Pathology Flashcards
When is inflammation a good reaction ?
Infection
Injury
When is inflammation bad ?
Autoimmunity
Over-reaction to stimulus
How is acute inflammation classified?
Sudden Onset
Short duration
Usually resolves
How is chronic inflammation classified?
Slow onset or sequel to acute
Long duration
May never resolve
What cells are involved in inflammation?
Neutrophil polymorphs - acute inflammation Macrophages Lymphocytes Endothelial cells Fibroblasts
What are Neutrophil polymorphs?
• Short lived cells
• First on the scene of acute inflammation
• Cytoplasmic granules full of enzymes that
kill bacteria
• Usually die at the scene of inflammation
• Release chemicals that attract other
inflammatory cells such as macrophages
What are Macrophages?
- Long lived cells (weeks to months)
- Phagocytic properties
- Ingest bacteria and debris
- May carry debris away
- May present antigen to lymphocytes
What are lymphocytes?
• Long lived cells (years)
• Produce chemicals which attract in other
inflammatory cells
• Immunological memory for past infections
and antigens
What is the importance of endothelial cells in inflammation?
• Line capillary blood vessels in areas of
inflammation
• Become sticky in areas of inflammation so
inflammatory cells adhere to them
• Become porous to allow inflammatory cells
to pass into tissues
• Grow into areas of damage to form new
capillary vessels
What are fibroblasts?
- Long lived cells
* Form collagen in areas of chronic inflammation and repair
What is an example of acute inflammation?
• Acute appendicitis
What happens during acute appendicitis?
– Unknown precipitating factor – Neutrophils appear – Blood vessels dilate – Inflammation of serosal surface occurs – Pain felt – Appendix either surgically removed or inflammation resolves or appendix bursts with generalised peritonitis and possible death
Give an example of Chronic inflammation?
Tuberculosis
What happens during TB inflammation
– No initial acute inflammation – Mycobacteria ingested by macrophages – Macrophages often fail to kill the mycobacteria – Lymphocytes appear – Macrophages appear – Fibrosis occurs
What is the definition of acute inflammation?
The initial and often
transient series of tissue reactions to injury
What is the definition of chronic inflammation?
The subsequent and
often prolonged tissue reactions following the
initial response.
What type of cells are commonly seen histologically in TB?
Multinucleate giant cell - macrophages fused together
seen also in reaction to silica in the lungs.
What is commonly seen on a X-ray of a patient that has overcome TB?
Apical fibrosis
What is resolution?
–initiating factor removed
–tissue undamaged or able to regenerate
What is repair?
–initiating factor still present
–tissue damaged and unable to regenerate
How does repair work?
• replacement of damaged tissue by fibrous tissue • collagen produced by fibroblasts • examples –heart after myocardial infarction –brain after cerebral infarction –spinal cord after trauma
Which cells regenerate?
- hepatocytes
- pneumocytes
- all blood cells
- gut epithelium
- skin epithelium
- osteocytes
which cells do not regenerate?
- myocardial cells
* neurones
What is chirrosis?
Liver fibrosis and regenerative nodules causes by repetitive injury ie: alcoholism
What is Lobar Pneumonia?
- affects only 1 lobe of the lung.
- lobe fills with pus, neutrophil polymorphs.
- treat with antibiotics
- pneumocytes can regenerate
How to abrasions heal?
ie: Road rash, scraped knee
•scab formed over surface
•epidermis growing out from the adnexa, protected by scab
•thin confluent epidermis
How does healing by 1st intention work? (skin wounds)
- Incision
- -> Exudation of fibrinogen - weak fibrin join
- -> Epidermal regrowth and collagen synthesis - Strong collagen join (white scar)
what is granulation tissue?
new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process
What are the clinical features of inflammation?
- tissue that is: Swollen, red, tender and warm.
* may be some loss of function depending on the degree of inflammation and tissue type.
What are some causes of inflammation?
- Necrosis/infarction/direct trauma
- Infection (bacteria, virus, fungi,portazoa,parasites)
- Chemical or other physical agents for example radiotherapy
- Autoimmune reactions, particularly hypersensitivity states.
What is a granuloma?
- Collection of histocytes
* A form of chronic inflammation (type IV hypersensitivity)
What is Rheumatoid arthritis?
•Inflammatory arthritis with granulomatous features with no overt cause.
•affects mainly joints
•can also cause: lung nodules and fibrosis
cardiovascular arteritis and valvitis
and other systemic conditions ie amyloid
Name some drugs that can be used in Rheumatoid arthritis
analgesics NSAIDs Steroids Disease modifying drugs: Methotrexate, sulphasalazine, Lefunomide
What are the key cells seen in acute inflammation?
Polymorphonuclear neutrophils
What is an abscess?
Acute inflammation with fibrotic wall.
why don’t blood clots form all the time?
- Laminar flow - cells travel in the centre of arterial vessels and don’t touch the sides
- Endothelial cells which line vessels are not ‘sticky’ when healthy
What is thrombosis?
The formation of a solid mass from blood constituents in
an intact vessel in a living person.
What are the 3 factors that can cause thrombosis?
- Change in vessel wall
- Change in blood flow
- Change in blood constituents.
How does thrombosis work?
- Platelet aggregation
- Clotting cascade
- Formation of large protein molecule fibrin.
Platelets release chemicals when they aggregate which cause other platelets to stick to them and also which start off the cascade
of clotting proteins in the blood. Both these reactions
involve positive feedback loops so that once they have started they are difficult to stop. Once the clotting cascade has started there is formation of the large protein molecule fibrin which makes a mesh in which red blood cells can become entrapped.
What is an embolism?
Is the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel.
What is the most common cause of an embolism?
Thrombus (e.g. a deep venous thrombosis of the leg veins which breaks off and embolises through the large veins and right side of the heart to the lungs).
What are other causes of embolisms?
- Air ( pressurised system ie: IV/blood)
- Cholesterol crystals (atheromatous plaques)
- Tumour
- Amniotic fluid (rare)
- Fat ( severe trauma)
What happens if an embolus enters the venous system?
It will travel to the vena cava through the right side of the hear and lodge somewhere in the pulmonary arteries.
Why can an embolus in the venous system not enter arterial circulation?
The blood vessels in the lung split down to capillary size (through which only single red blood cells can squeeze) so the lungs
act as a filter for any venous emboli.
What is ischaemia?
A reduction blood flow to a tissue without any other implications.
What is an infarction?
The reduction in blood flow to a tissue that is so reduced that it cannot even support mere maintenance of the cells in that tissue so they die.
What usually causes an infarction?
macroscopic event caused by thrombosis of an artery
e.g. thrombus in the left anterior descending coronary artery causing infarction of the anterior
wall of the left ventricle.
Which organs are less susceptible to infarction due to dual arterial supply?
Liver - with portal venous and hepatic artery supplies,
Lung - with pulmonary venous and bronchial artery supplies
Brain around the circle of Willis with multiple
arterial supplies.
what conditions is commonly seen in the aorta of patients over the age of 60- 70?
atherosclerosis
Where are atherosclerotic plaques not seen
In low pressure systems eg: pulmonary arteries
Where is atherosclerosis commonly seen?
High pressure systems:
eg: porter and systemic arteries
What is a plaque?
Fibrous tissue
lipids - cholesterol
lymphocytes
what are the risk factors for atherosclerosis?
- smoking - cigarettes
- hypertension
- poorly controlled diabetes
- Hyperlipidaemia
What is the mechanism of atherosclerosis?
Endothelial damage theory:
- Endothelial damage
- Platelet aggregation
- Thrombus formations
- endothelial cells grow over the thrombus
- atherosclerotic clot
What can damage/kill endothelial cells?
- Smoking: free radicals, nicotine, CO
- Hypertension: Shearing forces
- Poorly controlled diabetes: superoxide anions, glycosylation products
- Hyperlipidaemia: high lipid levels damage cells.
Which drug can be used as to reduce formation of plaques?
Asprin - inhibits platelet aggregation
What are the complications of atherosclerosis?
- Cerebral infarction
- Carotid atheroma: emboli causing transient ischaemic attacks or cerebral infarcts
- MI - cardiac failure
- Aortic aneurysms- rupture causes sudden death
- Peripheral vascular disease with intermittent claudication
- Gangrene
What is apoptosis?
Programmed cell death - Single cell
What is necrosis?
Traumatic cell death - group of cells
What are some clinical examples of necrosis?
• Toxic spider bite • Frostbite • Cerebral infarction • Avascular necrosis of bone ( seen commonly in #NOF) • Pancreatitis
What are 3 types of necrosis?
Coagulative necrosis - semi solid
Liquifactive necrosis - liquid (common in brain)
Caseous necrosis
How does apoptosis work?
- Nucleus condenses (pyknosis), cytoplasmic blebs form, cell shrinkage.
- breaks down into apototic bodies
- Phagocytes engulf bodies.
When does apoptosis happen?
- Fully differentiated cells
2. Resting cell
what can cause a cell to apoptose?
- DNA damage (resting cell)
- non functioning cells
- cell damage
what protein detects DNA damage in the cell?
p53 gene
What enzymes are present in apoptosis?
Caspases - effector molecules of apoptosis
What are the external factors acting on caspases during apoptosis?
Fas receptor when Fas ligand binds to receptor sends signal to cell to switch on caspases and activate apoptosis.
What are the internal factors acting on caspases during apoptosis?
Bcl2 : inhibits caspases so prevents apoptosis
Bax : Switches on caspases so activates apoptosis
Which disease causes too much apoptosis?
HIV - infects CD4 T helper cells and induces apoptosis
What is caseous necrosis?
Appearance of cheese
eg: seen in TB.
What are the 3 types of spina bifida?
- Spina Bifida occulta
- Meningocele
- Myelomeningocele
What is a congenital disorder ?
Condition or disorder present at birth
What is an inherited disorder ?
Condition or disorder caused by an inherited
genetic abnormality, but may not manifest itself until later in life
What is an acquired disorder ?
Condition or disorder caused by non-genetic
environmental factors
How does spina bifida present?
failure of neural tube formation/closure leaving the spinal chord exposed
What is the difference between meningocele and myelomeningocele?
meningocele: Sac includes spinal fluid, but does not contain neural tissue, may be covered with skin or with meninges.
myelomeningocele: severe form of spina bifida in which the spinal cord and nerves develop outside of the body and are contained in a fluid-filled sac.
What is an example of an internal developmental defect?
Ventricular septal defect
What group of genes control the migration and differentiation of cells during development?
Homeobox genes
what is an example of a congenital disorder?
club foot
what is an example of an inherited disorder?
chromosomal abnormalities:
Trisomy 21 -Downs syndrome
What is mendelian inheritance?
Single gene inheritance
What is autosomal inheritance?
Non sex linked inheritance
What is an example of autosomal dominant inheritance condition?
Familial adenomatous polyposis - predisposed to colorectal cancer.
Dominant gene only needs one copy to have an effect
1/2 chance of children being effects.
What is an example of autosomal recessive inheritance condition?
Cystic fibrosis
Need 2 copies in order to be expressed - 2 unaffected carrier parents have 1/4 chance of having affected child.
What is an example of autosomal co-dominant inheritance?
Blood groups
A and B are co- dominant so can produce AB blood group.
What is polygenic inheritance?
multiple genes effected.
ie: BRCA gene - breast cancer
what is an example of a congenital acquired condition?
Fetal alcohol syndrome
- small eye openings
- smooth philtrum
- thin upper lip
What can a pituitary gland tumour (adenoma) cause?
Excess growth hormone leading to excess hight (usually before puberty) and acromegaly (after puberty)
What is acromegaly?
excess growth of face, hand and feet due to excess growth hormone after puberty likely due to pituitary tumour
What does a mutation in COL2AI gene cause?
Collagen type II defect causing small stature
What is achondroplasia?
Short bones are small ie; legs and arms.
head and body are normal size for age
What is hypertrophy?
Increase in size of a tissue caused by an increase in size of the constituent cells
What is hyperplasia?
Increase in size of a tissue caused by an increase in number of the constituent cells
What is a common hyperplasia process seen?
BPH of the prostate
Where is hypertrophy commonly seen?
Body builders
Myofibril hypertrophied muscle - Stronger and larger
Sarcoplasmic hypertrophic muscle - only larger
What would a mutation in the myostatin gene cause?
myostatin stops muscles growing when big enough. This mutation causes muscles to keep growing
eg belgian blue bull
What causes endometrial hyperplasia?
hormonal imbalance: too much oestrogen and not enough progesterone.
What types of hyperplasia can occur?
endothelial
Neuronal - peripheral nerve
prostatic
endometrial
where does combined hyperplasia and hypertrophy most commonly occur?
Pregnancy - the uterus
What is atrophy?
Decrease in size of a tissue
caused by a decrease
in number of the constituent cells or a decrease in their size.
What would happen to the brain in atrophy?
Demential causes cerebral atrophy - increase in size of sulci
Where is atrophy commonly seen?
Broken legs - when leg has been potted and immobilised then there is loss of muscle.
optic atrophy, cerebral atrophy.
What is metaplasia?
change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type
What metaplasia is commonly seen in smokers?
Bronchi metaplasia in smokers.
Ciliated columnar epithelium ➜ squamous epithelium
Give some examples of metaplasia
Bronchi Metaplasia - Smokers
Cervical metaplasia - in puberty
glandular ➜ squamous
Oesophagus - acid reflux
(Barrats oesophagus)
Squamous ➜ columnar
What is dysplasia?
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer
What causes dysplasia?
Persistent sever injury or irritation
What can cause dysplasia of the skin?
Exposure to UV sunlight and repetitive damage to skin.
Name 2 conditions where ‘dysplasia is used to describe a developmental abnormality?
Focal cortical dysplasia - frontal lobe underdeveloped
Hip dysplasia - femoral head and acetabulum not formed fully.
Why do cells stop dividing?
Telomeres - gets shorter with age
What are some examples of dividing tissues?
GI
Skin
What are some examples of non- dividing tissues?
Brain
Heart muscle
What does UV-B light do to the skin?
cross links proteins - skin loses elasticity.
What effect does UV-b light have on the eyes?
Causes protein cross linking leading to cataracts
What is Osteoporosis?
lack of bone mass
What is the effects of oestrogen on the bone?
lack of oestrogen: increased bone reabsorption and decreased bone formation.
What is a BCC?
Basal cell carcinoma - BCC of the skin only invaders locally, never metastasises to other parts of the body.
What is the cure for a Basal cell carcinoma (BCC)?
Complete excision, diagnosis may be confirmed with a punch biopsy but WLE needed for complete clearance.
What are some common symptoms of leukaemia?
Systemic: Weight loss, fever, frequent infections
Psychological: fatigue and loss of appetite.
Lymph node: swelling
Lungs: SOB
Muscular: Weakness
Bones or joints: Pain or tenderness
Skin: Night sweats, easy bleeding and bruising, purplish patches/spots.
Spleen and or liver: enlargement.
What are the treatments for leukaemia?
Systemic chemotherapy (Adriamyocin, Etoposide) Antibody treatment
How do carcinomas often spread?
Via the lymph nodes that drain the site of the carcinoma.
Example: Breast cancer spreads to the axillary lymph nodes. If breast cancer is located medially then may spread to internal mammary lymph below the sternum
How can carcinomas spread?
Via: blood to bone, lymph.
Which cancers commonly metastasise to the bone?
Breast Prostate Lung Thyroid Kidney
What is the difference between sclerotic and lytic bone lesions.
Sclerotic: grows new bone looks white on MRI/imaging
Lytic: eats away at bone so looks darker than normal bone on MRI/imaging
How would you treat breast cancer?
- Confirm diagnosis with Needle core biopsy
- Auxiliary node clearance: U/S, US needle guided bx if needed.
- Has spread to rest of body? Bone scan, CT CAP -
➜If yes systemic chemo needed
➜If no surgery on the breast.
Could a tumour have metastasised if completely excised?
Yes - the tumour could have micro metastasised which would not have been visible on CT/imaging
What is adjuvant therapy?
Extra treatment given after surgery.
eg adjuvant chemotherapy or radiotherapy
What treatment can be given to oestrogen positive receptor breast cancer?
Adjuvant anti-oestrogen therapy eg:
Tamoxifen
Arimidex
What treatment can be given to HER2 breast cancer?
Herceptin
What is carcinogenesis?
The transformation of normal cells to neoplastic cells though permanent genetic alterations or mutations.
What is oncogenesis?
Oncogenesis = benign & malignant tumours
What does carcinogenic, mutagenic and oncogenic mean?
Carcinogenic = cancer causing
Oncogenic = tumour causing
Mutagenic = acts on DNA
What are the occupational/behavioural risks for Lung, bladder and scrotal cancer?
Lung cancer =
Smoking
Bladder cancer =
↑incidence in aniline dye and rubber industries
B-naphthylamine
Scrotal cancer =
↑ incidence in chimney sweeps - Polycyclic aromatic hydrocarbons
What biological agents can increase risk of cancer?
Hormones:
↑ Oestrogen = ↑mammary and endometrial carcinoma.
Mycotoxins:
Aflatoxin B1 = hepatocellular carcinoma
Parasites:
Chlonorchis sinensis = cholangiocarcinoma
Shistosoma = bladder cancer
What are some common premalignant conditions?
Colonic polyps
Cervical dysplasia (CIN)
Ulcerative colitis
Undescended testis
What is a tumour?
Any abnormal swelling:
Neoplasm
Inflammation
Hypertrophy
Hyperplasia
What is a Neoplasm?
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed.
A new growth
How is a neoplasm classified?
Behavioural: benign/maligant
Histogenetic: cell of origin
What is angiogenesis?
Formation of new blood vessels to support the growth of tissues.
How might neoplasms be behaviourally classified?
Benign
Borderline (ovary)
Malignant
How are benign neoplasms described?
⦿ Localised non invasive ⦿ slow growth rate ⦿ low mitotic activity ⦿ close resemblance to normal tissue ⦿ circumscribed or encapsulated
What are some examples of benign neoplasms?
Uterine Fibroids (Leiomyoma) Tubulovillous Adenoma
Can benign neoplasms be fatal?
Yes: ⦿pressure on adjacent structures ⦿Obstruct flow ⦿Production of hormones ⦿ transformation to malignant neoplasm.
How are malignant neoplasms described?
⦿Invasive ⦿Metastasises ⦿Rapid growth rate ⦿ Variable resemblance to normal tissue. ⦿ Poorly defined or irregular border.
What features might be seen in malignant neoplasms?
⦿Necrosis ⦿Ulceration ⦿Pleomorphic nuclei ⦿Increased mitotic activity ⦿Hyperchromatic nuclei.
What are some examples benign epithelial neoplasm?
Papilloma - Benign non-glandular, non secretory epithelial neoplasm
Adenoma- Benign glandular or secretory epithelial neoplasm
What are some examples malignant epithelial neoplasm?
Carcinoma - malignant neoplasm/tumour of epithelial cells
Adenocarcinoma: carcinoma of glandular tissue.
What are the names of the benign connective tissue neoplasms?
Lipoma: adipocytes (fat) Chondroma: cartilage Osteoma: bone Angioma: vascular Rhabdomyoma: striated muscle Leiomyoma: smooth muscle Neuroma: nerves
What are the names of the malignant connective tissue neoplasms?
Liposarcoma: adipose tissue Rhabdomyosarcoma: striated muscle Leiomyosarcoma: smooth muscle Chondrosarcoma: cartilage Osteosarcoma: bone Angiosarcoma: blood vessels
Which ‘-omas’ are not neoplasms?
Granuloma: inflammation
Mycetoma: Ball of fungus in lung
Tuberculoma: Inflammation due to TB
Which malignant tumour are not named carcinoma or sarcoma?
Melanoma: malignant neoplasm of melanocytes
Mesothelioma: malignant neoplasm of mesothelial cells
Lymphoma: malignant neoplasm of lymphoid cells
Which tumours are named after the person who first recognised/described them?
⦿ Burkitt’s lymphoma
⦿ Ewing’s sarcoma: bone cancer
⦿ Grawitz tumour: RCC
⦿ Kaposi’s sarcoma: Angiosarcoma
What is a teratoma?
Can be benign or malignant and made up of all three germ layers of the embryo
Which tumours more commonly metastasise to the liver?
⦿ Colon
⦿ Stomach
⦿ Pancreas
⦿ Carcinoid tumours of intestine.
Which tumours more commonly metastasise to the lungs?
⦿ Sarcomas
⦿ Common cancers
What does Carcinoma in situ mean?
Carcinoma in situ (CIS) is a group of abnormal cells that are found only in the place where they first formed in the body.In general, carcinoma in situ is the earliest form of cancer, and is considered stage 0.
How would you describe invasive carcinoma?
Once the cancer has breached the basement membrane and has the potential to spread.
Micro-invasive carcinoma: only a small amount on invasion.
How does a cancer invade the basement membrane and extracellular matrix?
⦿Proteases ⦿collagenases ⦿cathepin D ⦿urokinase - type plasminogen activator. ⦿Cell motility
