Pathology Flashcards
When is inflammation good?
During infection or injury
When is inflammation bad?
In autoimmunity, due to an overreaction to a stimulus
What is acute inflammation (cells, duration, resolution?
- Lots of neutrophils
- Sudden onset and short duration
- Usually resolves
What is chronic inflammation (cells, duration, resolution)?
- Lots of lymphocytes and macrophages
- Slow onset or occurs after acute
- Long duration and may never resolve
What are the characteristics of neutrophil polymorphs?
- Filled with cytoplasmic granules that kill bacteria
- Short lived cells that die at the scene
- Release chemicals attracting other immune cells
What are the characteristics of macrophages?
- Last weeks to months
- Phagocytic properties, ingest bacteria and debris
- Can antigen present to lymphocytes
What are the characteristics of mature lymphocytes?
- Last several years
- Produce chemicals to attract other inflammatory cells
- Immunological memory
- Large nucleus, little cytoplasm and little ER as they don’t really produce proteins
What are the characteristics of plasma cells?
- Only antibody producing
- Have a lot of ER for antibody production
- Smaller nucleus
How do endothelial cells work?
- Produce nitric oxide to stop things sticking
- Line capillaries in inflammation
- Become sticky to allow inflammatory cells to adhere
- Become porous to allow inflammatory cells to pass into tissues
- Grow into areas of damage to form new vessels
What happens to fluid in acute inflammation?
- More fluid leaking out of tissues, even at venous ends of capillaries
What are the characteristics of fibroblasts?
- Lots of ER
- Produce collagen in areas of chronic inflammation and repair
What are the characteristics of acute appendicitis?
- Unknown precipitating factor
- Neutrophils appear
- Blood vessels dilate
- Inflammation of serous surface
What is the sequence of acute inflammation?
- injury or infection
- neutrophils arrive and phagocytose and release enzymes
- macrophages arrive and phagocytose
- either resolution with clearance of inflammation or progression to chronic inflammation
What is the sequence of chronic inflammation?
- either progression from acute inflammation or starts as ‘chronic’ inflammation
- no or very few neutrophils
- macrophages and lymphocytes, then usually fibroblasts
- can resolve if no tissue damage (e.g. viral infection like glandular fever) but often ends up with repair and for- mation of scar tissue
What is a granuloma?
- Particular type of chronic inflammation: collections of macrophages surrounded by lymphocytes
- Significance: due to mycobacterial infection
- May be seen around foreign material in tissue
What is resolution?
- initiating factor removed
- tissue undamaged or able to regenerate
What is repair?
- initiating factor still present
- tissue damaged or unable to regenerate
- Can lead to replacement of damaged tissue by fibrous tissue
What types of cells can’t regenerate?
myocardial cells and neurones
What is thrombosis?
The formation of a solid mass from blood constituents in an intact vessel in a living person
What is an embolism?
Anything that moves through the blood vessels and when it reaches an area too small to pass through, blocks the blood flow.
What is ischaemia?
A reduction in blood flow to a tissue without any other implications
What is an infarction?
Reduction in blood flow to a tissue so reduced that it cannot support the maintenance of cells in the tissue so they die. Organs with end arterial supply are more prone to this
What is the implication of an embolus entering the venous system?
- Travels through vena cava > RHS of heart > lodges in pulmonary arteries >
What are the 3 factors of Virchow’s triad?
Causes of thrombosis:
- Change in vessel wall
- Change in blood flow
- Change in blood constituents
What are the possible causes of embolus?
- thrombus
- air
- cholesterol crystals
- tumour
- amniotic fluid
- fat
What are some differences between arterial and venous thromboses?
- Arterial occurs over decades, venous is rapid.
- Arterial circulation: platelet rich
- Venous circulation: fibrin rich
What are risk factors for venous thrombosis?
Major surgery, infection, inflammation
What are risk factors for arterial thrombosis?
smoking, diabetes, high BP, high cholesterol, lack of activity, poor diet, family history
What is apoptosis?
Programmed cell death in single cells
What protein triggers programmed cell death?
p53
What is apoptosis important for?
- Development: removal of cells e.g. interdigital webs
- Cell turnover: removal during normal turnover e.g. in intestinal villi
What is the role of apoptosis in cancer?
- Cells don’t apoptose when they should leading to increase in tumour size and accumulation of genetic mutations.
- Mutations in the p53 protein mean DNA damage lies undetected and apoptosis can’t be initiated
What is the role of apoptosis in HIV?
HIV induces apoptosis in CD4 helper cells, reducing their number and causing immunodeficiency
What is necrosis?
Traumatic cell death due to external factors. It occurs in a large number of cells
What are clinical examples of necrosis?
- Infarction
- Frostbite
- Toxic venom
- Pancreatitis
What is atherosclerosis?
The accumulation of fibrolipid plaques in the intima of systemic arteries. It reduces blood flow to important areas
Describe the time course of atherosclerosis?
- birth: no atherosclerosis
- late teens/20s: fatty streaks form
- 30s-50s: development of established plaques
- 40s-80s: complications of plaques e.g. thrombosis, haemorrhage
What are risk factors for atherosclerosis?
- hypertension
- hyperlipidaemia
- cigarette smoking
- diabetes mellitus
What are some complications of atherosclerosis?
Organ death if it is an end arterial supply/ reduced blood supply. Could cause embolism.
What is endothelial damage theory?
- Endothelial cells are easily damaged.
- Smoking: free radicals, nicotine and CO damage
- High BP: more pressure on side of blood vessels particularly in bifurcation
- Hyperlipidaemia: damages endothelial cells (is cholesterol synthesised by body, not from food)
What is hyperplasia and where does it occur?
Increase in the tissue size caused by increase in the number of constituent cells. Occurs in tissue where cells can’t divide e.g. skeletal muscle in bodybuilders
What is hypertrophy?
Increase in tissue size caused by increase in size of cells e.g. uterine hypertrophy
What is atrophy?
Decrease in the size of tissue caused by decrease in size of cells/decrease in constituent number e.g. Alzheimer’s
What is metaplasia?
Change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type e.g. Barrett’s oesophagus (squamous > columnar due to stomach acid)
What is the cause of metaplasia and give an example?
A consistent change in the environment of an epithelial surface e.g. bronchial epithelium from ciliated columnar > squamous due to cigarette smoke
What is dysplasia?
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer
How can be dysplasia be investigated?
H&E staining is cheap and easy
When do most chromosomal abnormalities occur?
Within the first month after conception
What are the different stages of spina bifida?
- initial epithelium formation
- columnar base forms
- invagination
- tube formation and closure
What does congenital mean?
Present at birth
What is genetic disease?
Caused by a DNA mutation
What is acquired disease?
Caused by non-genetic environmental factors but may still be congenital
What is an effect of Down’s syndrome?
Susceptible to bacterial infections, early dementia and cataracts due to chromosome 21 being affected.
What is an inherited disease?
Caused by an inherited genetic abnormality. Disease may not manifest until later life
What is an example of autosomal co-dominance?
Mixing blood groups which works in transfusions
What is polygenic inheritance?
Quantitative inheritance, where multiple independent genes have an additive/similar effect on a single trait
What is an example of mixed hypertrophy/hyperplasia?
When number and size of constituent cells increases e.g. smooth muscle cells in uterus in pregnancy
How does cell division show proof of ageing?
There is a limit to the number of times that cells can divide (Hayflick limit). Skin cells from older people divide less times in a culture than cells from younger people
How is telomere length related to ageing?
- The telomere region at the end of chromosomes shortens after each division
- Eventually becomes so short that it isn’t possible for the chromosomes to divide and replicate
- Cell no longer divides
What are some causes of death of non-dividing cells?
- free radical generation
- accumulation of toxic by-products of metabolism
- loss of DNA repair mechanisms
- perioxidation of membranes
- cross linking of DNA/proteins
What is the only definitive mechanism of slowing down ageing and why?
Calorie restriction because there is reduction of metabolic products
What is adjuvant therapy?
Extra treatment given after surgical excision
What is carcinogenesis?
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
What is the difference between carcinogenesis and oncogenesis?
Carcinogenesis applies to malignant tumours but oncogenesis applies to malignant and benign
What are the 5 classes of carcinogens?
- Chemical
- Viral
- ionising/non-ionising radiation
- hormones, parasites, mycotoxins
- misc
What are the 5 cardinal signs of inflammation?
- Rubor (redness due to dilation of vessels)
- Calor (heat)
- Tumour (swelling from oedema)
- Dolor (pain)
- Loss of function
How do atherosclerotic plaques form?
- Endothelial cells damaged
- Increased permeability for LDL allowing inflammatory cells and lipids to enter
- Macrophages attracted and take up lipids forming foam cells
- Foam cells die and spill lipids forming a fatty streak
- Activated macrophages release cytokines and PDGF causing proliferation of smooth muscle
- Synthesis of collagen + elastin occurs and formation of a fibrous cap around lipid core
What are risk factors for atherosclerosis?
- Smoking: damage to endothelial cells
- Hypertension
- High cholesterol
- Diabetes
- Male
- Age
- Diabetes
- Sedentary
What are some methods of prevention of atherosclerosis?
- Smoking cessation
- BP control
- Exercise
- Low dose aspirin to inhibit platelet aggregation
- Statins
What is the role of platelets in thrombosis?
- Αlpha granules cause platelet adhesion
- Dense granules cause platelet aggregation
- Platelets get activated and release granules when coming into contact with collagen
- Causes thrombus formation in an intact vessel
How are arterial thrombi formed?
- Plaque causes turbulent blood flow
- Intimal cells lost, fibrin deposited and platelet aggregation occurs
- Positive feedback loop
- RBC trapped in fibrin mesh
- More growth, more turbulence, more platelet deposition
How are venous thrombi formed?
- Lower pressure in veins, thrombus begins at valves
- Valves produce turbulence and can be damaged
- BP falls, flow slows allowing thrombus formation
What is a possible effect of venous emboli?
- pulmonary embolism due to emboli travelling to vena cava and lodging in artery
How are tumours classified?
T: 1-4 (tumour size)
N: 0-2 (lymph nodes affected)
M: 0-2 (metastasis)
What are the stages of metastasis and secondary tumour formation?
- Detachment
- Invasion of connective tissue
- Intravasation > vessels
- Circulation + evasion of host defence
- Adhesion to vessel wall
- Extravasation
- Growth of secondary tumour
What cancer type is the exception to metastasis?
Basal cell carcinoma
What is the difference between a neoplasm and a tumour?
Neoplasm: A new growth lesion resulting from autonomous abnormal growth of cells persisting after the original stimulus has been removed
- Tumour: any abnormal swelling
What is suppuration?
- Formation of pus
- Becomes surrounded by pyogenic membrane
- Leads to scarring
What is organisation?
- Replacement of acute inflammation by granulation tissue
- New capillaries form into inflammatory exudate, macrophages migrate, fibrosis occurs
Where does cancer most commonly metastasise from?
Lung, breast, kidney, thyroid, prostate
What are characteristics of benign tumours?
- Doesn’t invade basement membrane
- Grows outwards (exophytic)
- Low mitotic activity
- Defined
- Necrosis and ulceration rare
What are the characteristics of malignant tumours?
- Invade basement membrane
- Endophytic
- High mitotic activity
- Poorly defined
- Necrosis and ulceration common
How can neoplasms cause morbidity and mortality?
- Pressure on adjacent structures
- Obstruct flow
- Production of hormones
- Transformation to malignant neoplasm
How can malignant neoplasms cause morbidity and mortality?
- Destruction of adjacent tissue
- Metastases
- Blood loss from ulcers
- Paraneoplastic effects
- Anxiety and pain
What is a sarcoma?
Malignant connective tissue neoplasm
Describe neutrophil polymorph emigration
- Migration of neutrophils to plasmatic zone due to slowing plasma flow
- Adhesion of neutrophils to endothelium in venues
- Neutrophil emigration onto basal lamina then vessel wall
- Diapedesis: RBC can also escape
From where are neoplastic cells derived?
- Nucleated, usually monoclonal cells
- Growth pattern and synthetic activity is related to the parent cell
What are neoplasms of glandular/secretory epithelium called?
Benign: adenoma
Malignant: adenocarcinoma
What is a papilloma?
Benign tumour of non-glandular, non-secretory epithelium. e.g. squamous cell papilloma
What is a carcinoma?
Malignant epithelial neoplasm
What is a:
1. lipoma
2. chondroma
3. osteoma
4. angioma
5. rhabdomyoma
6. Leiomyoma
7. Neuroma
- adipocytes
- cartilage
- bone
- blood vessels/vascular
- striated muscle
- smooth muscle
- nerves
What are occupational/behavioural causes of these cancers:
1. lung
2. bladder
3. scrotal?
- smoking
- dye/rubber industries: β-naphthylamine
- polycyclic aromatic hydrocarbons in chimney sweeps
What lifestyle factors can lead to cancers?
alcohol: mouth, oesophagus, liver, colon, breast
obesity: breast, oesophagus, colon, kidney
unprotected sex: HPV (cervix, penis, oropharyngeal)
How can ethnicity increase cancer risk?
- inc risk of oral cancer from reverse smoking in india
- decreased risk of skin cancer from increased melanin
Which cancers do these viruses lead to:
1. Epstein Barr
2. Hepatitis B/C
3. Merkel cell polyomavirus
4. Human Herpes Virus 8
- Burkitt lymphoma/nasopharyngeal carcinoma
- Hepatocellular carcinoma
- Merkel cell carcinoma
- Kaposi sarcoma
Which cancers commonly metastasise to bone?
breast, lung, prostate, renal, thyroid
