Pathophysiology - The Cytoplasm and Its Organelles

The Cytoplasm and Its Organelles:
The cytoplasm surrounds the nucleus, and it is in the
cytoplasm that the work of the cell takes place. Embedded
in the cytoplasm are various membrane-enclosed
compartments (endoplasmic reticulum, Golgi apparatus,
mitochondria, lysosomes) that function as the organs of
the cells. Most organelles are surrounded by one or two lipid membranes, similar to plasma membrane, that separate
the organelles from the cytosol.
Ribosomes, Endoplasmic Reticulum,
and Golgi Apparatus
The ribosomes, endoplasmic reticulum, and Golgi apparatus
represent the primary sites of protein synthesis in
the cell (Fig. 1-4). Because these organelles lack direct
communication with the cytosol, they use transport vesicles
to move newly synthesized proteins, membrane components,
and soluble molecules from one organelle to
another. These transport vesicles bud off from the membrane
of one organelle and fuse with another, carrying
the transported material.
Ribosomes(definition and it functions): The ribosomes are small particles of nucleoproteins
(rRNA and proteins) that are held together by
a strand of mRNA to form polyribosomes (also called
polysomes). Polysomes exist as isolated clusters of free
ribosomes within the cytoplasm or attached to the membrane
of the endoplasmic reticulum (Fig. 1-4). Free ribosomes
are involved in the synthesis of proteins, mainly
enzymes that aid in the control of cell function, whereas
those attached to the endoplasmic reticulum translate
mRNAs that code for proteins secreted from the cell
or stored within the cell (e.g., granules in white blood
cells).
Endoplasmic Reticulum(definition and it functions) : The endoplasmic reticulum
(ER) is an extensive system of paired membranes and
flat vesicles that connect various parts of the inner cell (Fig. 1-4). Between the paired ER membranes is a fluidfilled
space called the matrix. The matrix connects the
space between the two membranes of the nuclear envelope,
the cell membrane, and various cytoplasmic
organelles. It functions as a tubular communication system
for transporting various substances from one part of
the cell to another. A large surface area and multiple
enzyme systems attached to the ER membranes also provide
the machinery for a major share of the cell’s metabolic
functions.
Two forms of ER exist in cells: rough and smooth.
Rough ER is studded with ribosomes attached to specific
binding sites on the membrane. The ribosomes,
with the accompanying strand of mRNA, synthesize
proteins. Proteins produced by the rough ER are usually
destined to be incorporated into cell membranes, used
in the generation of lysosomal enzymes, or exported
from the cell. The rough ER segregates these proteins
from other components of the cytoplasm and modifies
their structure for a specific function. For example, the
production of plasma proteins by liver cells takes place
in the rough ER.
The smooth ER is free of ribosomes and is continuous
with the rough ER. It does not participate in protein synthesis;
instead, its enzymes are involved in the synthesis
of lipid molecules, regulation of intracellular calcium,
and metabolism and detoxification of certain hormones
and drugs. It is the site of lipid, lipoprotein, and steroid
hormone synthesis. The sarcoplasmic reticulum of skeletal
and cardiac muscle cells is a form of smooth ER. Calcium
ions needed for muscle contraction are stored and
released from cisternae of the sarcoplasmic reticulum.
The smooth ER of the liver is involved in glycogen storage
and metabolism of lipid-soluble drugs.
Golgi Apparatus(definition and it functions): The Golgi apparatus, sometimes
called the Golgi complex, consists of stacks of thin, flattened
vesicles or sacs (see Fig. 1-4). These Golgi bodies
are found near the nucleus and function in association
with the ER. Substances produced in the ER are carried
to the Golgi complex in small, membrane-covered transport
vesicles. Many cells synthesize proteins that are
larger than the active product. The Golgi complex modifies
these substances and packages them into secretory
granules or vesicles. Insulin, for example, is synthesized
as a large, inactive proinsulin molecule that is cut apart
to produce a smaller, active insulin molecule within the
Golgi complex of the beta cells of the pancreas. In addition
to producing secretory granules, the Golgi complex
is thought to produce large carbohydrate molecules that
combine with proteins produced by the rough ER to form glycoproteins.

Figure 1-4. Three-dimensional view of the rough and the
smooth endoplasmic reticula (ER) and the Golgi apparatus. The
ER functions as a tubular communication system through
which substances can be transported from one part of the cell
to another and as the site of protein (rough ER), carbohydrate,
and lipid (smooth ER) synthesis. Most of the proteins synthesized
by the rough ER are sealed into transfer vesicles and
transported to the Golgi apparatus, where they are modified
and packaged into secretory granules.






Lysosomes(definition and it functions):
The lysosomes, which can be viewed as the digestive
organelles of the cell, are small, membrane-enclosed sacs
filled with hydrolytic enzymes. These enzymes can break
down excess and worn-out cell parts as well as foreign
substances that are taken into the cell. All of the lysosomal
enzymes are acid hydrolases, which means that they
require an acid environment. The lysosomes provide this
environment by maintaining a pH of approximately 5.0
in their interior. The pH of the cytosol and other cellular
components is approximately 7.2 and are therefore protected
from escaped lysosomal enzymes. Like all other
cellular organelles, lysosomes not only contain a unique
collection of enzymes, but also have a unique surrounding
membrane that prevents the release of its digestive
enzymes into the cytosol.
Lysosomes are formed from digestive vesicles called
endosomes. These vesicles fuse to form multivesicular
bodies called early endosomes (Fig. 1-5). The early endosomes
mature into late endosomes as they recycle lipids,
proteins, and other membrane components back to the
plasma membrane in vesicles called recycling vesicles.
Lysosomal enzymes are synthesized in the rough ER and
then transported to the Golgi apparatus, where they are
biochemically modified and packaged for transport to
the endosomes. The late endosomes mature into lysosomes
as they progressively accumulate newly synthesized
acid hydrolases from the Golgi apparatus.
Depending on the nature of the substance, different
pathways are used for lysosomal degradation of unwanted
materials. Small extracellular particles such as extracellular
proteins and plasma membrane proteins form endocytotic
vesicles after being internalized by endocytosis and
receptor-mediated endocytosis (Fig. 1-5A). These vesicles
are converted into early and late endosomes, after which
they mature into lysosomes as they accumulate newly synthesized hydrolases and vesicular proton pumps.
Large extracellular particles such as bacteria, cell debris,
and other foreign particles are engulfed in a process
called phagocytosis (Fig. 1-5B). A phagosome, formed as
the material is internalized within the cell, fuses with a
lysosome to form a phagolysosome. Intracellular particles,
such as entire organelles, cytoplasmic proteins, and
other cellular components, are engulfed in a process
called autophagy (Fig. 1-5C). These particles are isolated
from the cytoplasmic matrix by endoplasmic reticulum
membranes to form an autophagosome, which then fuses
with a lysosome to form an autophagolysosome.
Although the lysosomal enzymes can break down
most proteins, carbohydrates, and lipids to their basic constituents, some materials remain undigested. These
undigested materials may remain in the cytoplasm as
residual bodies or be extruded from the cell. In some
long-lived cells, such as neurons and heart muscle cells,
large quantities of residual bodies accumulate as lipofuscin
granules or age pigments. Other indigestible pigments,
such as inhaled carbon particles and tattoo
pigments, also accumulate and may persist in residual
bodies for decades.
Lysosomes are also repositories where cells accumulate
abnormal substances that cannot be completely
digested or broken down. In some inherited diseases
known as lysosomal storage diseases, a specific lysosomal
enzyme is absent or inactive, in which case the digestion
of certain cellular substances (e.g., glucocerebrosides,
gangliosides, sphingomyelin) does not occur. As a result,
these substances accumulate in the cell. In Tay-Sachs disease
(see Chapter 6), an autosomal recessive disorder,
hexosaminidase A, which is the lysosomal enzyme
needed for degrading the GM2 ganglioside found in nerve
cell membranes, is absent. Although the GM2 ganglioside
accumulates in many tissues, such as the heart, liver,
and spleen, its accumulation in the nervous system and
retina of the eye causes the most damage.

Figure 1-5. Pathways for digestion of materials by lysosomes.
(A) Receptor-mediated endocytosis with formation of
lysosomes from early and late endosomes. Vesicle contents are
sorted in the early endosome with receptors and lipids being
sent back to the membrane. Transport vesicles carry lysosomal
enzymes to the late endosomes, converting them into lysosomes
that digest proteins and other components acquired
from the endocytotic vesicles. (B) Phagocytosis involving the
delivery of large extracellular particles such as bacteria and
cellular debris to the lysosomes via phagosomes. (C)
Autophagy is the process in which worn-out mitochondria and
other cell parts are surrounded by a membrane derived from
the rough endoplasmic reticulum (RER). The resulting
autophagosome then fuses with a lysosome to form an
autophagolysosome. Undigested material may be extruded
from the cell or remain in the cytoplasm as lipofuscin granules

or membrane-bound residual bodies.

Peroxisomes (definition and it functions):
Smaller than lysosomes, spherical membrane-bound
organelles called peroxisomes contain a special enzyme
that degrades peroxides (e.g., hydrogen peroxide). Peroxisomes
function in the control of free radicals (see Chapter
2). Unless degraded, these highly unstable chemical
compounds would damage other cytoplasmic molecules.
Peroxisomes also contain the enzymes needed for breaking
down very–long-chain fatty acids, which are ineffectively
degraded by mitochondrial enzymes. In liver cells,
peroxisomal enzymes are involved in the formation of the
bile acids.
Proteasomes (definition and it functions):
Proteasomes are small compartmentalized protein complexes
that are responsible for proteolysis of malformed
and misfolded proteins. The process of cytosolic proteolysis
is carefully controlled by the cell and requires that
the protein be targeted for degradation. This process
involves ubiquitination, a process whereby several small
ubiquitin molecules (small 76-amino-acid polypeptide
chain) are attached to an amino acid residue of the targeted
protein. Once a protein is so tagged, it is degraded
by proteasomes. After the targeted protein has been
degraded, the resultant amino acids join the intracellular
pool of free amino acids and the ubiquitin molecules are
released and recycled.
Mitochondria (definition and it functions):
The mitochondria are literally the “power plants” of the
cell because they transform organic compounds into
energy that is easily accessible to the cell. They do not
make energy, but extract it from organic compounds.
Mitochondria contain the enzymes needed for capturing most of the energy in foodstuffs and converting it into
cellular energy. This multistep process requires oxygen
and is often referred to as aerobic metabolism. Much of
this energy is stored in the high-energy phosphate bonds
of compounds such as adenosine triphosphate (ATP) that
power the various cellular activities. Mitochondria are
found close to the site of energy consumption in the cell
(e.g., near the myofibrils in muscle cells). The number of
mitochondria in a given cell type is largely determined by
the type of activity the cell performs and how much
energy is needed to undertake the activity. For example,
a dramatic increase in mitochondria occurs in skeletal
muscle repeatedly stimulated to contract.
The mitochondria are composed of two membranes:
an outer membrane that encloses the periphery of the
mitochondrion and an inner membrane that forms
shelflike projections, called cristae (Fig. 1-6). The narrow
space between the outer and inner membranes is
called the intermembrane space, whereas the large space
enclosed by the inner membrane is termed the matrix
space. The outer mitochondrial membrane contains a
large number of transmembrane porins, through which
water-soluble molecules may pass. The inner membrane
contains the respiratory chain enzymes and transport
proteins needed for the synthesis of ATP. In certain
regions, the outer and inner membranes contact each
other; these contact points serve as pathways for proteins
and small molecules to enter and leave the matrix
space.

Pathophysiology - Definition and functions of the Nucleus.

The nucleus of a nondividing cell appears as a rounded
or elongated structure situated near the center of the cell
(see Fig. 1-1). It is enclosed in a nuclear envelope and contains chromatin, the genetic material of the nucleus,
and a distinct region called the nucleolus. All eukaryotic
cells have at least one nucleus (prokaryotic cells, such as
bacteria, lack a nucleus and nuclear membrane).
The nucleus can be regarded as the control center for the
cell. It contains the deoxyribonucleic acid (DNA) that is
essential to the cell because its genes encode the information
necessary for the synthesis of proteins that the cell must produce
to stay alive. The genes also represent the individual
units of inheritance that transmit information from one generation
to another. The nucleus also is the site for the synthesis
of the three types of ribonucleic acid (messenger
RNA, ribosomal RNA, and transfer RNA) that move to
the cytoplasm and carry out the actual synthesis of proteins.
Messenger RNA (mRNA) copies and carries the DNA
instructions for protein synthesis to the cytoplasm; ribosomal
RNA (rRNA) is the site of protein synthesis; and transfer
RNA (tRNA) transports amino acids to the site of
proteins synthesis for incorporation into the protein being
synthesized (see Chapter 5).
The complex structure of DNA and DNA-associated
proteins dispersed in the nuclear matrix is called chromatin.
Depending on its transcriptional activity, chromatin
may be condensed as an inactive form of chromatin
called heterochromatin or extended as a more active
form called euchromatin. Because heterochromatic
regions of the nucleus stain more intensely than regions
consisting of euchromatin, nuclear staining can be a
guide to cell activity. The nucleus also contains the darkly
stained round body called the nucleolus. Nucleoli are
structures composed of regions from five different chromosomes,
each with a part of the genetic code needed
for the synthesis of rRNA, which is transcribed exclusively
in the nucleolus. Cells that are actively synthesizing
proteins can be recognized because their nucleoli are
large and prominent and the nucleus as a whole is
euchromatic or slightly stained.
Surrounding the nucleus is the nuclear envelope
formed by an inner and outer nuclear membrane containing
a perinuclear cisternal space between them (Fig.
1-3). The inner nuclear membrane is supported by a rigid
network of protein filaments attached to its inner surface,
called nuclear lamina, that bind to chromosomes
and secure their position in the nucleus. The outer
nuclear membrane resembles the membrane of the endoplasmic
reticulum and is continuous with it. The nuclear
envelope contains many structurally complex circular
pores where the two membranes fuse to form a gap filled
with a thin protein diaphragm. Many classes of molecules,
including fluids, electrolytes, RNA, some proteins,
and hormones, can move in both directions through the
nuclear pores.

Figure 1-3. Schematic drawing of the inner and outer membranes
of the nuclear envelope. The double-membrane envelope
is penetrated by pores in which nuclear pore complexes
are positioned and continuous with the rough endoplasmic
reticulum. The nuclear lamina on the surface of the inner
membrane bind to DNA and hold the chromosomes in place.

Pathophysiology - The Functional Organization of the Cell

■ Cells are the smallest functional unit of the
body. They contain structures that are strikingly
similar to those needed to maintain total body
function.
■ The nucleus is the control center for the cell. It
also contains most of the hereditary material.
■ The organelles, which are analogous to the organs
of the body, are contained in the cytoplasm. They
include the mitochondria, which supply the energy
needs of the cell; the ribosomes, which synthesize
proteins and other materials needed for cell function;
and the lysosomes and proteosomes, which
function as the cell’s digestive system.
■ The cell membrane encloses the cell and provides
for intracellular and intercellular communication,
transport of materials into and out of the
cell, and maintenance of the electrical activities
that power cell function.

Pathophysiology - Definition and functions of the Plasma (Cell) Membrane.

In many respects, the plasma membrane (also called the
cell membrane) is one of the most important parts of the
cell. It acts as a semipermeable structure that separates
the intracellular and extracellular environments. It controls
the transport of materials from the extracellular fluids
to the interior of the cell, provides receptors for
hormones and other biologically active substances, participates
in the generation and conduction of electrical
currents that occur in nerve and muscle cells, and aids in
the regulation of cell growth and proliferation.
The cell membrane is a dynamic and fluid structure
consisting of an organized arrangement of lipids, carbohydrates,
and proteins (Fig. 1-2). A main structural
component of the membrane is its lipid bilayer. It is a
bimolecular layer that consists primarily of phospholipids,
with glycolipids and cholesterol. This lipid
bilayer provides the basic fluid structure of the membrane
and serves as a relatively impermeable barrier to
all but lipid-soluble substances. Approximately 75% of
the lipids are phospholipids, each with a hydrophilic
(water-soluble) head and a hydrophobic (water-insoluble)
tail. Phospholipid molecules along with the glycolipids
are aligned such that their hydrophilic heads face
outward on each side of the membrane and their
hydrophobic tails project toward the middle of the
membrane. The hydrophilic heads retain water and help
cells stick to each other. At normal body temperature,
the viscosity of the lipid component of the membrane is
equivalent to that of olive oil. The presence of cholesterol
stiffens the membrane.
Although the lipid bilayer provides the basic structure
of the cell membrane, proteins carry out most of the specific functions. The integral proteins span the entire lipid
bilayer and are essentially part of the membrane. Because
most of the integral proteins pass directly through the
membrane, they are also referred to as transmembrane
proteins. Other proteins, called the peripheral proteins,are bound to one or the other side of the membrane and
do not pass into the lipid bilayer.
The manner in which proteins are associated with the
cell membrane often determines their function. Thus,
peripheral proteins are associated with functions involving
the inner or outer side of the membrane where they
are found. Several peripheral proteins serve as receptors
or are involved in intracellular signaling systems. By contrast,
only the transmembrane proteins can function on
both sides of the membrane or transport molecules
across it. Many integral transmembrane proteins form
the ion channels found on the cell surface. These channel
proteins have a complex morphology and are selective
with respect to the substances they transmit.
A fuzzy-looking layer, called the cell coat or glycocalyx,
surrounds the cell surface. The structure of the cell
coat consists of long, complex carbohydrate chains
attached to protein molecules that penetrate the outside
portion of the membrane (i.e., glycoproteins); outwardfacing
membrane lipids (i.e., glycolipids); and carbohydrate-
binding proteins called lectins. The cell coat
participates in cell-to-cell recognition and adhesion. It
contains tissue transplant antigens that label cells as self
or nonself. The cell coat of a red blood cell contains the
ABO blood group antigens. An intimate relationship
exists between the cell membrane and the cell coat.

Figure 1-2. Structure of the plasma (cell) membrane, showing the hydrophilic (polar) heads and
the hydrophobic (fatty acid) tails (inset) and the position of the integral and peripheral proteins in
relation to the interior and exterior of the cell.

Pathophysiology - Functional Components of the Cell

Functional Components of the Cell
The Plasma (Cell) Membrane
The Nucleus
The Cytoplasm and Its Organelles
Ribosomes, Endoplasmic Reticulum, and Golgi
Apparatus
Lysosomes
Peroxisomes
Proteasomes
Mitochondria
The Cytoskeleton
Microtubules
Microfilaments
Cell Metabolism and Energy Storage
Anaerobic Metabolism
Aerobic Metabolism
Integration of Cell Function
Cell Communication Mechanisms
Cell Surface Receptors
Intracellular Receptors
Membrane Transport Mechanisms
Diffusion
Active Transport
Vesicular Transport
Generation of Membrane Potentials
Body Tissues
Embryonic Origin of Tissue Types
Epithelial Tissue
Simple Epithelium
Stratified and Pseudostratified Epithelium
Glandular Epithelium
Epithelial Cell Renewal
Connective Tissue
Loose Connective Tissue
Adipose Tissue
Reticular and Dense Connective Tissue
Muscle Tissue
Skeletal Muscle
Smooth Muscle
Nervous Tissue
Extracellular Tissue Components
Cell Junctions
Extracellular Matrix

Cell Adhesion Molecules

 Although diverse in their organization, all eukaryotic
cells (cells with a true nucleus) have in common structures
that perform unique functions. Seen under a light
microscope, three major components of the eukaryotic
cell become evident: the plasma membrane, the nucleus,

and the cytoplasm (Fig. 1-1).

The living part of the cell is called protoplasm. Protoplasm
is composed of water, proteins, lipids, carbohydrates,
and electrolytes. Two distinct regions of protoplasm
exist in the cell: the cytoplasm, which lies outside the
nucleus, and the nucleoplasm, which lies inside the
nucleus. The bulk of the cytoplasm is water, in which
inorganic and organic chemicals are dissolved. This fluid
suspension is called the cytosol. The cytosol contains
membrane-enclosed compartments or organelles that
perform distinctive functions. In addition to the
organelles, the cytosol contains a system of tubules and
filaments known as the cytoskeleton that maintains the
shapes of cells and their ability to move. Cells also contain
inclusions, which consist of metabolic by-products,
storage forms of various nutrients, and inert crystals and

pigments.

Pathophysiology - Definition - What is cell and it functions?

The cell is the smallest functional unit that an organism
can be divided into and retain the characteristics necessary
for life. Cells with similar embryonic origin or
function are often organized into larger functional units
called tissues. These tissues in turn combine to form the
various body structures and organs. Although the cells
of different tissues and organs vary in structure and function,
certain characteristics are common to all cells. Cells
are remarkably similar in their ability to exchange materials
with their immediate environment, obtain energy
from organic nutrients, synthesize complex molecules,
and replicate themselves. Because most disease processes
are initiated at the cellular level, an understanding of cell
function is crucial to understanding the disease process.
Some diseases affect the cells of a single organ, others
affect the cells of a particular tissue type, and still others
affect the cells of the entire organism.

Figure 1-1 : composite cell designed to show in one cell all of the various components of the nucleus and cytoplasm.