Inflammation

By Dr Madeeha Minhas
For Pathophysiology for Nursing PNUR-213
Learning objectives
After the completion of this topic the student should be able to recognize and describe:
• Session 1 (Inflammation- Acute inflammation)
• Define inflammation and its types i.e., acute, and chronic.
• Enlist the cardinal signs of inflammation.
• Enlist the causes of acute inflammation
• Describe the process of acute inflammation with outcomes
• Describe the vascular and cellular events
• Name the various inflammatory mediators and outline their role.
• Define and differentiate exudate and transudate
• Differentiate between the types of acute inflammation with examples.

• Session 2 (Inflammation-Chronic inflammation)

• Define Chronic inflammation
• Enlist the causes of chronic inflammation
• Describe the process of chronic inflammation with outcomes
• Compare and contrast acute and chronic inflammation.
Lecture outline
Inflammation
• A protective response from vascularized tissue to injury
• Intended to Recognize, Remove-the injurious agent and Repair
the injured tissue (3Rs)
• Suffix “-itis” signifies disease process with inflammation
• Two types
• Acute
• Chronic
Inflammatory process- pathogenesis
In Vascularized tissue this
protective response occurs in 2
main phases:
1. Blood vessels experience=
vascular changes:
• Vasodilation
• Increased permeability
• Turbulent blood flow
2. Cellular events:
Types of WBCs • White blood cells (WBCs)
https://en.wikiversity.org/wiki/WikiJournal_of_Medicine/Medical_gallery_of_
Blausen_Medical_2014 • Chemical mediators
Vascular events
1. Vasodilatation i.e., widening of blood vessels due
to relaxation of smooth muscle cells within the
vessel walls. It leads to more blood flow to the area
of inflammation, resulting in redness and heat.
2. Vascular permeability: endothelial cells become
"leaky" either from direct endothelial cell injury or
via chemical mediators released at the site of
inflammation.
3. Exudation: fluid, proteins, red blood cells, and
white blood cells escape from the intravascular
space as a result of increased vascular permeability
and raised intravascular hydrostatic pressure
 Changes in blood flow
Normal Inflammation

The diagram illustrates the process of exudation, aided

by endothelial cell contraction and vasodilatation,
which is most pronounced in VENULES
Cellular events
• Prominent cell in acute inflammation is Neutrophil
• Their number peaks within 12-24 hrs & declines in 24-48 hrs.
• After that macrophages increase in number in the next 2-3 days
Sequence of cellular events in inflammation
1. Margination:
WBCs start occupying peripheral
position at the margins of the
blood column (near the
vascular endothelium). This
phenomenon is called
margination-Turbulent flow
Turbulent flow allows margination
to occur because WBCs
encounter endothelial cells
2. The WBCs tumble over the 3. Then WBCs adhere to the
endothelium i.e., Rolling- Selectins endothelial surface i.e., Adhesion-
Integrins

4. WBCs assume a flattened 5. Transmigration is the emigration

appearance (as paving stones) i.e., of WBCs from the blood to tissue
Pavementing spaces. It occurs at the endothelial
gaps of post capillary venules
6. Chemotaxis:
It is a directed migration of WBCs after extravasation towards the site of
injury. This takes place under the effect of chemotactic agents
• Chemotactic agents:
• Bacterial products (C3b)
• Complement system components (C5a, C3a)
7. Phagocytosis:
Engulfment of debris, infectious agents (bacteria/ fungi) and dead cells
by the phagocytic cells i.e., Macrophages & Neutrophils.
Acute inflammation
• Rapid, and Transient response
from the vascularized tissue
• Clinically this type begins
immediately and lasts for less
than 3 weeks
• In acute the 3Rs are in sequence
• Predominant cell type is
Neutrophils
Causes of acute inflammation
• Physical agents
• Trauma (blunt/sharp), radiation, extremes of temperature
• Infection
• Most bacteria, some viruses (influenza/ rhinovirus)
• Chemicals
• Acid, Alkali, Toxins
• Ischemia/ Infarction– lack of blood supply
• Immune reactions- hypersensitivity
Types of acute inflammation (based on exudate)
1. SEROUS: seen on body surface or mucosa in mild injury such as blisters, upper
respiratory infection. Straw-yellow or clear fluid rich in protein with few cells
(inflammatory edema)

2. FIBRINOUS: more than mild injury as in pericarditis, Pleuritis. Fibrinogen leaks

into interstitial space

3. SUPPURATIVE: characterized by the production of large amounts of purulent

exudate or pus. Pus is a thick creamy fluid composed of intact and
disintegrating neutrophils, within a background of liquefied necrotic tissue. It
is a characteristic response to certain types of bacteria that are “pyogenic”
(pus producing), e.g., Staphylococcus aureus

4. HAEMORRHAGIC: hemorrhage predominates, seen following trauma or severe

injury to blood vessels: e.g., hematoma
Cardinal signs of inflammation
Description of inflammation involves identification of specific
features at the site of injury known as cardinal signs
Seen mostly with acute inflammation
Cardinal sign Corresponding changes that cause the sign to appear
Rubor (redness) Hyperemia: As capillaries and venules dilate the blood flow to the
injured area increases. Inflamed area appears red & hot because of
Calor (heat) hyperemia
As blood flow increases capillary Hydrostatic pressure rises, so fluid
Tumor (swelling) moves out of vessels into the tissues, leading to the swelling .i.e.
Transudate formation
Dolor (Pain) Increased permeability at post capillary venules: This increases the
outflow of fluid, plasma proteins & WBCs from the capillaries into
Functio laesa (loss of the tissues, known as Exudate. Increase in swelling leads to pain
function)
Increased permeability creates edema
• Transudate
• Result of raised hydrostatic pressure
• No change in vascular permeability
• Ultra filtrate of plasma
• Low protein content
• Specific gravity <1.012

• Exudate
• Seen in inflammation
• Vascular permeability increases
• High protein content
• Specific gravity >1.020
Outcomes of acute inflammation
• Resolution:
Short lived injury with minimal
tissue damage, outcome is
complete restoration of tissue.
• Abscess formation (Pus)
• Progression to chronic inflammation:
If the offending agent is not
removed chronic inflammation
follows
• Scarring and fibrosis:
Seen after extensive tissue
destruction or when inflammation
occurs in tissues which do not
regenerate
Chemical mediators
• Substances that are released at the • Types of CM:
site of injury and bring about • Plasma derived
changes in inflammation are called
chemical mediators • Cell-derived
• Preformed
• Functions: • Newly synthesized
• Mediate vascular and cellular events
• Produce signs and symptoms of
inflammation

• Factors causing release of CM:

• Microbial products (LPS or C3b)
• Complement proteins (C3a, C5a etc)
• Antigen-antibody complex
Plasma derived
• Circulating in the plasma
• synthesized in the liver as
inactive precursors
• These get activated at the site of
inflammation by action of
certain enzymes
Cell-derived
Produced by the cells at the site of
injury
Preformed
• intracellular granules
• rapidly secreted when cells are
activated by a stimulus
Synthesized (new)
• after injury in response to a
stimulus
Plasma derived- mostly originate from liver

• C-reactive protein (CRP)* and serum amyloid A

Acute phase
(SAA)* because of IL-1 cause fever and increase
proteins
inflammation

Factor XII • Clotting/ Fibrinolytic system

(Hageman factor
• Kinin (bradykinin)
activation)

Complement • C3a, C5a (neutrophil chemotactic agents)

system • C3b (opsonin)

* Jain S, Gautam V, Naseem S. Acute-phase proteins: As diagnostic tool. J Pharm Bioallied Sci. 2011 Jan;3(1):118-27. doi: 10.4103/0975-7406.76489. PMID: 21430962; PMCID: PMC3053509.
Cell derived
Histamine • Mast cells and Platelets
Preformed
Serotonin • Platelets only

Prostaglandins
(PGE2, PGD2 etc) • All WBCs + mast cells

Leukotrienes
(LTC4, LTD4 etc) • All WBCs + mast cells

Platelet activating
factor (PAF) • All WBCs + Endothelial cells
Synthesized Nitric oxide (NO) • Macrophages + Endothelial cells

Cytokines (TNFα, • Macrophages + Lymphocytes+ endothelial cells

IL-1) + mast cells

Reactive Oxygen
• All WBCs
Species (ROS)
Role of Chemical mediators in Inflammation
• Histamine
Vasodilation • Prostaglandin PGI2
• Platelet activating factor (PAF)

• Serotonin
Increased permeability • Prostaglandin (PGE2)

• Leukotrienes LTC4, LTD4, LTE4

Chemotaxis • Chemotactic cytokines= Chemokines e.g., C3a, C5a

Pain • Bradykinin
Chronic Inflammation
• Prolonged and delayed response
from the vascularized tissue
• Clinically complains from this
type can persist for months or
years
• 3Rs are not in sequence i.e.,
occur together
• Injury+inflammation+repair
• Predominant cell type
• Agranulocytes like (images)
Causes of Chronic inflammation
1. Atypical bacteria-
Mycobacterium tuberculosis (TB), Treponeme pallidum (Syphilis-STD)
2. Virus-
HBV/HCV
3. Recurrent acute inflammation (comes and goes)
e.g., Chronic bronchitis
4. Unresolved acute inflammation (never resolved)
e.g., Chronic Cholecystitis
5. Foreign substances
Glass, sutures etc
6. Idiopathic
Pathogenesis
• Injurious agent is either not successfully recognized or removed and
the repair process involves angiogenesis and fibrosis

• Infiltration by Mononuclear cells (macrophages, lymphocytes &

plasma cells) indicating continuous reaction to injury

• Tissue destruction done by Inflammatory cells & injurious agent.

• Repair to replace the lost tissue. So, angiogenesis and fibrosis is seen
Cells of Chronic Inflammation (Mononuclear cells)
• Monocytes
• Present in blood as monocyte.
• Reach site of injury and transform into
macrophages in tissue within 24–48 hrs

• Lymphocytes
• B- cells à plasma cells à antibodies
• T-cells
Types of chronic inflammation
• Two patterns under the microscope give two types:
1. Chronic Non-specific
2. Chronic Granulomatousà (two further types) Caseating or non-caseating

• There is diffuse accumulation of lymphocytes, plasma cells and

macrophages at the site of injury in Chronic Non-specific Chronic
inflammation (as seen in causes #2,3,4)
• Formation of a specific lesion known as Granuloma is seen in Chronic
Granulomatous Inflammation (as seen in causes #1, 5, 6)
Granuloma
Caseating Non-caseating
Causes of Granuloma by types
• Infective Granulomas: • Based on the type of giant cells-
- Tuberculosis (TB) aggregated epithelioid cells
- Syphilis
- Fungal Infection
• Caseating- TB- Langhan cells
• Foreign Body Granulomas:
- Talc and sutures
- Asbestos • Non-caseating- Foreign body,
sarcoidosis
• Idiopathic (unknown cause)
Granulomas:
- Sarcoidosis
Systemic signs of inflammation
• In addition to the local/ cardinal signs there may be effects on the entire body
caused by chemical mediators in the circulation-
• Some of these are measurable in the laboratory by a blood test
• Total WBCs
• Leukopenia: decreased number of circulating white cells e.g., Typhoid fever
• Leukocytosis: Elevated white blood cell count e.g., most typical bacterial infections

• DLC- differential leukocyte count (gives % of specific cell change)

• Bacterial infection (neutrophilia)
• Parasitic infection (eosinophilia)
• Viral infection (lymphocytosis)

• ESR- Erythrocytic sedimentation rate (increased in inflammation)

• CRP- C-reactive protein (increased in inflammation)
• Specific antibody levels
Systemic signs of inflammation
Features affect the entire body observed in the clinic with cause
• Fever
• Hypotension
• Tachycardia Chemical mediators TNF-α and IL-1
• Anorexia (Loss of appetite)
• Loss of weight
• Fatigue
• Sweats
• Chills