The Foundations of Structure:

Organelles, Cells and Tissues

Medicine of the Ancients

--Interpreted through the lens of animism, superstition
--Handicapped by lack of any appreciation of physical or
functional anatomy
--Restricted by religious and social taboos which limited
physical access to patients
--No tradition of experimentalism

Medicine of the Egyptians

An ailment which I will
treat
An ailment with which
I will contend
An ailment not to be
treated

The Medicine of Hippocrates of Cos

Health is the balance of the four vital components
that comprise the body. Disease is the imbalance
of these components to the detriment of body
action. Therapy is the restoration of this balance
by altering humoral content

Blood (heart)
Phlegm (brain)
Yellow Bile (liver)
Black Bile (spleen)

Treatment from Hippocrates to 18th Century

Starve
Purge
Bleed
If patient survives treatment and is still ill, repeat
treatment until cured, cautious or dead.

The Homunculus

 Emergence of the Cell Theory

Identification of cells- Schleiden &
Schwann
Blastema-Rokitansky

Omnis cellula e cellula

Rudolf Virchow, 1858

Implications of Cell Theory

Genetics
Embryology
Biochemistry
Cellular Pathology

Organization of Structure
Cells: smallest functional unit that a larger
organism can be divided into and which retains
characteristics of life
Tissues: groups of similar cells, specialized in a
common direction and dedicated to performance
of a common function
Organs: somewhat independent portions of the
body performing specific functions
Systems: groups of organs whose functions are
integrated and coordinated

Composition of the Cell

85% water
10% protein
2 % lipid
0.4% DNA
0.7% RNA
0.4% organic compounds
0.7% inorganic compounds

Major Organelles
Biosynthetic/metabolic

Nucleus
Nucleolus
RER/polyribosomes
SER

Bioenergetic
Mitochondria
Glycogen

Structural
Microtubules
Intermediate filaments
Microfilaments

Housekeeping

--

Lysosomes
Peroxisomes
Phagosomes
Proteasomes

Barrier/Membranous
Plasma membrane
Nuclear membrane
Organelle membranes

Plasma Membrane
All cells are surrounded by a plasma membrane consisting of lipid

(phospholipids, glycolipids and cholesterol), proteins and

carbohydrates.
Lipids are polar, possessing an uncharged, hydrophobic and a
charged, hydrophilic segment. These segments spontaneously
organize, yielding a bilayered membrane.
Proteins are either anchored to a membrane lipid or fatty acid
(termed integral membrane proteins), or reside at the inner or outer
membrane surface (termed peripheral membrane proteins).
Plasma membrane receptors are proteins on or in the plasma
membrane which bind to ligands such as drugs, neurotransmitters,
endogenous proteins such as hormones.
Plasma membrane receptors can also bind infectious agents (such
as specific receptors for HIV present on certain lymphocytes).
Channels are specialized membrane proteins which allow movement
of ions, water or solutes down their electrochemical gradient.
Plasma membranes represent the interface with the extracellular
milieu, and are hence often the first organelle altered by diseases.

Plasma Membrane

Junctional Complexes

Nucleus

All mammalian cells are eukaryotic or derived from eukaryotic cells

(RBCs or platelets).
Nuclei are surrounded by two membranes. The outer membrane is
derived from the endoplasmic reticulum, the inner is unique to the
nucleus.
The nucleus contains the majority of the cells DNA, DNA-binding
proteins (histones and non-histones) and supportive proteins.
Histones control the translational activity of the DNA and hence
many facets of cell function (epigenetics).
Chromatin (DNA and histones) is present as uncoiled DNA
(euchromatin) which is translationally active, and dense, highlycoiled DNA (heterochromatin), believed to be largely inactive.
RNA is localized to the nucleolus.
Translated RNA leaves the nucleus through pores in the nuclear
membrane.

Mitochondrion

Site of most cellular energy metabolism through oxidative

phosphorylation
Ultimate energy product is ATP via the citric acid (Krebs) cycle
Production of ATP is dependent upon the availability of molecular
oxygen. Loss of oxygen rapidly inhibits mitochondrial ATP
production, requiring the cell to use anaerobic sources (eg.,
glycogen) for energy production
Cyanide, carbon monoxide, 2.4-DNP poison mitochondria
Number of mitochondria reflects metabolic activity of cell
Mitochondria have two membranes
Mitochondria contain high (mM) concentrations of calcium, which
may be burped from cells by mitochondrial pore transition. Also
contains cytochrome c and proteins involved in the apoptotic cell
death pathway. Release of apoptotic mediators from the
mitochondrion is termed the intrinsic cell death pathway.
Not all mitochondria within a cell are active at one time
Mitochondria contain single-stranded DNA, derived entirely from the
maternal line. This has special application in forensic pathology.

Endoplasmic Reticulum
Two general types: rough (RER), which is
involved in protein synthesis, and smooth (SER),
involved in synthesis and metabolism of
steroids, drug metabolism and regulation of
calcium
Consists of networks of tubules and vesicles
RER is decorated with ribosomes which are
present on the outside of the organelle. Loss of
ribosomes will disturb protein synthesis,
particularly of proteins destined for export from
the cell
SER consists of aggregates of small vesicles.
SER can proliferate when stimulated, as occurs
frequently with use of drugs requiring metabolic
activation or detoxification

Golgi Apparatus
Stack of vesicular membranes involved in
posttranslational modification (phosphorylation,
glycosylation) and packaging of proteins and
lipids following synthesis
Proteins leaving RER are transferred to Golgi for
modification
Golgi apparatus produces vesicles destined for
extracellular release and lysosomes

Golgi Apparatus

Lysosomal System
Lysosomes arise from the Golgi apparatus and are
associated with the digestion of cellular debris and
extracellular invaders (eg., bacteria)
Lysosomes contain acid hydrolases, lipases, proteases,
nucleases and amylase
Lysosomal enzymes are largely inactive at physiologic
pH (~7.42). They are activated when the interior of the
lysosome becomes acidic (particularly <5.0)
Leakage of lysosomal enzymes into the cytoplasm is
associated with severe cell injury
Many inborn errors of metabolism involving lysosomes
result in genetic diseases (eg., Tay-Sachs, Pompes)

Lysosome

Proteasome/Ubiquitin System

Relatively newly described system critical for the proteolytic

degradation of proteins and other housekeeping chores
Protein destruction is a multistep process involving tagging of
protein with ubiquitin by means of a ubiquitin ligase
Tagged protein is directed to the proteasome. The protein
undergoes proteolytic destruction while the ubiquitin tags are
recycled
Defects in the proteasome/ubiquitin system are implicated in many
diseases, notable those in which misfolded proteins accumulate
(eg., Alzheimers disease), and in the process of apoptotic cell death
Proteasome inhibiting drugs are used in cancer chemotherapy

Proteosome

Cytoskeleton
Network of filamentous proteins seen in all eukaryotic
cells
Comprised of three broad classes of proteins:
microtubules, intermediate filaments and microfilaments,
differing by molecular structure and size
Microtubules are the largest and most dynamic. Many
MTs have a lifespan measured in seconds to minutes.
MTs are critical for cell division, transport of materials
within the cell and cell motility
Intermediate filaments help maintain cell structure,
transport and dynamic functions such as contraction
Microfilaments serve to reinforce the plasma membrane
and as a scaffold for internal structure. They also
function in cell contraction

Organ Elements
Epithelia:

cells which perform the basic function of

an organ. Derived from ectoderm or endoderm. Situated
on basement membrane, epithelia generally lack an
independent blood supply.

Stroma: cells that provide support and maintenance of

epithelia. Derived from mesoderm.

Embryonic Origin of Tissues

Functions of Epithelia

Protection-epidermis
Transport-bronchi
Secretion-sweat glands
Excretion-kidney
Absorption-gastrointestinal tract
Lubrication-rectum
Sensory input-touch endings
Reproduction-ovaries/testes

Connective Tissues
Connective
Loose
Strong
Hematopoietic

Muscle
Skeletal
Cardiac
Smooth

Hematopoietic Tissue

Neural Cells and Derivatives

Neurons (the parenchymal unit of the
nervous system)
Glial cells
Astrocytes
Oligodendroglia
Microglia
Ependyma

Terminology in Medicine
Primarily Greek and Latin roots-eg., nephro-,
pneumo-, osteo Suffix defines process; prefix is descriptor, core is
the organ/structure
eg. oma (tumor) lipoma, myxoid liposarcoma
--itis (inflammation) bronchitis, nephritis
--iasis (process) cholelithiasis
--plasia (growth/formation) neoplasia
--orrhea (flow) diarrhea, dysmenorrhea