Pathophysiology

Mechanisms of Disease
Inflammation & Healing

By
Shah Faisal
Lecturer, KMU
 Terms Used In Pathophysiology
• Pathogenesis = the development of a disease
» Diseases develops in stages
» Infectious disease example:
(A)incubation (b)disease (c)convalescence
• Pathophysiology = the study of the functional changes
associated with a specific disease
» How the disease affects specific functions of the body
• Subjective findings
» The patient’s symptoms
» Described by the patient----(the patient’s history)
• Objective findings
» Health provider’s findings---( the physical exam)
• Occurrence of disease defined by 2 factors
• Incidence = # new cases per unit of time
• Prevalence = # new & old cases per unit of time
• Disease terminology
– Etiology = cause of the disease
– Idiopathic = disease with unknown cause
– Iatrogenic = disease caused by human intervention
– Congenital diseases = diseases occurring at birth
– Remission = period when symptoms & signs of disease abates
– Exacerbation = period when symptoms & signs increase
– Endemic disease = disease native to local area
– Epidemic = many people affected in a given area
– Pandemic = many people affected in large areas
– Incubation = latent period of the disease before developing signs &
symptoms
– Prognosis = probability for recovery
– Morbidity = disease rates within a group
– Mortality = death rates within a group
– Epidemiology = how the disease occurs & spreads through an area
 Disease terminology

• Communicability: is the capacity to spread

from one individual and cause disease in
others.
• Immunogenicity: is the ability of pathogens
to induce an immune response.
• Infectivity: enables pathogens to invade and
multiply in a susceptible host.
 cntd

• Toxigenicity is the ability to produce

soluble toxins or endotoxins.
• Virulence is the pathogen’s capacity to
cause disease; measles virus has low
virulence, while rabies virus is highly
virulent.
Predisposing Factors (risk factors)
• Age
• Young are prone to accidents
• Getting diseases such as diabetes, heart disease, and certain
cancers increase with age
• Very old are prone to drug interactions
• Sex
• More frequent in woman: osteoporosis
• More frequent in men: gout, Parkinson’s disease
• Lifestyle
• Examples of harmful lifestyle:
» occupation
» Smoking
» Excess alcohol
» Poor nutrition
» Sedentary activity
• Environment
• Air pollution
• Water pollution
• Poor living conditions
• Excessive noise
• Chronic psychological stress
• Heredity
• Deals with genetic predisposition (inheritance)
» Genetic predisposition + certain type of environment =
mental retardation , lung cancer, etc.
• Preventive health care
• The best treatment of a disease is prevention !!
• Deals with altering risk factors that can be changed
 Homeostasis
• Definition = internal constancy or a stable internal environment
• A “body in balance” is in homeostasis
• Homeostatic regulation ---- works by using feedback loops
• Feedback loops utilize 3 components
(1) receptor (2) control center (3) effector
– 2 types of feedback loops
(1) negative feedback
– Restores any change back to normal
– Resembles “teeter-totter”
– Stabilizing
– Most common
(2) positive feedback
– Exaggerates the change
– Resembles “domino effect”
– Stimulating
– Least common
• Cell damage is the main reason to lose homeostasis
– Deficiency of oxygen (hypoxia) = most common reason
• Mechanism of progression:
ischemia -to- necrosis -to- gangrene

• Cell death
– Once it occurs, lysis occurs with release of lysosomal enzymes
• This causes inflammation

• After inflammation, the dead cells(tissue) is either:

• Replaced by scar tissue
• Regenerated to resemble original tissue
 Mechanism of infection

• Pathogen enters the body

• The pathogen reproduce and make toxins
• T-Lymphocytes help recognize the
pathogen.
• B-Lymphocytes make antibodies
• The antibodies help destroy pathogen
• The person begins to feel well
 Mechanisms of infection and cellular
injury by bacteria

• Bacteria are prokaryotes lacking discrete nuclei;

they are relatively small.
• Their survival and growth depend on the
effectiveness of the host’s defense mechanisms
and on the bacterium’s ability to resist these
defenses.
• Some bacteria have coatings that protect them
from phagocytosis
• These coatings include polysaccharide coverings
for the Pneumococcus, the waxy capsule
surrounding the tubercle bacillus, and the M
protein cell wall of the Streptococcus.
• Other bacteria survive and proliferate in the body
by producing hemolysins, leukocidins, coagulases,
exotoxins, and endotoxins that injure cells and
tissues.
• Exotoxins are metabolic proteins released into the
environment primarily from gram-positive
bacteria during bacterial growth. These proteins
have highly specific effects on host cells.
• Endotoxins are lipopolysaccharides contained in
the cell walls of gram-negative bacteria that are
released from cell walls during lysis or destruction
of the bacteria. Their effects are generalized.
 Viruses

• Viruses are intracellular parasites that take over the genetic

and metabolic machinery of host cells and use them for
their own survival and replication.
• Virusescontain genetic information in either DNA or RNA.
This genetic material is protected by a protein coat that
must be removed in the cytoplasm of the host cell if the
virus is to replicate.
 Function of Virion
• 1) cell protein synthesis cessation,
• 2) disruption of lysosomal membranes resulting in release
of enzymes that can kill the host cell,
• 3) fusion of host cells,
• 4) alteration of antigenic properties causing the immune
system to attack the host cell as if it were foreign,
• 5) transformation of host cells into cancerous cells,
• 6) promotion of secondary bacterial infections that result
from tissue damage by the viral infection.
 Fungi

• Fungi are relatively large organisms with thick walls that

grow as either single-celled yeasts or multicelled molds.
Molds are aerobic, and yeasts are facultative anaerobes.
Pathogenic fungi release mycotoxins and enzymes that
damage connective tissues.
• Diseases caused by fungi are called mycoses.
• Most fungi grow as parasites on or near skin or mucous
membranes and usually produce mild and superficial
disease
 fungi
• Fungi causing deep infection enter the body through
inhalation or through open wounds.
• Deep infections are most common in association with other
diseases or as opportunistic infections in
immunosuppressed individuals.
• Some fungi are part of the normal body flora and become
pathogenic when antibiotics kill bacteria that normally
compete for nutrients and preclude fungal growth.
For example, yeasts in the vagina may undergo rapid
proliferation when antibiotics kill vaginal bacteria.
 Parasites
• Parasites range from unicellular protozoa, which are
eukaryotic, to large worms.
• Parasitic worms include Helminthes, roundworms, and
tapeworms.
• Tissue damage may result from infestation in the tissue or
may be secondary to the individual’s immune and
inflammatory responses.
• Parasitic and protozoal infections are rarely transmitted
from human to human.
Infection spreads mainly through vectors or through
contaminated water or food.
 The Inflammatory Response
• Key purposes = DEFENSE

• To hunt & kill invaders

• To limit their spread
• To prepare tissue for repair

• Key events

• Increase of vascular permeability

• Recruitment (margination) & emigration (diapedesis) of WBC’s
• Phagocytosis
 The Inflammatory Response
• Inflammatory response = normal body defense mechanism to tissue injury
» Note: Inflammation is NOT infection

• Cells of the inflammatory response when get tissue injury

– Main groups;
• Phagocytes --- “the eaters”
– Macrophages --- become active as APC’s (antigen presenting cell)
– Neutrophils --- “little eaters”
– Monocytes --- become tissue macrophages
• T- lymphocytes (helper-T) ---- produce cytokines which “ call all to action”

• Platelets ---- release PAF (platelet activating factor) which in turn begins call
to action and release of chemical mediators

• Mast cells --- release chemical mediators that begin inflammation

 Chemical Mediators

• The initial “macrophage (APC cell) – antigen complex” causes chemical

mediators to be released:
– Histamine
• From basophils & mast cells
• Cause vasodilation & increased permeability of vessels via release of
nitric oxide
– Prostaglandins
• Made in mast cell membrane from fatty acid (arachidonic)
• Cause pain & vasodilation

– Leukotrienes
• “bad” prostaglandins since cause symptoms of inflammation (pain
& swelling)
• Cause chemotaxis
• Very important for causing allergies, asthma, & anaphylaxis
 Chemical Mediators

– Complement
• Coats bacterial surface; enhances phagocytosis & lyses bacteria
• Inactive plasma proteins become activated by initial An-Ab complex

– Interferon
• Proteins that are released by helper T’s & kill viruses

– Bradykinins
• From inactivated plasma protein
• Cause similar effects like histamine
• Cause pain
• Induce WBC’s into area (chemotaxis
• Local effects of inflammation
– 5 cardinal signs of inflammation
• Redness (rubor) – from increased blood supply
• Heat (calor) – from increased blood supply
• Swelling (tumor) – from increased permeability & increased proteins in
interstitial fluid
• Pain (dolar) – from chemical mediators
• Loss of function
– Also get inflammatory exudate
• Serous – from allergic reactions & burns
• Purulent – from infections
– May lead to abscess
• Systemic effects of inflammation
– General malaise
– Fatigue
– Headache
– Fever
• Caused by pyrogens (chemicals released from phagocytes)
• Beneficial
– Inhibits growth of pathogens
– Enhances repair process via increased metabolic rate
• Leukocytosis
• Chemotaxis
• Margination
• Diapedesis
• Potential complications of inflammation
• Infection
• Ulceration – from chronic inflammation
– May lead to:
» perforation of viscera
» excess scar formation
• Skeletal muscle spasm
• Local tissue reactive changes
– Joints from decreased ROM become stiff
– Lungs cannot exchange gases

• Diagnostic tests for inflammation

• Differential WBC count
• ESR
• Cell enzymes – may or may not be tissue specific
– C-reactive protein
• Chronic Inflammation
– The acute inflammatory reaction usually subsides within 48 –72 hours as
long as the cause is removed (e.g. touching a hot stove)
– If the cause persists, you get chronic inflammation
– Clinically:
• Increase in connective tissue reaction to the chronicity
– Get more fibroblasts & more collagen
» Thus get more scar tissue
» Can get granulomas (collection of chronically inflamed tissue)

• Treatment of inflammation
• Aspirin
• NSAID’s
• Glucocorticoids
• Heat & cold
• Physiotherapy if chronic
» Prevents contractures
 Healing
• 3 ways depending on the tissue involved & degree of injury
– Resolution
• Damaged cells recover in short time
• Exp = mild sunburn
– Regeneration
• Damaged cells replaced by identical cells via mitosis
• Only occurs in epithelia & connective tissue
• If complex organ, some damaged tissue replaced by regeneration
& some by scar
– Scar formation
• Key tissue = granulation tissue(highly vascular connective tissue)
» Collagen produced by fibroblasts makes granulation
tissue into scar tissue
• Scar tissue is non-functional
• Healing by primary or secondary intention
– Depend weather edges of lesion can be brought together
– Primary (first) intention gives small scar formation
– Secondary intention gives large scar formation
– Heals via granulation tissue
• Complications from large scar formation
– Loss of function
– Contractures & obstructions
• Can lead to stenosis
– Adhesions
– Ulceration
• Factors promoting healing
• Nutrition
• Blood supply
• Cleanness of area
• Lack of complications
• Factors delaying healing
• Old age
• Presence of foreign material
• Poor blood supply
• Poor nutrition
• Complications (bleeding, hematoma, excessive mobility)