DEPARTMENT OF ANATOMY

Microscopic Human Structural Biology (MHSB)

WEEK 1 | CELL/ PARENCHYMA/ STROMA

UNIT OUTCOMES (UO)

At the end of this unit, the students are expected to:

Cell
1. Differentiate prokaryotes from eukaryotes
2. Describe the principal parts of the cell
3. Describe the different specialized structures/specializations of the cell
4. Discuss the methods on how the cell divides and its associated anomalies
5. Name some structural and functional abnormalities of the cell.

Parenchyma/ Stroma
1. Define “parenchyma”
2. Explain the role of parenchyma citing examples in each of the organs
3. Define “stroma”
4. Explain the role of stroma, citing examples in each of the organs
5. Give the basis of characterizing cells, citing example for each
6. Discuss the intercellular spaces and its content

LECTURE GUIDE
Cell – basic structural and functional unit of all living organism

Two basic cell types

1. Prokaryotic cell – small, single-celled organism that lack a nuclear envelope and various
organelles
2. Eukaryotic cell – exist primarily as components of multicellular organism, contains a nuclear
envelope and is composed of organelles

3 Basic Parts of the Cell

1. Cell membrane
2. Cytoplasm
3. Nucleus

I. Cell Membrane
- also called plasma membrane or plasmalemma- selectively permeable envelope that separates the
cytoplasm from the external environment.
- appear as a trilaminar structure with two peripheral dense lines which are hydrophilic and a pale
intermediate zone which is hydrophobic
- primarily made up of:
A. Carbohydrates
- mainly as oligosaccharides and glycolipids
- oligosaccharide component may form a superficial coat known as GLYCOCALYX
that participates in cell adhesion and recognition.
B. Fats
- mainly exists in the cell membrane as phospholipids and cholesterol with some
sphingolipids
C. Proteins
- make up more than 50% of the membrane weight.
- may act as channel proteins, carries or receptors
- most membrane proteins are globular
- divided into two groups:
1. Integral Proteins – extend throughout the membrane with ends exposed on
its outer and/or inner surfaces. Those that protrude on both surfaces are called
as TRANSMEMBRANE PROTEINS. Other forms are integrins and cadherins
2. Peripheral Proteins – not within the bilayer but bound to inner or outer end
of some of its integral protein.
II. Nucleus
- a large membrane limited compartment most commonly located near the center of the cell
- most conspicuous because of its basophilia
- spherical or ovoid that contains the genetic materials
- command center of the cell and repository of its archives
- site of replication (DNA), transcription (RNA) and plays a role in translation (protein)
- mainly made up of:
A. Nuclear Envelope/ Membrane
- 2 parallel membrane separated by perinuclear cisternae.
- outer membrane is continuous with the membrane of rough endoplasmic reticulum
- the outer membrane is also continuous with the inner membrane at sites around the
periphery which form nuclear pores and serve as communication between
nucleoplasm and cytoplasm.

Nuclear pore complex – the pore and its living components and is made up
of 30 different proteins.
Nuclear laminae – adjacent the innermost nuclear membrane

- in EM, appear as pale layer between the peripheral clumps of heterochromatin and
nuclear membrane.
 - composed of a meshwork of compacted filaments –laminins
- contribute to the structural stability of the interphase nucleus
- influence the disposition of the chromosomes at earliest stages of cell division.

B. Nucleolus
- spherical refractile body located eccentrically in the nucleus
- basophilic surrounded by heterochromatin.
- in EM, consist of dense strands that branch and rejoin to form a continuous compact
network – nucleolemma
- this network is made up of packed, dense granules – pars granulose which
represents maturing ribosomal units.
- the newly synthesized primary transcripts of rRNA which exist as dense pack of
fibers in the network is termed as – pars fibrosa
- the lighter, non granular areas within the nucleolus are fibrillar centers or otherwise
called as pars amorpha. These consist of segments of DNA that code fro rRNA.

C. Nucleoplasma
- get matrix inside the nucleus that contains chromatin materials
Chromatin – clumps of intensely basophilic materials adjacent the
nuclear envelope
- consist of DNA and associated proteins in a condensed state. These DNA molecules
are coiled 1 ½ turns around a histone.
- a histone complex with DNA nucleosome.
- this coiling of DNA causes a six-fold shortening of the DNA molecules
- further shortening occurs by helical coiling around a central channel for chromatin
fibers
Heterochromatin- inactive DNA on its condensed states
Euchromatin – active, less highly coiled chromatin which arise by
uncoiling of some heterochromatin.

III. Cytoplasm
- semi-fluid matrix that contains organelles inclusion bodies and cytoskeleton.
- organelles maybe membrane or non-membrane bound

A. Membrane- Bound Organelles

1. Mitochondria
- generator of chemical energy necessary for most biochemical reactions within the ce
- most numerous in muscles and neurons.
- slender, sausage – shaped structures
- contain its own DNA which closely resembles that of bacterial DNA
- mitochondrial DNA are transferred from mother to offspring.
- divide by binary fission.
 - bound by 2 membranes; a smooth outer membrane and an inner membrane that is
thrown into folds called cristae mitochondriales.
a. outer membrane – contains porins which form channels to allow free diffusion of
small molecules.
b. inner membrane – less permeable with higher protein content that any other
membrane of the cell
- associated with minute protein granules attached to F1
subunits which are principal sites of generation of ATP.

Intermembrane space – narrow space between the outer and the inner membranes
extending into the cristae.
Mictochondrial matrix – contains matrix granules as calcium phosphate and
mitochondrial DNA

2. Endoplasmic Reticulum
- largest cytoplasmic organelles
- lace-like network of delicate branching and anastomosing strands.
- some portions are widened flat saccules called cisterns
- exists in two forms:
a. rough Endoplasmic Reticulum (rER)
- studded with robosomes
- primarily for protein synthesis which are for extracellular use.
- proteins unique to rER are docking proteins are ribophorins I and II
- docking proteins function as receptor while ribophorins serve to anchor large
ribosomes to rER.

b. smooth Endoplasmic reticulum (sER)

- with no ribosomess attached
- synthesizes cholesterol and steroid hormones as in interstitial cells of Leydig and
adrenal cortex.
- in the liver detoxifies drugs and alcohol and participates in glycogen synthesis
- in the muscles, site of storage and release of calcium for contraction.

3. Golgi Apparatus
- further processed, sorts and packages secretory products for transport to their final destination in
the cell.
- found largest in secretory cell types.
- area stacks of parallel, membrane-bound, flat saccules and associated small vesicles.
- golgi associated vesicles may be coated with clathrin and other associated coat proteins like COP
I and II.
- COP I coat transport proteins from rER to golgi complex.
- COP II’s function is unclear whether they transport proteins between golgi apparatus and cisternae
or recycle membrane from golgi to rER.

Faces of Golgi Apparatus

a. cis face – convex or forming face which are adjacent the dilated endoplasmic reticulum
- fuses with the vesicles that transport newly synthesize protein.
b. trans face - concave or maturing face with is a part of the golgi that faces away the
nucleus

Trans Golgi Network – fenestrated cisternae at the exit face of Golgi apparatus.

4. Lysosomes
- contain more than 30 hydrolytic enzymes that have acid pH and function as “digestive system” of
the cell
- assembled by fusion of vesicles from golgi apparatus with vacuoles from the plasma membrane.
- are involved in autograph
a. Primary Lysosomes
– storage form of lysosomes which contain inactive enzymes.
- found most abundant in phagocytic cells like macrophages
b. Secondary Lysosomes
– formed by fusion of one or more primary lysosomes with a phagosome.
- contain active enzymes
- its number reflects the phagocytic activity of the cell
c. Residual bodies
- terminal phases of lysosome function.
- contain indigestible materials of the cell as in the lipofuscin granules.

5. Peroxisomes
- resemble lysosomes structurally but are more spherical.
- in some species may contain crystalline inclusions called nucleoid.
- abundant in hepatocytes which are involved in the detoxification of alcohols, drugs and other toxins.
- contain 40 different enzymes including catalases and oxidases.

6. Phagosomes
- membrane-limited vesicles of various sizes containing materials destines for lysosomal digestion.

B. Non-membrane-Bound Organelles
1. Ribosomes
- protein synthesizing organelle that are for intracellular use (fro free or cytoplasmic
ribosomes)
-consist of two unequal ribosomal subunits
- maybe in the form of ergastoplasm in the glands of the Nissl bodies in the neurons.
2. Cytoskeleton
- dynamic filamentous structures that continuously depolymerize and repolymerize to
alter cell shape and move organelles and/or cell as a whole.

a. microfilaments
– thinnest cytoskeletal components
- appear in the cytoplasm as single globular molecule (G-actin) and in the form
of filaments (F-actin)
- are usually composed therefore of one or several types of actin filaments
- contractile filaments.
e.g. filamin, ankyrin
b. intermediate filaments
- diameter is intermediate between microfilaments and microtubules.
- are class of filaments of similar appearance and diameter with proteins of
widely differing molecular weight.
- are involved in maintaining cell shape and possibly as components of
microtrabecular lattice.
e.g. vimentin – found in fibroblast of connective tissue or
mesenchymally –derived cells
desmin – muscles
keratin – epidermis of the skin
neurofilaments – neurons
GFAP (glial fibrillary acidic protein) – glial cells
c. microtubules – thickest cytoskeletal components
- are polymers of tubulin which is a heterodimer, alpha and beta.
- serve as tracks for the movement of organelles and which are effected
by kinesin and dynein.
- are building blocks of centrioles and axoneme of cilia and flagella

i. centrioles
– cylindric group of 9 microtubule triplets in a pinwheel array.
- organizes cytosolic microtubules to mitotic spindles during cell division.
- also divides by binary fission
ii. cilium/ cilia
– cell surface evaginations covered by plasma membrane which contains a
core - axoneme
- the axoneme is made u of 9 peripheral microtubule doublet surrounding a pair
of unjoined microtubules.
iii. flagellum
- usually one or two in a cell surface
- structurally similar to cilia only that they are longer
 - its axoneme is similar to that of the cilia and is made up of 9 doublets of
microtubules
iv. basal bodies
- made up of 9 microtubule triplets which are seen in the apical plasma
membrane
- also serve as anchoring points and microtubule organizers

C. Cytoplasmic Inclusions
- are not seen in all cell types
- spherical bodies which serves as storage depots.
- less essentials to cell viability
- maybe transient like the glycogen granules and the lipid droplets or maybe permanent like lipofuscin
pigments which increases in size as one grows old.

Cell Surface Modifications

1. Microvili
- non-motile cellular extensions that increases absorptive surface of the cell
- maybe in various forms like:
a. striated borders – seen in intestinal epithelium especially the small bowel
b. brush border – found in proximal convoluted tubules of nephron of kidneys
c. stereocilia – can be located on some portions of male reproductive ducts.
2. Cilium – maybe found in the respiratory tract and female reproductive tracts
3. Flagellum – the only flagellum in humans are seen in the spermatozoa of males

ENDOCYTOSIS
- it is taking up of extracellular materials and brings them into the cytoplasm in membrane limited
vesicles.
- there are 3 modes of endocytosis
a. Pinocytosis – known as ”cell drinking”
- non-selective engulfment by the cell of small and large particles
b. Phagocytosis – “cell eating”
- cell engulfs insoluble substances like macromolecules and bacteria
which are intended for destruction within the cell.
c. Receptor - mediated endocytosis
- cell takes up foreign substances with their surface receptors.
- the foreign materials are coated by coating proteins as clathrin before
they are recognized by the cell.

CELL CYCLE AND DIVISION

Chromosomes - are mostly highly condensed form of chromatin materials which are often visible
during mitosis. These are the structural units of genetic materials of the cell. Humans have 22 pairs
of autosomal and a pair sex chromosomes.

Interphase:
a. G1 phase – gap 1, follows telophase of mitosis.
- no NA synthesis occurs but RNA and protein synthesis do occur.
- each daughter cells grows the size of the parent.
- longest and most variable phase of the cell cycle.
b. S phase - synthesis phase.
- replication of DNA occurs and centrioles self-duplicate during this phase.
c. G2 phase - gap 2 final preparation for cell division occurs during this phase.
- synthesis of tubulin and accumulation of ATP.
- further increase in cell volume and synthesis of enzymes and other proteins.
d. Mitosis - brief continuous process of cell division which divided into 4 phases ( sometimes 5,
with a prometaphase included)
- referred to as the 4th phase of the cell cycle.
- a division undergone by autosomal chromosomes.
- daughter cells produced have diploid number of chromosomes.

i. prophase – chromatin coils extensively to form chromosomes nuclear

membrane disappears with the nucleoli, centrioles migrate on the opposite
poles and microtubules assembles as mitotic spindles, this last mechanism is
sometimes referred to as pasrt of th transient prometaphase in which the
microtubules from opposite poles attach.

ii. metaphase – chromatids align at the equatorial plate.

iii. anaphase – chromatids migrate towards the opposite poles by the

translocation of the spindle microtubules.

iv. telophase – chromosomes uncoil, nucleoli and nuclear membranes

reappear at the opposite ends of the cell, a purse string constriction of bands
of microfilaments appear at the equatorial plate dividing the cytoplasm and
eventually the daughter cells.
Meiosis
- cell division that occurs in gametes or sex cells.
- daughter cells produced are haploid
Meiosis I – replication of DNA has occurred before the division.
- consist also of 4 phases; prophase I, metaphase I, anaphase I, and telophase
I
 - prophase I is further subdivided into pachytene, leptotene, zygotene,
diplotene.

Meiosis II – division without prior replication of DNA after first meiosis division.

CELL DEATH
Apoptosis
- programmed cell death.
- active, energy-dependent, gene directed process.
- early biochemical event involves the activation of specific endonucleases that condense and
degrade DNA.
- cell membrane and organelles are intact with no cellular swelling or any signs of inflammatory
processes.
- cells eventually shrink and is phagocytosed by the neighboring cells.

Necrosis
- usually results from anoxia, mechanical injury, cell invasion by viruses exposure to toxins or to
irradiation.
- usually preceded by signs of inflammation resulting to cellular swelling, clumping of the chromatin
and destruction of the organelles followed by lysis of the cell.

Pyknosis
– shrinking of the nucleus.

Karyorrhexis
- fragmentation of the nucleus

Karyolysis
- nuclear dissolution

CLINICAL CORRELATIONS
Lebr’s optic neuropathy
- results from mutation from mitochondrial DNA that cause reduced capacity to carry out
oxidative phosphorylation. Person becomes blind between 15 and 30 years old due to
optic nerve degeneration.
Pompe’s disease
- a lysosomal storage disease in which the enzyme acid maltase is deficient or entirely
absent resulting in massive accumulation of glycogen in muscles, nerves and other
organs.
Epdermolysis bullosa
 - due to the mutation of one of the gene for keratin prevents the assembly of intermediate
filaments in the epidermis. The epidermis therefore becomes very fragile that results to
formation of bullae (blisters)
Kartagener’s Syndrome
- the dyenin arms of the doublet microtubule of he axoneme are absent. Cilia found on
the different parts of the body become non-motile predisposing them to having respiratory
infections and sterility due failure to assist movement of the sperms of the males and
ovum in the female reproductive organs
Familial Hypercholesterolemia
- due to a defective LDL receptors hence there is a failure to take up LDL from the blood.
This may lead to atherosclerosis and eventually obstructing blood flow.
Trisomy 21
- more commonly known as Down’s syndrome
- there are three copies of chromosome 21 due to errors in meiosis
Klinefelter’s Syndrome
- due to an extra X chromosome which results to mild mental retardation and infertility
Turner’s Syndrome
- has only a single X chromosome hence ovaries fail to develop

PARENCHYMA
- structural and functional characteristic cells of a tissue or an organ
- most numerous cell found in the area
e.g.1. Neurons – parenchyma of spinal cord
2. Pyramidal cells – parenchyma of cerebrum
3. Purkinje cells – parenchyma of cerebellum
4. Osteocytes – for bones
5. Chondrocytes – for cartilages
6. Hepatocytes – for the liver
7. Cardiac muscle cell – for the heart
8. Epidermal cells/ squamous cells – epidermis of the skin

STROMA
- supporting tissue of the organ
- usually are forms of connective tissue
e.g.1. Perimysium, epimysium, endomysium – stroma of skeletal muscle
2. Meninges/ neuroglial cells (astrocytes, oligodendrocytes, microglial) – spinal cord
3. Glisson’s capsule/ interlobular connective tissue – liver
4. Perichondrium – cartilage
5. Endosteum/ Periosteum – bones

Cells are characterized based on;

1. Size
 – how large the cells are.
- are measure in micron or micrometer
- most of the cells are microscopic but with few exceptions like the ovum and the skeletal
muscles which are macroscopic or are possibly seen with the naked eye.
2. Shape
a. fattened or squamous – e.g. found in the epidermis of the skin and endothelium
b. cuboidal – e.g. thyroid follicles, distal convoluted tubules of the kidney
c. columnar – e.g. gall bladder, trachea
d. stella/ star shape – e.g. neurons, osteocytes
e. cylindrical/tubular- e.g. skeletal muscle, cardiac muscle
f. fusifrom – e.g. pirkinje cells of the cerebellum
g. polyhedral/ polygonal – e.g. hepatocytes
h. ovoid – e.g. osteocytes
i. disc shape – e.g. erythrocytes (RBC)
j. spindle – smooth muscle, fibroblast
3. Cell number
- maybe expressed absolutely as in exact counts of blood cells or relatively with the use
of words as few, many or plenty.
4. Arrangement of cells
a. in layers/sheet – e.g. epidermis of the skin, smooth muscle cell
b. in bundles/fascicles – e.g. cardiac muscle cell, skeletal muscle cell
c. concentric – e.g. osteocytes of compact bone
d. haphazard/ random – o definite arrangement
- e.g. neurons of spinal cord, osteocytes of spongy bone
e. isogenous – e.g. chondrocytes of hyaline and elastic cartilage
f. cords/ rows/ columns – e.g. hepatocytes, chondrocytes of fibrocartilage
5. Location of the nucleus
a. central – e.g. cardiac muscle, cells, hepatocytes, nenuron
b. peripheral – e.g. skeletal muscle
6. Number of nucleus
a. mononucleated – e.g. neurons, cardiac muscle cell, hepatocytes
b.binucletaed – e.g. cardiac muscle cell, hepatocytes
c. multinucleated – e.g. skeletal muscle cell

INTERCELLULAR SPACE
- space found in between cells of tissues
- usually nil to nothing in epithelial tissues
- characteristically found in between connective tissues.
- contents include;
a. tissue fluid – derived from blood plasma
- constiturtes the extracellular matrix
- may contain fibers and cells
 - fluid in nature
b. ground matrix- semi-solid to solid in nature
- secreted by connective tissue cells or characteristic cells of the tissues
- contains connective tissue cell and fibers.
- made up of glycosaminoglycans (GAGs) like hyaluronic acid, keratin SO 4,
heparin SO4, Chondroitin SO4, and dermatan SO4,
c. tissue fibers – maybe;
i. collagen fibers – have the greatest tensile strength
- most abundant fiber of the connective tissue
- grossly white in color.
ii. elastic fibers - by the term itself, it is elastic
- found on walls of elastic blood vessels
- yellow fibers
iii. reticular fibers – supporting tissue fibers
- agyrophilic fibers, stain on methenamine silver
- found in hematogenous organs
d. tissue cells
i. fibroblast – characteristic cell of connective tissue
- synthesizes ground matrix and collagen fibers
ii. mesenchymal cell – pluripotent, able to transform from one from to the other
- are precursor cells
- mostly found in embryo
- in adults are found in walls of blood vessels and bone marrow
iii. fat cells – adipose cells
- spherical or globular in shape
- synthesizes and stores lipids
- acts as inculators
iv. macrophages – phagocytes
- part of Monocyte-Pahgocte System (MPS)
- important in maintenance and repair of tissues and defense
against invading organism
v. lymphocytes – agranular leukocytes
- parts of the immune system
vi. plasma cells – derived from activated B lymphocytes
- “cart-wheel” in appearance
- produce antibodies or immunoglobulins
vii. mast cells – active cells of inflammation
- releases pharmacological active substance like histamine
serotonin and heparin.
viii. pigment cells – maybe a melanocyte or other forms of cells that give color to
the tissues.
e. blood and lymph vessels
f. nerve