BLD 204 First Exam

General physiology, phagocytosis, cell injury, inflammation, and cell healing

Hypertrophy

Increased cell/organ size in response to stress

Why does hypertrophy happen?

Increased workload on cells that CANNOT divide (i.e. ventricular hypertrophy)

Hyperplasia

Increase in number of cells

Why does hyperplasia happen?

Increased workload on tissue with cells that CAN divide (i.e. cancer)

Atrophy

Cells shrink by loss of cell substance

Why does atrophy happen?

Resources/workload is low (i.e. malnutrition)

Metaplasia

REVERSIBLE change of one adult cell type by another

Why does metaplasia happen?

Improves function during stress (i.e. ciliated columnar cells replaced by squamous in smoker’s lung)

Etiology

Cause of disease

Pathogenesis

Mechanisms of disease

Diagnosis

Condition/disease individual has

Prognosis

Predicted outcome

Hypoxia

Oxygen deficiency

Causes of hypoxia

• Ischemia (reduced blood flow)

• Inadequate blood oxygenation

• Lower blood oxygen carrying capacity (CO poisoning)

Causes of chemical damage (cellular injury)

• Too much of a good thing (caffeine)

• Poisons

• Alcohol/ethanol

• Air pollutants

• Asbestos

Causes of genetic problems (cellular injury)

• Inherited defects

• Accumulation of damaged DNA/proteins

Causes of physical damage (cellular injury)

• Temperature

• Mechanical damage

• Electric shock

• Barometric pressure

• Radiation

Irradiation is what type of cellular injury mode?

Physical damage because you need physical interaction with it

Where do we get most (80%) of our normal sources of radiation?

• Cosmic radiation

• Elements/minerals in the earth

• Radionuclides in our bodies

What is the average daily background dose of radiation?

0.001 rads

Causes of cellular injury

• Physical

• Chemical

• Genetic

• Infection

• Immune system problems

• Nutrition issues

• Aging

• Biochemical

Senescence

Cells that do not have functionality, but linger in the body

Causes of biochemical damage (cellular injury)

• Mitochondria

• Calcium homeostasis

• Membranes (cell/lysosomes/mitochondria)

• DNA

• Protein folding

What cellular injuries cause necrosis?

• Hypoxia/ischemia

• Multiple injurious stimuli

• Infections

• Immunologic disorders

How does hypoxia/ischemia cause necrosis?

Decrease ATP production → decrease energy-dependent functions

How does multiple injurious stimuli cause necrosis?

Increase in radical oxidative species → damaged lipids, proteins, and nucleic acids

How does infection/immunologic disorders cause necrosis/apoptosis?

Chronic inflammation → increased presence of lymphocytes → increased toxic chemical production

What cellular injuries cause apoptosis?

• Mutations/cell stress/infections

• Radiation

• Infection/immunological disorders

How does mutations/cell stress/infection cause apoptosis?

Accumulation of misfolded proteins in the endoplasmic reticulum

How does radiation cause apoptosis?

DNA damage → decrease in functionality

What problems arise because of low ATP production?

• Osmosis disruption (Na⁺ pumps not functioning properly)

• Increase in anaerobic glycolysis

• Ca²⁺ pumps fail

• Protein synthesis disrupted

If ischemia/radiation causes an overproduction of ROS, what happens?

• Lipid peroxidation (damage to cell membranes bc of phospholipids)

• Breakdown/misfolding of proteins

• Oxidative destruction of phagocytes

Why is a disruption in calcium pump function problematic?

• Increased concentration of Ca²⁺ inside the cell

• Clogging/damage to endoplasmic reticulum (causes misfolded proteins)

• Ca²⁺ is a cofactor for enzymes

• Increased Ca²⁺ in cell → increased phospholipase (phospholipid breakdown) + protease (disrupt cytoskeletal structure and membranes) + endonuclease (cut up DNA) + ATPase (decrease ATP)

What are common clinical signs of cell death?

• Swelling

• Fat accumulation

Necrosis

Cells swelling to the point of membrane disintegration

Characteristics of necrosis

• Loss of membrane integrity

• Leakage of lysosome/cell contents

• Autolysis

• Uncontrollable cell death

Autolysis

Cell dissolution from enzymes released by cells themselves

Cellular morphology of necrosis

• Increased eosinophilia in cytoplasm from denatured proteins

• Pyknotic/karyorrhexic/karyolytic nucleus

Pyknosis

Shrinkage and basophilia

Karyorrhexis

Fragmentation

Karyolysis

Fade away via DNA nucleases

Coagulative necrosis

• Dead cells coagulate (persist for days)

• Firm texture

• Leukocyte accumulation for degradation

• Infarct solid organs (except brain)

Liquefactive necrosis

• Tissue liquefies

• Bacterial and fungal infections

• Liquid can be pus if necrosis is from acute inflammation

• CNS infarcts

Caseous necrosis

• ‘Cheese-like’

• Fragmented/lysed cells can be seen

• No visible tissue architecture

• Body walling off problem areas

• Granulomas (TB)

Fat necrosis

• Traumatic injury in high-fat areas/release of activated pancreatic enzymes

• Lipolysis

• Phagocytes have lipid in them from munchin’

• Saponification from pancreatic type, basophilic Ca²⁺ deposits in cells

Fibrinoid necrosis

• Immune complex deposition (antigen/antibodies sticking around)

• Immune-mediated diseases

• Net-like appearance (fibrinoid)

Apoptosis

Cell-controlled death under normal physiological or pathologic conditions

Why is apoptosis important?

Because it gets rid of cells WITHOUT eliciting an immune response