Pathology Flashcards
What is inflammation?
The local physiological response to tissue injury
Give the 5 cardinal signs of inflammation
- ) Rubor/redness
- ) Calor/heat
- ) Tumor/swelling
- ) Dolor/pain
- ) Function laesa/loss of function
What is rubor due to?
Dilation of small blood vessels in area
What is calor due to?
Hyperaemia (increased blood flow) and systemic fever
What is tumor due to?
Oedema and a mass of inflammatory cells migrating to area
What is dolor due to?
Stretch and distortion of tissues from oedema/pus, and chemical mediators such as bradykinin, serotonin and prostaglandins inducing pain
What is functio laesa due to?
Movement consciously and reflexively inhibited by pain/tissue and may be immobilised by swelling
Give the 3 main inflammatory cells
- ) Neutrophil polymorphs
- ) Lymphocytes
- ) Plasma cells
What does acute inflammation involve?
- ) Tissue macrophages
- ) Lymphatics
- ) Neutrophil polymorphs
Give the 3 steps of acute inflammation
1) Changes in vessel calibre and flow
2) Increased vascular permeability due to transient chemical mediators and formation of fluid exudate
3) Formation of cellular exudate then emigration of neutrophil polymorphs
Give 2 chemical mediators of inflammation
- ) Histamine
- ) Bradykinin
- ) NO
What is fluid exudate?
The leakage of protein rich fluid
Give 3 beneficial effects of fluid exudate
- ) Dilution of toxins for removal
- ) Entry of antibodies due to increased vascular permeability
- ) Transport of drugs
- ) Fibrin formation
- ) Stimulation of immune response
Give 2 harmful effects of fluid exudate
- ) Digestion of normal tissue
- ) Swelling leading to airway obstruction
- ) Inappropriate inflammation
Give the 4 outcomes of acute inflammation
- ) Resolution to normal
- ) Suppuration (pus formation)
- ) Organisation via replacement by granulation tissue
- ) Progression to chronic
What is resolution of acute inflammation?
Initiating factor is removed, and the tissue is left undamaged or able to regenerate
What is pus a mixture of?
Living, dying, dead neutrophils/bacteria with cellular debris
What is the stimulus for suppuration?
Fairly persistent, usually infective
What is pus surrounded by once it accumulates?
Pyogenic membrane of capillaries, neutrophils and some fibroblasts
What does the pus accumulation eventually become?
Granulation tissue and leads to scarring
What is organisation in acute inflammation?
The repair of specialised tissue by the formation of a fibrous scar
How do organisation occur?
Production of granulation tissue and removal of dead tissue by phagocytosis
What is scar tissue made mainly of?
Collagen
Give 3 causes of acute inflammation
- ) Microbial infections
- ) Hypersensitivity reactions
- ) Physical agents
- ) Chemicals
- ) Tissue necrosis
What is chronic inflammation?
A prolonged or persistent inflammation marked by new tissue formation (fibrosis)
What are the 4 main cell types in chronic inflammation?
- ) Plasma cells
- ) Macrophages
- ) Lymphocytes
- ) Eosinophil polymorphs
Give 3 signs of chronic inflammation
- ) Chronic ulcer
- ) Chronic abscess cavity
- ) Fibrosis
- ) Granulomatous inflammation
Give 3 causes of chronic inflammation
- ) Resistance of infective agent to killing
- ) Necrotic tissue/foreign material
- ) Autoimmune diseases
- ) IBD/Crohn’s
- ) Transplant rejection
- ) Outcome of acute, usually suppurative
What is granulomatous inflammation?
A type of chronic inflammation associated with granulomas
What is a granuloma?
Aggregate of epithelioid histiocytes (activated macrophages) surrounded by mature lymphocytes
Give 2 granulomatous diseases
- ) TB
- ) Crohn’s
- ) Leprosy
Give a product of epithelioid histiocytes (and thus granulomas)
ACE
What is a clot?
A solid mass of blood constituents
What is laminar flow?
Cells generally travel in the centre of arterial vessels
What is a thrombus?
A clot formed within an intact vascular system during life
What is an embolus?
A thrombus that breaks loose and travels to another vessel in the body
Give 2 factors which are needed for a thrombus to form
- ) Change in vessel wall
- ) Change in blood constituents
- ) Change in blood flow
Give an example of an antiplatelet
Aspirin
What do antiplatelets do?
Inhibit thromboxane production from platelets to stop new platelet activation and aggregation
Give an example of an anticoagulant
Warfarin
What do anticoagulants do?
Target clotting factors by competing with vitamin K
What clotting factors do anticoagulants inhibit? (4)
- ) II
- ) VII
- ) IX
- ) X
What does an atherosclerotic plaque consist of?
- ) Lipid
- ) Necrotic core
- ) Connective tissue
- ) Fibrous cap
- ) Inflammatory cells
- ) Possible calcification
Which vessels is atherosclerosis most common in?
High pressure arteries
Give 3 risk factors for atherosclerosis
- ) Increasing age
- ) Male sex
- ) Smoking
- ) Obesity
- ) High cholesterol
- ) Fatty diet
- ) DM
- ) High BP
- ) FHx
Give the 5 steps of atherosclerosis formation
1) Fatty streaks
2) Intermediate lesions
3) Fibrous plaque
4) Plaque rupture
5) Plaque erosion
Give 3 complications of atherosclerosis
- ) MI
- ) Angina
- ) Thrombosis
- ) Embolism
- ) Stroke
- ) Limb ischaemia
- ) Organ infarction
- ) Haemorrhage
- ) Aneurysm
Give the 3 parts of Virchow’s triad
- ) Hypercoagulability
- ) Blood stasis
- ) Endothelial damage
What is a thromboembolism?
Formation of a blood clot in a vessel
What is an infarction?
When blood flow to a tissue is obstructed, and the tissue dies to a lack of oxygen
Give 3 complications of a MI
- ) Cerebral infarction
- ) Arrhythmia
- ) Cardiogenic shock
- ) Cardiac rupture
What is ischaemia?
Inadequate blood flow to tissues
Define atrophy
Decrease in size of tissue due to decrease in number of constituent cells/decrease in cellular size
Define hypertrophy
Increase in size of tissue due to increase in size of constituent cells
Define hyperplasia
Increase in size of tissue due to increase in number of constituent cells, or by lack of apoptosis
Dedine dysplasia
Imprecise term for morphological changes in cells in the progression to becoming cancer
Define metaplasia
The change in differentiation of a cell from one fully differentiated type to another fully differentiated type
Define apoptosis
Progreammed cell death occurring in old/damaged cells so that they aren’t replicated
What regulates apoptosis?
p53
Define necrosis
Traumatic cell death
Give 2 causes of necrosis
- ) Infarction
- ) Frostbite
- ) Toxins
What is intraepithelial neoplasia?
Potentially premalignant dysplasia of cells
What is a neoplasm?
The formation of abnormal and uncoordinated tissue growth that persists after withdrawal of the initiating cause
Give 4 features of benign neoplasia that differentiate it from malignant (brackets are malignant)
- ) Slow growing (fast)
- ) Infrequent mitoses (frequent)
- ) Good histological resemblance to normal tissue (poor)
- ) Near normal nuclear morphology (enlarged irregular)
- ) No invasion or mets (occur)
- ) Often well bordered (poorly defined)
- ) No necrosis or ulceration (common)
- ) Exophytic/outward growth (endophytic/inward)
What are the 2 ways in which we classify tumours?
- ) Behavioural
- ) Histogenetic
Give 2 benign epithelial tumours
- ) Papilloma
- ) Adenoma
What is a papilloma?
Benign tumour of non-glandular and non-secretory epithelium
What is an adenoma?
Benign tumour of glandular or secretory epithelium
What are malignant epithelial tumours called?
Carcinomas or adenocarcinomas (glandular)
Give 2 benign connective tissue tumours
- ) Lipoma
- ) Leiomyoma
- ) Rhabdomyoma
- ) Chondroma
What are malignant connective tissue tumours called?
Sarcomas
What are lymphoid/haematopoietic malignant tumours called?
Lymphomas or leukaemias
What is Kaposi’s sarcoma?
Malignant neoplasm derived form vascular endothelium
What is Kaposi’s sarcoma associated with?
AIDS
What does the grade of neoplasms correlate with?
The amount of histological differentiation (and growing speed)
What does T1N1M0 mean?
Small tumour, 1 nodal met, no other mets
Give the staging/grading system used for colorectal carcinomas
Duke’s ABCD
Give the 7 steps of the formation of a metastatic tumour
1) Detachment from other cells
2) Invasion of basement membrane
3) Intravasation
4) Evasion of host defences
5) Arrest by binding to endothelial ligands for adhesion to endothelium
6) Extravasation by integrins
7) Proliferation and vascularisation of tumour
How does detachment from other cells occur in the formation of a metastatic tumour?
Loss of adhesion molecules
What make invasion of the basement membrane and intravasation occur in the formation of a metastatic tumour?
Metalloproteinases
Give 3 ways in which malignant tumours cause mortality
- ) Pressure on tissue
- ) Destruction of tissue
- ) Mets
- ) Haemorrhage from ulcerated surfaces
- ) Obstruction of flow
- ) Formation production
- ) Pain
- ) Weight loss
- ) Debility
Give 3 ways in which benign tumours cause mortality
- ) Pressure on adjacent tissues
- ) Obstruction of flow
- ) Hormone production
- ) Possible transformation into malignant
What is a germline mutation?
Altered gene in gamete that can be passed on
Give an example of a germline mutation
BRCA1 mutation
What is a somatic mutation?
Genetic mutation that will be present in subsequent cell divisions but will not be in gametes
Give an example of a somatic mutation
Philadelphia chromosome
Give 3 things carcinogenesis requires
- ) Expression of telomerase to avoid shortening
- ) Loss of tumour suppressor genefunction
- ) Enhanced expression of dominant oncogenes
What is Knudson’s 2 hit hypothesis?
Cancer is the result of accumulated mutations to a cell’s DNA
What are the 2 hits in Knudson’s hypothesis?
1) Inheritance of defective allele or acquired mutation
2) Mutational loss of function of normal allele
Define carcinogenesis
The transformation of normal cells into neoplastic cells through permanent genetic alterations or mutations (malignant)
Define oncogenesis
The transformation of normal cells into neoplastic cells through permanent genetic alterations or mutations (benign and malignant)
Define carcinogen
Agents suspected or known to cause tumours
Define carcinogenic
Cancer causing
Define oncogenic
Tumour causing
Give 2 problems with identifying carcinogens
- ) Long latent interval
- ) Complexity of environment
- ) Ethical constraints
How is the location of cancer caused by chemical carcinogens related to that chemical?
Cancer likely localised to where the enzyme that converts the pro-carcinogen to it’s active form is
Give 3 treatment options for treating cancers
- ) Radiotherapy
- ) Chemotherapy
- ) Surgery
Give 2 ways in which conventional chemotherapy works
- ) Bind to mitotic spindles to stop contraction and thus division of cell
- ) Bind to DNA so synthesis is inhibited
- ) Bind to enzymes that are needed for DNA replication
What is a problem with conventional chemo?
It also affects normal dividing cells
Give 2 ways in which targeted chemotherapy works
- ) Create antibodies to receptors to prevent growth factor
- ) Inhibit receptors inside cells
- ) Antibodies against growth factors
Define histogenesis
The specific cell of origin for a tumour
Define osteosclerotic
New bone growth
Define osteolytic
Holes in bone
What do caretaker genes do?
Repair DNA damage
What do gatekeeper genes do?
Promote damaged cell death
What are oncogenes?
If expressed, they drive the neoplastic behaviour of cells
What is the most frequently mutated gene in cancers?
Tumour suppressor gene p53
What type of gene is p43?
Gatekeeper gene
What does germline mutation of p53 lead to?
Li-Fraumeni syndrome
What is Li-Fraumeni syndrome?
Autosomal dominant hereditary disorder that pre-disposes carriers to cancer development
What gene gives rise to familiar retinoblastoma when germline mutated?
RB1
What type of gene is BRCA1/2?
Caretaker
Give the 8 principles of screening
- ) Important condition
- ) Recognisable latent/early stage
- ) Natural course must be understood
- ) Suitable, acceptable test
- ) Case finding should be continuous (repeated tests)
- ) Accepted and available treatment
- ) Agreed policy on who to treat
- ) Cost consideration
What must screening be? (5)
Cheap, reliable, acceptable, sensitive, specific
What are the 2 main types of autopsy?
Hospital and medico-legal
What are the 2 types of pathologists, and what do they each do?
Histopathologist (hospital and coronial), forensic pathologist (coronial)
Give 3 questions to answer in an autopsy
- ) Who was the deceased?
- ) When did they die?
- ) Where did they die?
- ) How did they come about their death?
What is healing by 1st intention?
Wound heals back together
What is healing by 2nd intention?
Wound doesn’t heal back together, is filled in by other tissue
Define congenital disorders
Present at birth
Defined inherited disorders
Caused by inherited genetic abnormality
Defined acquired disorders
Caused by non-genetic environmental factors, can be congenital
What is dermal elastosis?
Wrinkles in skin due to UV damage
Why do cataracts occur?
Cross linking of proteins in lenses due to UV
What is sarcopenia?
Loss of muscles mainly due to decreased growth hormone and testosterone
Why does deafness occur?
Loss of hair cells in cochlea
