Pathology
Chapter 4: hemodynamic disorders
Pathological conditions can affect the circulation
-> Disturbed balance
-Altered endothelial function
-Increased vascular hydrostatic pressure
-Decreased plasma protein content
-Compromised structural integrity -> more permeable than normal.
-Perfusion disturbances
Hemodynamic disorders:
a. Hyperemia
Increased blood volume within a tissue/organ (more blood in the vessels). More
oxygen into organ.
b. Congestion
Less outflow -> accumulation of blood in the organ.
c. Hemorrhage
Extravasation of blood from vessels. The blood is not staying in the vessel -> blood
goes out and is leaking in the tissue.
d. Edema
Accumulation of fluid in tissue. Fluid/Water is leaking out of the vessels into the
tissue.
e. Embolism
Embolism is an obstruction of an artery, typically by a clot of blood or an air bubble.
f. Infarction
The blood vessel is stuck and there will be too less blood and oxygen present so
there will be necrosis -> ischemia. (thrombus)
g. Hemostasis and Trombosis
Hemostasis: A precisely orchestrated process involving platelets, clotting factors and
endothelium that occurs at the site of the vascular injury and culminates in the
formation of a blood clot.
Step 1: vasoconstriction. Endothelial cells release endothelin, which cause a
Stimulation of smooth muscle cells. It makes wound smaller and easy
to repair.
Step 2: Platelet activation and aggregation. The is an exposure of vWF
vulnerability factor. This will connect to damaged place. This causes
a shape change and release of granules. This causes some products
which attract more of these platelets aggregation.
Step 3: Activation of clotting factors and formation of fibrin. Tissue factor:
Result in activation of thrombin. This enzyme can convert fibrinogen
into fibrin fibrin polymerization. Platelets more together.
Step 4 : Clot resorption. Thrombin causes the expression of: - t-PA
(fibrinolysis) - Thrombomodulin (blocks coagulation cascade).
There will be an inhibition of platelet aggregation.
Thrombosis: Pathological counterpart in intact vessels (no damaged vessel).
h. Shock
Less blood flow and not enough blood (loss of blood) causes to cellular hypoxia (not
enough oxygen). By a shock there is an inflammation all over the body because there
is a problem in the blood stream. It is life-threatening because it is not localized.
1. Septic shock: Related to the amount of bacteria in the circulation. Bacteria
will affects all organs but also endothelial cells and leukocytes. Causes
Vasodilation and edema.
,How do endothelial cells respond to bacterial products?
- Directly:
* Toll-like receptors (TLR)
- Indirectly:
* Complement activation
* Production of IL-1 and TNF by neutrophils/monocytes/macrophages
Toll-like receptors are the receptors that sense bacterial products.
1. Production of TNF, IL01 and HMHB1 activation endothelial cells.
2. The anti-fibrinolytic is activated and also the Procoagulant is activated. This causes
vasodilation all over body.
3. There will be edema formation. Fluid is even more leaving our blood system.
Thrombin changes from procoagulant to anticoagulant when encountering normal
endothelium than the process of clotting will be stopped. This process is balanced.
The Tissue plasmin activator (t-PA) changes plasminogen into plasmin and plasmin
causes that Fibrin will be converted into fibrin degradation products. tPA will be produced by
the endothelial cells. Plasmin is the enzyme that can degrade the fibrin products.
- there is also a Plasminogen Activator inhibitors and this inhibits the converting
from plasminogen to plasmin. By this system fibrin will not further be broken
down. Plasmin is inactivated by a2-antiplasmin Complex formation.
The role of ADP in the thrombus formation is that this factor activates fibrinolysis, in which
fibrin is degraded and the thrombus formed can dissolve again.
Thrombosis: endothelial cell injury, stasis of turbulent blood flow, hypercoagulability of
blood.
Atherosclerosis is a process in which the walls of your arteries thicken due to calcification.
This thickening can lead to narrowing of the blood vessel and problems with blood flow to
organs and tissues.
- LDL: wordt in een plaque omgezet in geoxideerd LDL, en dit oxLDL wordt
opgenomen door macrofagen wat leidt tot vorming van foam cellen.
- Foam cells: Lipid loaded macrophages and SMC
Factors influencing fluid movement across capillary walls
-Increased hydrostatic pressure
-Reduced osmotic pressure
-Lymphatic obstruction.
Oedeem vorming: hartfalen rechterkant.
Chapter 5: Neoplasia.
Cancer is a genetic defect when one genetic defect has happened other genetic defects
will occur.
Repeated mutations lead to new characteristics: both gain of function (grow even more
rapidly) as well as loss of function is possible.
, Two types of tumors
- Benign (good) tumors: sharply bordered, stay local well differentiated (no de-
differentiation), slow progress often encapsulated
- Malignant (bad): infiltration in surrounding tissue metastasis to other tissue sometimes
rapid growth (some grow slowly).
A malignant or benign tumor look very different under the microscope. Malignant big nucleus
lots of cells. Benign small nucleus, less cells, often encapsulated and there is no metastasis.
And benign has large cytoplasm and malignant not. Benign tumor is good but it can be
damaging. If a benign tumor is next to a blood vessel it can be life-threatening. Gigantism
by benign tumor is hypophysis (pituitary) (production of growth hormone by the tumor)
Malignant tumors 4 Main groups (dependent on tissue of origin):
Carcinoma Originating from epithelial cells (epithelial cells are between the outside and
the inside environment -> skin)
Sarcoma Originating from mesenchymal tissue (fat-, muscle-, bone- & connecting
tissue)
Leukemia Originating from leucocytes
Lymphoma Originating from lymphoid tissue
Metastasis = cancer spreads to a different body part from where it started.
Teratoma: Tumor that arises in the germinal cells and it is originate from undifferentiated
stem cells. These tumors mostly go to the embryonic state. A cell can de-differentiate to an
embryonic germ cell and than differentiate again (stem cells). The stem cells can transform in
all kind of tissues or cells.
Tumor cells that originate from different germ layer behave differently. The tumor
goes back to the embryonic state to become stem cells and the tumors act in 3
different layers.
Ectoderm -> brain, skin and some other tissues.
Endoderm -> Blood vessels and intestinal form.
Mesoderm -> Fat and muscles. The tumor cells can go back to that stage
Morphology of a tumor
-Well-differentiated malignant tumor:
*Little variation in cell shape, later cytoplasm, cell resemble other cells in surrounding
tissue.
-Badly-Differentiates malignant tumor:
*More variation in cell mythology, nucleus/cytoplasm ratio varies strongly
-Undifferentiated (anaplastic) malignant tumor:
*Cells do not resemble the surrounding tissue, huge variation in cell morphology.
Dysplasia: Increased cell division, associated with incomplete maturation.
Anaplasia = growth of undifferentiated cells
Apoptosis and tumor growth
Tumors can be divided very fast but it can also be broken down fast apoptosis.
- Bcl-2 is a gene that blocks apoptosis
- Bcl-2 = oncogene Increased expression -> less apoptosis -> tumor growth
Carcinoma in situ -> Basement membrane is intact. When a tumor is not in situ it is not in
the same place anymore than this is a bad prognosis.
Chapter 4: hemodynamic disorders
Pathological conditions can affect the circulation
-> Disturbed balance
-Altered endothelial function
-Increased vascular hydrostatic pressure
-Decreased plasma protein content
-Compromised structural integrity -> more permeable than normal.
-Perfusion disturbances
Hemodynamic disorders:
a. Hyperemia
Increased blood volume within a tissue/organ (more blood in the vessels). More
oxygen into organ.
b. Congestion
Less outflow -> accumulation of blood in the organ.
c. Hemorrhage
Extravasation of blood from vessels. The blood is not staying in the vessel -> blood
goes out and is leaking in the tissue.
d. Edema
Accumulation of fluid in tissue. Fluid/Water is leaking out of the vessels into the
tissue.
e. Embolism
Embolism is an obstruction of an artery, typically by a clot of blood or an air bubble.
f. Infarction
The blood vessel is stuck and there will be too less blood and oxygen present so
there will be necrosis -> ischemia. (thrombus)
g. Hemostasis and Trombosis
Hemostasis: A precisely orchestrated process involving platelets, clotting factors and
endothelium that occurs at the site of the vascular injury and culminates in the
formation of a blood clot.
Step 1: vasoconstriction. Endothelial cells release endothelin, which cause a
Stimulation of smooth muscle cells. It makes wound smaller and easy
to repair.
Step 2: Platelet activation and aggregation. The is an exposure of vWF
vulnerability factor. This will connect to damaged place. This causes
a shape change and release of granules. This causes some products
which attract more of these platelets aggregation.
Step 3: Activation of clotting factors and formation of fibrin. Tissue factor:
Result in activation of thrombin. This enzyme can convert fibrinogen
into fibrin fibrin polymerization. Platelets more together.
Step 4 : Clot resorption. Thrombin causes the expression of: - t-PA
(fibrinolysis) - Thrombomodulin (blocks coagulation cascade).
There will be an inhibition of platelet aggregation.
Thrombosis: Pathological counterpart in intact vessels (no damaged vessel).
h. Shock
Less blood flow and not enough blood (loss of blood) causes to cellular hypoxia (not
enough oxygen). By a shock there is an inflammation all over the body because there
is a problem in the blood stream. It is life-threatening because it is not localized.
1. Septic shock: Related to the amount of bacteria in the circulation. Bacteria
will affects all organs but also endothelial cells and leukocytes. Causes
Vasodilation and edema.
,How do endothelial cells respond to bacterial products?
- Directly:
* Toll-like receptors (TLR)
- Indirectly:
* Complement activation
* Production of IL-1 and TNF by neutrophils/monocytes/macrophages
Toll-like receptors are the receptors that sense bacterial products.
1. Production of TNF, IL01 and HMHB1 activation endothelial cells.
2. The anti-fibrinolytic is activated and also the Procoagulant is activated. This causes
vasodilation all over body.
3. There will be edema formation. Fluid is even more leaving our blood system.
Thrombin changes from procoagulant to anticoagulant when encountering normal
endothelium than the process of clotting will be stopped. This process is balanced.
The Tissue plasmin activator (t-PA) changes plasminogen into plasmin and plasmin
causes that Fibrin will be converted into fibrin degradation products. tPA will be produced by
the endothelial cells. Plasmin is the enzyme that can degrade the fibrin products.
- there is also a Plasminogen Activator inhibitors and this inhibits the converting
from plasminogen to plasmin. By this system fibrin will not further be broken
down. Plasmin is inactivated by a2-antiplasmin Complex formation.
The role of ADP in the thrombus formation is that this factor activates fibrinolysis, in which
fibrin is degraded and the thrombus formed can dissolve again.
Thrombosis: endothelial cell injury, stasis of turbulent blood flow, hypercoagulability of
blood.
Atherosclerosis is a process in which the walls of your arteries thicken due to calcification.
This thickening can lead to narrowing of the blood vessel and problems with blood flow to
organs and tissues.
- LDL: wordt in een plaque omgezet in geoxideerd LDL, en dit oxLDL wordt
opgenomen door macrofagen wat leidt tot vorming van foam cellen.
- Foam cells: Lipid loaded macrophages and SMC
Factors influencing fluid movement across capillary walls
-Increased hydrostatic pressure
-Reduced osmotic pressure
-Lymphatic obstruction.
Oedeem vorming: hartfalen rechterkant.
Chapter 5: Neoplasia.
Cancer is a genetic defect when one genetic defect has happened other genetic defects
will occur.
Repeated mutations lead to new characteristics: both gain of function (grow even more
rapidly) as well as loss of function is possible.
, Two types of tumors
- Benign (good) tumors: sharply bordered, stay local well differentiated (no de-
differentiation), slow progress often encapsulated
- Malignant (bad): infiltration in surrounding tissue metastasis to other tissue sometimes
rapid growth (some grow slowly).
A malignant or benign tumor look very different under the microscope. Malignant big nucleus
lots of cells. Benign small nucleus, less cells, often encapsulated and there is no metastasis.
And benign has large cytoplasm and malignant not. Benign tumor is good but it can be
damaging. If a benign tumor is next to a blood vessel it can be life-threatening. Gigantism
by benign tumor is hypophysis (pituitary) (production of growth hormone by the tumor)
Malignant tumors 4 Main groups (dependent on tissue of origin):
Carcinoma Originating from epithelial cells (epithelial cells are between the outside and
the inside environment -> skin)
Sarcoma Originating from mesenchymal tissue (fat-, muscle-, bone- & connecting
tissue)
Leukemia Originating from leucocytes
Lymphoma Originating from lymphoid tissue
Metastasis = cancer spreads to a different body part from where it started.
Teratoma: Tumor that arises in the germinal cells and it is originate from undifferentiated
stem cells. These tumors mostly go to the embryonic state. A cell can de-differentiate to an
embryonic germ cell and than differentiate again (stem cells). The stem cells can transform in
all kind of tissues or cells.
Tumor cells that originate from different germ layer behave differently. The tumor
goes back to the embryonic state to become stem cells and the tumors act in 3
different layers.
Ectoderm -> brain, skin and some other tissues.
Endoderm -> Blood vessels and intestinal form.
Mesoderm -> Fat and muscles. The tumor cells can go back to that stage
Morphology of a tumor
-Well-differentiated malignant tumor:
*Little variation in cell shape, later cytoplasm, cell resemble other cells in surrounding
tissue.
-Badly-Differentiates malignant tumor:
*More variation in cell mythology, nucleus/cytoplasm ratio varies strongly
-Undifferentiated (anaplastic) malignant tumor:
*Cells do not resemble the surrounding tissue, huge variation in cell morphology.
Dysplasia: Increased cell division, associated with incomplete maturation.
Anaplasia = growth of undifferentiated cells
Apoptosis and tumor growth
Tumors can be divided very fast but it can also be broken down fast apoptosis.
- Bcl-2 is a gene that blocks apoptosis
- Bcl-2 = oncogene Increased expression -> less apoptosis -> tumor growth
Carcinoma in situ -> Basement membrane is intact. When a tumor is not in situ it is not in
the same place anymore than this is a bad prognosis.
