heart failure

1. Alterations on body defense
• Revision of body defense mechanisms
• Inflammation (acute and chronic)

2. Types of Immunity
– Innate (nonspecific) – 1st line of defense
• Anatomic barriers (e.g, skin and mucous
membranes)
• Physiologic barriers (body temp., low pH in
stomach)
• Phagocytic cells (granulocytes)
• Inflammation
– Acquired (specific):
• Activation of white blood cells (lymphocytes)
• Develops following exposure to certain pathogens

3. Types of Leukocytes
• Granulocytes: Includes neutrophils,
eosinophils and basophils:
– Granular appearance
– Nuclei have multiple lobes
– Phagocytose foreign invaders
– Aid in inflammatory response
Phagocytosis: the cellular process of engulfing solid particles by the cell
membrane to form an internal phagosome, which is a food vacuole, or pteroid. The
phagosome is usually delivered to the lysosome, an organelle involved in the
breakdown of cellular components, which fuses with the phagosome. The contents
are subsequently degraded and either released extracellularly via exocytosis, or
released intracellularly to undergo further processing.

4. Types of Leukocytes, Continued
• Monocytes:
– Large phagocytic capability
– Play key roll in inflammation response
• Lymphocytes/plasma cells:
– Includes T- and B-cells
– Part of acquired immune response
– Lymphocytes have memory cells, give rapid response
when exposed to same pathogen
– Lymphocytes also have effector cells, producing
antibodies and try to remove foreign invaders

5. Intravascular Cells
• white blood cells
neutrophil eosinophil basophil
monocyte
lymphocyte
Granulocytes

7. Actions of Neutrophils
• Killing via phagocytosis
• Release of signaling molecules

8. Phagocytosis
• Phagocytosis:
• Engulfing and
degradation or digestion of
fragments of tissue or
material
1. long membrane evaginations,
called pseudopodia.
2. Ingestion forming a
"phagosome," which moves
toward the lysosome.
3. Fusion of the lysosome and
phagosome
(phagolysosome), releasing
lysosomal enzymes
4. Digestion of the ingested
material.
5. Release of digestion products
from the cell.

9. Secretion of Chemical Mediators
• Neutrophils secrete cytokines
Definition: cytokines are a category of signaling proteins and glycoproteins that, like
hormones and neurotransmitters, are used extensively in cellular communication.

10. Role of other Leukocytes
Monocytes/macrophages
Monocytes arrive at injury ~6 hrs after inflammatory response begins
They enlarge to form macrophages. Macrophages take up to 8 hours to
mature and form a large quantity of lysosomes, or digestive enzymes.
Macrophage then becomes the dominant type of cell. They are similar
to neutrophils, but with greater killing capacity.
Macrophages:
•Phagocytose foreign invaders
•Secrete chemical mediators
•Coordinate response of other body systems
•Act as intermediary between innate and acquired immune response
systems

11. Secretion of Chemical Mediators
• Macrophages secrete chemical mediators
to stimulate
– Inflammatory response
– Acquired immune response
– Systemic effects
Examples of chemical mediators include:
Interlukin 1 (IL-1)
Interlukin 6 (IL-6)
Tumor Necrosis Factor a (TNF-a)

12. Other Granulocytes
• Eosinophils
– Respond as neutrophil, but have less
phagocytic ability
– Attach and destroy parasites
– Prevent spread of inflammation
• Basophils:
– Release heparin, histamine, bradykinin,
serotonin (soluble mediators of inflammation)

13. Inflammation
• Nomenclature
• Inflmmatory lesions are usually
named by adding the suffix ‘ itis'
• -Inflammation of the appendix-
appendisitis, meninges - meningitis
• Exceptions =>Pneumonia, typhoid fever

14. General Features of
Inflammation
• In Cell Injury – various exogenous and
endogenous stimuli can cause cell injury
which involve the cells, nuclei and
organelles of the cells.
• In Vascularized Tissue – same
exogenous and endogenous stimuli
produce inflammation.

15. INFLAMMATION
Inflammation:
Inflammation is the reaction of blood
vessels, leading to the accumulation of
fluid (Serum) and leukocytes in extra
vascular tissue.

16. Role Of Tissue And Cells In
Inflammation
• Many tissue and cells are involved in
inflammation.
The tissue & fluid are:
• The fluid and proteins of plasma.
• Blood vessels.
• Cellular and extra cellular constituents of
connective tissue (mast cells & fibroblast).

17. Role of tissue and cells in
inflammation
The circulating cells are:
• Neutrophils.
• Monocytes.
• Eosinophils.
• Lymphocytes.
• Basophils.
• Platelets.

18. Sign & Symptoms Of
Inflammation
These are:
• Fever (increase temperature).
• Pain.
• Tissue damage.
• Swelling of tissue.
• Redness of tissue.
• Loss of movements or restricted
movement, if near joints.

19. Types Of Inflammation
Based on the duration and histologic
appearances Inflammation is divided into
I - Acute inflammation, which occurs over
seconds, minutes, hours, and days.
II - Chronic inflammation, which occurs
over longer times, days & months.

20. Acute Inflammation
• Acute inflammation, begins within
seconds to minutes following the injury of
tissues.
• The damage may be purely physical, or it
may involve the activation of an immune
response.

21. ACUTE INFLAMMATION
• Immediate response of living
(vascularized) tissue towards an injury
• The changes are essentially the same
whatever the cause & wherever the site

22. Causes of acute inflammation
• Microbial infections; bacteria, viruses,
fungi, etc
. immunologic disorders - autoimmunity,
hypersensitivity
. genetic/metabolic disorders . DM , gout
• Physical agents e.g., trauma, heat,
electricity, irradiation, etc
• Chemicals e.g., drugs, acid, alkaline
• Tissue necrosis , etc...
• “All causes of cellular injury ”

23. The classic clinical signs of
acute inflammation:
English Latin
Redness Rubor
Heat Calor
Swelling Tumor
Pain Dolor
Loss of function

24. Definition of terms
• EXUDATION: the escape of fluid,
proteins & blood cells from the vascular
system in to the interstitial tissue and
body cavities
• EXUDATE: an inflammatory extravascular
fluid that has a high protein
concentration, much cellular debris and SG
> 1.020
• TRANSUDATE: low protein content &
specific gravity of < 1.020.( ultra filtrate
of blood plasma resulting from hydrostatic
imbalances across the vascular endothelium)

25. • EDEMA : excess of fluid in the
interstitial tissue or serous body
cavities. It can be either an exudate or
transudate
• PUS : a purulent inflammatory exudate
rich in leukocytes and parenchymal cell
debris

26. DIFFERENCE BETWEEN EXUDATE AND
TRANSUDATE
EXUDATIVE FLUID TRANSUDATIVE
FLUID
CAUSE ACUTE INFLAMMATION NON INFLAMMATORY
APPEARANCE COLORED,TURBID,
HEMMORRHAGIC
CLEAR,TRANSLUCENT,
OR PALE YELLOW
SPECIFIC GRAVITY >1.020 <1.020
SPONTANOUS
COAGULABILITY
YES NO
PROTEIN CONTENT >3gm%
CELLS ABOUNDANT
WBC,RBC,&CELL
DEBRIES
ONLY FEW
MESOTHELIAL CELLS
BACTERIA PRESENT ABSCENT

27. Response Of Inflammation
The main processes are:
I - Increased blood flow.
II - Increased permeability.
III - Migration of neutrophils.
IV - Chemotaxis.
V - Leucocytes recruitment & activation.

28. Response Of Inflammation
The main processes are:
I - Increased blood flow due to dilation of
blood vessels (arterioles) supplying the region.
II - Increased permeability of the capillaries,
allowing fluid and blood proteins to move into
the interstitial spaces

29. Response Of Inflammation
III - Migration of neutrophils (and
perhaps a few macrophages) out of the
venules and into interstitial spaces.

30. Role of Macrophages and
Neutrophils
• Macrophages: 1st line of defense, followed by
granulocytes, neutrophils
• Move from blood vessels to tissue: extravasation
• Migration of neutrophils:
– Neutrophil extravasation takes 4 steps:
• Rolling
• Activation
• Arrest
• Adhesion

31. Rolling: neutrophils bind briefly to endothelium
through weak selectin-carbohydrate interactions
Activation: neutrophils activated by
chemoattractants, substances that cause
neutrophils to migrate toward site of injury
Definition: Selectins are receptors on
endothelial cells that have a carbohydrate-like
portion that binds with proteoglycans (mucins)
on neutrophil surface
Definition: chemotaxis is the movement of cells
in response to chemical stiuli
Arrest/adhesion: neutrophils stop rolling and
attach to endothelial cells
Transendothelial migration: diapedesis, or the
squeezing of parts of the cell at a time through
the endothelial cells

32. Response Of Inflammation
IV - Chemotaxis
Once outside the blood vessel, a
neutrophil is guided towards an infection
by various diffusing chemotactic factors.
Examples include the chemokines and
the complement peptide C5a, which is
released when the complement system is
activated either via specific immunity or
innate immunity.

33. Response Of Inflammation
V - Leucocytes recruitment &
activation.
• This is the first step is the binding of the
neutrophils to the endothelium of the blood
vessels.
• The binding is due to molecules, called
cell adhesion molecules (CAMs), found
on the surfaces of neutrophils and on
endothelial cells in injured tissue.

34. Response of Inflammation
V - Leucocytes recruitment &
activation (contd.)
The binding of leukocytes occur in two steps:
• In the first step, adhesion molecules called
selectins tightly gather the neutrophil to the
endothelium, so that it begins rolling along
the surface.

35. Response of Inflammation
V - Leucocytes recruitment &
activation (contd).
• In a second step, a much tighter binding
occurs through the interaction of ICAMs
on the endothelial cells with integrins on
the neutrophil.

37. Response of Inflammation
Eosinophils.
However, in some circumstances
eosinophils rather than neutrophils
predominate in acute inflammation. This
tends to occur with parasites (worms),
against which neutrophils have little
success.

38. Response of Acute Inflammation
• Increased Blood Flow, increased
permeability and Edema in
Inflammation:
• The increased blood flow & increased
permeability are readily visible within a few
minutes following a scratch that does not
break the skin.

39. Response of Acute Inflammation
• At first, there is pale red line of scratch.
• Later on there is accumulation of
inflammatory cells lead swelling,
(inflammation).
• Finally, there is accumulation of interstitial
fluid cause edema.

40. Acute Inflammation
(recruitment of neutrophils).

41. Acute Inflammation

42. Acute Inflammation

43. Acute Inflammation
(Acute Bronchitis)

44. Acute Inflammation

45. Chronic Inflammation
Chronic inflammation It is the
inflammation of prolong duration (weeks
or months).
is associated histologically with the
presence of:
• Lymphocytes and macrophages.
• The proliferation of blood vessels.
• Fibrosis and tissue necrosis.

46. Chronic inflammation
• It is occurred as:
• Following acute inflammation.
• Occurs, incidentally as active
inflammation.
• With tissue destruction.
With repair process.

47. Chronic Inflammation
(Chronic Bronchitis)

48. Causes of Chronic inflammation
I - Persistent infection.
II - Prolonged exposure to potentially toxic
agents.
III - Autoimmunity.

49. Chronic Bronchitis

50. Causes of Chronic inflammation
I - Persistent infection:
• Bacteria.
• Viruses.
• Fungi.
• Parasites

51. Chronic Gastritis

52. Chronic Inflammation

53. Causes of Chronic inflammation
II - Prolonged exposure to potentially
toxic agents:
• Endogenous, (atherosclerosis).
• Exogenous, ( particulate silica-Silicosis).

54. Causes of Chronic inflammation
III - Autoimmunity:
Occurs in:
• Rheumatoid arthritis.
• Lupus erythmatosus.

55. Chronic Inflammation
(Rheumatoid arthritis)

56. Chronic inflammation
• Lymphocyte, macrophage, plasma cell
(mononuclear cell) infiltration
• Tissue destruction by inflammatory cells
• Attempts at repair with fibrosis and angiogenesis
(new vessel formation)
• When acute phase cannot be resolved
– Persistent injury or infection (ulcer, TB)
– Prolonged toxic agent exposure (silica)
– Autoimmune disease states (RA, SLE)

57. Morphological Features of
Chronic Inflammation
These are characterized by:
I - Infiltration by mononuclear cells.
II - Tissue destruction.
III - Removal of damaged tissue, (healing).

58. Comparison between acute and
chronic inflammation:
Acute Chronic
• Causative agent Pathogens, injured tissues Persistent acute inflammation due to non-
degradable pathogens, persistent foreign
bodies, or autoimmune reactions
• Cells involved Neutrophils Mononuclear cells (monocytes, macrophages,
lymphocytes, plasma cells), fibroblasts
• Mediators Vasoactive amines IFN-γ and other cytokines, growth factors,
reactive oxygen species, hydrolytic enzymes
• Onset Immediate Delayed
• Duration Few days Up to many months, or years
• Outcomes Healing, abscess, Tissue destruction, fibrosis
Chronic inflammation

59. Systemic effects of inflammation
Fever (pyrexia)
– IL-1, IL-6 & TNF-alpha (endogenous
pyrogens) or exogenous pyrogens (stimulate
leukocytes to release IL-1 & TNF) => ↑ PG
=> ↑ cAMP => act on the hypothalamus to
reset the temperature set-point at a
higher level (1-40C)

60. Systemic effects
• Leukocytosis- Elevated white blood cell
count
– Bacterial infection (neutrophilia)
– Parasitic infection (eosinophilia)
– Viral infection (lymphocytosis)

61. Systemic effects of inflammation
ctd
 Acute phase response:
• Behavioural e.g., chills, rigor (shivering), malaise,
anorexia, etc
• Autonomic e.g. ↑ pulse & Bp, etc
• Acute phase proteins (about 30) e.g. C-reactive
protein (CRP), Serum amyloid A (SAA), fibrinogen,
complement, alpha 1-antitrypsin, etc
• In severe bacterial infections (sepsis) => ↑↑↑ TNF &
IL-1 => TNF => disseminated intravascular coagulation
(DIC), hypoglycemia & cardiovascular failure

62. Systemic effects of inflammation
ctd
 Hematologic changes
• ↑↑↑ erythrocyte sedimentation rate (ESR) 20 to
fibrinogen which facilitate aggregation of RBCs
• Leukocytosis 20 to IL-1 & TNF, Colony Stimulating
Factor 40-100,000 cells/µl => leukemoid reactions
• Neutrophilia => bacterial
• Lymphocytosis => viral infection
• Eosinophilia => Bronchial asthma, hay fever, &
parasitic infestation
• Leukopenia => Typhoid fever, Rickettsiae, Tb, etc
• Anemia

63. Systemic effects of inflammation
ctd
Weight loss 20 to IL-1 & TNF
Reactive hyperplasia of the reticulo-
endothelial system