Pathology lecture

General pathology
1.Introduction to pathology
2. Cell injury and adaptation
3.Inflammation
4.Healing and repair
5. Neoplasm
6. Hemodynamics
7. Disease of blood and bone marrow
8. Infectious
9. Genetics
10.Environmental pathology
11. Transfusion medicine
12. Immunopathology









Cellular Injury And Adaptation:

These are the visible changes that Definition:
occur in cells as a result of exposure to causative
agents of disease, the degree of this changes are
vary according to the severity and duration of
damaging processes.

Cells injury can be divided into:

Indicated that . Reversible cell injury: 1
the changes will regress and disappear
when the injurious agent is removed and
the cell will return to the normal
morphologically and functionally.
Occur when the . Irreversible cell injury: 2
injury is persist or when its sever from the
outset. Here the cell alternations reach
the point of no return and progression to
cell death is inevitable.

e.g. If the blood supply to a portion of the heart
musculature is cut off for few minutes and then
restored, the muscles cells will sustain reversible
injury i.e. after restoration of blood supply, the cell
injury will recover and function normally as in
if cessation of blood supply is But angina pectoris
continuous for more than 60 minutes and then
restored, the myocardial cells in this instance sustain
irreversible injury that terminates invariably to
death as in myocardial infarction..
So there is spectrum of cellular changes in response
to injurious agents ranging from adaptation to cell
death
Classification of Injurious Agents:

Injurious agents can be classified into:
1. Hypoxia (Oxygen deprivation).
2. Physical agent.
3. Chemical agents.
4. Infectious agents.
5. Immuonological reaction.
6. Genetic derangement.
7. Nutrional.

This refers to a decrease in . Hypoxia (Oxygen deprivation):. 1
the oxygen supply to the cells. Its acts through interference
with oxidative respiration of the cells.
Hypoxia results from:
A. Loss of the blood supply(Ischemia)which is the most
common causes and occur when arterial flow is interfered
with by .e.g. narrowing of the lumen of an artery by
atherosclerosis, thrombi or emboli.

B. Inadequate blood oxygenation due to for e.g. cardiac
failure and or respiratory failure.

C. Decrease in oxygen carrying capacity of the blood e.g.
anemia and carbon- monoxide poisoning.

Depending on the severity and duration of
hypoxia, the cells may show one of the following
changes:
1. Adaptive atrophy.
2. Injury.
3. Necrosis (the morphological expression of the
cell deaths).

e.g. If the femoral artery is narrowed , the
muscles of the leg will shrink in size
(atrophy),this adaptive response continuous till
there is a balance between the metabolic needs
of the cells(low in this instance)and available
oxygen supply. More sever hypoxia (for e.g.
when there is more sever narrowing or
complete occlusion of the artery) will induce
injury (reversible then irreversible that progress
to cell death).


That include: . Physical Agents: 2
-Mechanical trauma.
-Deep cold.
-Extreme heat.
-Radiation.


That include: . Chemical Agents: 3
-Simple chemicals such as glucose and salts in hypertonic solution.
-Oxygen in high concentration.
-Poisons such as arsenic or cyanide.
-Air pollutions.
-Insecticides.
-Occupational exposure e.g. to asbestos.
-Social poisons such as alcohols and narcotic drugs.
These include viruses, bacteria, . Infectious agents: 4
fungi and parasites.
These are primarily . Immunological reaction: 5
protective defense mechanism against for e.g. infectious
agents; however, sometime they are harmful and
injurious
e.g.
A. Hypersensitivity reactions (triggered for e.g. by drugs).
B. Directed to self-antigens (autoimmune disease).


Exemplified by the wide rang of . Genetic derangements: 6
hereditary diseases that rang from those that are the result of
gross chromosomal defects leading to sever congenital
malformation e.g. Downs syndrome, to those that are caused
by a single amino acid substitution in the structure of the
hemoglobin that leading to the synthesis of abnormal Hb. e.g.
Hb.s in Sickle cell anemia.

. Nutritional Imbalance: 7

-Deficiency as of proteins-calorie malnutrition or vitamins
deficiency, etc.
-Excess as of lipids that leads to obesity with all its
consequences including fatty changes in cells and
predisposition to atherosclerosis.
Mechanisms of cells injury:
Injurious agents induce cell injury through their effects on
one or more of the following cellular targets:
1. Aerobic respiration
2. Cell membrane.
3. Protein synthesis.
4. Cytoskeleton.
5. Genetic apparatus (chromosome and their contents of
genes).

Factors influencing the severity of cell injury:

1. Type, duration and severity of the injurious
agents.
2. Type of the affected cells: Cells differ in their
susceptibility to the effects of injurious agents
for e.g.
Time for damage Susceptibility to damage
by ischemia
Types of cells
3-5 minutes High Neurons
30-60 minutes Intermediate Myocardial cells
Hepatocytes
Many hours Low Skeletal muscles
Epidermis of skin
Fibroblast
Types Of Cell And Tissues Damage:


processes; it's of two types either: irreversible This is . Cell Death: 1
A. Apoptosis.
B. Necrosis.


processes, its include all the irreversible This is . Degeneration: 2
changes in the cells which is short of necrosis (i.e. before the stage of
cells death and necrosis)
e.g. Fatty changes.
_ Pigmentation.

Apoptosis:

processes by which physiological cell death, its a programmed Its Definition:
cell eliminated when they are no longer required by the body, its part of
normal turn over of body cells.
_ Here there is no inflammatory reaction against apoptosis because it's
normal physiological processes.
_ the cell become shrinkage and compact and become eosinophilic in color,
later its fragmented and then other cell in the body will come and eat this
fragment of cell by processes called phagocytosis.
_ Apoptosis is irreversible processes.
E.g. include
1. During embryogenesis i.e. it's responsible for shaping various organs and
structure (morphogenesis).
2. Hormone-dependent involutionggg:
A. Physiological e.g. involution of endometrium during the menstrual
cycle or lactating breast after weaning.
B. Pathological e.g. atrophy of prostate after castration.

Necrosis:

The morphological changes that follow cell death Definition:
in living tissues or organ.
_ Necrosis represent cell death while still forming a part of
living body.
_ It's always pathological, and it's occur as a result of sever
cell damage.
_ Its always associated with inflammatory reactions.
_ Necrosis results from the degrading action of enzymes on
irreversibly damage cells with denaturation of cellular
protein.
In necrosis, there are cytoplasmic as well as a nuclear
changes.

Cytoplasmic Changes:
In the Hematoxylin-Eosin stain (H&E stain), the
hematoxylin stain acidic materials (Including the nucleus)
blue, whereas eosin stains alkaline materials (including the
cytoplasm) pink.
The necrotic cells are more eosinophilic than viable cells (i.e.
more intensely pinkish) this is due to:
1. Loss of cytoplasmic RNA.
2. Increase binding of eosin to the denaturated protein.
The cells may have more glass homogenous appearance than
normal cells; this is due to loss of glycogen particles (which
normally give the granular appearance to the cytoplasm).


Nuclear Changes:
The earliest changes is Chromatin Clumping, which is
follow by one of two changes
1. The nucleus may shrink and transformed into small
wrinkled mass (Pyknosis)
With time there is progressive disintegration of the
chromatin with subsequent disappearance of nucleus
together (karyolysis) or
2. The nucleus may break into many clumps
(Karyorrhexis).



Cell necrosis
Nuclear changes
normal
pyknosis
karyorrhexis
karyolysis
Macroscopically there are Types Of Necrosis:
five types of necrosis:
1. Coagulative Necrosis.
2. Liquefactive Necrosis.
3. Fat Necrosis.
4. Caseation (Gaseous) Necrosis.
5. Gangrenous Necrosis.

Necrosis: Coagulative . 1
_ Results from sudden sever ischemia in such organs as the
heart, kidneys, etc..
_ Microscopically, the fine structural details of the affected
tissues and cells are lost but their outlines are maintained.
- The nucleus is lost.
- The cytoplasm is converted into homogenous deeply
eosinophilic and structure less material.
- The outlines of the affected cells are still discernible.


Necrosis: Liquefactive . 2
This type of necrosis usually seen in two situations:
1. Brain infarctions i.e. ischemic destruction of the
brain tissues.
2. Abscesses i.e. suppurative bacterial infections.

Liquefactive necrosis is characterized by complete
digestion of dead cells by enzymes and thus necrotic area
is eventually liquefied i.e. converted into a cyst filled with
debris and fluid.


Liquefactive necrosis brain
The infarcted area is converted into a cavity (cyst) through liquefaction of the necrotic cells.
. Fat Necrosis:
_ This is a specific pattern of cell deaths seen in
adipose tissues due to actions of lipase.
_ Its more commonly seen in acute pancreatitis.
The released fatty acids from necrotic cells,
complex with calcium to create calcium soaps.
These are seen grossly as chalky white
deposit.
_ Fat necrosis can also be inducing by
mechanical trauma as female breast (traumatic
fat necrosis).

. Caseation (gaseous necrosis): 4
_ This combined the features of Coagulative and Liquefactive
necrosis.
_ Its encountered principally in the center of Tuberculous
Granuloma.
_ The body response to Tuberculous infections is specific form
of chronic inflammation, the morphologic unit of this is called
Granuloma.
_ Grossly, the caseaus material is soft, friable, whitish-gray
cheesy material.
_ Microscopically, the area is surrounded by granulomatous
inflammation, it has distinctive amorphous granular
pinkish debris.

. Gangrenous necrosis: 5
_ Its describe the limb ( usually the lowegggr )that has lost
its blood supply and has subsequently attacked by
bacteria, so its a combination of Coagulative necrosis
modified by Liquefactive action of enzymes derived from
bacteria and inflammatory cells.
_ When Coagulative pattern is dominates ,the affected
parts shrink and appear contracted (dry),the processes is
termed dry gangrene, conversely when the
Liquefactive action is more prominent, the affected parts
are swollen (edematous), so the processes termed wet
gangrene.

Gangrene-lower limb
Left: this is gangrene, or necrosis of the toes that were involved in a frostbite injury. This is
an example of "dry" gangrene in which there is mainly coagulative necrosis from the anoxic
injury.
Right: this is gangrene of the lower extremity. In this case the term "wet" gangrene is more
applicable because of the liquefactive component from superimposed infection in addition
to the coagulative necrosis from loss of blood supply. This patient had diabetes mellitus.