Basics of pathophysiology
18/09/2024
BADER REMAWI
Understanding cells
• Cell:
• The smallest living component of an organism
• Contains many components (CM, cytoplasm, organelles)
• Subject to wear and tear; they reproduce and are regularly replaced
• Cells (myocyte, neuron) →
• Tissues (muscle, bone) →
• Organs (brain, heart, liver, kidney) →
• Systems (CNS, CVS)
Pathophysiologic concepts
• The cell faces several challenges through its life, which can alter its normal functioning
• Underlying stressor may be physical or psychological; real or perceived
• e.g. health changes, diseases, other extrinsic and intrinsic factors
• Generally, cells continue functioning despite such challenging conditions
• However, severe or prolonged stress may injure or destroy cells
• When cells become under stress, they undergo adaptive changes to keep functioning:
• Atrophy
• Hypertrophy
• Hyperplasia
• Metaplasia
• Dysplasia
Adaptive cell changes
• Atrophy: reduction in the size of the cell
• Caused by disuse, insufficient blood flow, malnutrition, denervation, or
reduced endocrine stimulation
• Hypertrophy: increase in the size of the cell
• Caused by conditions that increase workload (physiologic or pathologic)
• Hyperplasia: increase in the number of cells
• Caused by increased workload or hormonal stimulation
• Metaplasia: replacement of one differentiated mature cell with
another mature cell that can better endure change or stress
• Usually a response to chronic inflammation or irritation
• Dysplasia: deranged cell growth of a tissue; resulting in abnormal size,
shape, and appearance
• Dysplastic cell changes are adaptive and potentially reversible, but can
precede cancerous changes
Cell injury
• A person’s state of wellness and disease is reflected in the cells
• Injury to any of the cell’s components can lead to illness
• Causes/types of cell injury:
• Toxic injury
• Infectious injury
• Physical injury
• Deficit injury
Causes of cell injury
• Toxic injury:
• Caused by endogenous or exogenous factors
• Endogenous factors: genetic/metabolic errors, gross malformations, hypersensitivity reactions…
• Exogenous factors: alcohol, lead, CO, medications (chemotherapeutics, immunosuppressives)…
• Infectious injury:
• Caused by viral, fungal, protozoan, and bacterial agents
• These organisms interfere with cell synthesis/processes; affecting cell integrity and causing mutations
• e.g. HIV replicates in the cell’s RNA and causes alterations
Causes of cell injury
• Physical injury:
• Caused by a disruption in the cell or miscommunication between the organelles
• Thermal injury: electrical injury, radiation therapy, X-rays, UV radiation…
• Mechanical injury: trauma, surgery, motor vehicle crashes…
• Deficit injury:
• Caused by a deficit of water, oxygen, or nutrients
• Caused by the inability to maintain constant temperature and dispose of waste
• Such conditions interfere with cellular synthesis
Cell degeneration
• Cell degeneration: non-lethal cell damage, usually affecting metabolically active organs
(e.g. liver, heart, kidneys)
• Causes of cell degeneration:
• Cellular swelling
• Fatty infiltrates
• Hyaline infiltration
• Calcification
• Autophagocytosis
• Atrophy, hypertrophy, hyperplasia, dysplasia…
• Early identification of cellular changes (e.g. through an electron microscope) →
Prompt treatment → Slowing degeneration or preventing cell death
• Subclinical identification: early diagnosis of a disease (before symptoms)
• Difficult as many cellular changes remain unidentifiable even under a microscope
Cell death
• Apoptosis:
• Programed cell death
• Necrosis:
• Cell death due to injury
Cell aging
• Cell aging:
• A normal process (wear and tear), where cells lose structure, function, size, and numbers
• An inherent self-destructive mechanism that increases with a person’s age! → Limits the human life span
• May be accelerated by cellular injury
• Signs of cell aging occur in all body systems:
• Reduced blood vessels elasticity
• Reduced bowel motility
• Reduced muscle mass
• Reduced subcutaneous fat…
Factors affecting cell aging
Homeostasis
• Homeostasis: a dynamic, steady state of internal balance
(equilibrium) that the body is constantly striving to maintain
• Every cell is involved in maintaining homeostasis, both on the
cellular level and organism level
• Any change at the cellular level can affect the entire body
• Diseases occur when homeostasis is not maintained or due to
maladaptive response to stress
• The patient has specific subjective complaints, medical history,
signs/symptoms, and lab/radiologic findings
Brain role in maintaining homeostasis
• Medulla oblongata: part of brain stem; associated with vital functions (e.g. respiration, circulation)
• Reticular formation: complex network of brainstem neurons and nuclei; help control vital reflexes
(e.g. cardiovascular function, respiration)
• Pituitary gland: pea-sized gland below the hypothalamus; regulates the function of other glands;
regulates growth, maturation, and reproduction
Feedback mechanisms to maintain
homeostasis
• Components of feedback mechanisms:
• Sensor mechanism: senses disruptions in homeostasis
• Control center: regulates the body’s response to disruptions in homeostasis
• Effector mechanism: acts to restore homeostasis
• Types of feedback mechanisms:
• Negative feedback: works to restore homeostasis by correcting a deficit within the system
• Positive feedback: occurs when hormone secretion triggers additional hormone secretion
(a trend away from homeostasis!)
Negative vs Positive feedback
Disease etiologies
• Causes (etiologies) of a disease:
• Idiopathic: no known cause
• Intrinsic: inherited traits, age…
• Extrinsic: infectious agents, mechanical trauma, smoking, chemical exposure, nutritional problems,
medications, temperature extremes, radiation exposure, psychological stress…
• The cells’ response to disease depends on the causative agent and the affected cells
• Signs and symptoms of a disease may indicate:
• Cellular hypofunction (e.g. constipation)
• Cellular hyperfunction (e.g. increased mucus production, seizure)
Disease prognosis
• Pathogenesis (disease development and course):
• Some diseases are self-limiting and resolve quickly with limited or no intervention
• Other diseases are chronic and never resolve; patients may undergo periods of
relapse/exacerbation (more severe or aggravated symptoms) and
remission/recovery (less severe or absent symptoms)
• Factors affecting disease prognosis:
• Genetic factors (e.g. tendency toward obesity)
• Unhealthy behaviors (e.g. smoking, alcohol, sedentary lifestyle)
• Personality type (e.g. stressed, relaxed)
• Patient’s attitude/perception of the disease (acceptance, denial)
• Medical treatment (pharmacologic, non-pharmacologic)
Disease trajectories
Disease stages
• Exposure/injury: target tissue is exposed to a causative agent or is injured
• Latent/incubation period: no evident signs or symptoms
• Prodromal period: mild, nonspecific signs and symptoms
• Acute phase: the disease reaches its full intensity and complications commonly arise
• Remission: a second latent phase; commonly followed by another acute phase
• Convalescence: progress toward recovery after disease termination (rehabilitation)
• Recovery: regain of health or normal functioning; no evident signs or symptoms
• These are typical disease stages; some diseases are progressive and end in patient death
