheral, under the capsule
15% of the cortex
Cells
Arranged in short curved cords
Pseudoglomerular appearance
Small cubic or pyramidal
Pale basophilic cytoplasm
Round hyperchromatic nuclei
contain
Abundant sER
Multiple Golgi complexes
Large mitochondria
Free ribosomes
Reduced rER
Rich network of fenestrated sinusoid capillaries
Secretes mineralocorticoids

237
Zona fasciculata
Approximately 80% of the cortex
Cells
Arranged in long parallel cords separated by sinusoids
Large, polygonal
Central pale round nucleus
Often binucleated
Pale eosinophilic cytoplasm with vacuolar appearance
Neutral fats, fatty acids, cholesterol, phospholipids
Well developed sEN, mitochondria, developed Golgi
complex, some rER

Secretes glucocorticoids

238
Zona reticularis
In contact with the medulla
5-7% of the cortex
Cells
Much smaller than in zona fasciculata
Anastomosed cords separated by fenestrated
capillaries
Two types: clear and dark
Eosinophilic cytoplasm
Relatively low lipid content
Lipofuscin pigment
Rich sER, numerous mitochondria, underdeveloped rER
Secrets mainly masculine hormones

239
Adrenal medulla
Neuroendocrine cells
Chromaffin cells react with chrome salts
Connective tissue
Numerous fenstrated capillaries
Nerves
Cells
Islets or short anastomosed cords
Large, polygonal
Basophilic granular cytoplasm
Large round nucleus
Numerous secretory granules, rER, well developed Golgi
complex

240
Adrenal medulla

Secretory granules
contain
norepinephrine - large dense granules
epinephrine - smaller, paler granules

241
Function of the adrenal gland
Mineralocorticoids
Main example: aldosterone
Regulates electrolyte homeostasis
Increases sodium re-absorption and potassium
elimination in renal tubes
Regulates blood pressure
Renin-angiotensin-aldosterone system

242
Function of the adrenal gland
Glucocorticoids
Main example: cortisole
Regulates glucidic metabolism
Increases glycemia and glycogen synthesis

Increases protein catabolism


Frees lipids from tissular reserves

Function of the adenal gland


Adrenalin and noradrenalin
Metabolic effects
Stimulate glycogenolysis
Frees fatty acids from the adipose tissue
Increase blood pressure
Induce coronary vasodilatation
Induce vasodilatation in skeletal muscles
Induce vasoconstriction in skin and intestinal vessels
Increase heart rate
Increase respiratory rate
fight or flight reaction

243
ENDOCRINE PANCREAS

Islets of Langerhans
Four main cell types:
B or cells
70%
Secrete insulin
A or cells
15-20%
Secrete glucagon
D or cells
5-10%
Secrete somatostatin
PP or F cells
1-2%
Secrete pancreatic polypeptide

Minor types
VIP secreting cells (Vasoactive Intestinal Polypeptide)
EC (enterochromaffin) cells secrete secretin, motilin, P substance

244
DIFFUSE NEUROENDOCRINE
SYSTEM (DNES)

245
Introduction
Neuroendocrine cells dispersed throughout the body
Secrete hormones and active peptides with local action
Amine Precursor Uptake and Decarboxylation (APUD)
Characteristic organelles
Dense core granules neurosecretory vesicles
Difficult to identify in usual stains
Silver stains
Argentaffin cells reduce silver
Argyrophilic cells - absorb silver
Electron microscopy, IHC
Over 20 different types

Gastro-intestinal DNES
Gastrin
Secretin
Colecistokinine-pancreozymine (CCK-PZ)
Enteroglucagon
Somatostatin
P substance
Vasoactive intestinal peptide (VIP)
Bombesin
Gastric inhibiting polypeptide (GIP)
Motilin
Pancreatic polypeptide (PP)

246
Gastro-intestinal DNES

Small cellse mici


Round nucleus
Pale cytoplasm
Located near the basal lamina
Open/closed-type cells

Respiratory DNES
Isolated or grouped cells
Within the wall of large extra-/intrapulmonary
respiratory ducts
Occasionally within the alveolar wall
Pale in HE
On the basal lamina
Cytoplasmic processes
Numerous and well developed at birth
Numbers decrease rapidly with age

247
248
Integumentary system

Largest organ of the body (16% of body weight)


Two components:
Skin
Epidermal derivates (hair, nails,
sebaceous glands, sweat glands, mammary glands)

Skin
is of particular significance in a clinical physical examination
the color of the skin may indicate the existence of a pathologic
condition:
a yellow color indicates jaundice;

a blue-gray color may indicate cyanosis, reflecting a pathologic

condition of cardiovascular and respiratory function;


a pale color is indicative of anemia;

lack of skin pigmentation suggests albinism, a genetic trait

characterized by lack of the enzyme tyrosinase, involved in the


conversion of the amino acid tyrosine to melanin

many infectious and immunologic diseases produce characteristic


skin changes leading to a correct diagnosis
the skin has diseases peculiar to itself

249
Skin - functions
(1) protection (mechanical function);

(2) as a water barrier;

(3) regulation of body temperature (conservation and dissipation of


heat);

(4) nonspecific defense (barrier to microorganisms);

(5) excretion of salts;


(6) synthesis of vitamin D;
(7) as a sensory organ, and
(8) sexual signaling.

Skin - structure
EPIDERMIS keratinized stratified squamous epithelium

DERMIS dense irregular, mostly collagenous CT


elastic fibers are significant

HYPODERMIS adipose connective tissue

ADNEXA (accessories) sweat & sebaceous glands,


hair follicles & hairs, nails, mammary glands , nerves &
nervous receptors, special blood vessels

250
Skin - structure
two types:
1) thick skin
more than 5 mm

covers the palms of the hands and the soles of the

feet
has a thick epidermis and dermis

2) thin skin
1 to 2 mm in thickness

lines the rest of the body


the epidermis is thin

Skin - structure
the surface of the skin
(palms,soles,digits of hands and
feet)
has narrow epidermal ridges
each ridge corresponds to
an underlying dermal papilla
ridges and papillae are
permanent,
have a constant pattern,
and
are unique to each
individual.
impressions of the ridges
create fingerprint patterns,
useful for forensic
identification
separated by furrows.

251
Epidermis
derived from ectoderm
composed of stratified squamous keratinized epithelium
(keratinocytes)

five morphologically distinct zones


(1) stratum basale (germinativum)
(2) stratum spinosum, stratum of Malpighi

(3) stratum granulosum,


(4) stratum lucidum, and
(5) stratum corneum

composed of four populations of cells:


keratinocytes (keratin) main cell population
Langerhans cells (antigen-trapping cells)
melanocytes (melanin)
Merkel cells (tactile sensation)

252
EPIDERMIS: Cell types

dead

Keratinocytes Melanocyte to
make &
alive transfer
pigment

Langerhans Merkel cell


APC cell sensory
immunity

Nerve cell represented by its axon

Caution - The KERATOCYTE is the fibroblast of corneal connective tissue

Epidermis
stratum basale (or stratum germinativum)
a single layer of columnar or high cuboidal keratinocytes
resting on a basement membrane separating it from papillary layer
of dermis
the cytoplasm contains intermediate filaments (keratin 4 and 15) -
bundles of intermediate filaments, visible under the light
microscope, are called tonofilaments
associated with desmosomes (intercellular junctions)
hemidesmosomes and associated intermediate filaments anchor
the basal domain of basal cells to the basement membrane
cells of the stratum basale undergo mitosis (renewing the stem
cell population; renewing the sloughed off surface cells)
Merkel cells and melanocytes are also present in this layer

253
Epidermis
stratum spinosum
thickest layer of epidermis,
keratinocytes - known as prickle cells,
interdigitate with one another by forming intercellular bridges and a
large number of desmosomes;
have numerous tonofilaments
keratins change keratin 1 and 10 replace keratin 5 and 14
membrane-coating granules
cells are mitotically active;
this layer also houses Langerhans cells

EPIDERMIS: stratum spinosum

} S. SPINOSUM

} The spines arise from two properties:


Macula adherens/
Desmosome

-the keratinocytes are attached by many


desmosomes:
As the cells shrink, they are held together by the
desmosomes, which get swung through 90
degrees, while a gap otherwise separates the
cells:

254
Epidermis
- compound cell envelope epidermal permeability barrier

stratum granulosum
three to five cell layers thick;
keratinocytes still retain nuclei;
major product of cells filaggrin (nonintermediate protein filament)
induces aggregation of keratins coarse keratohyalin
granules
lamellar bodies formed of lipids
stratum lucidum
lightly stained thin layer
keratinocytes without nuclei and organelles;
cells contain densely packed keratin filaments and eleidin
stratum corneum
numerous layers of
dead flattened keratinized cells,
keratinocytes, without nuclei and organelles (squames, or horny
cells)
that will be sloughed off

255
EPIDERMIS: Layers & events

STRATUM CORNEUM of dead, but


} attached, hardened & wrapped cells ,
will slough off
S. GRANULOSUM multiple syntheses

} to make cornified cells


S. SPINOSUM upward migration of
keratinocytes, while keratins IFs
increase & change
S. BASALE mitosis of stem cells

Keratinocyte **structural protein produced by the


keratinocytes is keratin
differentiation
Epidermal growth factor (EGF) and Transforming growth factor (TGF)
interleukin (IL-1) influence the growth suppresses keratinocyte proliferation
and development of keratinocytes and differentiation

256
Components of the epidermal
permeability barrier

Components of the epidermal


permeability barrier
multilamellar lipid layer (outer layer) cross-linked to involucrin
make the cell membrane impermeable to fluids
cornified cell envelope
a compex of three proteins
involucrin

small proline-rich proteins (SPRs)

loricrin

provides elasticity and mechanical resistance


aggregates of filaggrin and keratin (keratin-filaggrin komplex) that
interact with the inner side of the plasma membrane

tight junctions between cells of the stratum granulosum (claudin1 and


4)

257
Other cells of the epidermis -
Melanocytes
branching cells located in the stratum
basale of the epidermis (choroid plexus,
retina, and ciliary body of the eye)
derive from melanoblasts, a cell
precursor migrating from the neural
crest.
independent cells without desmosome
attachment to the differentiating
keratinocytes
produce melanin filamentous structure
(melanofilaments)
initially stored in a membrane-bound
premelanosome derived from the Golgi
apparatus than in melanosomes
oxidation of tyrosine to 3,4- Albinistic girl Papua New Guinea
dihydroxyphenylalanine (DOPA) by the
enzyme tyrosinase.
DOPA is then transformed to melanin
Ultraviolet light darkens the melanin and speeds
tyrosinase synthesis, thus increasing melanin
production

258
Other cells of the epidermis -
Langerhans cells (dendritic cells)
bone marrow-derived cells
present in the epidermis as immunologic sentinels, involved in
immune responses, in particular the presentation of antigens to T cells

cytoplasmic processes (dendritic cells) extending among keratinocytes


of the stratum spinosum without establishing desmosomal junctions

in the cytoplasm - proteins langerin and CDa1 involved in uptake and


delivery of antigens
Langerhans cells, containing an epidermal antigen,
enter a lymphatic vessel in the dermis and
migrate to a regional lymph node
where they interact with T cells in the deep cortex (T cell zone).
activated T cells reenter the blood circulation,
reach the site where the epidermal antigen is present
release proinflammatory cytokines in an attempt to neutralize the
antigen.

259
Other cells of the epidermis - Merkel
cells
numerous in the fingertips
resemble modified keratinocytes
found in the stratum basale
mechanoreceptor cells linked to adjacent keratinocytes by
desmosomes

in contact with a
an afferent myelinated nerve fiber (projecting from the dermis into
the epidermis)
that becomes unmyelinated after passing through the basal
lamina of the epidermis
and expands into a platelike sensory ending, the nerve plate, in
contact with the Merkel cell
nucleus is irregularly shaped and the
cytoplasm contains abundant granules, presumably neurotransmitters.

260
THICK, HAIRLESS SKIN

}
Meissners
corpuscle
EPIDERMIS
capillary
loop
DERMIS
} Papillary layer

duct

} DERMIS
Reticular layer

Sweat gland

Pacinian
corpuscle } HYPODERMIS
Fat cells

Dermis
formed by two layers without distinct boundaries:
(1) the papillary layer, consisting of
numerous papillae interdigitating with epidermal pegs forming the
dermal-epidermal junction.
hemidesmosomes anchoring basal keratinocyte cells to the basal
lamina.
attach the epidermis to the basement membrane and the papillary layer
of the dermis by a plate/plaque-anchoring filament complex
loose connective tissue (fibroblasts, macrophages, plasma cells,
mast cells, and other cells, collagen fibers, and thin elastic fibers)
provides mechanical anchorage and nutrients to the overlying
epidermis
many capillary loops, which extend to the epidermis-dermis interface
pear-shaped encapsulated Meissner corpuscles (tactile stimulation),
Krause end bulb (respond to cold)

(2) the reticular layer, containing


thick bundles of collagen fibers and coarse elastic fibers

sweat glands ducts, hair follicles and muscles, sebaceous glands

261
Hypodermis (superficial fascia)
or subcutaneous layer of the skin
deeper continuation of the dermis
loose connective tissue and adipose cells

a layer of variable thickness depending on its location in the body


facilitates mobility of the skin
the adipose tissue contributes to thermal insulation and storage of
metabolic energy and acts as a shock absorber.

Pacini corpuscles
sweat glands glomerules

262
Glands of the skin
Sweat glands - two types of sweat glands:
eccrine (merocrine) sweat glands
simple coiled tubular gland
role in the control of body temperature.
the secretory portion - convoluted tube composed of three cell types:
(1) clear cells, (2) dark cells, and (3) myoepithelial cells.
excretory portion - is lined by a bilayer of cuboid cells
helical path when it approaches the epidermis and opens on its
surface at a sweat pore

apocrine sweat glands


coiled
occur in the axilla, mons pubis, and circumanal area
larger secretory acini
excretory duct opens into the hair follicle

Glands of the skin

263
Glands of the skin
Sebaceous gland is a
holocrine simple saccular gland
extending over the entire skin except for the palms and soles

secretory portion of the sebaceous gland lies in the dermis


groups of alveoli connected to the excretory duct by a short ductule
each alveolus is lined by cells resembling multilocular adipocytes with
numerous small lipid droplets
excretory duct opens into the neck of the hair follicle.
lined by stratified squamous epithelium continuous with the external
root sheath of the hair and the epidermis (the malpighian layer).

can be independent of the hairs and open directly on the surface of the
skin of the lips, the corner of the mouth, the glans penis, the labia
minora, and the mammary nipple.

the oily secretion of the gland (sebum) is released on the surface of the
hair and the epidermis

Glands of the skin

264
Hair
Hair follicles are
tubular invaginations of the epidermis responsible for the growth of
hair
consists of two parts
the hair shaft - filamentous keratinized structure present almost all
over the body surface, except palms, soles, sides of fingers and
toes etc.
the hair bulb - expanded end portion of the invaginated hair follicle

dermal papilla -vascularized connective tissue core that projects into


the hair bulb.
Hair follicle is
-surrounded by a connective tissue layer
-associated with the arrector pili muscle, a bundle of smooth muscle
fibers aligned at an oblique angle to the hair follicle and attached to the
follicular bulb.
-autonomic nervous system controls the arrector pili muscle, which
contracts during fear, strong emotions, and cold temperature.

THIN HAIRY SKIN Hair shaft Sebaceous gland

Epidermis
D
E
R
Root M
sheath
I
Matrix S
H
Y
P
Sweat gland O
Papilla of Hair follicle Arrector pili muscle D
E
R
M
[Thin keratin layer] I
S

265
THIN HAIRY SKIN: Innervation

Epidermis
D
E
R
M

Arrector pili muscle I


S

pilomotor Sweat gland Vessel


Sensory sudomotor
Autonomic motor
vasomotor
thermoregulation

266
Sensory receptors - Mechanoreceptors
respond to mechanical deformation/temperature changes (for example,
stretch, vibration, pressure, and touch)

naked nerve ending


which lacks a myelin covering.
epidermis of the skin,cornea of the eye
respond to light pressure and touch stimuli.

Merkel disk
discriminates touch and
the nerve ending of this receptor forms a flattened discoid structure
attached to the Merkel cell found in the stratum basale of the
epidermis

peritrichial nerve ending


very sensitive
wrapped around the base and shaft of the hair follicle.
stimulated by the movement of the hair

Sensory receptors - Mechanoreceptors


encapsulated receptors:
Meissner corpuscle
in the dermal papillae

accounts for half the tactile receptors of the digits and hand

well suited for the detection of shape and texture during active
touch
consist of flattened supportive cells arranged as horizontal
lamellae
surrounded by a connective tissue capsule

an unmyelinated nerve fiber meanders between the lamellae

pacinian corpuscle
in the hypodermis, or deep dermis.

responds to transient vibratory stimuli and is the receptor for


deep pressure
wrapped by a connective tissue layer

20 to 60 concentric lamellae - modified Schwann cells

in the centre a single afferent unmyelinated nerve fiber

267
268

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