Pathology Flashcards
What is cancer?
Uncontrolled cell division that can invade other tissue and impede their function
What is a tumour?
Any swelling Can be benign or malignant
What is a neoplasm?
New growth not in response to any stimulus
Define malignant
Metastatic potential is present This involves any neoplasm invading the basement membrane
What is metastasis?
The spreading of a neoplasm to a different part of the body
Give three pre-malignant stages
- Dysplasia - disordered growth with no stimulus (no invasion of basement membrane)
- Metaplasia - change of one cell type to another
- Hyperplasia - increase in cell number
Metaplasia is a response to _____
Stress
What can initiate metaplasia?
- Injurious or noxious stimuli
- Cytokines and cell signals
Why are post-menopausal obese women at risk to hyperplasia (and cancer)?
Oestrogen will cause proliferation of the endometrium as part of the menstrual cycle. Cholesterol is similar in structure to oestrogen Obese women have high cholesterol which can cause proliferation in the endometrium Due to increased (an unnecessary) proliferations, these women have more “chances” for cells to begin to grown autonomously and for hyperplasia to occur
What occurs in dysplasia that does not occur in either metaplasia or hyperplasia?
A genetic abnormality is developed
What is carcinoma in-situ?
This is the final stage a neoplasm goes through before becoming malignant (invading basement membrane and spreading by metastases) This is the same as high-grade dysplasia
How is the N:C (nuclear:cytoplasmic) ratio affected in malignant cells affected?
N:C ratio is high
List some causes of cancer
- Genes
- Smoking
- Alcohol
- UV radiation, and other rdiation types
- Drugs
- Infections
- Obesity
- Burnt toast…supposedly Etc.
What are Weinberg Hallmarks?
These are “bad decisions” made by a cell that are key to becoming malignant.
. Increased growth signals
. Growth suppression removed
. Avoiding apoptosis
. Achieving immortality
. Becoming invasive
. Making own blood supply (angiogenesis)
. Lose cellular DNA spellchecking
What is Li-Fraumeni syndrome?
Genetic condition affecting the tp53 gene which codes for p53. This means sufferers from LFS are unable to stop excessive growth and attempt DNA repairs (or activate apoptosis)
How does radiation cause cancer
Pyrimidine dimers are formed in DNA which are molecular lesions involving two consecutive bases on a single DNA strand to bind together ruining the normal base pairing Numerous instances can cause repair mechanisms to become overwhelmed
Describe briefly the cell cycle
- Cyclin D activated CDK4 (cyclin dependent kinase)
- CDK4 phosphorylates Rb (retinoblastoma)
- Rb now unbinds from DNA allowing for DNA replication to occur - access to DNA is now possible
- Synthesis phase now occurs involving DNA replication
- M phase follows after G2 and the cell divides
- Cytokinesis is when the cell physically divided
What are oncogenes?
A gene with the potential to cause cancer It involves increased growth
What are tumour supressors?
These are genes preventing the pathway to cancer
How can neoplastic cells evade DNA spellchecking?
Destroying spellcheck proteins such as P53
What happens to a tumour in the bloodstream?
It will aggregate with platelets This means it will eventually slow down and stop within a blood vessel and grow in this new location
Name 2 growth factors that can aid angiogenesis (for neoplasms)
- VEGF (vascular endothelial growth factor)
- PDGF (platelet derived growth factor)
What are the three stages involved in the pathway of mutations and neoplasm development?
- Initiation - first mutation
- Promotion - accumulation of mutations (dysplasia)
- Persistance - malignant
FISH is better than PCR for _____ genetic abnormalities
Large
PCR is ideal for _____ genetic abnormalites
Small
What are the functions of p53? (4)
- Cell cycle arrest at G1
- Increase levels of p21 to inhibit CDKs preventing Rb phosphorylation and hence DNA replication
- Apoptosis activation when damage is too great
- Activate repair mechanisms when damage is minimal
What are first principles in relation to identifying neoplasms?
These are quick decisions that can make an estimate as to whether the neoplasm appears malignant or not
How do benign tumour look?
- round and smooth
- homogenous
- symmetrical
- Normal N:C ratio
- Slow growth
How do malignant tumours look?
- Not symmetrical
- jagged edges
- heterogenous
- High N:C ratio
- Fast growth
What is differentiation?
The process by which stem cells develop into mature cells types
What can poor cell differentiation indicate?
Neoplasms Potentially malignant
What is pleomorphism?
The presence of many forms of the “same” cell type - poor differentiation has taken place
What is hyperchromasia?
A cell which has a nucleus that stains very darkly - highlights large amount of genetic material suggesting fast growth and malignancy
Why does rapid cell division in neoplasms impact the number of mutations developed?
The more divisions that take place, the more chances there is for mutation
What is a neoplasm of the epithelium called?
Carcinoma - always malignant
What is a benign neoplasm of glandular cells called?
Adenoma
What is a benign neoplasm of squamous cells called?
Papilloma
What is a neoplasm of bladder epithelial cells called?
Urothelial cell carcinoma - always malignant
What is a malignant neoplasm of glandular cells called?
Adenocarcinoma
What is a malignant neoplasm of squamous cells called?
Squamous cell carcinoma
What are malignant neoplasms of connective tissue (mesenchyme) called?
Sarcomas
What are the names of benign/malignant neoplasms of fat tissue?
Benign - lipoma
Malignant - liposarcoma
What are the names of benign/malignant neoplasms of bone?
Benign - osteoma
Malignant - osteosarcoma
What are the names of benign/malignant neoplasms of cartilage?
Benign - enchondroma
Malignant - chondrosarcoma
What are the names of benign/malignant neoplasms of skeletal muscle?
Benign - rhabdomyoma
Malignant - rhabdomyosarcoma
What are the names of benign/malignant neoplasms of smooth muscle?
Benign - leiomyoma
Malignant - leiomyosarcoma
What are the names of benign/malignant neoplasms of nerves?
Benign - neurofibroma (or schwannoma)
Malignant - peripheral nerve sheath tumour
What are the names of benign/malignant neoplasms of blood vessels?
Benign - haemangioma
Malignant - angiosarcoma
What are the names of benign/malignant neoplasms of the CNS?
Benign - gliomas
Malignant - named after benign version with malignant added in front
What is the name of malignant neoplasms of the skin?
Melanoma
What are names for blood neoplasms?
All are malignant Leukaemia Lymphoma
When referring to neoplasms what does “stage” refer to?
Distance from origin
In relation to neoplasms, what do karyotypes allow for?
Translocations to be discovered and defined
When referring to neoplasms what does “grade” refer to?
Level of differentiation
What is the difference between neoplasia and dysplasia?
Neoplasia - autonomous growth
Dysplasia - disordered growth
What do cancers do to the body?
- Compression/blockage of vessels/airways or ducts
- Impacts tissue function
- Haemorrhage - by infiltration
- Infiltrating bone marrow can weaken the immune system
Tumours are very metabolically active using large amounts of energy, what is the name of the weight loss associated with this?
Cachexia
In which two ways can growing occur?
Hyperplasia - increase in cell number
Hypertrophy - increase in cell size
What causes hyperplasia?
An external stimulus
(when removed, growth is reversed)
What is atrophy?
The decrease in cell size
What is metaplasia?
The reversible change from one mature cell type to another
Metaplasia occurs in a response to signals delivered to stem cells. What can some of these signals be due to?
Cytokines
Growth factors
Other chemicals such as noxious stimuli
What are the four main stages in the cell cycle?
G1
S
G2
M
In the cell cycle what does G1 consist of?
. The cell increases in size as protein synthesis increases
. Cyclin dependent kinase 4 (CDK4) becomes activated by cyclin D due to phosphorylation and a complex is formed between the two
. After sufficient CDK4 is activated the cycle can proceed
. Retinoblastoma (Rb) can be phosphorlated by the complex and it comes free from E2F
. E2F can now act as a transcription factor
What is retinoblastoma?
A transcription inhibitor
(normally binds to E2F)
What occurs in stage S of the cell cycle?
DNA replication occurs
What occurs in stage G2 of the cell cycle?
. The cell grows more due to increased protein synthesis
. P53 checks for errors in DNA replication
. It can attempt to fix errors or initiate apoptosis if the errors are too severe
Some cells are terminally differentiated and cannot divide or repair (e.g. neurones). What is a term to describe this?
Replicative senescence
What are telomeres?
They consist of a TTAGGG sequence at the end of a chain
They prevent the chromosome from degrading and “unravelling”
Telomere shortening is linked to ageing
What does the term “resolution” mean in terms of wound repair?
Returns tissue completely to normal
(occur when injury is minimal, there is good vascualr supply and the injurious agent is easily removed)
What is suppuration?
The production of pus
In terms of tissue repair, what does the term “organisation” mean?
Resolution cannot occur, and despite healing, scar tissue is present
This often occurs when the injury goes beyond the basement membrane
(occur if there is necrosis, large quantities of fibrin produced or poor blood supply)
What is granulation tissue?
When tissue becomes injured, the site is infiltrated with capillaries and myofibroblasts (muscle cells)
Collagen and smooth muscle are depositied
This tissue is ganulation tissue and has a red shiny appearance
Why does scarring occur and what is the consequence?
It occurs when myofibroblasts mature and produce collagen which causes the scar
This therefore means the functioning of that tissue segment is lost
Depending on what is found pathologically during autopsy, how can the recency or cause of death be determined?
Presence of neutrophils mean recent injury
Granulation tissue means there has been around 2 weeks since injury
Scarring can mean anything in excess of 6 weeks
What is scarring of the liver called?
Cirrhosis
What is the consequence of cirrhosis?
Liver failure
(toxins cannot be removed from the blood as efficiently, and proteins are not as easily synthesised)
What are the cell types that are most dominant in both acute and chronic inflammation?
Acute - neutrophils
Chronic - lymphocytes
What are the two categories of foreign bodies?
Both can potentially lead to granuloma formation
- Exogenous - talc, asbestos, oil
- Endogenous - keratin, bone, crystals
Which types of infections may lead to granuloma formation?
. Parasites
. Worms
. Eggs
. Syphilis
. Mycobacterium (TB)
Tb granuloma is cause by what?
Caseous necrosis (cheesy)
What are the two types of cell death?
- Apoptosis
- Necrosis
What are the three types of necrosis?
- Coagulative necrosis
- Liquefactive necrosis
- Caseous necrosis
Describe coagulative necrosis
. Dead cells are consumed by enzymatic processes and other cells
. Ghost outlines exist since the nucleus is no longer present
. Cells are therefore no longer living so do not degrade properly
Describe liquefactive necrosis
. No cell structure is maintained
. Cells are liquefied
. This is normally associated with bacterial or fungal infections
Describe caseous necrosis
. Associated with Tb
. A Ziehl-Neelson stain can aid identification of caseous necrosis
. Involves granulomatous inflammation with central necrosis
What is the key difference between apoptosis and necrosis?
Apoptosis requires energy, necrosis does not
Apoptosis is normally physiological, but when may it be pathological?
. Injury
. Radiation damage
. Chemotherapy
. Viral infections
. Cancers
. After transplant
What are the two mechanisms for apoptosis?
. Extrinsic
. Intrinsic
Describe the extrinsic pathway for apoptosis
. It involves death receptor initiation
FasL binds to death receptor Fas which activates caspases
. FADD, an adapter protein, bridges the gap between the Fas receptor and the caspases
. It is the death inducing signalling complex that undergoes conformational change when the Fas receptor is bound
. A caspase cascade occurs
Describe the intrinsic pathway for apoptosis
. Normally growth signals promote anti-apoptotic molecules in the mitochondrial membrane
. Growth signals become deactivated
. They are replaced by Bax and Bak - apoptotic regulators
. This increases the permeability of the mitochondria
. Proteins called cytochrome C escape inducing apoptosis
After apoptosis is induced, what then happens to the cell
. Cells shrink by pyknosis (irreversible condensation of chromatin in the nucleus)
. The nucleus clumps and break up
. The cytoplasm breaks up forming blebs
. Macrophages remove debris
How is cellular ageing caused? (3)
- Oxidative stress by free radical damage
- Accumulation of metabolic by products such as lipofuscin (this accumaltes with age and is toxic to cells)
- Finite cell divisions
What are telomeres?
The TTAGGG sequence at the end of a chromosome
This prevents DNA unwinding
The number of repeats is reduced with each division and will eventually become depleted meaning cells can no longer divide
Why do stem cells never die?
Telomerase continually renews the TTAGGG repeats
This maintains telomere length
Telomerase is not active in normal cells, but can be in cancerous cells conferring immortality
After injury describe the vascular changes that occur
. Vasodilatation occurs
. Histamine and nitric oxide control this process
. This causes calor and rubor
What is the consequence of vasodilatation in vessels after injury?
Blood flow is slowed down (stasis) leading to white cell margination
As a result of white cell margination, how do white cells interact with the endothelial wall
. They will bind, via carbohyrate groups, to selectins which are luminal proteins on the endothelial wall
. This attraction has low affinity so the white cell rolls along the vessel wall
. The release of chemokines, by macrophages will activate white cells allowing them to bind to selectins more strongly and also to the vessel wall via integrin to ICAM-1 and VCAM-1 which results in much stronger affinity
. TNF and IL-1 will increase expression of ICAM-1 and VCAM-1
. Histamine and thrombin are released from inflammatory cells which increase selectin expression
. After coming to a halt, white cells undergo diapedesis
During inflammation, why do vessels become leaky?
White cells need to undergo diapedesis and reach the site of infection or injury
“Leaky” vessels during inflammation is brought about by many mechanisms, what are these?
. Endothelial cell contraction (muscle tissue) - this is caused by histamine, bradykinin, substance P and leukotrienes
. Direct injury
. White cells - self harm will release damaging toxins
. Transcytosis - VEGF mediated, macromolecules are captured in vesicles on one side of the cell, drawn across the cell and ejected from the other side
. New vessel formation - new vessels are weaker and leakier, their production is mediated by VEGF
What is VEGF?
Vascular endothelial growth factor
What is chemotaxis?
Movement of cells along a chemical gradient migrating to the source of injury
What are the three phases of phagocytosis?
- Recognition and attachment
- Engulfment
- Killing and degredation
Describe the recognition phase of phagocytosis
Bacterial surfaces express mannose receptors
Opsonins are antibodies or any other substance increasing suceptibility to phagocytes
The complement system will also surround foreign material
Describe the engulfment phase of phagocytosis
Pseudopods (arms) of the phagocyte surround the foreign material forming a vesicle termed a phagosome
The phagosome will then join with a lysosome and form a phagolysosome
Describe the killing an degredation phase of phagocytosis
Reactive oxygen species within lysomes kill pathogens
This ROS is created due to NADPH which oxidises oxygen
What are the 4 clinical features of inflammation?
- Rubor
- Calor
- Tumour
- Dolor
Why are neutrophils classed as polymorphs?
They have many lobes to their nucleus
