D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 1 - INTRODUCTION, RESPONSE TO INJURY
Introduction, Chapter 1
1.
Introduction: - principles & terminology
• homeostasis: range of cellular & extracellular conditions that support normal
function; departure from this range leads to disease state
• pathophysiology: altered function resulting from disease state
- etiology: study of agents that cause disease; (idiopathic = unknown cause)
- genetic diseases (caused by faulty gene) may be distinguished from
congenital diseases (caused by abnormal embryonic/fetal development)
- syndrome: collection of signs (features evident to observer, e.g.
temperature) & symptoms (features subjectively experienced by patient, e.g. pain)
- pathogenesis (fig. I - 1): progression of changes that characterize a disease
state, e.g. an initial lesion (event of tissue damage) may lead to sequelae (changed
conditions resulting from disease)
- diagnosis (identification of a disease) may guide therapy (medical
treatment), which may lead to a favorable or unfavorable prognosis (prediction of
outcome) (fig. I - 2)
2.
Parts of normal cell (ppt. 1):
• plasma membrane (fig. 1 – 1 & ppt. 2): selective permeability controls
interaction with cellular environment (ECF)
- diffusion (through channels or through lipid bilayer)
- carrier-mediated transport (protein shuttles)
- active transport: carriers energized by ATP (aka 'ion pumps')
- endocytosis (phagocytosis & pinocytosis)
- exocytosis (secretion & excretion)
- receptors: signal transduction, cellular recognition & specific endocytosis
• mitochondrion (fig. 1 – 2 & ppts. 3 - 5): ‘powerhouse of the cell’ (provides
energy – synthesis of ATP)
- enzymes of Krebs cycle
Bio 307/607 lec. 1
- p. 2 -
- enzymes of fatty acid oxidation
- enzymes of electron transport
Bio 307/607 lec. 1
- p. 3 -
• endoplasmic reticulum (figs. 1 – 3, 1 – 5 & ppts. 6 & 7): smooth & rough –
site of biosynthesis reactions
- enzymes of protein synthesis (ribosomes of rough ER)
- enzymes of lipid biosynthesis or detoxification reactions (smooth ER)
• Golgi apparatus (fig. 1 – 4 & ppt. 8): modification & distribution of ER
products
- formation of lysosomes
• lysosome (fig. 1 – 6 & ppt. 9): bag of digestive enzymes; role in endocytosis,
role in removal of endocytic damage
• cytoskeleton: maintenance of cell shape & regulation of movement in the cell
• nucleus: stores genetic material; provides genetic control of cell activities
3.
Cellular Injury:
• agents of cellular injury
• deficiency (fig. 1 – 7 & ppt. 10):
- lack of dietary nutrient (primary) or inability to absorb or utilize nutrient,
e.g., malabsorption, hypoxemia
- genetic diseases disrupt processes that produce needed substances
- infections disrupt processes that produce needed substances or use up
needed substances
• intoxication:
- endogenous (fig. 1 – 8 & ppt. 11) - due to genetic defects or impaired
circulation
- exogenous - arise from infections, direct ingestion, or inhalation
Bio 307/607 lec. 1
- p. 4 -
- toxic injury - usually involves binding to critical cell component, thereby
disrupting normal function
Bio 307/607 lec. 1
- p. 5 -
• trauma (fig. 1 – 9 & ppt. 12):
- extremes of temperature produce hypothermia (may produce frostbite) or
hyperthermia (may produce burns)
- ionizing radiations produce free radicals (box fig. 1 – 2 & ppt. 13) that can
damage lipids, proteins, and DNA in the cell
- mechanical pressure, resulting from external sources, from tumors, or
from aneurysms may disrupt cellular integrity
- infections may produce physical injury to cells, or may instigate attack by
the immune system
• responses to injury (ppts. 14 & 15) – adaptive (reversible) or non-adaptive
(irreversible)
- adaptive: altered metabolism (e.g., modified energy metabolism), change in
size (hypertrophy or atrophy (fig. 1 – 10 & ppts. 16 to 18)), apoptosis (fig. 1 – 11 &
ppts. 19 & 20), formation of stress proteins (box fig. 1 – 1 & ppt. 21) (stabilize
damaged proteins), & change in organelle size & number (swelling or shrinkage)
- accumulations: hydropic change (figs. 1 – 12, 1 – 13 & ppt. 22) (osmotic
upset), fatty change (figs. 1 – 14, 1 – 15, 14 – 16 & ppts. 23 & 24) (metabolic
disturbance), residual bodies (figs. 1 – 16, 1 – 17 & ppt. 25) (lipofuscin granules),
hyaline change (accumulation of glassy material – usually protein)
- plasma membrane damage: (fig. 1 – 18 & ppt. 26) blebs or myelin figures,
often by attack from free radicals (ppt. 27)
- swollen organelles (nucleus excepted) (fig. 1 – 18 & ppt. 26)
- irreversible: lead to necrosis (cell death) (fig. 1 – 20 & ppt. 28)
- nuclear damage – karyolysis, pyknosis, karyorrhexis (fig. 1 – 19 & ppt. 29)
- membrane rupture, cytoskeletal tangles
- necrosis – coagulation (fig. 1 – 21 & ppts. 30 & 31) (tissue architecture
maintained)
- caseous necrosis (cheesy consistency) (ppt. 32)
- gangrene (anaerobic bacterial infection of ischemic tissue)
- liquefactive necrosis involves digestion of dead cells (lysosomal &/or
microbial enzymes) (ppt. 33)
- calcification often follows necrosis (dystrophic calcification)
Bio 307/607 lec. 1
- p. 6 -
• differential vulnerability to injury
- ischemia: more severe in brain than most other tissues
- intoxication: toxicity may depend on conversion of initial toxin, which
renders liver more vulnerable
- ionizing radiation: affects mostly actively mitotic tissues (e.g., bone
marrow, hair follicles)
- viral infection: selective for specific target cells
• consequences of severe injury (findings contributory to diagnosis)
- functional losses, e.g., immobility, metabolic deficiency
- microscopic changes detected with biopsy examination
- detection of serum enzymes (box fig. 1 - 3)
- altered electrical properties, e.g., EKG, EEG (fig. 1 - 22)