Cellular pathology (EXAM 1- MODS)

What are the mechanisms of the four basic types of cellular adaptation ?

• Hyperplasia

• Hypertrophy

• Atrophy

• Metaplasia

Describe Hyperplasia in cellular adaptation

An increase in the number of cells in an organ or tissue, which may increase its volume.

What are physiological adaptations for hyperplasia

occurs due to normal stressor:

• Hormonal: ^# of glandular epithelial breast cells during pregnancy → enlargement of breasts→ preparation for lactation

• Increased functional demand: Living at high altitude leads to hyperplasia of erythrocyte precursors in bone marrow

• Compensatory: Regeneration of liver following partial hepatectomy. Regeneration of epidermis after abrasion

What are pathologic adaptations for hyperplasia

Occurs due to an abnormal stressor: ( ex; excessive stimulation of hormones)

• Endometrial hyperplasia (increased estrogen)

• Benign prostatic hyperplasia (androgens)

• Epidermal hyperplasia in psoriasis

Describe Hypertrophy in cellular adaptation

An increase in the size of a cell, resulting in an increased organ size.

What are pathologic adaptations for hypertrophy

increase in size of heart due to aortic stenosis

What are physiological adaptations for hypertrophy

caused by functional demand/ hormones

• Enlargement of skeletal muscle with exercise (increased functional demand)

• Physiological growth of uterus during pregnancy (Hyperplasia + Hypertrophy)

Describe Atrophy in cellular adaptation

decrease in the size of a cell (organ)

• May be due to loss of blood supply, loss of endocrine stimulus, disuse, decreased workload, aging etc.

What are physiological adaptations for atrophy

caused by normal aging or hormonal drops

• Atrophy of brain with aging

• Atrophy of gonads after menopause (decreased hormones)

• Decrease in the size of the uterus after pregnancy

What are pathologic adaptations for atrophy

Caused by disuse

• Immobilization of a limb after fx (disuse)

• Cachexia (starvation, insufficient nutrients)

• Ischemic process (inadequate supply of oxygen)

Describe metaplasia in cellular adaptation

change of epithelium at a site, or location, from one type to another (change in cell type)

• epithelium normally present at a site cannot handle the new environment so it converts to a type of epithelium that can adapt.

What are pathologic adaptations for metaplasia

abnormal changes

• Cigarette smoking

• Barrett’s esophagus

What are physiological adaptations for metaplasia

Normal cervical changes at the transformation zone

describe/ list the causes of cell injury

• occurs when the cells cannot adapt to their new environment

• Causes:

  • Hypoxia (common)

  • Ischemia (common)

  • Physical agents

  • chemical agents

  • infectious agents

  • radiation and toxins

  • metabolic abnormalities

  • immune dysfunction

  • Nutritional imbalances

  • Aging

List the mechanisms of cellular injury?

1. Hypoxia

2. Free radicals

3. Chemical injury

4. Increased mitochondrial cytosolic calcium (mitochondrial damage)

Describe the mechanism of hypoxia in cellular injury

• No Blood → No Oxygen→ No ATP

• Results in: Swelling (pump fails), Acid/Clumping (backup power fails), and Fat Build-up (protein factories break).

• refer to diagram

Describe the mechanism of generation of oxygen-derived free radicals in cellular injury

• chemically unstable and react with other molecules → damage

• Produced by physiologic oxidation-reduction reactions, UV light, ionizing radiation, metals, chemicals (smoking, pollution), inflammation, stress

Describe the mechanism of chemical injury in cellular injury

• can affect any of the processes listed on the chart

  • membrane damage

  • DNA and protein damage

  • ATP depletion

  • Mitochondrial damage

  • Entry of Ca 2+

  • Increase of ROS

Describe the mechanism of Increased mitochondrial cytosolic calcium in cellular injury

• Results in:

  • Lipid peroxidation

  • Mitochondrial injury

  • Loss of calcium homeostasis

  • ↓ ATP production

  • Apoptosis

Define and explain the process of reversible cell injury

• Stress is mild → moderate

• injured cell may recover

• caused by hypoxia, decreased ATP, sodium potassium pump failures, or failures of calcium channels

• Result= cellular swelling, Mitochondrial swelling, ER swelling → blebbing of those membranes

• Ca enters cell→ ribosomal detachment→ decreased protein synthesis and alteration of lipids → clumping of chromatins

• Leads to protein denaturation and changes in the structure of DNA

• Goes back into a state of homeostasis and becomes a normal cell

Define and explain the process of irreversible cell injury

• Rupturing of the organelles → overall rupturing of those cells

• Depositions/ densities in mitochondria

• myelin fissures → nuclear degradation/ nuclear changes can result in:

  • Pyknosis (condensation)

  • Karyorrhexis (fragmentation)

  • Karyolysis (nuclear pallor)

Define apoptosis

controlled (programed) cell death/breakdown of cells occurring in response to irreversible cellular damage or as part of normal growth and development.

Phases:

• Initiation: caspases become catalytically active

• Execution: action of caspases causes cell death

What is the microscopic morphology of Apoptosis?

Chromatin condensation and fragmentation

What is the microscopic and gross morphology of Necrosis?

Gross:

• softening and discoloration of the organ

Micro:

• Coagulative necrosis

• Liquefactive necrosis

• Fat necrosis

• Caseous necrosis

Define necrosis

uncontrolled breakdown of cells/cell death in response to irreversible cellular injury; triggers inflammatory response

Compare and contrast apoptosis and necrosis

• KEY DIFFERENCE:

  • Apoptosis does not generate an inflammatory response, where as necrosis does

• Refer to chart

Define coagulative necrosis and describe the microscopic morphology

• Due to ischemia, infarction

• Increased eosinophilia of the cytoplasm (denatured proteins) and decreased basophilia of the nucleus (loss of DNA/RNA).

• General cellular architecture is initially preserved.

Define liquefactive necrosis and describe the microscopic morphology

• enzyme breakdown in lipid-rich organs

• loss of organ cellular architecture

• lipid-laden macrophages replace the dead tissue

Define fat necrosis and describe the microscopic morphology.

• Change in adipose tissue due to trauma or the release of enzyme from adjacent organs

• Large, lipid filled vacuoles

Define caseous necrosis and describe the microscopic morphology.

• Immune system cannot successfully remove a foreign stimuli (e.g. tuberculosis). Forms granuloma

• granuloma with central necrosis, eosinophilia

List the substances that can accumulate

• Lipofuscin

• Calcium

• Protein

• Iron

• Fat

• Cholesterol

• Glycogen

• Pigments

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of Lipofuscin.

• Mechanism of formation: product of lipid peroxidation which accumulates in lysosomes as cells ages; cells cannot get rid of it

• Organs affected: commonly in the heart, liver, skin

• Gross morphology: brown discoloration to organs

• Microscopic morphology: finely granular, yellow-brown pigment, which often surrounds the nucleus

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of Calcium

2 types of mechanism

• Mechanism of metastatic calcification: patients who have hypercalcemia have deposition of calcium within normal or abnormal tissue

• Mechanism of dystrophic calcification: patients who have normal levels of calcium have deposition of calcium only within abnormal tissue (necrosis or damage)

• Organs affected:  vasculature, kidneys, lungs

• Gross morphology: hard, yellow nodules

• Microscopic morphology:  chunky, smooth, purple granules

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of protein

• Mechanism of formation: Increased protein absorption in proximal renal tubule (renal disease), Increased cytoskeletal proteins, increased protein production, amyloidosis, defect in intracellular transport and protein secretion.

• Organs affected: liver and kidneys

• Gross morphology: blue-black foci on tissue once stained

• Microscopic morphology:

  • Amyloidosis: amyloid deposits stain eosinophilic/pink-pale; pink or red on Congo red stain

  • Alzheimer’s disease: neurofibrillary tangles

  • Fatty liver: Mallory hyaline-eosinophilic, pink, rope-like deposits

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of iron

• Mechanism: accumulation of hemosiderin due to ↑ iron

  • Hemosiderosis: accum. of iron in organs w/o resultant side effects

  • Hemochromatosis: accum. of iron in parenchymal cells resulting in side effects

• Organs affected by hemochromatosis: liver, skin, pancreas, heart

• Gross morphology: dark brown color

• Microscopic morphology: chunky, yellow-brown granules on H & E stain; blue on Prussian blue stain

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of fat (steatosis)

• Mechanism: can indicate reversible damage or may be a sign of intrinsic abnormality in fat metabolism

  • Seen in fatty liver disease (alcohol use, nonalcoholic), diabetes mellitus, obesity

• Organs affected: liver, kidney, heart, skeletal muscle

• Gross morphology:  yellow discoloration of an organ

• Microscopic morphology: one or several clear vacuoles within the cell

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of cholesterol

• Mechanism: Hypercholesterolemia; elevated blood cholesterol levels lead to disruption in cellular function, oxidative stress, inflammation

• Organs affected: blood vessels (atherosclerosis)

• Gross morphology:  yellow discoloration of an organ

• Microscopic morphology: foam cells (lipid-laden macrophages)

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of Glycogen

• Mechanism: accumulates due to glycogen storage disorders or disease of glucose metabolism

• Organs affected: liver and skeletal muscle

• Microscopic morphology: clear vacuoles in the cytoplasm

what are the types of pigments

• Exogenous pigments (produced outside of the body): Melanin

• Endogenous pigments (produced inside of the body): Bilirubin

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of bilirubin

• Mechanism: produced from the breakdown of RBCs and excreted through bile and urine

  • Hyperbilirubinemia (hemolysis, obstruction, genetic disorders, drugs)

• Organs affected:

  • Jaundice- yellowing of skin, eyes

  • Kernicterus-brain

• Gross morphology: yellow pigmentation

• Microscopic morphology: brown deposits

• bilirubin is a component of bile

Describe the mechanism of formation, sites of accumulation, and gross/ microscopic morphology of mealnin

• Mechanism: brown-black pigment formed by melanocytes and transferred to keratinocytes

  • Function is to prevent the harmful effects of ultraviolet (UV) light

• Organs affected: skin, eye

• Gross & microscopic morphology: brown–black pigment

Describe the role of the telomere in relation to cellular aging

As a cell divides, its telomeres shorten. Eventually, the telomeres become so short that the cell can no longer divide, which leads to cellular aging (senescence).