PATHOLOGY COPY Flashcards
Causes of acute inflammation
Microbial infections Hypersensitivity reactions Physical agents Chemicals Tissue necrosis
What makes up the cellular exudate for acute inflammation?
Neutrophil polymorphs
Macrophages
Lymphocytes
Causes of chronic inflammation
Primary chronic inflammation
Transplant rejection
Progressing from acute inflammation
Recurrent episodes of acute inflammation
Causes of primary chronic inflammation
Exogenous materials
Endogenous materials
Resistance of infective agent to phagocytosis and intracellular killing – TB
Autoimmune diseases – rheumatoid arthritis
Primary granulomatous diseases – Crohn’s
What is the cellular exudate in chronic inflammation mainly made of?
Lymphocytes
Plasma cells
Macrophages
Fibroblasts
How does organisation occur?
Granulation tissue is formed and dead tissue is removed by phagocytosis
Granulation tissue contracts and accumulated collagen to form a scar
When does an arterial thrombosis normally occur?
When superimposed on atheroma
How does an arterial thrombus occur?
Vessel wall damage
Laminar flow disruption
Collagen exposed
Platelets stick to collagen and aggregate - positive feedback
Rbc’s can get trapped - thrombus formation and fibrin deposition (fibrinogen –> fibrin by platelet factors)
Fibrin mesh holds it all together
Thrombus can then build up and occlude artery
What are the outcomes of a thrombus?
- Lysis and resolution
- Organisation – into a scar
- Recanalisation – scar and residual thrombus
- Embolism – breaks off
What are the functions of histamine?
Vasodilation Emigration of neutrophils (chemotaxis) Increase vascular permeability Pain Itching
Role of plasma factors
Complement system
Kinin system
Coagulation cascade (pro-clotting)
Fibrinolytic system (anti-clotting)
What is the microscopic appearance of chronic inflammation?
Chronic ulcer
Abscess cavity
Granulatomous inflammation
Fibrosis
What is a histiocytic giant cell?
Indeigestible foreign material causes macrophages to fuse together - multinucleate giant cells
Can collect and form granulomas
What is end arterial supply?
Single artery supplies organ - more susceptible to infarction
What are watershed territories?
Parts of the brain the have a dual blood supply, but low BP can cause ischaemia
Explain the pathogenesis of atherosclerosis
- Endothelial cell damage – see risk factors
- Repeated endothelial damage -> multiple thrombi -> aggregation -> atheroma formation
- Vascularised plaque can haemorrhage – propagates atheroma formation
What are the complications of atherosclerosis?
Cerebral/myocardial infarct
AAA –> weakens aorta and leads to aortic rupture
Peripheral vascular disease - gangrene
What types of DNA damage cause apoptosis to occur?
Single/double stand break
Base alteration
Cross linking
Explain mechanism of apoptosis
- P53 (gatekeeper of genome) detects DNA damage -> acts as switch for apoptosis
- Bcl2 and Fas ligand receptor signal for capsases -> apoptosis
- Membrane bound cell fragments engulfed by macrophages
Example of normal apoptosis
Removal of finger webbing during development
In what is excess apoptosis present?
HIV mediated T cell destruction
Give examples of necrosis
Myocardial/cerebral infarction
Avascular necrosis of bone - scaphoid or head of femur break
Caseous necrosis - pathological sign of TB
Define hypertrophy
Increase in size of a tissue caused by an increase in size of the constituent cells (eg skeletal muscle)
Define hyperplasia
Increase in size of a tissue caused by an increase in number of the constituent cells (eg. enlarged prostate)
What are other examples of developmental conditions?
Cleft lip/palate - cells fail to migrate and join
Ventricular septal defect (VSD)
What is congenital development?
Present at birth - can be inherited or acquired
Name 5 types of necrosis
Caseous necrosis Coagulative necrosis Colliquative necrosis Fibrinoid necrosis Fat necrosis
What is coagulative necrosis?
Cells become firm and pale
Seen in most tissues
What is colliquative necrosis?
Dead area is liquefied
Seen in brain
What is fibrinoid necrosis a microscopic feature of?
Malignant hypertension - in arterioles
What can cause necrosis?
Ischaemia
Metabolic
Trauma
Name 5 cancers that commonly spread to bone
- Breast
- Thyroid
- Kidney
- Lung
- Prostate
What does oncogenesis refer to?
Benign and malignant tumours
Define carcinogen
Mutagenic (act on DNA) agents that cause (or are suspected to cause) tumours
Name the carcinogen classes
Chemical
Radiation
Biological organisms
Miscellaneous
Give an example of a mycotoxin carcinogen
Mycotoxin (Aflatoxin B1) –> hepatocellular cancer
Name host factors for carcinogenesis
Race
Constitutional
Premalignant conditions
Transplacental exposure
Define Neoplasm
A lesion resulting from the NEW AUTONOMOUS ABNORMAL growth of cells that PERSISTS after removal of initiating stimulus
What is the structure of a neoplasm?
Neoplastic cells
Stroma - connettive tissue framework
What does the stroma provide of the neoplasm?
Mechanical support
Nutrition
Intracellular signalling
Contains blood vessels which perfuse the tumour
A tumour <2mm is known as a …?
Avascular nodule
What neoplasms do epithelial cells form?
Carcinomas
What neoplasms do connective tissues form?
Sarcomas
What is a papilloma?
A benign non glandular epithelial neoplasm
What is a carcinoma?
A malignant non glandular epithelial neoplasm
What is a adenocarcinoma?
A malignant glandular epithelial neoplasm
Name some benign connective tissue neoplasms
Lipoma = adipocytes Chondroma = cartilage Osteoma = bone Angioma = vascular Rhabdomyoma = striated muscle Leiomyoma = smooth muscle Neuroma = nerves
Name some malignant connective tissue neoplasms
Liposarcoma = adipose tissue Chondrosarcoma = cartilage Osteosarcoma = bone Angiosarcoma = vascular Rhabdomyosarcoma = striated muscle Leiomyosarcoma = smooth muscle
What are the types of grade of malignancy?
Low grade – looks like parent tissue (well differentiated)
High grade – doesn’t look like parent tissue (poorly differentiated)
Anaplastic – unknown origin cell type
What is a carcinoma in situ?
Carcinoma fills cavity but has not invaded any other tissue
What are the 8 stages of metastasis?
- Detachment
- Invasion
- Intravasation
- Evasion
- Adherence
- Extravasation
- Growth
- Angiogenesis
Explain invasion
Some cells go through the basement membrane into the extracellular matrix using enzymes (proteases, collagenase, cathepsin D, urokinase-like plasminogen activator)
What is intravasation?
Tumour cells move from ECM to blood/lymph vessels
What is evasion?
Aggregate with platelets, shed surface antigens and stick to other tumour cells
Explain adherence
Adherence of ells to endothelium at a remote location
Explain extravasation
Tumour cells move from vessels to new tissue area
What is angiogenesis?
Formation of blood vessels
Name 3 routes of metastasis
Haematogenous - by blood stream
Lymphatic
Transoelomic - in pleural, pericardial and peritoneal cavities
What tumours commonly metastasise to the liver?
Colon, stomach, pancreas, intestine (portal system)
Give 2 promoters of tumour angiogenesis
- Vascular endothelial growth factors
2. Fibroblast growth factors
Give 3 inhibitors of tumour angiogenesis
- Angiostatin
- Endostatin
- Vasculostatin
Give 3 endogenous chemical mediators of acute inflammation
- Bradykinin
- Histamine
- Nitric Oxide
The activity of what enzyme in the blood can act as a marker for granulomatous disease?
Angiotensin converting enzyme
Define abscess
Acute inflammation with a fibrotic wall
what are the steps of acute inflammation?
- Initial reaction of tissue to injury
- Vascular component: dilation of vessels
- Exudative component: vascular leakage of protein-rich fluid
what is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
What protein can switch on apoptosis if DNA damage is present?
p53 protein
Activation of which family of protease enzymes can turn on apoptosis?
Caspases.
Activation of what receptor can activate caspase and therefore apoptosis?
FAS receptor.
What is required for a tumour to enter the blood stream (intravasation)?
- Collagenases.
2. Cell motility.
What is required for a tumour to exit the blood stream (extravasation)?
- Adhesion receptors.
- Collagenases.
- Cell motility.
What causes the pain associated with acute inflammation?
- Stretching and distortion of tissues due to oedema and pus under high pressure in an abscess cavity.
- Chemical mediators e.g. bradykinin and prostaglandins, are also known to induce pain.
Describe the process of neutrophil polymorph migration into tissues as seen in acute inflammation.
- Margination of neutrophils.
- Pavementing of neutrophils.
- Neutrophils pass between endothelial cells.
- Neutrophils pass through basal lamina and migrate into adventitia.
Chemical carcinogens: what types of cancer do polycyclic aromatic hydrocarbons cause?
Lung cancer and skin cancer.
Chemical carcinogens: what can expose people to polycyclic aromatic hydrocarbons?
Smoking cigarettes and mineral oils.
Chemical carcinogens: what types of cancer do aromatic amines cause?
Bladder cancer.
Chemical carcinogens: what types of people are more susceptible to bladder cancer caused by aromatic amine exposure?
People who work in the rubber/dye industry.
Chemical carcinogens: what type of cancer do nitrosamines cause?
Gut cancer.
Chemical carcinogens: what type of cancer do alkylating agents cause?
Leukaemia; the risk is small in humans.
