Nursing 301
Pathophysiology
Week 1 Lecture
Juliet Chandler PhD, FNP/WHNP, JD
Week 1 Objectives
• 1. Describe the basic cellular
responses and adaptations to injury
• 2. Explain the genetic basis of
disease, congenital abnormalities and
cancer--deferred
OBJECTIVE 1
Describe the basic cellular
responses and adaptations to
injury
Cellular Biology
Alterations to Cellular
Biology
Cells respond to various stimuli or conditions
(physiologic or pathologic) by doing the
following:
1. they adapt (cell adaptation)
2. they are injured (cell injury)
3. they die (cell death)
1. Cell Adaptation
Cells adapt to stimuli (normal, physiologic OR
adverse pathologic) by:
1. changing their size
2. changing the amount/number of cells
3. exchanging cell types to less differentiated
cells
4. growing in a disorderly manner (shape, size
and number)
Cell Adaptation
• Hyperplasia
• Increase in cell number
not related to stress
• Metaplasia
• Reversible increase
older cells are replaced
by less mature cells
• Dysplasia
• Abnormal and
disorganized growth
• Shrinkage in cells
• Increase in size of cells
• Atrophy
• Hypertrophy
Cellular Adaptation
Adaptive Cellular Responses
I’ll see you tomorrow at 10 am.
Hypertrophy
Increase in size in
Dividing cells
PHYSIOLOGIC
PATHOLOGIC Adaptation- How
Heart Muscle Cells- Grow in Size
or Hypertrophy
A clinical example of
hypertrophy: Left Ventricular
Hypertrophy
2. Cell Injury
• ͎Cells are injured when a stress or
stimuli is significant enough that it
cannot maintain homeostasis (which
is a normal or adaptive steady state)
• The injury can be
• Reversible: injured cells may
recover
• Irreversible: injured cells die
Types of Cellular
Injury
• Ischemia and Hypoxic Injury
• Reperfusion Injury: Free radicals
/oxidative stress
• Nutritional Injury
• Infectious and Immunologic Injury
• Chemical Injury
• Physical and Mechanical Injury
Ischemia &Hypoxic
Injury
• Tissue hypoxia is most common
cause of cellular injury
• Hypoxia is most often caused by
ischemia (or reduced blood supply to
a tissue).
• Ischemia: causes power failure in the
cell
• Cellular injury occurs as a
combination of disruption of oxygen
supply with accumulation of
Causes of Ischemia
• Gradual narrowing of arteries
(atherosclerosis)
• Complete blockage of blood vessels
(thrombosis)
Ischemic Injury
Ischemia
• Cellular events lead to lactic acidosis
• Cellular proteins and enzymes
become more dysfunctional
• Up to a point, ischemic injury is
reversible
• Persistent ischemia leads to
irreversible injury- cell death occurs
when plasma, mitochondrial, and
lysosomal membranes are critically
Reperfusion Injury
• Reperfusion is when the area
deprived of oxygen (or affected by
ischemia) is reoxygenated
(restoration of blood flow and
oxygen)
• The reoxygenation (reperfusion)
process can also cause additional
damage→ also known as ischemiareperfusion injury
• There are different mechanisms that
Reperfusion Injury
Process
Free Radicals
● Ischemiareperfusion leads
to the production
of free radicals.
● When oxygen is
limited, reactive
oxygen species
(ROS, a type of free
radical) forms).
Oxidative Stress
Oxidative stress is a type of cellular
injury caused by free radicals, i.e.,
reactive oxygen species (ROS).
Oxidative stress is the cause of
different disease states and disorders
Oxidative stress and
Inflammation
3. Cell Death
Irreversible Cell Injury: or Cell
Death
▪ Apoptosis
▪ Necrosis
Cell Death
Necrosis
• Cellular self-digestion after
irreversible cell injury
• Usually occurs as a
consequence of ischemia or
toxic injury
Cell Death: Necrosis
▪
CHARACTERISTICS OF NECROSIS:
▪ -Enlargement of the cell
▪ Cell bursts- contents leaks out
▪ Leads to Inflammatory response
Cell Death: Necrosis
• Types of Necrosis: depend on tissue
type
• Heart (coagulative)
• Brain (liquefactive)
• Lung (caseous)
• Pancreas (fat)
Cell Death: Necrosis
Four Types of Tissue Necrosis
• Coagulative (most common type)- Cardiac,
Kidneys
•
•
•
Process that begins with ischemia
Ends with degradation of plasma membrane
Cells change from gelatinous to opaque mass“infarct”
• Liquefactive- Brain (neurons, glial cells)
•
•
Liquification of cells by lysosomal enzymes
Formation of abscess or cyst from dissolved
dead tissue
Cell Death: Necrosis
Four Types of Tissue Necrosis
• Fat necrosis- Pancreas, Breasts, Abdomen
•
•
•
Death of adipose tissue
Usually the result of trauma or pancreatitis
Appears as a chalky white area of tissue
• Caseous necrosis- Lungs
•
•
Characteristic of lung damage secondary to
tuberculosis
Resembles clumpy cheese
“Granuloma”- appears in chest Xray
Cell Death: Apoptosis
Apoptosis
• Programmed cell death
• Apoptosis is cell death resulting from
activation of intracellular signaling
cascade that cause cell suicide
• Apoptosis is tidy and is not usually
associated with systemic manifestations
of inflammation
• phagocytes engulf remains of dead cellsno bursting of cell contents
Cell Death: Apoptosis
Apoptosis
• Occurs in response to injury that does
not directly kill the cell
• Triggers intracellular cascades
• Activates a cellular suicide response
• Not always a pathologic process
• Does not cause inflammation
Cell Death: Apoptosis
• Examples:
• Infection: viruses are killed by T
lymphocytes through apoptosis
• Duct obstruction- organs with
obstruction undergoes apoptosis and
atrophies
• Severe cell injury: cells cannot repair
itself undegoes self-destruction through
apoptosis
OBJECTIVE 2
Explain the genetic basis of
disease, congenital abnormalities
and cancer
Genetic Mechanisms
of Cancer
• Carcinogen
•
Potential cancer-causing agent
• Proto-oncogene
•
Enhance growth-producing pathways
• Oncogene
•
Proto-oncogene in its mutant overactive form
• Tumor suppressor gene
•
•
Inhibits cell proliferation
Cancers may arise when tumor suppressor gene
function is lost or abnormally inhibited
Case Study 2-A
Colon Cancer
Onocoge
nes
Reference:
http://homepage.smc.edu/wi
ssmann_paul/anatomy2textb
ook/neoplasia.html
Proto-Oncogenes
• Normal cellular genes that can be
transformed into oncogenes by
activating (gain-of-function) mutations
• Gain-of-function mutations code for
• Growth factors
• Receptors
• Cytoplasmic signaling molecules
• Nuclear transcription factors
From ProtoOncogene to
Oncogene
Proto-Oncogene
Activation
Tumor-Suppressor
Genes
• Contribute to cancer only when not present
• Both copies of tumor suppressor genes are
inactivated when cancer develops
• One can inherit a defective copy of tumor
suppressor gene
•
At much higher risk for cancer development
p53 Gene
• Most common tumor-suppressor gene defect
identified in cancer cells
•
More than ½ of all types of human tumors lack
functional p53
• Normally p53 inhibits cell cycling
•
•
•
Accumulates only after cellular (DNA) damage
Binds to damaged DNA and stalls division to
allow DNA to repair itself
May direct cell to initiate apoptosis
p53 Gene (Cont.)
Normal vs Abnormal p53 Gene
p53 Gene (Cont.)
• Mutated or damaged p53 allows genetically
damaged/unstable cells to survive and continue
to replicate
• Chemotherapy/radiation
•
•
Damages target/cancer cell to trigger p53mediated cell death
Cancer cells that lack functional p53 may be
resistant to chemotherapy/radiation
Angiogenesis
• Process by which cancer tumor forms new
blood vessels in order to grow
• Usually does not develop until late stages of
development
• Triggers are not generally understood
• Inhibition of angiogenesis is important
therapeutic goal
BRCA1 and BRCA2
Genes
• These are Tumor suppressor genes
• Associated with breast cancer
• Family history and inherited defect in BRCA1
increases risk of breast cancer
Benign vs. Malignant
Growth (Cont.)
Grading and Staging
of Tumors
• To predict clinical behavior of malignant tumor
and guide therapeutic management
• Grading
•
•
•
•
Histologic characterization of tumor cells
Degree of anaplasia
3 or 4 classes of increasing degrees of
malignancy
Greater degree of anaplasia=greater degree of
malignant potential
Grading and Staging
of Tumors (Cont.)
• Staging
•
•
•
•
•
Location and patterns of spread within the host
Tumor size
Extent of local growth
Lymph node and organ involvement
Distant metastasis
Metastasis
Mechanisms of
Metastasis
Patterns of Spread
• Cancer cells generally spread via circulatory or
lymphatic systems
• Tumor markers help identify parent tissue of
cancer origin
•
•
•
Rely on some retention of parent tumor
characteristics
Some released into circulation
Others identified through biopsy
OBJECTIVE 3
Discuss inflammation and
malfunction of immune cell
responses to cellular injury,
infection or hypersensitivity
Inflammation
• Know the inflammatory
process
• Mediators involved in the
inflammatory response
• Local and Systemic
Manifestations of
Inflammation
• The role of inflammation in
Take Home Lessons
1. Know the different forms of cell adaptation
2. Describe the most common way cells are
injured
3. Describe ischemia reperfusion injury
4. Explain oxidative stress
5. Describe the 2 processes of irreversible cell
injury/cell death
6. Distinguish between apoptosis and necrosis
7. Know the 4 types of necrosis
Take Home Lessons
• 8. Describe carcinogenesis
• 9. Describe the relationship between protooncogenes and oncogenes
• 10. What are tumor suppressor genes and
their role in carcinogenesis? What are BRCA
1/BRCA2 genes?
• 11. Define benign and malignant cells
• 12. What is metastasis, and the role of
angiogenesis in the pattern of spread?
Take Home Lessons
• 13. Describe the inflammatory response
and know the mediators involved in the
process.
• 14. What are the local and systemic
manifestations of inflammation?
• 15. What are the phases of wound
healing? What is the role of
inflammation in wound healing?