Lecture # 23
CELL INJURY & RESPONSE-6
Dr. Iram Sohail
Assistant Professor
Pathology
College of Medicine
Majmaah University
OBJECTIVES
• Discuss intracellular accumulation
– (fat, cholesterol, protein, glycogen, pigments)
• Discuss pathological calcification
• Discuss cellular ageing
INTRACELLULAR ACCUMULATION
• Cell may accumulate abnormal amount of
various substances, which may harmless or
harmful to cell.
• There are 3 pathways of intracellular
accumulation.
1. A normal substance is producing in normal or
increased rate, but the metabolic rate is
inadequate to remove it.
• Example
– Fatty liver
2. A normal or abnormal endogenous substance
is accumulating in the cell because of defects
in folding, packaging, transport or secretion.
• Example
– Alpha 1 antitrypsin deficiency
3. An abnormal exogenous substance is
depositing in the cell because cell does not
have enzymes to degrade it.
• Example
– Silica
– carbon
1. FATTY CHANGE
• Accumulation of triglyceride (fat) in liver,
kidney, heart and skeletal muscle cells.
Causes
• Toxin (CCL4)
• Protein malnutrition
• Diabetes mellitus
• Obesity
• Alcohol
Mechanism
Morphology
i.
Liver
Grossly
– Large, yellow, greasy
Microscopically
– Clear vacuoles in liver cells
– Special stains used oil red O, Sudan IV
ii. Heart
Grossly
– Tigered effect
Microscopically
– Clear vacuoles in heart cells
2. CHOLESTROL AND CHOLESTROL ESTERS
In atherosclerosis
• Cholesterol will accumulate in the smooth
muscle cells and macrophages of
atherosclerotic plaque.
In xanthoma
• Macrophages filled with cholesterol will
accumulate in skin.
3. PROTEINS
Nephrotic syndrome
• In nephrotic syndrome, because of increase
leakage of protein through glomerulus, the
protein will accumulate in proximal
convoluted tubules.
Alcoholic liver disease
• In alcoholics, Mallory body (protein) will
accumulate in liver cells.
Alzheimer’s disease
• Neurofibrillary tangles (protein) will deposit in
brain cells.
4. GLYCOGEN
• In diabetes mellitus, the glucose or glycogen
will accumulate in heart, pancreas and kidney.
• In glycogen storage disorders, glycogen will
accumulate in different cells of body.
PIGMENTS
• Pigments are colored substances.
They can be
• Exogenous
Or
• Endogenous
Exogenous
Carbon
– The most common exogenous pigment is carbon.
– Coal mine workers and urban residents may have
increased amount of carbon in their lungs and
causes lung diseases.
Endogenous
i. Melanin
• It is a brown black pigment, present in skin
and save us from harmful ultraviolet rays of
sun.
ii. Lipofuscin
• It is a brown yellow, wear & tear pigment,
accumulates in different tissue of body in old
age or in atrophy.
iii. Hemosiderin
• It is a hemoglobin derived, golden yellow to
brown pigment, accumulates in iron overload
conditions (like hemosiderosis,
hemochromatosis).
PATHOLOGICAL CALCIFICATION
• It is the abnormal deposition of calcium salt
together with small amounts of iron,
magnesium and other minerals.
• There are 2 types of calcifications
1. Dystrophic calcification
2. Metastatic calcification
1. Dystrophic calcification
• It occurs in dead dying tissue(necrotic tissue)
in the presence of normal levels of calcium.
Examples
– In atheroma of atherosclerosis
• In damaged heart valves
• In ageing
Morphology
Gross
– White, gritty granules or clumps
Microscopy
• Basophilic (purple) deposits (sometimes bone
can be seen in calcified focus)
2. Metastatic calcification
• It occurs in normal tissue in the presence of
hypercalcemia (increased blood calcium
levels).
There are 4 major cause of hypercalcemia
I. Increased secretion of parathyroid hormone
II. Destruction of bone (in Paget disease, tumor,
immobilization)
III. Vitamin D related disorders (vit.D
intoxication)
IV. Renal failure
Morphology
• The morphology will be same as dystrophic
calcification.
• In kidney ------ nephrocalcinosis
Aging
• Cellular ageing is the result of a progressive
decline in the proliferative capacity and life
span & the effects of continuous exposure to
exogenous factors that cause accumulation of
cellular and molecular damage.
Mechanisms
There are three mechanisms
1. DNA Damage
– Cellular ageing is associated with,
• Reduced capacity of cells to divide (replicative
senescence)
• Telomeres are short repeated sequences of
DNA present at both ends of chromosomes &
protecting the ends from fusion and
degradation.
• With each replication, the telomere becomes
shortened.
• The length of the telomere is maintained by
an enzyme called telomerase.
• Because of decreasing amount of telomerase
in old age, progressive shortening of
chromosomal ends (telomeres) occurs.
2. Reduced regenerative capacity of tissue
stem cells
• With age, P16 (inhibitor of cell cycle
progression) accumulates in cell and causes
loss of self-renewal capacity of cells.
3. Accumulation of metabolic damage
For example
• Reactive oxygen species will accumulate in cell
4. Increasing DNA damage
• This DNA damage is caused by free radicles.
DNA damage is mostly repaired by DNA repair
enzymes but sometimes persists and cause
cellular aging.
• It is proposed that calorie restriction can
prolonged life span.
• Werner syndrome is a syndrome which is
associated with premature aging.
Summary of Aging