Cellular Adaptations

what is pathology?

The study of understanding the cause of disease and the changes in cells, tissues, and organs that are associated with disease

what is etiology?

Underlying causes and modifying factors that are responsible for initiation and progression of disease

what is pathogenesis?

Mechanisms of development and progression of disease, which account for the cellular and molecular changes that give rise to the specific abnormalities that characterize any particular disease

what is homeostasis?

• Steady state of normal cells
• Equilibrium between the cells and their environment
• Cells actively interact with their environment, constantly adjusting their structure and function to accommodate changing demands and extracellular stresses

what happens when homeostasis is disturbed?

If disturbed, the cell can be predisposed for onset of pathology

what are adaptations to environmental stress?

reversible changes in the number, size, phenotype, and metabolic activity cellular functions in response to change in their environment

Cell injury within limits is reversible. If the stressor is severe, persistent, or rapid in onset it
will result in …?

irreversible injury and death of the affected cell

what are causes of cell injury?

• Hypoxia and ischemia
• Toxins
• Infectious agents
• Immunologic reactions
• Genetic abnormalities
• Nutritional imbalances
• Physical agents
• Aging

what is reversible cell injury?

The deranged function and morphology of the injured cells can return to normal if the
damaging stimulus is remove

what are the 2 main morphologic correlates of reversible cell injury?

1. cellular swelling

2. fatty change

what is cellular swelling?

Injury associated with increased permeability of the plasma membrane

• Cells and organelles take in water due to failure of the energy dependent ion pumps

• Pallor due to compression of capillaries

• Increased organ weight

what is fatty change?

Appearance of triglyceride containing lipid vacuoles in the cytoplasm

• Nucleus is displaced and the cell swells

• Seen frequently in liver, heart, and kidney

  • Ex: secondary to alcoholism, diabetes mellitus, malnutrition, obesity, and poisoning

• Imbalance among uptake, utilization, and secretion of fat

what are the 2 pathways of irreversible injury?

1. apoptosis

2. necrosis

what is apoptosis?

programmed cell death (How we eliminate potentially harmful cells or cells that have outlived their usefulness (physiologic apoptosis)

• No inflammatory cell response

• Eliminates cells damaged beyond repair (apoptosis in pathologic conditions)

  • Ex: exposed to radiation, cytotoxic drugs, certain infections or viruses

what is necrosis?

accidental cell death (Cell death in which cellular membranes fall apart, and cellular enzymes leak out and ultimately digest the cell)

• inflammatory cell response

• Due to severe disturbances like loss of oxygen or nutrients

• Rapid and uncontrollable

how does apoptosis work?

1. Fragments of the apoptotic cells break off (“apoptotic bodies”)

2. Apoptotic bodies are consumed by phagocytes

3. plasma membrane remains intact = liitle leakage of cellular contents so no inflammatory process

what is physiologic apoptosis?

• During normal development, some cells die and are replaced by new ones

  • In these situations, cell death is always via apoptosis

  • Unwanted cells are eliminated without eliciting potentially harmful inflammation

• In the immune system, apoptosis eliminates excess leukocytes and lymphocytes left at the end of an immune response

what is pathologic apoptosis?

• Cells damaged beyond repair

  • Ex: DNA damage after radiation or cytotoxic drugs

• Misfolded proteins

• Certain infectious agents like viruses elicit apoptosis

what are morphologic characteristics of apoptosis?

• Cells shrink

• Chromatin condensation and aggregation

• Fragmentation of DNA

• Cells form cytoplasmic buds and fragment into apoptotic bodies

  • Composed of membrane bound pieces of cytosol and organelles

• Rapid extrusion of fragments and phagocytosis

  • No inflammatory response

necrosis involves nuclear changes resulting from…?

breakdown of DNA and chromatin

Pyknosis- shrinkage of nucleus into a basophilic (darker) mass due to DNA condensing

Karyorrhexis- fragmentation of nucleus into multiple small pieces

Karyolysis- fading of nucleus, less and less basophilic as DNA is digested

what are some cytoplasmic changes that occur during necrosis?

• Increased pink cytoplasm – eosin dye binding to denatured proteins

• Glassy, homogenous appearance

• Vacuolated or “moth eaten” once the organelles have been digested by enzymes

normal

early necrosis

necrosis (irreversible)

what are types of necrosis?

• Coagulative
• Liquefactive
• Gangrenous
• Caseous
• Fat
• Fibrinoid

what is the most common type of necrosis?

COAGULATIVE NECROSIS

what is COAGULATIVE NECROSIS?

• Sudden loss of blood supply to an organ (ischemia)

  • Does not occur in the brain

• Denaturation of proteins and enzymes resulting in blockage of proteolysis of
  dead cells

• Underlying tissue architecture is preserved for a few days after death of the cells in the tissue

what is liquefactive necrosis?

• Seen in focal bacterial and occasional fungal infections

• Microbes stimulate rapid accumulation of inflammatory cells

  • Enzymes of the leukocytes digest (“liquefy”) the tissue

• Hypoxic death of cells in the CNS

• If initiated by acute inflammation like in bacterial infection the liquid will be pus

liquefactive necrosis

what is GANGRENOUS NECROSIS?

• A clinical descriptor, not a distinct pattern of necrosis

• Usually refers to a limb that has undergone coagulative necrosis involving multiple
  tissue layers

what is “dry” gangrene?

Coagulative necrosis without liquefaction

what is “wet” gangrene?

• Bacterial infection superimposed

• Results in liquefactive necrosis

CASEOUS NECROSIS is most often seen in?

tuberculosis

CASEOUS NECROSIS

what is the histopathology of CASEOUS NECROSIS?

• architecture is not preserved

• Fragmented or lysed cells

• Amorphous pink and granular

• Often surrounded by a collection of macrophages and other inflammatory cells (granuloma)

describe the histopathology of fat necrosis

• Shadowy outlines of necrotic fat cells

• Basophilic calcium deposits

• Inflammatory reaction

FAT NECROSIS

what is traumatic FAT NECROSIS?

severe injury to areas with high fat content
• Breast- post-cancer procedures and radiation
• Thigh and buttock- following medical and cosmetic procedures

what is enzymatic FAT NECROSIS?

complication of acute pancreatitis
• Pancreatic enzymes leak out of pancreas and destroy fat cells in peritoneum
• Triglyceride esters within the fat are split releasing fatty acids
• Fatty acids combine with calcium to produce chalky white areas (fat saponification)

what is FIBRINOID NECROSIS?

Can only be seen by microscopic examination
• Often associated with complexes of antigens and antibodies deposited in the walls of blood vessels
• Deposited immune complexes and plasma proteins that leak into the wall of the damaged vessels produce a bright pink amorphous appearance on H&E staining that pathologists call fibrinoid (fibrin-like

FIBRINOID NECROSIS

Adaptations are reversible changes in cells in response to changes in the environment such as

• Number
• Size
• Phenotype
• Metabolic activity or
• Functions of cells

what are physiologic adaptions?

responses to normal stimulation by hormones or endogenous chemical mediators or to demands of mechanical stress

what are pathologic adaptations?

responses to stress.

Cells modulate their structure and function to escape injury, but at the expense of normal
function

what is hypertrophy?

Increase in the size of cells resulting in increase in size of the organ

when does hypertrophy occur?

when there is a limited capacity to divide

hypertrophy is caused by?

increased functional demand or by growth factor or hormonal stimulation (physiologic and pathologic causes)

what are some physiologic causes of hypertrophy?

smooth muscle of uterus during pregnancy

skeletal muscles during weightlifting

what are some pathologic causes of hypertrophy?

cardiac enlargement due to hypertension or aortic valve disease

what is hyperplasia?

Increase in the number of cells in an organ that stems from increased proliferation (Can be physiologic or pathologic)

hyperplasia takes place if…?

if the tissue contains cell populations capable of replication (May occur concurrently with hypertrophy and often in response to the same stimuli)

what is an example of physiologic hyperplasia?

• Hormonal hyperplasia- glandular epithelium in breast tissue at puberty and during pregnancy

• Compensatory hyperplasia- residual tissue grows after removal or loss of part of an organ as in liver resections

what is an example of pathologic hyperplasia?

Excessive hormonal or growth factor stimulation

what characteristic distinguishes pathologic hyperplasia from cancer?

responsiveness to normal regulatory contro (hyperplastic process remains controlled; if the signals that initiate it abate, the hyperplasia disappears)

what is atrophy?

The shrinkage in the size of cells by the loss of cell substance

• If significant number of cells are involved, the entire tissue or organ is reduced in size

• Cells may have diminished function, but are not dead

what are some causes of atrophy?

• Decreased workload
• Loss of innervation (pathologic)
• Diminished blood supply
• Inadequate nutrition
• Loss of endocrine stimulation
• Aging

Progressive Hemifacial Atrophy

what is metaplasia?

Change in which one adult cell type is replaced by another adult cell type

• A cell type sensitive to a particular stress is replaced by another cell type better able to withstand the adverse environment

• Example- respiratory epithelium in habitual cigarette smokers

what are intracellular accumulations?

• cells may accumulate abnormal amounts of various substances (harmless or harmful)

  • in cytoplasm, within organelles, or in nucleus

  • may be synthesized by affected cells, or it may be produced elsewhere

what are some examples of intracellular accumulations?

• Fatty change (steatosis)
• Cholesterol and cholesteryl esters
• Proteins
• Glycogen
• Pigments

what are the main pathways of abnormal intracellular accumulation?

• Inadequate removal or degradation of the substance
• Excessive production of an endogenous substance
• Deposition of abnormal exogenous material

fatty change can be due to

• alcohol abuse

• obesity

(can affect many organs, but commonly the liver)

example of protein intracellular accumulation

amyloidosis: Proteins are misfolded and deposited into the tissue. This can rarely be seen in the oral cavity

what are some pigments that can be intracellular accumulations?

• Carbon- most common, pollution
• Melanin
• Hemosiderin- local or systemic excess of iron
• Drug or drug metabolites

oral amyloidosis

drug-related discoloartion (pigment)

what is pathologic calcification?

Abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals

pathologic calcification can occur as: (2 types)

• Dystrophic calcification- calcium metabolism is normal, but it deposits in injured or dead tissue

• Metastatic calcification- associated with hypercalcemia and can occur in normal tissues

dystrophic calcification can cause

organ damage

For example: calcification in aging or damaged heart valves resulting in severely compromised valve motion

dystrophic calcification is common in areas of

aseous necrosis in tuberculosis

calcific stenosis of aortic valve

metastatic calcifcation is associated with

hypercalcemia

what are the main causes of hypercalcemia?

1. Increased secretion of parathyroid hormone

2. Destruction of bone

3. Vitamin D-related disorders (sarcoidosis)

4. Renal failure