Basic concepts in Humane pathology

1. INFLAMMATION
Prof DR AHSAN KAZMI
Pathology Department
Sahara Medical College
Narowal

2. SOURCES OF CHEMICAL
MEDIATORS

3. KININ SYSTEM
 Leads to formation of bradykinin from cleavage of precursor
High molecular-weight Kininogen (HMWK) and rapidly
inactivate kininase.
 A circulating plasma protein which participates in the
initiation of blood coagulation, and in the generation of the
vasodilator bradykinin via the kallikrein-kinin system.
 HMWK is inactive until it either adheres to binding proteins
beneath an endothelium disrupted by injury, thereby
initiating coagulation; or it binds to intact endothelial cells
or platelets for functions other than coagulation.
 Activation of this system results in pain initiation by
increasing vascular permeability and smooth muscle
contraction.

4. Function of complement product
• C3a,C5a……..anaphylatoxin , chemotaxis
• C3b……opsonization. fix the bacterial cell wall ,act as
opsonin causing phagocytosis
• C5b-9…… membrane attack complex MAC

5. Vasodilation Prostaglandins
Histamine
Nitric oxide
Increased vascular permeability Vasoactive amines
C3a C5a Bradykinin
Leukotrienes C4, D4, E4
PAF
Substance P
Chemotaxis, leukocyte
recruitment and activation
C5a
Leukotriene B4
Chemokines
IL-1, TNF
Bacterial products
Fever IL-1, TNF
Prostaglandins
Pain Prostaglandins
Bradykinin
Tissue damage Lysosomal enzymes
Oxygen metabolites
Nitric oxide
Inflammation
Events
And
Related
Chemicals

6. Task
• A photomicrograph of inflamed
tissue showing a vessel and
surrounding interstitium.
• Describe the sequence of vascular
and cellular events which have
resulted in accumulation of fluid
and neutrophils in the interstitium
• What is the purpose of this
process?

7. Defects in leukocyte function
Following Defects in:
• Adhesion : genetic defects in integrins selectins
• Chemotaxis: Lazy leukocyte syndrome (abnormal neutrophil motility)
• Phagolysosome function e.g. Chediak –Higashi syndrome
• Microbicidal activity
• Acquired deficiencies: immunosuppression

9. Response of Lymphatic Vessels
and Lymph Nodes
• Lymphatics drain the small amount of extravascular fluid
that seeps out of capillaries under normal circumstances
• In inflammation, lymph flow is increased to help drain
edema fluid that accumulates because of increased
vascular permeability
• Lymphatic vessels, like blood vessels, proliferate during
inflammatory reactions to handle the increased load.
• Leukocytes cell debris and microbes, may also find their
way into lymph

10. Responses of Lymphatic Vessels and
Lymph Nodes
• Lymphangitis-The lymphatics may become secondarily
inflamed
• Lymphadenitis- inflammation of draining lymph nodes
• Inflamed lymph nodes are often enlarged because of increased
cellularity.
• This constellation of pathologic changes is termed Reactive,
Or Inflammatory Lymphadenitis

11. Responses of Lymphatic Vessels and Lymph
Nodes
For clinicians
• The presence of red streaks near a skin wound is a telltale sign of an infection in
the wound.
• indicates the presence of lymphangitis
• It may be accompanied by painful enlargement of the draining lymph nodes,
indicating lymphadenitis

12. Outcomes/Consequences Of Acute
Inflammation
• Complete resolution
• Little tissue damage
• Capable of regeneration
 Abscess formation
occurs with some bacterial or
fungal infections
• Scarring (fibrosis)
• In tissues unable to regenerate and excessive damage
• Progression to chronic inflammation

14. 15

15. Acute
Inflammation
• Rapid onset
• Short duration
• Neutrophils
• Usually mild and self-
limited tissue injury
• Local and systemic signs
prominent
• Exudate
Chronic Inflammation
• Insidious onset
• Long duration
• Lymphocytes &
macrophages
• Often severe and
progressive
• Less prominent
• Proliferation of blood
vessels and fibrosis in
addition

16. Comparison of Acute and Chronic Inflammation
• Chronic inflammation
• Persistent injurious
agent
• Non-degradable
foreign matter
• Auto-immune reactions
• T-lymophocytes &
macrophage products-
cytokines and GF’s
• Proteases and reactive
oxygen
• Complement, lipid
mediators
• Acute inflammation
• Microbial surfaces &
fragments
• Injured tissue & tissue
fragments
• Mast cell products
(histamine)
• Bradykinin
• Lysosomal
components
• Complement, lipid
mediators
• Process
• Initiators
• Mediators

17. Comparison of Acute and Chronic Inflammation
• Chronic
inflammation
• Angiogenesis
• Monocytes/Macrop
hages, Plasma
cells, Fibroblasts
• Insidious onset,
weeks  years
• Resolution, Tissue
destruction fibrosis
• Acute
inflammation
• Vasodilatation &
permeability
• Neutrophils
• Acute onset,
minutes  days
• Resolution,
Abscess
• Process
• Vascular
changes
• Cell
populations
• Time course
• Outcome

18. SYSTEMIC EFFECTS OF INFLAMMATION
ACUTE-PHASE RESPONSE:
• Fever cytokines (TNF, IL-1) stimulate production of
prostaglandins in hypothalamus
• Elevated plasma levels of Acute-phase Proteins:
• C-reactive protein (CRP)
• Fibrinogen
• Serum Amyloid A (SAA) protein
• Leukocytosis
raised WBC count 15,000 to 20,000 cells/µL .
leukemoid reactions 40,000 to 100,000 cells/µL

19. Laboratory Diagnosis
• Leukocytosis: Acute Inflammation
• Neutrophilia: Bacterial infection
• Eosinophilia: Parasitic infection
• Lymphocytosis: Viral infection,Chronic
infection
• ESR: raised in inflammation
• CRP: raised in inflammation

20. Blood CP

21. Morphological patterns of
Acute Inflammation

22. Types/ Morphological patterns of Acute
Inflammation
• Serous
inflammation:
inflammation in
which there is
out pouring of
thin serous fluid
derived from
plasma or
mesothelial
secretion .
• e.g. Skin blister
skin blister showing the epidermis separated from
the dermis by a focal collection of serous effusion

23. Morphological patterns
• Fibrinous inflammation: inflammation in which exudate
contains a lot of fibrin. Present in body cavities, e.g.
meningitis, pericarditis, pleuritis , peritonitis
Fibrinous pericarditis. A, Deposits of fibrin on the pericardium. B,
A pink meshwork of fibrin exudate (F) overlies the pericardial
surface (P).

24. Morphological patterns
• Purulent
inflammation/abscess:
characterized by
production of pus
consisting of
neutrophils,
liquefactive necrosis
and edema fluid.
An abscess, containing
neutrophils and cellular
debris and is
surrounded by
congested blood

25. Morphological patterns
• Ulcer: a local defect or
excavation of surface of
organ or tissue produced
by sloughing of inflamed
necrotic tissue
Ulcer. A: A chronic duodenal
ulcer.
B: Low-power crosssection of a
duodenal ulcer crater with an
acute inflammatory exudate in
the base

26. A 68-year old man presents with fever, shaking chills,
and shortness of breath. Physical examination shows
rales and decreased breath sounds over both lung
fields. The sputum displays numerous neutrophils.
Removal of bacteria from the alveolar air spaces in
this patient involves opsonization.
• This is an important step in mediating which of the
following leukocyte functions?
• (A) Chemotaxis
• (B) Diapedesis
• (C) Stasis
• (D) Margination
• (E) Phagocytosis

27. ANSWER
This is an important step in mediating which of the
following leukocyte functions?
• (E) Phagocytosis

28. • Why are there numerous neutrophils in the sputum?
• What might be the duration of his illness ?
• Why did the physician find rales and decreased breath
sounds over both lung fields?
• What will you find in blood CP report in this patient?

29. THANK YOU