Understanding Health, Disease, and Their Determinants

Health (WHO, 1948)

• Is a state of physical, mental, and social well-being, beyond the absence of disease or infirmity
• Achieving this state requires identifying and realizing aspirations, satisfying needs, and adapting to the environment

Disease

• All bodily cells maintain a dynamic, steady internal state called homeostasis
• Diseas results from the disruption of homeostasis due to cellular changes or damage

Determinants of Health and Illness:

• Involves individual, societal, and environmental factors
• Individual factors include biomedical aspects like genetics and age along with behavioral elements such as skills
• Societal factors encompass socioeconomic aspects like education and employment with sociocultural influences such as religion and media
• Environmental determinants include air and soil quality, water pollution and extreme weather

Etiology

• Refers to the cause of a disease
• Nonspecific causes involve multiple agents leading to one disease
• Specific causes involve single agent causing multiple diseases
• Congenital conditions manifest from birth; may appear later in life
• Acquired conditions arise after birth due to injury or exposure.

Morphology

• Is the structure or form of cells within tissue, involving gross anatomic features and microscopic changes

Pathogenesis

• Is the sequence of events at the cellular and tissue level from the initial contact with an agent to disease expression

Clinical Features

• Functional and structural changes occur during disease
• Symptoms are subjective complaints by the patient
• Signs are objective manifestations of the disease noted by an observer

Syndrome

• A syndrome is a compilation or group of signs and symptoms characterizing a particular disease state (e.g., Down syndrome)

Complication

• Is an unfavorable evolution of a disease, health condition, or therapy, potentially leading to adverse outcomes or treatment consequences

Sequelae

• Sequelae are lesions or impairments resulting from a disease, such as chronic kidney disease after diabetes or neck pain following whiplash

Diagnosis

• Involves identifying the nature and cause of a health problem.
• Requires careful history taking, physical examination, and weighing possibilities
• Clinical diagnosis is aided by laboratory tests and radiologic studies.

Clinical Course

• Natural history or progression refers to the evolution of a disease without intervention
• An acute course is relatively severe and self-limiting
• A subacute course is between acute and chronic, with less abrupt onset and milder symptoms
• A chronic course is continuous and long-term, potentially with exacerbation and remissions

Prognosis

• Is the probable outcome or recovery from a disease, including full recovery, complications, or anticipated survival time

Terminology

• Preclinical stage is when accurate diagnosis isn't possible
• Symptoms are not yet apparent
• Clinical stage involves disease progression
• Signs and symptoms are present
• Subclinical stage shows no clinical evidence of disease
• Has nonspecific symptoms
• Can be diagnosed with antibody or culture tests, e.g., TB
• Carrier state involves a person carrying the organism without being infected
• There are no signs or positive laboratory tests but the person can still infect others

Epidemiology

• Is the study of disease occurrence within the human population, examining causes, distribution, and control measures
• Its goal is to study risk factors for multifactorial disease
• Heart disease and cancer are examples
• It targets whom, where, and when diseases occur
• Aims to answer how to control, prevent, or eliminate them

Contributions of Epidemiology

• Studying disease history
• Forming clinical decisions
• Evaluating new strategies
• Allocating funding
• Developing policies
• Exploring delivery
• Predicting needs

Mechanisms of Cell Injury

• Involves free radical formation
• Hypoxia and ATP depletion
• Disruption of intracellular calcium homeostasis

Free Radical Formation

• Involves partially reduced, highly reactive, unstable oxygen molecules
• Once formed, it causes additional free radical formation in an autocatalytic chain reaction
• It is generated during radiation damage, enzyme catabolism of drugs and chemicals, inflammation, and normal metabolic processes.
• Causes lipid peroxidation of membranes, oxidative damage to proteins, and single-stranded breaks in nucleic acids

Hypoxia/Ischemia

• Hypoxia is an inadequate amount of oxygen
• Ischemia is an impaired delivery of oxygen
• Acts on the mitochondria, leading to ATP depletion

Depletion of ATP

• Caused by interruption of the energy-dependent Na+/K+-ATPase pump
• Causing increased influx of sodium and water, accumulation of intracellular fluids, dilated ER, increased membrane permeability, and decreased mitochondrial function
• Leads to increased anaerobic metabolism, reduction of glycogen stores, and intracellular pH
• Results in detachment of ribosomes as well as reduced protein synthesis and lipid deposition

Disruption of Intracellular Calcium Homeostasis

• Increases intracellular calcium
• Causes inappropriate enzyme activation, damage to cell organelles, hastens ATP depletion, and fragments chromatin

Cell Injury

• Depends on the intensity and duration of injury as well as the type of cell involved
• Can either be reversible or irriversible
• Is influenced by the severity of injury, blood supply, nutritional status, and regenerative capacity
• Cell injury may result in cell death

Causes of Cell Injury

• Physical agents, mechanical forces, extremes of temperature, electrical forces
• Radiation and exposure to damaging chemicals
• The causes also include biologic agents and nutritional factors
• Chemical agents such as pesticides, drugs, and alcohol

Pathophysiology of Chemical Injury

• Can be nonspecific
• Injury to cell membrane and structure
• Blocks enzymatic pathways and coagulation of cell proteins, and disrupts osmotic and ionic balance
• Can be specific
• Penetrates body surface directly (acids/alkalis)
• Is breathed in (air pollutants, carbon monoxide) and injures lungs
• Is ingested (drugs); or is ingested via food, toys (lead)

Biologic Agents

• Involves viruses, bacteria, fungi, protozoa and parasites
• These agents replicate to produce injurious effects
• Enter a site and cause damage at another
• Bacteria can enter the body through the skin and travel to inflict injury

Definition of Cell Adaptation

• Reversible functional and structural response
• Results in an altered, steady state
• Allows function and survival
• Reverts when stress/stimuli is removed

Forms of Adaptation

• Invloves atrophy (decrease in cell size)
• Hypertrophy (increase in cell size)
• Hyperplasia (increase in cell number)
• Metaplasia (change in phenotype)

Atrophy

• Results from a decrease in cell size
• Reduces O2 consumption and cellular functions
• Decreases the organelles within a cell
• Due to disease, denervation, loss of endocrine stimulation, inadequate nutrition, or decreased blood flow

Hypertrophy

• Results from an increase in workload
• Also from an increase in cell size and functioning tissue
• Causes: normal physiological cases, or abnormal pathological cases (adaptive or compensatory)

Hyperplasia

• Increase in cell proliferation
• Occurs in mitotic tissues
• Involves activation of gene replication
• As well as cellular message distribution
• Response is from all types stimuli

Physiologic Hyperplasia

• Comes from hormonal uterine enlargement(oestrogen stimulation)
• Regeneration after hepatectomy
• Connective tissue wound healing

Non-Physiologic Hyperplasia

• Increase in hormonal stimulation such as the endometrium
• From growth factors, especially in skin warts

Metaplasia

• Replacement of one adult cell type (not primary tissue)
• Reprogramming of undifferentiated stem cells
• In response to irritation/inflammation
• Also from stimulus exposure, predisposes cancer

Intracellular Accumulations

• Comes from substance buildup that isn't being used
• Substances accumulate in various places in the cell
• Altered metabolism or supply
• Genetic mutations can be a cause
• Lack or enzyme activity
• Accumulations depend on cause, effect, and organ failure
• Includes substance by body or abnormal causes from metabolism

Accumulation of Intracelluar Substances

• Transient or permanent
• Harmless or toxic
• Genetic disorders/enzyme replacement

Examples of Accumulations

• Fatty Liver changes (starvation, alcoholics)
• Glycogen from Gierke disease (deficiency)
• Tay-Sachs disease in babies

Accumulations

• Endogenous are found in biliruben.
• Coal miners, blue gum margins are an accumulation of toxins
• Tattoo pigment is a deposit in the skin

Pathologic Calcifications

• Mineral salt deposition
• Has two types

Dystrophic Calcification

• Calcium deposits in dead tissue
• Hard rock material deposits
• From dead/dying cells, internal cell fluid
• Advanced lesions, Tb, Aortic Stenosis

Metastatic Calcification

• Normal tissue calcium deposits
• Has high presence levels
• From parathyroid dysfunction
• Renal failure, bones, cancers

Necrosis

• Cell is still part of human tissue
• Digestion of enzymes or cell components
• Interferes with cell replacement
• Characteric appearance

Types of Necrosis

• Coagulative from enzume denaturing
• Hypoxic area
• Liver kidney damage
• Liquefactive from enzymes, abscess, brain region
• Caseous with soft cheese like debris and centres

Gangrene

• Is necrosis occurring during tissue death
• Dry involves coagulative necrosis
• Is slow spreading in the extremities
• Wet Gangrene involves liquefactive necrosis
• Foul odor, moist, untreated
• Gas gangrene
• From anaerobic infection, spore release
• In trauma patients only

Apoptosis

• Programmed death for cell growth
• Injured and aged cells
• Has morphological feautres
• Involves bodies shrinkage, membrane integrity
• It is not a reactive or harmful disease, but a response to change cellular degradation.
• All linked to immune diseases