CELLULAR ADAPTATION

Adaptations

are reversible changes in the number, size, phenotype, metabolic activity or functions of cells in response to changes in their environment.

• Physiologic adaptations

• Pathologic adaptations

TWO ADAPTATIONS:

adaptation to stress

An __ can progress to functionally significant cell injury if the stress is not relieved

Physiologic Adaptations

Represent responses of cells to normal stimulation by hormones or endogenous chemical mediators.

• Hormone-induced enlargement of the breast and uterus during pregnancy

• Demand of mechanical stress

Physiologic Adaptations:

Pathologic Adaptations

Responses to stress that allow cells to modulate their structure and function.

• Squamous metaplasia of bronchial epithelium in smoke

Pathologic Adaptations:

Hypertrophy

is an increase in the size of cells resulting in increase in the size of the organ.

Hypertrophy

No new cells, just bigger cells, enlarged by an increased amount of structural proteins and organelle

• Enlargement of the uterus during pregnancy

• Increased work load the striated muscle cells in both skeletal and heart

Physiologic Cellular Hypertrophy:

Pathologic Cellular Hypertrophy

Cardiac enlargement that occurs with hypertension or aortic valve disease

gravid uterus

removed for postpartum bleeding

Small spindle-shaped uterine smooth muscle cells from a normal uterus.

NORMAL UTERUS:

large, plump hypertrophied smooth muscle cells from a gravid uterus

GRAVID UTERUS:

The type of reversible injury is ischemia, and the irreversible injury is ischemic coagulative necrosis.

The type of reversible injury is ___, and the irreversible injury is ___

2 cm (normal, 1–1.5 cm)

In myocardial hypertrophy , the left ventricular wall is thicker than __

triphenyltetrazolium chloride

an enzyme substrate that colors viable myocardium magenta

enzyme loss after cell death.

failure to stain a triphenyltetrazolium chloride is due to __

HYPERPLASIA

takes place if the tissue contains cell populations capable of replication

HYPERPLASIA

it may occur concurrently with hypertrophy and often in response to the same stimuli

• hormonal hyperplasia

• compensatory hyperplasia

Two types of physiologic hyperplasia:

hormonal hyperplasia

exemplified by the proliferation of the glandular epithelium of the female breast at puberty

hormonal hyperplasia

during pregnancy

compensatory hyperplasia

in which residual tissue grows after removal or loss of part of an organ.

Pathologic Hyperplasia

Occurs due to an abnormal stressor

• Benign prostatic hyperplasia

• Excessive hormonal or growth factor stimulation

• Endometrial hyperplasia

• Papillomaviruses

Pathologic Hyperplasia:

ATROPHY

Shrinkage in the size of the cell by the loss of cell substance

ATROPHY

Decreased cell and organ size as a result of decreased nutrient supply or disuse

ATROPHY

Associated with decreased synthesis and increased proteolytic breakdown of cellular organelles.

• Decreased Workload

• Diminished Blood Supply

• Inadequate Nutrition

• Aging (Senile Atrophy)

• Loss of Innervation

• Loss of Endocrine Stimulation

CAUSES OF ATROPHY

combination of decreased protein synthesis and increased protein degradation in cells.

MECHANISM OF ATROPHY:

reduced metabolic activity

Protein synthesis decreases because of __

ubiquitin-proteasome pathway

The degradation of cellular proteins occurs mainly by the __

MECHANISM OF ATROPHY

increased autophagy

PHYSIOLOGIC ATROPHY

occurs as a natural consequence of maturation

PHYSIOLOGIC ATROPHY

atrophy of the thymus and lymphoid tissues during puberty

50 years of age.

Sexual organs and brain begin to undergo physiologic atrophy at about __

SENILE ATROPHY

occurs in old age

• brittle bones which easily break

• atrophy of the ligaments

• gray hair

• dry, lusterless, wrinkled skin due to atrophy of sweat and sebaceous glands

• loss of fat

SENILE ATROPHY:

PATHOLOGIC ATROPHY

refers to a decrease in size of tissues or organs

PATHOLOGIC ATROPHY

outside the range of normal variability

Metaplasia

is a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type.

METAPLASIA

response to chronic irritation that makes cells better able to withstand the stress

METAPLASIA

usually induced by altered differentiation pathway of tissue stem cells

METAPLASIA

may result in reduced functions or increased propensity for malignant transformation

EPITHELIAL METAPLASIA

occurs in epithelium exposed to mechanical trauma or chronic irritation of prolonged inflammation

EPITHELIAL METAPLASIA

prolonged vitamin A deficiency

EPITHELIAL METAPLASIA

most commonly leading to replacement of columnar cells by stratified squamous epithelium

• respiratory passages

• linings of gland ducts

• mucosal lining of endocervix

EPITHELIAL METAPLASIA seen in:

MESENCHYMAL METAPLASIA

occurring in connective tissues whereby fibroblasts are transformed into more highly differentiated forms such as osteoblasts, fat cells or tissue macrophages.

INTRACELLULAR ACCUMULATIONS

Under some circumstances cells may accumulate abnormal amounts of various substances may be harmless or associated with varying degrees of injury.

• Cytoplasm

• organelles (typically lysosomes)

• nucleus

• May be synthesized by the affected cells or may be produced elsewhere.

The substance may be located: (INTRACELLULAR ACCUMULATIONS)

mechanisms of packaging and transport

Inadequate removal of a normal substance secondary to defects in __

steatosis

fatty change in the liver

• as a result of genetic or acquired defects in its folding,

• packaging, transport, or secretion, as with certain mutated forms of α1-antitrypsin

Accumulation of an abnormal endogenous substance:

Failure to degrade a metabolite

due to inherited enzyme deficiencies.

storage diseases

Failure to degrade a metabolite:

The resulting disorders are called __

• Accumulation of carbon or silica particles

Deposition and accumulation of an abnormal exogenous substance:

• Fatty Change (Steatosis)

• Accumulation of proteins

• Pigments

ABNORMAL INTRACELLULAR ACCUMULATIONS:

FATTY CHANGE

steatosis

Fatty change

refers to any abnormal accumulation of triglycerides within parenchymal cells.

FATTY CHANGE

It is most often seen in the liver

liver

major organ involved in fat metabolism,

• heart

• skeletal muscle

• kidney

• and other organs.

FATTY CHANGE may also occur in:

• protein malnutrition

• obesity

• anoxia

• toxins

• diabetes mellitus

Causes of Steatosis:

• Alcohol abuse

• diabetes

Common causes of fatty change in the liver (fatty liver):

Hepatotoxins (alcohol)

alter mitochondrial and SER function

Hepatotoxins (alcohol)

inhibit fatty acid oxidation

CCl4 and Protein Malnutrition

decrease the synthesis of apoproteins

• physiologic atrophy

• pathologic atrophy

• senile atrophy

TYPES OF ATROPHY:

Anoxia

inhibits fatty acid oxidation

Starvation

increases fatty acid mobilization

triglycerides

The possible mechanisms leading to accumulation of __ in fatty liver.

• catabolism

• uptake

• secretion

Defects in any of the steps of __ can lead to lipid accumulation

• Decreased use of fat by cells

• Decreased secretion of fat from the cells

• Increased uptake of triglycerides

• Overproduction of fat in cells.

ACCUMULATION OF FAT IN THE HEPATOCYTES:

Cellular cholesterol metabolism

is tightly regulated to ensure normal cell membrane synthesis without significant intracellular accumulation.

• cholesterol

• cholesteryl esters

• triglycerides

However, phagocytic cells may become overloaded with lipid (__) in several different pathologic processes

• epithelial metaplasia

• mesenchymal metaplasia

METAPLASIA:

• Inadequate removal of a normal substance secondary to defects

• Accumulation of an abnormal endogenous substance

• Failure to degrade a metabolite

• Deposition and accumulation of an abnormal exogenous substance

MECHANISM/PATWAY OF ABNORMAL INTRACELLULAR ACCUMULATION:

Eosinophilic Russel bodies

Immunoglobulins that may occurs in the RER of some plasma cells

Eosinophilic Russel bodies

found in the peripheral areas of tumors.

Mallory Body, or “Alcoholic Hyalin”

Is an eosinophilic cytoplasmic inclusion in liver cells that is highly characteristic of alcoholic liver disease.

Mallory Body, or “Alcoholic Hyalin”

Damaged intermediate filaments within the hepatocytes

neurofibrillary tangle (NFTs)

Are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary marker of Alzheimer's disease.

TAU PROTEIN

proteins that stabilize microtubules

neurofibrillary tangle (NFTs)

Found in the brain in Alzheimer disease aggregated protein inclusion.

• Mallory Body, or “Alcoholic Hyalin,"

• Eosinophilic Russel bodies

• neurofibrillary tangle (NFTs)

INTRACELLULAR PROTEINS:

glucose or glycogen.

Excessive intracellular deposits of glycogen are associated with abnormalities in the metabolism of either __

• β cells of the islets of Langerhans

• renal tubular epithelium

• cardiac myocytes

Glycogen accumulates in:

glycogen storage diseases, or glycogenoses

Glycogen also accumulates within cells in a group of closely related genetic disorders collectively referred to as ___

Pigments

__ can occur in normal or in pathological conditions.

Endogenous pigments

are produced within the tissue to serve a physiological function, or may be byproducts of normal metabolism

Exogenous pigments

consist of foreign materials, usually minerals introduced to the body thru air, food, medication and injections

• hemosiderin

• hemoglobin

• bile pigment

hematogenous or blood-derived pigments:

• melanin

• lipofuscin

• chromaffin

nonhematogenous:

• iron

• copper

• calcium

endogenous minerals:

• hematogenous or blood-derived pigments

• endogenous minerals

• nonhematogenous

ENDOGENOUS PIGMENTS:

EXOGENOUS PIGMENTS

Carbon appearing as jet black pigments in lung sections and bronchial glands of chronic smokers.

• pulmonary parenchyma (anthracosis)

• lymph nodes

Aggregates of the pigment blacken the draining __

coal workers' pneumoconiosis .

Heavy accumulations may induce emphysema or a fibroblastic reaction that can result in a serious lung disease called __