UNIT TWO
ALTRATION IN BODY DEFENCE
Inflammation Definition: is a local response (reaction) of living vascularized tissues
to endogenous and exogenous stimuli (the same stimuli causing cell injury). The term is derived from the Latin "inflammare" meaning
to burn. Inflammation is fundamentally a protective (Physiologic)
response destined to localize and eliminate the causative agent and to limit tissue injury
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Causes: The same as causes of cell injury or diseases.
Nomenclature: The name of the inflamed tissue or organ is suffixed with
'itis'. Thus inflammation of appendix is called appendicitis and of
meninges as meningitis, etc. Exceptions = Pleura -- pleurisy, rectum – proctitis, lung –
pneumonia, etc.
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Inflammation accomplishes its missions by trying to dilute, destroy or otherwise neutralize the offending agents.
The inflammatory response is followed by a
set of repair processes designed to regenerate the damaged tissue and/or fill the gaps with fibrous tissue (scar).
Components of the Inflammatory Response
Acute Inflammation Transient and early response to injury (e.g., bacterial infection) Involves release of chemical mediators, causing stereotypic
vessel and leukocyte responses.
Cardinal signs of inflammation Rubor (redness): histamine-mediated vasodilation of arterioles Calor (heat): histamine-mediated vasodilation of arterioles Tumor (swelling): histamine-mediated increase in permeability
of venules Dolor (pain): caused by prostaglandin E2 and bradykinin
Vascular events 1. Transient vasoconstriction of arterioles
lasts only seconds
2. Vasodilation of arterioles
mast cells release histamine, which acts on vascular smooth muscle and causes increased blood flow.
3. Increased permeability of venules:
histamine contracts endothelial cells of the vessels, causing movement of a transudate into interstitial tissue.
4. Swelling of tissue:
outflow of fluid surpasses lymphatic ability to remove fluid.
5. Reduced blood flow:
caused by outflow of fluid from blood vessels
Cellular events 1. Margination:
Red blood cells (RBCs) aggregate into rouleaux ("stacks of coins") in venules, with the neutrophils pushed to the periphery.
2. Rolling:
Selectin molecules on the cell surfaces cause the neutrophils to "roll" along the endothelium or to adhere to it temporarily.
3. Adhesion:
neutrophils adhere to endothelial cells.
4. Transmigration:
neutrophils move through the basement membrane of venules and release type IV collagenase, producing an exudate in the interstitial tissue.
5. Chemotaxis:
neutrophils migrate toward bacteria.
6. Phagocytosis:
neutrophils ingest opsonized bacteria.
7. Bacterial killing by neutrophils
PNEUMONIA Microbial invasion of the lung parenchyma evoking exudative solidification
(consolidation) of the lung tissues. Etiology: Pneumonia can be caused by bacteria, viruses, fungi, parasites,
chemicals etc... Classification Based on etiologic agents bacterial: pneumococcal, staphylococcal, mycoplasma, etc: viral: iffluenza, respiratory syncythial virus etc fungal: Histolasopasma captulatum, Aspagilla Fumigatus, etc paracytic: chemicals:
Based on the gross anatomic distribution of the disease broncho pneumonia and lobar pneumonia
PATHOGENESIS The resparatory airways and alveoli are exposed air containing
hazardous dusts,chemicals and micro-organisms. Small particles about the size of most bacteria 1-5µm are
deposited in the terminal airways and alveoli. The normal lung is free from bacteria There are potent defence mechanisms that clear or destroy
any bacteria inhaled with with air. Nasal clearance
Sneezing,or blowing.
Tracheo-brnchial clearance
Mucocilliary action that eventually expectoriated or swallowed.
Alveolar clearance
Bacteria or solid particles deposited in alveoliare phagocytosed by alveolar macrophages.
Pneunonia can result whenever these defencesmechanisms are impaired or the resistance of the host in general is lowered.
Factors that affect the resistance in general include chronic diseases, immunologic deffieciencies, treatment with immunosuppressive agnts and unusal virulent infections
The Clearance mechamims can be interfered by
many factors including Loss or suppression of cough reflex, as a result of
coma,
anesthsea,
neuromuscular disorders, drugs or chest pain (this may lead to aspiration of gastric contents).
Injury of mucocilliary apparatus
Owing to cigarette smok
Inhalation of hot or corrosive gases,
Viral diseases
Intrefrance with phagocytic or bactericidal
action of alveolar macrophages Alcohol Tobacco s anoxia
LOBAR peumonia
Brochopeumonia
First L ung infection
First bronchi and bronchioles then lung parenchyma
Age
Young adult
Extremes of age
Organisms
Pnumococci, and Any organism occasionally Klebssella
Health status (previous)
Healthy
Predisposed by viral infection, bronchitis, cancer etc..
Site
any lobe
Most lower lobes or bilaterally
Gross
Consolidative
Patchy (3 - 4 cm elevatel, granular)
Prognosis
Bad
Worse
Resolution
Common
Uncommon, with complications
Route
Morphology of lobar pneumonia Pneumooococci and Klebsiela mainly cause lobar pneumonia Lolar pneumonia is characterized by four stages. Acute congesition
lasts - 2 days.
The lung heals, dark and firm.
The alveoli are filled with eosinophilic edema, containing many grampositive diplococci and PMNs
Red hepatization
lasts 2nd to 4th day.
Lung is dry, firm, red and granular.
The pleural surface, grey-white and friable.
The capillaries engorged, filled with fibrin exudates, RBC and numerous neutrophils.
Grey hepatization –
lasts 4th - 8th day:
Cut surface is dry, granular and grey.
Alveoli contain fibrins, dead and live neutrophiles and occasionally degenerating erythrocytes.
Resolution –
after 8th day:
migration of macrophages from the alveolar space into the exudate, which latter liquefied by fibrinolytic system
Complete resolution and aeration takes 1-3 weeks, but pleural adhesion between the two layers usually persists.
These classic stages (phases) of lobar pneumonia are now
infrequent owing to effective antibiotic thrapy that prevent the deveopment of full blown lobar consolidations.
Malaria Mosquito- born, hemolytic, febrile illness. It infects over 200 million persons per year and kills
more than 1 million Four species of plasmodium cause malaria: P. falciparum P. Vivax P. Ovale P. Malariae
P. falciparum causes more severe disease than the
others.
Epidemiology Common in tropical and subtropical areas
especially in African, South and central America, and South East Asia. If is transmitted by the bite of female
Anopheles mosquito. P. fellciparum and P. Vivax are the most
common causes in Ethiopia
Pathogenesis Sporozoites inside Anopheles mosquito Human skin Sporozoites Liver Gametocytes Schizonts Merozoites Rupture of RBCs
RBCs
Schizonts Inside RBCs
P. Falciparum the cause of severe malaria is distinguished from other malarial parasites in four
aspects:
has no secondary hepatic stage.
there is high parasitemia and anemia.
there may be several parasites in a single RBC.
it charges the flow characteristics and adhesive qualities of infected RBC so that
they adhere to the endothelial cells of small blood vessels. The obstruction of small blood vessels frequently produces severe tissue ischemia,
which is probably the most important factor , in the virulence of P. falciparum
Pathology Enlargement of the liver & spleen by sequestered red
blood cells. These organs appear dark because of macrophages filled
with hemosiderin and malarial pigment. Obstruction of Capillaries of deep organs by P.
falciparum infected RBCs leading to ischemia of different organs ( Kidneys, lungs, brain, etc) Intravascular hemolysis causes hemoglobinuric
nephrosis (“ black water fever”) In the lungs damage to alveolar Capillaries leads to
pulmonary edema and acute alveolar damage.
Clinical Feature High grade intermittent fever Chills Headache nausea, Vomiting and abdominal Pain Hypotension hepatosplenomegally anemia
P. falciparum: Ischemic injury to the brain Somnolence Hallucinations Seizure & coma. the mortality is 20 % to 50 %
Chronic Inflammation Inflammation of prolonged duration (weeks to years) most often results from persistence of an injury-
causing agent. Injurious agents include infectious diseases (e.g.,
hepatitis C, tuberculosis) and alcohol.
Morphology 1. Cell types:
Monocytes and/or macrophages,
Lymphocytes and/or plasma cells, eosinophils, fibroblasts, endothelial cells
2. Necrosis:
not as prominent a feature as in acute inflammation
3. Destruction of parenchyma:
loss of functional tissue,with repair by fibrosis
Granulomatous inflammation 1. Causes Infectious agents
include tuberculosis and systemic fungal infection;
usually associated with caseous necrosis
Noninfectious causes include
sarcoidosis and Crohn's disease;
associated with noncaseating necrosis
2. Morphology Gross: pale
white nodule with or without central caseation
Microscopic
Usually well-circumscribed
Cell types: epithelioid
cells (activated macrophages),
mononuclear
(round cell) infiltrate(CD4 helper T cells,
or TH cells of the TH 1 type)
Multinucleated giant cells: fusion
of epithelioid cells; nuclei usually at the
periphery
TUBERCULOSIS Tuberculosis is a chronic communicable
disease Etiology M. tuberculosis (Principal) M. bovis (rare) M. hominis (rare)
The lungs are the prime target, but any organ may
be infected. M. tuberculosis is a slender beaded, non- motile
acid fast bacillus.
Epidemiology Disrupted through out the world Annual incidence: USA: 12/100,000 Some developing countries 450/100.000
It is transmitted by aerosolized depletes during coughing,
sneezing and talking all create aerosolized respiratory droplets. Tuberculosis can also be caused by M. bovis Humans acquire infection by these rare organisms following
ingestion of raw milk
Generally, tuberculosis infection is divided into two.
1.
Primary infection
This is an infection of persons who have not had prior
contact with the tubercle bacillus. Pathogenesis
1.
Inhaled droplets containing M. tuberculosis are
deposited in the alveoli. 2.
The organisms are phagocytosed by alveolar
macrophages but resist Killing by these unsensitized cells.
3.Proliferation of the organisms with in the macrophage 4.Degeneration of macrophages and release of organisms attracting additional macrophages and lymphocytes and eventually producing inflammation. 5.Some macrophages carry organisms from the lung to regional (hilar or mediastinal) lymphondes, and from their they may be disseminated by the blood stream to other sites in the body (kidneys, meninges, bones and other parts of the lungs) 6.Infected macrophages present tuberculous antigens to lymphotytes, which are then transformed and produce cytokines.
7. Cytokines activate macrophages increasing their concentration of lytic enzymes and augmenting their capacity to kill mycobacteria. The lytic enzymes also destroy host tissues. Epithelioid cells and Langhan’s giant cells are
activated macrophages.
The development of a population of activated
lymphocytes constitutes the hypersensitivity response to the organism. The related development of activated
macrophages capable of ingesting and destroying the organism comprises the cell medicated immune responses.
Pathology Macroscopic: Ghon focus is a small ill- defined area of inflammatory
consolidation which is found on the lower lobe. Ghon complex is the combination of Ghon focus and
involved hilar or mediastinal lymph node.
Microscopic Caseous granuloma is the classic lesion. It has soft Semisolid core surrounded by epithelioid
cells, Langhan’s giant cells, lymphocytes and peripheral fibrous tissue.
Out Come: > 90% have a self- limited course Progressive primary tuberculosis in which the immune
system fails to control the primary infection Miliary tuberculosis refers to infection at disseminated
sites that produces multiple, small, yellow and nodular lesions in several organs.
Clinical Picture of Primary Tuberculosis Primary tuberculosis is generally asymptomatic.
2.
Secondary (Cavitary) Tuberculosis
This results from the proliferation of the organisms
in a person who has been previously infected and has mounted an immunologic response. The sources of infection are: Dormant organisms from old granuloma. Newly acquired bacilli.
Causes: - Cancer,Chemotherapy, AIDS,
Malnutrition, Old age & Others
Pathology The lungs are the commonest sites The apical lobe is mainly affected Hypersensitivity and cell-mediated immunity lead to tissue
necrosis and the production of tuberculous cavities. Cavities are typically 2 to 4cm in diameter.
Clinical picture Cough, low grade fever, malaise, fatigue, anorexia, weight
loss night sweats. Hemoptysis (Coughing up of blood) Chest x- ray shows apical cavities.
Leprosy (Hansen’s Disease) Is a chronic slowly progressive, distractive process involving
peripheral nerves, skin, and mucous membranes.
Etiology: M. leprae (slender, acid- fast rod)
Epidemiology: M. leprae is shed in nasal secretions or from ulcerated lesions
of an infected person. The mode of infection is unclear, but it probably involves
inoculation of bacilli into the respiratory tract or into open wounds. Years of close contact with an infected person are required for
successful transmission of the disease. 15 million people are infected world wide
Pathogenesis M. leprae multiplies best at temperatures colder than
core human body temperature and lesions tend to occur in coaler parts of the body (e.g, the hands and the face) Depending on the differences in immune reactivity, the
lesions of leprosy may vary from small, insignificant and self healing macules of tuberculosis leprosy to the diffuse, disfiguring lepromatous. 95% of all persons have a natural protective immunity
to M. lepae and are not infected even though there is intimate and prolonged exposure.
Susceptible people (5%) may develop any one of the
following three clinical varieties of leprosy: 1. Anergic patients (those with little or no resistance) have lepromatous leprosy. 2. Hyperegic patients (those with high resistance) develop tuberculous leprosy. 3. Border line leprosy falls in between. The majority of patients belong to this group.
1. Tuberculosis leprosy This occurs in infected persons who manifest an effective graunlomatous
response that limits the proliferation of the bacillus and the extent of the disease.
Pathology Single lesion or very few lesions on the skin are characteristics. The lesions appear on the face, trunk or extremities. Microscopic : Well- formed, circumscribed. dermal granulomas. Composed of epitheliod cells, Langhans giant cells, and lymphocytes. There is no caseaus necrosis. Neurons are swollen and infiltrated with lymphocytes which is
responsible for sensory loss. Bacilli are rare and often not found with acid fast stain.
Clinical picture. Skin: Well- demarcated hypopigmented or erythematous, dry, hair-less
patches with raised outer edges. There is diminished sensation with in the patches. The lesions are not infectious. They cause only minimal disfigurement.
2.
Lepromatous leprosy
Occurs in persons who fail to develop adequate immune
response to the bacteria. There are progressive destructive lesions filled with
mycobacteria.
Pathology Multiple tumor- like lesions of the skin eyes, testes,
nerves, lymph nodes, and spleen. There is nodular or diffuse infiltrates of foamy
macrophages which contain the bacilli. The epidermis stretched thinly over the nodules There is a clear- zone of dermis between the tumor
and the epidermis. Globi is the name given to aggregates of acid- fast
materials with in the foamy macrophages.
Clinical picture Nodular skin lesions with or without ulceration Claw- shaped hands Hammer toes Saddle- nose Pendulous ear lobes Lion- like appearance (leonine facies) Chronic nasal discharge & voice change Blindness.
3.
Border line leprosy
These patients have variable combination of features of
both lepromatous and tuberculoid leprosy.
Wound Healing Demonstrates Epithelial regeneration (healing of the epidermis) and Repair by scarring (healing of the dermis).
Two patterns of wound healing
1. Healing by first intention (primary union) Occurs with clean wounds when there has been little
tissue damage and The wound edges are closely approximated The classicexampleis asurgicalincision
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Day 1: fibrin clot (hematoma) develops. Neutrophils infiltrate the wound margins. There is increased mitotic activity of basal cells of squamous
epithelium in the apposing wound margins.
Day 2: squamous cells from apposing basal cell layers migrate under the
fibrin clot and seal off the wound after 48 hours Macrophages emigrate into the wound.
Day 3: granulation tissue begins to form. Initial deposition of type III collagen begins but does not bridge the
incision site. Macrophages replace neutrophils. 46
Days 4-6: granulation tissue formation peaks, and collagen bridges
the incision site. Week 2: collagen compresses blood vessels in fibrous tissue,
resulting in reduced blood flow. Tensile strength is about 10%.
Month 1: collagenase remodeling of the wound occurs, with
replacement of type III collagen by type I collagen Tensile strength increases, reaching 80% within 3 months. Scar tissue is devoid of adnexal structures (e.g., hair, sweat
glands) and inflammatory cells 47
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2. Secondary union (healing by secondary intention) Occurs in wounds that have large tissue defects and when
the two skin edges are not in contact requires larger amounts of granulation tissue to fill in the
defect Often accompanied by significant wound contraction Often results in larger residual scars
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Factors affecting Healing: Systemic Nutrition Vitamin def. Age Immune status Other diseases
Local necrosis Infection apposition Blood supply Mobility Foreign body