Pathology Flashcards
What does VINDICATE stand for?
Vascular Infection/Inflammatory Neoplastic Drugs Intervention/Iatorgenic Congenital/developmental Autoimmune Trauma Endocrine/Metabolic
What are some of the bodies responses to injury?
Vascular changes, cellular changes, chemical mediators, morphological patterns
In inflammation, vessels dilate. What mediates this?
Histamine’s and nitrous oxides
What mediates white cell rolling along the endothilium?
Low affinity binding
Selectins (endothilium) to glycoproteins (WBC)
What mediates white cell adhesion to the endothilium?
High affinity binding
ICAM/VCAM (endothilium) to integrins (WBC)
What does CAM stand for?
Cell Adhesion molocule- often glycoproteins on the WBC
What is an integrin and what is its function?
Protein expressed on WBCs and function mechanically by attaching the cell cytoskeleton to the extracellular matrix and biochemically by sensing whether adhesion has occurred.
What does ICAM/VCAM stand for
VCAM = vascular cellular adhesion molocule ICAM = intercellular adhesion molocule
What will increase selectin expression on the endothilium?
Histamine and thrombin from inflammatory cells
What will increase ICAM/VCAM expression on the endothilium?
TNF alpha and IL1
What increases the affinity (increased avidity/strength of binding) of ICAM/VCAM for integrins?
Proteoglycans
What causes tumor or swelling?
Increase vascular permeability => loss of protein => change in osmotic pressure => water leaves vessels and enters tissue
What causes an increase in vascular permeability?
1) Endothilial contraction due to histamines, bradykinin, substance P => gaps between epithilial cells
2) Direct injury (toxins can burn/damage vessels)
3) Immune response and degranulation can damage host tissue
4) Transcytosis- macromolocules are transported across interior of cell mediated by VEGF
5) New vessel formation (immature) mediated by VEGF
What is VEGF?
Vascular endothilial growth factor- generates new blood vessels
What is chemotaxis?
Directional response to a chemical stimuli
What are the clinical features of acute inflammation?
Rubor, calor, tumor, dolor and loss of function
What mediates pain in inflamation?
Bradykinin and prostaglandin
Which cell type is typical of acute inflammation?
Neutrophil with a multilobed nucleus and granules
Inflammation is good at damaging tissue. What measures are in place to limit the damage?
Mediators of inflammation are short lived
Neutrophils only survive outside the blood vessel for a few hours.
What is resolution and what are the features of resolution?
Complete restoration of the tissue to normal after the inflammatory response.
Minimal cell death
Occurs in tissues with capacity to repair and replace
Good vascular supply required to deliver inflammatory cells and remove injurious agent
Injurious agent easily removed.
What is Suppuration?
Formation and collection of puss.
What is Pus?
A collection of dieing and dead cells. Lots of neutrophils, bacteria and inflammatory deposits like fibrin
What is an abscess?
Collection of puss which has built up in the tissue of the body
What is a empyema?
Collection of pus without a vascular supply- normally in the pleural space
Soft and prone to rupture
Antibiotics will not get in
What is organization?
Process which leads to scarring
Which factors promote organization?
1) Lots of necrosis
2) Lots of fibrin- not easily cleared
3) Poor vascular supply- difficulty removing debris
4) Tissue type which will not regenerate
What will happen to an injury to the mucosa which has gone beyond the basement membrane?
Organization as a scaffold is needed for resolution to occur
What erosions and abrasions?
Injuries to the mucosa with the basement membrane intact- complete resolution
What is an ulcer?
An open sore on an external or internal surface of the body, caused by a break in the skin or mucous membrane which fails to heal and must go beyond the basement membrane
When does granulation tissue form?
When an injury goes beyond the basement membrane
How does granulation tissue form?
Injury infiltrated by capillaries- VEGF. Allowing fibroblasts to move to the site of injured. Smooth muscle and collagen is deposited => scarring, fibrosis and loss of function of tissue.
What is a fibroblast?
Cells that synthesise the extracellular matrix and collagen.
Liver has some regenerative capacity but this can be overwhelmed => cirrhosis. What are the consequences of cirrhosis?
Liver failure and loss of function- cannot remove toxins or make new proteins.
Vascular disturbance as blood is not filtered properly as it cannot pass through fibrous tissue
Can chronic inflammation occur without preceding acute inflammation?
Yes
Chronic inflammation implies nothing about the time period or time period? T of F?
True
What factors promote chronic inflammation?
Suppuration
Persistent injury
Infectious agent
Autoimmune injury
Which inflammatory cell characterises chronic inflammation?
Lymphocytes and macrohages
What is a granuloma?
A mass of granulation tissue produced by a mass of macrophages.
When do granulomas occur?
Foreign bodies (endogeneous and exogeneous) Specific infections- paracites, worms, eggs, syphilis and mycobacterium
What is hypertrophy?
Increased cell size
What is Hyperplasia?
Increased cell number
What is Atrophy?
Decrease in cell size
What is necrosis?
Pathological cell death requiring no energy
What is apoptosis?
Programmed cell death requiring energy and stimulus
What is coagulative necrosis?
1) Preservation of a cell outline (ghost outine with no nucleus or organelles) for a few days as the cells cannot be digested.
2) Dead cells are consumed by emzymatic processes and inflammatory cells as the microenvironment is to toxic for proteolysis
When is coagulative necrosis often seen?
Cardiac muscle following MI
What is liquefactive necrosis?
Liquid viscous mass where no cell structure remains.
Suppuration and pus present
Associated with local bacteria/fungal infections
When is liquefactive necrosis seen?
In the brain
What is caseous necrosis?
Microscopic necrosis usually associated with mycobacterium infections
Granulomatous inflammations with central necrosis
What are the physiological causes of apoptosis?
Normal growth esp in embryology
Removal of self reactive lymphocytes
Hormonal dependent involution (menstrual cycle, menopause, regression of lactating breast after weaning)
What is involution?
Shrinking or returning of an organ to its normal size
What are the pathological causes of apoptosis?
Usually in response to injury eg:
- Cross reacting lymphocytes
- Radiation/sunburn
- Chemotherapy/cancer
- Viral infections
- Graft v host disease post transplant
What is graft v host disease?
Attacking of transplanted tissue as it is recognised as non self. Drugs are given to suppress the immune system but this increases the risk of infection post surgery
What are the 2 methods of apoptosis?
Extrinsic- signal is from outside the cell
Intrinsic- signal is from inside the cell
What is the extrinsic pathway of apoptosis?
Death receptors linked with TNF and Fas.
1) Fas ligand binds to Fas which activates the caspase cascade => apoptosis
2) TNF induces apoptosis in association with inflammatory conditions
What is the intrinsic pathway of apoptosis?
Mitochondrial pathway. Growth sigals promote anti- apoptotic pathway in the mitochondrial membrane. When growth signals are removed they are replaced with Bax/Bak
=> Increased permeability of mitochondria
=> release of proteins eg cytochrome C that stimulate the caspase cascade
Which cascade is associated with apoptosis?
Caspase cascade
What happens with too much or too little apoptosis?
Too much- neurogenerative diseases
Too little- cancers and autoimmune diseases
How does apoptosis happen in order to prevent an inflammatory response?
1) Pyknosis- cell chrinks
2) Chromatin condensation- nucleus clumps and breaks up
3) Cytoplasmic blebs- cytoplasm breaks up
4) Macrophage comes to digest everything contained in vesicles
Are neutrophils present during apoptosis?
No
What is pyknosis?
Cell shrinkage
Why do cells age?
1) Oxidative stress- free radical damage
2) Accumulation of metabolic byproducts
3) Lipofuscin- pigment granules of lipid containing residues of lysosomal digestion
During an MI the Ca++ pump fails leading to increased intracellular calcium. What are the consequences of this?
1) Increasing ATPase
2) Increasing phospholipase => membrane damage
3) Increasing proteases => membrane and cytoskeletal damage
4) Increasing endonucleases => DNA damage and breakdown
5) Increasing mitochondrial permeability => release of proteins which stimulate the caspase cascade eg cytochrome C
Post MI- what changes are seen in 0-20 minutes?
No cellular changes in a micro or macroscopic level.
First signs are redness, pyknosis, nuclear shrinkage and darkening, marginal contraction bands appear
Post MI- what changes are seen in 0-24 hours?
Increased perfusion, vasodilation and vascular permeability.
Acute inflammation and coagulative necrosis
Gross changes = redness and cardiac perforation
When is the risk of cardiac rupture post MI greatest?
3-7 days post MI
Post MI- what changes are seen in 24-48 hours?
Neutrophils replaced by macrophages
Adaptive immune response- lymphocytes and chronic inflammation
What colour does tissue change at autopsy if macrophages are present?
Yellow
Why does suppuration not occur following MI?
No persistence of injury
Will resolution occur after MI?
No as the blood supply is poor due to ischemia.
Resolution will occur after angina
What cells characterise organization and scarring?
Fibroblasts
When does organization and scarring occur post MI?
2-6 weeks
Can you date an MI which occurred longer than 6 weeks ago?
No
What is pathology?
The study of the causes of disease and the sequence of events steming from the cause to the eventual disease process
What is homeostasis?
The maintenance of a constant internal environment.
When the body is subject to different stresses, if they are severer the cell maybe damage (apoptosis/necrosis).
Prior to this there is a period of adaption to change.