Altered Cellular and Tissue Physiology

BIO 300

Tissue Regeneration and Replacement• Permanent Cells

– Neurons and cardiac muscle cells

Tissue Regeneration and Replacement• Permanent Cells

– Neurons and cardiac muscle cells• Stable Cells (slow unless stimulated)

– Liver, smooth and skeletal muscle, cartilage, bone, endothelium

Tissue Regeneration and Replacement• Permanent Cells

– Neurons and cardiac muscle cells• Stable Cells (slow unless stimulated)

– Liver, smooth and skeletal muscle, cartilage, bone, endothelium

• Labile Cells (continuous, often by stem cells)– Epidermal cells, GI epithelium, spermatazoa, blood

cells

Chronic Inflammation

Continued tissue injury with release of growth factors

Altered growthAtrophy

HypertrophyHyperplasia

Cellular Adaptation

Adaptation in Cell Growth• Atrophy is a decrease or shrinkage in

cell size

Adaptation in Cell Growth• Atrophy is a decrease or shrinkage in

cell size• Hypertrophy is an increase in cell

size

Adaptation in Cell Growth• Atrophy is a decrease or shrinkage in cell size• Hypertrophy is an increase in cell size• Hyperplasia is an increase in the number of

cells via increased mitotic division– All of these can be caused by mechanical or

chemical stimuli

Chronic Inflammation

Continued tissue injury with release of growth factors

Altered growthAtrophy

HypertrophyHyperplasia

Fibrosis

Chronic Inflammation

Continued tissue injury with release of growth factors

Altered growthAtrophy

HypertrophyHyperplasia

Fibrosis

Altered differentiationMetaplasiaDysplasiaNeoplasia

Adaptation in Cell Differentiation• Metaplasia is the replacement of

one cell by another as an adaptive response

Adaptation in Cell Differentiation• Metaplasia is the replacement of one

cell by another as an adaptive response

• Dysplasia is the abnormal development of a tissue, often precancerous and in inflamed tissue

Adaptation in Cell Differentiation• Neoplasia is the abnormal formation

of tissue, often poorly differentiated and unresponsive to growth control mechanisms.– Can be classified as benign or

malignant

Benign Tumors• Similar to cell of origin• Encapsulated• Slow growth• Little or no vasculature• Seldom recur• Do not spread

Benign Tumors• Similar to cell of origin• Encapsulated• Slow growth• Little or no vasculature• Seldom recur• Do not spread

Malignant Tumors• Poorly differentiated• Invades• Fast growth• Marked vasculature• Often recur• Metastic

Metastic Tumor

Adaptation in Cell Differentiation• Metastasis is the process of cancer

cells separate from the original tumor spreading to other organs.

Biochemical changes from injury• 4 important sites in cell injury

–Mitochondria–Plasma membrane–Ionic channels–Cytoskeleton

Biochemical changes from injury• ATP depletion• oxygen-derived free radicals• Ca+ alterations• Membrane permeability

Manifestations of Injury• Ischemia

Manifestations of Injury• < ATP production• Na-K pump dysfunction• Cellular edema

– ER and mitochondrial swelling, ribosomes detach, blebbing

Cellular Injury

• Reversible

• Irreversible

Reversible Cell Injury• Swelling of Cell, mitochondria, ER• Ribosome detachment• Loss of microvilli• Blebbing• Chromatin clumping

Cellular Injury

Reversible Cell Injury• Cloudy swelling

–Edema and pale, granular cytoplasm

–Also known as hydropic degeneration

Hydropic Degeneration

Reversible Cell Injury• Fatty changes

– Excess intracellular lipids within vacuoles in cytoplasm

– Most frequent in liver

Irreversible Cell Injury• Lysosomal enzyme release• Protein digestion• Membrane disruption• Leakage of cell enzymes and proteins• Nuclear changes

Cellular Injury

Cellular Death

• Necrosis–Sudden change in cell leading to loss of function

and resulting in autodigestion•Changes in tissue are the result of the release of

denaturation and release of lysosomal denaturation

Cellular Death• Processes

–Karyolysis•Nuclear dissolution and chromatin lysis

–Pyknosis •Clumping of the nucleus

–Karyorrhexis•Fragmentation of the nucleus

Cellular Death

Necrosis

• Coagulative necrosis–Kidneys, heart, and adrenal glands–Loss of nuclei and cell, but architecture remains–Lysosomal enzymes lost

Coagulative Necrosis

Necrosis

• Liquefactive necrosis–Neurons and glial cells of the

brain, bacterial infection–Hydrolytic enzymes produce

proteinaceous soup

Liquefactive Necrosis

Necrosis

• Caseous necrosis–Tuberculous pulmonary infection–Combination of coagulative and

liquefactive necrosis

Caseous Necrosis

Necrosis

• Fat necrosis–Breast, pancreas, and other

abdominal organs–Action of lipases

Fat Necrosis

Necrosis

• Gangrenous necrosis–Death of tissue from severe hypoxic injury

•Dry vs. wet gangrene–Dry = coagulative–Wet = liquefactive

Gangrenous Necrosis

Apoptosis

• Programmed cellular death• Physiologic vs. pathologic

Apoptosis

• Physiological apoptosis is an important part of life.– Some examples include ….

Apoptosis

• Apoptosis was originally known as shrinkage necrosis

Signs of Apoptosis

• Loss of contact with neighboring cells• Nuclear fragmentation• Cytoplasmic shrinkage• Organelles parceled into vesicles• How is this different from necrosis?

Apoptosis vs. Necrosis

Apoptosis vs. Necrosis

• Which one requires energy?• Which one involves edema?• Which one produces localized inflammation?

– A = Necrosis– B = Apoptosis

Aging and Altered Cellular and Tissue Biology

• Aging vs. disease• Normal life span• Gender differences

Theories of Aging

• Accumulation of injurious events

• Genetically controlled program

• Theories– Genetic and environmental lifestyle

factors– Alterations of cellular control

mechanisms– Degenerative extracellular and vascular

changes

Aging

• Cellular aging– Atrophy, decreased function, and loss of

cells

• Tissue and systemic aging– Progressive stiffness and rigidity– Sarcopenia

• Frailty– Mobility, balance, muscle strength, motor

activity, cognition, nutrition, endurance, falls, fractures, and bone density

Somatic Death

• Death of an entire person

• Postmortem changes– Algor mortis– Livor mortis– Rigor mortis– Postmortem autolysis