Pathology Flashcards
What three factors could cause thrombosis?
- Change in vessel wall
- Change in blood flow
- Change in blood constituents
Define a Carcinoma In Situ
A malignant epithelial neoplasm that hasn’t invaded the original basement membrane
Define an Invasive Carcinoma
A carcinoma that has breached the basement membrane and is now free to spread elsewhere
Define a Micro-Invasive Carcinoma
A carcinoma that has breached the basement membrane BUT hasn’t invaded far from original carcinoma
Invasion of malignant neoplastic cells - what 3 factors is it dependant on?
- Decreased cellular adhesion
- Abnormal cellular motility
- Production of enzymes that have a lytic effect on surrounding tissues
What does invasion of neoplastic cells allow?
The cells to spread through tissue and gain access to blood vessels and lymphatic channels
Define metastasis
The process by which a malignant tumour spreads from its primary site to produce secondary tumours at a distant site.
Metastasis can occur through (5) …
- Blood vessels
- Lymphatics
- Across Body cavities
- Along nerves
- Through direct implantation of neoplastic cells during a surgical procedure
What are the 7 stages of the Metastasis cascade?
Detachment
Invasion
Intravasation
Survival in circulation
Arrest
Extravasation
Colonisation
What occurs during Invasion (Metastasis Cascade)?
Invading through the basement membrane
What occurs in Intravasation (Metastasis Cascade)?
Collagenases and Cell motility
What occurs during the Survival in Circulation (Mestastasis Cascade)?
Aggregation with platelets
Shedding of surface antigens
Adhesion to other tumour cells
What occurs during Extravasation (Metastasis Cascade)?
Adhesion Receptors
Collagenases
Cell motility
Growth at the metastatic site occurs using…
Autocrine growth factors
Name the process of a tumour growing its own blood vessels
Angiogenesis
At what diameter does angiogenesis occur?
1mm
What are some angiogenesis promoters?
Vascular endothelial growth factors
Basic fibroblast growth factors
What are some Angiogenesis inhibitors?
Angiostatin, endostatin, vasculostatin
What are the routes of metastasis?
- Can invade arterial side if grows large enough and breaks off
- Haematogenous (via blood stream)
- Lymphatic (lymph channels)
- Trans-coelomic (pericardial and peritoneal cavities)
Describe the haematogenous route of metastasis
Forms secondary tumours in organs perfused by blood that’s drained from a tumour
Describe the lymphatic route of metastasis
Forms secondary tumours in regional lymph nodes
What does the Trans-Coelomic route of metastasis result in?
Invariably results in neoplastic effusion
Which tumours commonly metastasise to the lung?
Sarcomas and any common cancers
Which tumours commonly metastasise to the liver?
Colon, stomach, pancreas and carcinoid tumour of the intestine
Which tumours commonly metastasise to bone?
Prostate, breast, thyroid, lung and kidney
What’s are some symptoms that breast cancer has spread to bone marrow?
Back pain
‘spontaneous’ fractures
Name two treatment options for breast cancer
Anti-Oestrogen drugs
Herceptin
How can oncologists determine whether breast cancer is likely to respond to anti-oestrogen therapy?
Tumours can be stain in lab for oestrogen receptors
What protein does Herceptin bind to?
Her2 protein
What does the HER2 gene code for?
Growth factor (tumour overexpresses this gf)
Name 2 benefits of inflammation
Destruction of invading microorganisms
Walling off of an abscess cavity (∴ prevents spread of infection)
Name 2 disadvantages of inflammation
Fibrosis (from chronic inflammation) may distort the tissue and permanently alter their function
An abscess in the brain would act as a space-occupying lesion - could compress vital surrounding structures
Name the 5 cells involved in inflammation
- Neutrophil polymorphs
- Macrophages
- Lymphocytes
- Endothelial cells
- Fibroblasts
What can apoptosis be triggered by?
DNA damage e.g. single-strand break, base alteration, cross linkage
What is apoptosis?
Programmed cell death
Define necrosis
Death of most or all cells in an organ or tissue due to disease, injury or failure of the blood supply
What are some clinical examples of necrosis?
Toxic spider venom, frostbite, cerebral infarction, avascular necrosis of bone, pancreatitis
Define a single gene disorder
Abnormality of a single gene causes a disease
Define a polygenic gene disorder
A genetic disease which is the result of the interaction of several different genes (usually on different chromosomes).
Name an example of a polygenic gene disorder
Breast Cancer
What genes have a significantly large individual effect on breast cancer?
BRCA1 and BRCA2
What’s an example of a single gene disorder?
Sickle Cell Anaemia
Define hypertrophy
Increase in size of a tissue caused by an increase in size of the constituent cells
Define hyperplasia
Increase in size of a tissue caused by an increase in number of the constituent
Define atrophy
Decrease in size of a tissue caused by a decrease in number of constituent cells or a decrease in their size
Define metaplasia
Change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type
At what point is the process of healing and repair of tissue complete?
When the initiating factor of damage is removed and when the tissue is undamaged or able to regenerate
Describe the difference between lobar pneumonia and bronchopneumonia
Lobar pneumonia affects a lobe of the lung rather than the entire lung
What occurs during lobar pneumonia?
Alveoli are filled with neutrophil polymorphs (acute inflammation) rather than air
In lobar pneumonia, how does the healing process occur?
Pneumocyte that line the aveoli can regenerate ∴ the lung can be regenerated. The pneumocytes divide and reline the alveoli
Define an abrasion (skin wound)
Most superficial skin wounds e.g. road rash
Describe the healing process of skin abrasions
Scab formed over surface of abrasion -> epidermis growing out from adnexa, produced by scab -> thin confluent epidermis present -> final epidermal regrowth
What is the reason incisions can heal relatively quickly?
because an incision causes very little damage to the tissue on either side of the cut, so as long as the two sides are brought together accurately, healing process is quick
Healing of an incised skin wound is called…
Healing by 1st intention
How can an incised skin wound be healed?
By suturing up the cut
Describe the process of healing an incised skin wound
The incision results in exudation of fibinogen -> weak fibrin join -> epidermal regrowth and collagen synthesis -> strong collagen join
Healing by 2nd intention occurs when…
A tissue loss injury occurs or when there’s another reason that the wound margins are not apposed (can’t bring the skin edges together since the cut is too deep)
Describe the process of healing tissue loss (healing by 2nd intention)
Loss of tissue -> granulation tissue formed -> organisation -> early fibrous scar -> scar contraction
Phagocytosis also occurs to remove any debris
Granulation tissue fills in defects and repairs specialised tissues lost
Epithelial regeneration to cover the surface of wound
Name cells that regenerate (6)
Hippos Play Ball, Giraffes Sleep Over
- Hepatocytes
- Pneumocytes
- Blood cells (all)
- Gut epithelium
- Skin epithelium
- Osetocytes (help remodel bone fractures)
Cells that don’t regenerate (2)
Myocardial cells & Neurones
Describe organisation
The process whereby specialised tissue is repaired by the formation of mature fibrovascular connective tissue. It occurs by the production of granulation tissue and the remocal of dead tissue by phagocytosis
Describe granulation
Loops of capillaries supported by myofibroblasts which actively contracts to reduce wound size, may result in a structure later.
What occurs during repair and give examples of repair
Replacement of damaged tissue by fibrous tissue. Collagen is produced by fibroblasts
e.g. Heart after MI
Brain after cerebral infarction
Spinal cord after trauma
Name 2 reasons clots are rare
- Laminar Flow - cells travel in the centre of arterial vessels and don’t touch the sides
- Endothelial Cells - line the blood vessels, are not ‘sticky’ when healthy
Describe thrombus formation
- Damage to endothelial cells in the vessel cause some of the cells to lift away from vessel wall, exposing collagen
- Platelets then begin to stick to the exposed collagen, and release chemicals –> causing platelet aggregation. Platelet aggregation also starts the cascade of clotting proteins in the blood
- RBCs get trapped within the aggregating platelets
- Clotting factors join the RBCs and platelets and clotting cascade forms fibrin. This is deposited and forms clot
- Positive feedback loop - can result in thrombus which can block the artery
What can be prescribed to reduce the risk of thrombosis and why?
Aspirin because it inhibits platelet aggregation
Define an embolus
Mass of material in the vascular system that’s able to become lodged within a vessel and block it
What is the most common cause of an embolus?
Usually caused by part of a thrombus that has broken off and circulates in the bloodstream
What are less common causes of an embolus? (4)
Air (pressurised systems of IV fluids/bloods)
Tumour
Amniotic fluid (rare in pregnant women)
Fat (severe trauma w/ fractures)
What occurs if an embolus enters the venous system?
It will travel to the vena cava and lodge in the pulmonary arteries. The lungs then act as a filter for venous emboli (since blood vessels split into capillaries - too small for emboli to travel through)
What happens if an embolus enters the arterial system?
It can travel anywhere downstream of its entry point
Define ischaemia
A reduction of blood flow to a tissue without any other implications
Define Infarction
A reduction of blood flow to a tissue - so reduced that it cannot even support the maintenance of the cells in the tissue ∴ they die
Define end artery supply
An organ that only receives blood supply from one artery
Name examples of organs with multiple arterial supplies
Pulmonary arteries and bronchial arteries supplying the lungs
Portal vein and hepatic artery supplying the liver
Circle of Willis supplying parts of the brain
Why is there a limit of the amount of cell division that can occur?
Telomeres gets shorter after each cell division ∴ limit on divisions ∴ ageing occurs
What is Dermal Elastosis?
The accumulation of abnormal elastic in the dermis of the skin
What causes Dermal Elastosis and why?
Prolonged/excessive sun exposure (photoaging) because UV light causes protein cross-linking
What causes Osteoporosis?
Loss of coupling in the bone remodelling process - due to ↑bone resorption OR ↓bone formation -> due to lack of oestrogen
(hence found often in post-menopausal women)
Describe the bone matrix and trabeculae in a patient with Osteoporosis and hence what this can result in
Bone matrix is mineralised as normal but trabeculae are thinned
∴ results in fractures from minor trauma
What can osteoporosis cause?
Osteopenia
Renal Stone Formation (Osteoporosis liberates calcium ∴ hypercalciura)
What causes cataracts?
The formation of opaque proteins within the lens which also results in a loss of lens elasticity
(UV-B light causes protein cross-linking)
What causes senile dementia?
Plaques and neurofibrillary tangles occur in the brain
What causes sarcopenia?
Decreased growth hormone, decreased testosterone, increased catabolic cytokines
What causes deafness?
Since hair cells cannot divide/regenerate, once damaged they cannot recover
Define carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
State the difference between carcinogenic and oncogenic
Carcinogenic = cancer causing
Oncogenic = tumour causing
What is a carcinogen?
Agents known or suspected to cause tumours
In which industries are there an increased incidence with bladder cancer?
Aniline dye and rubber industries
In which industry is there an increased incidence with scrotal cancer?
Chimney sweeps
Define a tumour
Any abnormal swelling
Define 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
What do solid neoplasms ALWAYS have?
Neoplastic cells and stroma (except leukaemia)
What can neoplasms be classified as?
benign, borderline, malignant
(but borderline tumours can’t be precisely classified e.g. some ovarian lesions)
Name 2 examples of benign neoplasms
Fibroid
Tubulovillous adenoma
Name 2 examples of malignant neoplasms
Prostate cancer
Squamous cell carcinoma
What can benign neoplasms cause?
Flow obstruction
Production of hormones
Transformation to malignant neoplasm
Anxiety
What can malignant neoplasms cause?
Destruction of adjacent tissue
Metastases
Blood loss from ulcers
Flow obstruction
Hormone production
Paraneoplastic effects
Anxiety and pain
Define papilloma
Benign tumour of non-glandular, non-secretory epithlium
Define adenoma
Benign tumour of glandular or secretory epithelium
What process is essential for a neoplasm to grow?
Angiogenesis
What may a neoplasia arise from?
Epithelial cells
Connective tissues
Lymphoid/Haemopoietic organs
How are benign epithelial neoplasms named? Provide examples
Prefix with cell type of origin
e.g. squamous cell papillom
thyroid adenoma
How are benign epithelial neoplasms named? Provide an example
Prefix with cell type of origin
e.g. transition cell carcinoma
adenocarcinoma (carcinoma of glandular epithelium)
How are benign connective tissue neoplasms named?
named according to cell of origin, then ‘-oma’
e.g. lipoma (adipocytes)
chondroma (cartilage)
osteoma (bone)
angioma (vascular)
Define acute inflammation
Initial, transient series of tissue reactions to injury
Lasts hours to days
What are the 2 types of Autopsy?
Hospital autopsies
Medico-legal autopsies
Which is the most common type of autopsy?
Medico-legal
When are hospital autopsies useful?
Audit
Teaching
Governance
Research
What are the types of death referred to by coroners?
Presumed natural - cause of death not known, not seen by a doctor in the last 14 days for illness
Presumed iatrogenic - anaesthetic deaths, abortion, complications of therapy, peri/postoperative
Presumed unnatural - accidents, suicide, industrial death, unlawful killing, neglect, custody deaths
What is the Coroners Act 1988?
Allows coroners to order autopsy when death is likely due to natural causes to obviate need for inquest.
Also allows coroners to order autopsy where death is unnatural and inquest is needed
What is the Coroners Rules 1984?
Autopsy ASAP by pathologist of suitable qualification and experience
Report findings ONLY to coroner
Autopsy only on appropriate premises
What is the Amendment Rules 2005?
Pathologist must tell coroner what materials have been retained
Coroner authorises retention and sets disposal date, also informs family of retention
& Family has choice of :
Return material to family
Retain for research/teaching
Respectful disposal
Coroner informs pathologist of family’s decision
What is the Coroners and Justice Act 2009?
Coroner can now defer opening the inquest and launch an investigation instead
Inquests not have conclusions, not verdicts
What is the Human Tissue Act 2004?
Autopsies only happen on licensed premises
Consent from relative for use of tissue retained at autopsy if not subject to coronial legislation or retained for criminal justice purposes
Public display requires consent from deceased
If you don’t follow the Human Tissue Act, penalties include up to 3 years of imprisonment and/or fine
