Cell Pathology

Pr. Peivand Pirouzi

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 Cell Injury

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http://cmapspublic2.ihmc.us/rid=1GM0B8Y47-W70KG4-1GNF/cell%20injury.cmap
Outline of Cell Pathology
• Structure & function of normal cell
• Integration & coordination of cell function; response to injury
• Reversible; Irreversible
• Cell adaptations
• Atrophy, hypertrophy, metaplasia, intracellular, accumulation,
aging
• Cell death
• Necrosis, apoptosis

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What Is a cell?
• Basic functional unit of the body
• Consists of smaller functional units called organelles (can be
seen with electron microscope)

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Structure & Function of a Cell
• Nucleus
• Cytoplasm
• Mitochondria
• Ribosome
• Endoplasmic reticulum
• Golgi apparatus
• Lysosome
• Cytoskeleton
• Plasma membrane

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 Structures of Normal Cell

http://www.google.com/imgres?q=structure+of+a+cell&um=1&hl=en&safe=off&client=aff-maxthon-newtab&channel=t2&biw=1316&bih=655&tbm=isch&tbnid=uvTMb34PL6gmPM:&imgrefurl=http://notesforpakistan.blogspot.com/2010/10/structure-and- 6
function-of-nucleus-
in.html&docid=9q00PCToH0r4MM&imgurl=http://4.bp.blogspot.com/_guSOnFRs_Ks/TLmKaC08CWI/AAAAAAAAAOs/BhPcXe_IgBI/s1600/cell_structure_001.jpg&w=640&h=480&ei=iVVPUMq3OuLc0QGwmYCgBA&zoom=1&iact=hc&vpx=378&vpy=191
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 The Nucleus
• Essential component of most living cells
• Contains DNA, RNA, nuclear proteins
• Major components seen by electron microscope:
• Nuclear membrane
• Chromatin (during mitosis becomes chromosomes)
• Nucleolus

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 Gene Expression

http://www.google.com/imgres?q=gene+expression+mrna&num=10&um=1&hl=en&safe=off&client=aff-maxthon- 8
newtab&channel=t2&biw=1316&bih=655&tbm=isch&tbnid=YkE3ibYS83wRpM:&imgrefurl=http://www.brighthub.com/science/genetics/articles/53514.aspx&docid=1YSPLwf8A7Vf4M&imgurl=http://img.
bhs4.com/a3/5/a35067eef2829818d543688ebe91eb128c0031cd_large.jpg&w=600&h=600&ei=SVZPULakI6jq0gH1xYD4Aw&zoom=1&iact=hc&vpx=181&vpy=136&dur=1322&hovh=225&hovw=225&t
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 Components of Cytoplasm

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http://www.enotes.com/topic/Endomembrane_system
Cytoplasmic Organelles
• Mitochondria: “powerhouse” of cell
• Ribosomes
• Endoplasmic reticulum (ER)
• Golgi apparatus
• Lysosomes

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 Lysosomes
• Membrane-
bound digestive
organelle
• Originate from
enzymes in Golgi
apparatus walls
• Give rise to
residual bodies
(lipofusion)

http://bioserv.fiu.edu/~walterm/FallSpring/review1_fall05_chap_cell3.htm 11
 Lipofusion
• Brown pigment composed of oxidized lipids
• Also known as “brown fat of aging”
• “Undigested complex lipids”
• Accumulates in aging tissues

Lipofusion in cardiac myocytes - golden

brown cytoplasmic granules derived from
cell membrane breakdown. accumulates
gradually in long-lived differentiated cells

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http://quizlet.com/6332065/pathology-case-series-1-flash-cards/
Cytoskeleton

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 Cytoskeleton

• Functions:
• Cell shape
• External pressure, cell movement
• Consist of three types of filaments:
1. Microtubules (22 nm): composed of tubulin
2. Microfilaments (5 nm): composed of actin and
myosin
3. Intermediate filaments (10 nm): composed of cell-
specific proteins
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http://photos.brentwood.bc.ca/v/Chemistry/2011Bio12/Cytoskeleton.jpg.html?g2_imageViewsIndex=5
 Plasma Membrane
• outer surface of cell
• Composed of proteins, lipids, carbohydrates
• Bilayer surface
• Internal
• External

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http://byallohgee.wikispaces.com/Cell+Membrane
 Interaction of Cells with Other Cells

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http://pgqb.blogspot.ca/2011/09/hormonal-feedback-regulatory-systems.html
Equilibrium of Cell
• Steady state maintained between cell & its surrounding

• Equilibrium = homeostasis

• External stimuli can alter homeostasis

• Imbalance in homeostasis can cause:

• Cell injury
• Cell death

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Steady State (Homeostasis)

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Cell Injury
• Reversible cell injury
• Cellular swelling
• Irreversible cell injury
• Cell death

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 Cell Injury

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http://cmapspublic2.ihmc.us/rid=1GM0B8Y47-W70KG4-1GNF/cell%20injury.cmap
 Substances in and out
through the membrane
• Necessities for the Movement
of Substances across the
Plasma Membrane

• To transport nutrients into the

cell
• For gases exchange
• To excrete metabolic waste
• To maintain the pH value and
ionic concentration of the cell

http://spmbiology403.blogspot.ca/2008/08/ 21
plasma-membrane.html
Causes of Cell Injury
• Hypoxia
• Anoxia*
• Microbes
• Inflammation
• Immune reactions
• Genetic & metabolic disorders

*Hypoxia refers to low oxygen, usually less than 2 mg/L of

dissolved oxygen (DO) in aquatic ecosystems, while anoxia
means a complete absence or total lack of oxygen. Only those
organisms that can live without oxygen (such as some
microbes) are residents of anoxic zones.

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Cell Hypoxia
• Cellular swelling (which is associated
with hypertrophy) is due to cellular
hypoxia, which damages the sodium-
potassium membrane pump. This in turn
changes the intracellular electrolyte
balance with an influx of fluids into the
cell, causing it to swell.

• Cell swelling is reversible when the cause

has been eliminated.

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 Hypoxic conditions

Hypoxia, or lack of oxygen to tissue,

is a common underlying factor in
morbidity and mortality for numerous
serious medical conditions. 

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Anoxic conditions
• Anemic Anoxia:  blood that cannot carry sufficient oxygen to the brain:
• lung disease
• chronic anemia

• Toxic Anoxia:  toxins prevent the blood’s oxygen from being used efficiently
• carbon monoxide poisoning

• Stagnant Anoxia:  or hypoxic-ischemic encephalopathy (HIE) or hypoxic-ischemic

injury (HII), caused by internal condition that blocks sufficient blood from reaching
the brain.
• Strokes
• heart attacks
• anesthesia accidents
• newborn babies deprived of oxygen during birth due to obstetrical malpractice during delivery,
hypoxic-ischemic injury, resulting in neonatal encephalopathy or cerebral palsy birth injuries

• Anoxic Anoxia:  Caused by insufficient oxygen in the air, as for example in high
altitudes. 25
Oxygen Radicals
• Hydrogen peroxide
• Superoxide
• Hydroxyl radical

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Post perfusion Injury

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Post perfusion syndrome
• Also known as "pumphead" is a constellation
of neurocognitive impairments attributed
to cardiopulmonary bypass (CPB) during cardiac surgery.

• Symptoms include defects associated with attention,

concentration, short term memory, fine motor function,
and speed of mental and motor responses

• Reversible: High incidence of neurocognitive deficit soon

after surgery, but the deficits are often transient with no
permanent neurological impairment

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Toxic Cell Injury
• Direct toxin: heavy metals (i.e., mercury) disrupt S-S bonds –
DNA damage

• Indirect toxin: carbon tetrachloride metabolized in liver to form

carbon trichloride, which is more toxic

• Transient or reversible if stress removed

• May present diminished cellular or tissue capacity

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Cell damage from toxicity and tissue
repair

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 Microbial Pathogens
• Bacteria: produce toxins (see notes below)

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http://wwwnc.cdc.gov/eid/article/5/2/99-0206-f1.htm
Viral Cell Injury
Viruses: “exploit and
control or kill cells from
within”

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 Cell Adaptations
• Occur as result of prolonged exposure to adverse or exaggerated
normal stimuli

• Main forms of adaptation:

• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Intracellular accumulation

Plasia: development (number)

Dys: abnormal
Trophy: growth (size)
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Atrophy
• Decrease in size of cell, tissue, organ, or entire body:
• Physiologic & predictable: atrophy caused by aging
• Pathologic: lack of nutrition, chronic ischemia, denervation,
inactivity

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 Cortical Atrophy

These two brains have both had their

arachnoid membranes removed.

The top brain is normal.

The brain underneath is from a patient with

Alzheimer's disease demonstrating significant
cortical atrophy.

http://missinglink.ucsf.edu/lm/ids_104_neurodegenerative/Case1/Ca 35
se1Gross.htm
 Hypertrophy
• Hypertrophy:
enlarged cells
• Hypertrophy of
heart in
hypertension
• Hypertrophy of
skeletal muscles in
bodybuilders
• Hypertrophy often
combined with
hyperplasia

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 Hypertrophy of right
Ventricle

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http://ocw.tufts.edu/Content/50/lecturenotes/635995/636024
 Hyperplasia
• Increased number of cells in tissue or
organ

• Endometrial hyperplasia caused by estrogen

• Benign prostatic hyperplasia (BPH) in elderly

men

• Callus (corn) on hand (in some occupations)

or on heels (high-heeled shoes, tight shoes)

• Hyperplastic polyps of intestine

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Intracellular Accumulations
• Exogenous materials
• Coal particles (anthracosis)

• Endogenous metabolites
• Hemosiderin (in iron overload
condition)
• Lipids

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 Death of a Cell
• Cell death occurs in two forms:

1. Necrosis: localized death of cells or tissues in living organisms

2. Apoptosis: programmed death of single cells within living

organisms

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http://php.med.unsw.edu.au/cellbiology/index.php?title=Cell_Death_2
Necrosis versus
Apoptosis

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Class - Apoptosis versus necrosis
Apoptosis Necrosis
ischemia,trauma or ATP
Regulation genetic programmed
depletion
Control controlled uncontrolled
Cell shape skrinkage, condensed swelling

Plasma membrane integrity maintained collasped

Cellular process budding blebbing

Cellular content packaged in apoptoic bodies leakage to extracellular fluid

fragmentation, chromatin
DNA no fragmentation
condensation

Energy ATP required not required

Inflammatory response absent present
Mediator caspase caspase-independent
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Types of Necrosis
• Coagulative necrosis: most common form

• Liquefactive necrosis: in brain

• Caseous necrosis: tuberculosis

• Enzymatic fat necrosis: acute pancreatitis

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 Coagulative Necrosis
Coagulative necrosis is the most common pattern of necrosis occurring in
tissues or organs.

Its morphological pattern is primarily a consequence of protein degradation

frequently caused by ischemia where lack of oxygen causes cell death in a
localized area.

Heart Coagulative necrosis

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http://www.medflux.com/gallery/details.php?image_id=90
Liquefactive Necrosis
Liquefactive necrosis is a pattern of necrosis which occurs as a consequence of
enzymatic degradation. This is in contrast to coagulative necrosis which occurs
as a result of protein degradation.

Cerebral infarct is a form of

liquefactive necrosis in which cavity of
fluid-filled space is formed in necrotic
area.

It results from a lot of tissue

destruction, in this case the
phospholipids of the brain tissues.

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http://www.cuhk.edu.hk/med/paf/slides/necrosis/i-13.htm
Caseous Necrosis
Caseous necrosis is a form of necrosis characteristic of mycobaterial infections
and is most commonly observed in tuberculosis lesions. The term ‘caseous’
(meaning cheese-like) arises from the gross morphology of the necrotic tissue,
described to resemble crumbly yellow-white cottage cheese.

Image is of a left kidney revealing

extensive caseous (‘cheese-like’)
necrosis as a result of renal
tuberculosis.

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Enzytmatic Fat necrosis
As the name suggests, fat necrosis occurs in tissues with a high lipid
content and is primarily characterised by focal areas of fat destruction.

It is usually caused by acute pancreatitis (inflammation of the

pancreas) or by direct physical trauma to fat (for example as a result
of surgery).

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 Dry Gangrene
Dry gangrene is ischemic coagulative
necrosis (usually a limb)

Wet gangrene is gangrene and an

infection with a liquifactive
component

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http://meded.utmb.edu/pathoimages/cell_injury.htm
Patient who developed Grade 4 skin
necrosis from stereotactic body radiation
therapy

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Necrotic leg wound caused by
a brown recluse spider bite

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Treatment of Necrosis
• The underlying cause of the necrosis must be treated before the dead tissue
itself can be dealt with.

• The standard therapy of necrosis (wounds, bedsores, burns, etc.) is surgical 

removal of necrotic tissue.

• Depending on the severity of the necrosis, this may range from removal of
small patches of skin, to complete amputation of affected limbs or organs.

• Chemical removal, via an enzymatic debriding agent, is another option.

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Apoptosis

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 Cell Injury

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