Cell Pathology Flashcards
Define atrophy
Shrinkage in the size of a cell and consequently the size of a whole organ, by the loss of cell substance
-We see a decrease in weight of an atrophic organ
Define hypertrophy
- Increase in the size of a cell and consequently the size of a whole organ
- Physiological or pathological
- important because muscle cells cannot divide in adult life so this is the only way in which an organ can get bigger (number of cells remain constant but there is an increase in cell size)
Define hyperplasia
- Increase in the number of cells in an organ
- Physiological or pathological
Define metaplasia
- Reversible change in which one normal adult cell type (mature cell) is replaced by another (normal adult cell replacement)
- Physiological or pathological
Define dysplasia
- Precancerous cells which show the genetic and cytological features of malignancy but do not invade the underlying tissue
- bridge between normality and cancer
- not invaded the basal lamina
- dysplasia is a worrying change
List the 5 adaptive responses of cells
Atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia
Give an example of atrophy
- Gastric atrophy causing pernicious anaemia (anaemia resulting from deficiency of vitamin B12)
- posterior cortical atrophy from the loss of neurones in Alzheimer’s disease
Give an example of hypertrophy
Physiological: muscle hypertrophy in the uterus during pregnancy
Pathological: left ventricular hypertrophy in response to hypertension
Give an example of hyperplasia
Physiological: oestrogen-induced endometrial hyperplasia
Pathological: benign prostatic hyperplasia, carcinoma
Give an example of metaplasia
Physiological: metaplasia in the cervix
Pathological: Barrett’s Oesophagus (otherwise known as columnar lined oesophagus)
Give an example of dysplasia
- Cervical intraepithelial neoplasia
- Barrett’s oesophagus is associated with a much greater risk of oesophageal cancer because metaplasia is typically followed by dysplasia
- dysplasia is the increased cancer risk
Define degenerative
Change of a tissue to a lower or less functionally active form
Define ulcer
Local defect or excavation of the surface of an organ or tissue, produced by the sloughing of necrotic inflammatory tissue
Recall the light microscopic changes of reversible cell injury
- fatty changes
- cellular swelling
Recall the light microscopic changes of irreversible cell injury
The different types of necrosis (coagulative, liquefactive, caseous and fat)
Specific cases reported to the Coroner in England and Wales
- When the cause of death is unknown
- When the deceased has not been seen by the certifying doctor either after death or 14 hours before death
- If the death was violent, unnatural or suspicious (example of a homicide)
- When the death may be due to an accident, regardless of when this occurred
- The death may be due to neglect by self or by others (subjective and difficult to define)
- The death may be due to an industrial disease or due to the deceased person’s employment (occupational such as mesothelioma linked to asbestos exposure)=includes accidents at work and if the death is actually at work
- The death may be due to the impact of abortion on the mother
- The death occurred during an operation or before recovery from the effects of anaesthetic
- The death may be a suicide
- The death may be related to poisoning
- The death occurred during or shortly after detention in police or prison custody (expection of DoLS=patients lack capacity to consent to their care and treatment)
Difference between a coroner’s autopsy and a hospital autopsy
Purpose and consent
Coroner’s autopsy purpose
- Conducted to establish the cause of death
- Once the Coroner has determined the cause of death, his remit is over
Hospital autopsy purpose
- Allows a very thorough examination of the deceased, the extent of their disease, their treatment and its effects
- Performed in the case of an audit where there is a major discrepancy between the stated cause of death and the actual cause of death
- Used for medical teaching purposes
- Used to monitor the effectiveness of new treatments
- Used in medical research (knowledge of variant CJD heavily relies on the study of post mortem brain tissue)
Define bruise
- Otherwise known as a contusion
- extraversated collection of blood which has leaked from damaged small arteries, venules and veins but not capillaries
Define abrasion
- graze or scratch
- most superficial of the blunt trauma injuries
- confined to the epidermis
Define laceration
-split to the skin as a result of blunt force trauma which overstretches the skin
Define a cut
- Otherwise known as a slash
- Split in the skin where the length of the injury is longer than its depth
Define a stab
- Otherwise known as a penetrating injury
- Split in the skin where the depth of the wound is greater than the width
Define incised wounds
- often discrepancy in terms used
- to some this means cuts and stabs
- to others it means the same as cuts
Define cancer
- malignant neoplasm
- an abnormal growth of cells which tend to proliferate in an uncontrolled way and, in some cases, to metastasise
Define neoplasm
- The autonomous growth of tissue which have escaped the normal constraints of cell proliferation
- all body cells divide and grow under tight control, but a neoplasia will develop when this control is lost
- growth in uncoordinated, independent of the body’s normal homeostatic growth-regulating mechanisms, purposeless and will continue after the stimulus which initiated the change is removed/ceased
- example of a neoplastic tumour is lung cancer
Define tumour
- any kind of MASS forming lesion
- abnormal swelling in or on a part of the body
- may be neoplastic, hamartomatous or inflammatory
- Example of a non-neoplastic tumour is nasal polyps with a chronic inflammatory cause
- usually applied to the abnormal growth of tissue (benign or malignant)
Define metastasis
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Define carcinogens
-any substance that, when exposed to living tissue, may cause the production of cancer
Define malignant
- classification of neoplasm
- invade tissue locally and have the potential to spread to distant sites in the body
- more difficult to remove because of local tissue invasion and metastasis
- Local surgery helps but focus is on chemo and radiotherapy
Define benign
- classification of neoplasm
- remain localised=defined, well demarcated
- cured by local surgery (easy to remove)
Example of a situation resulting in a bruise
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Example of a situation resulting in an abrasion
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Example of a situation resulting in an laceration
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Purpose of cancer screening
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Features/principles of a successful cancer screening programme
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Environmental carcinogen examples
- UV radiation= basal cell carcinoma, squamous cell carcinoma and multiple myeloma
- Asbestos=mesothelioma linked to cases reported to a coroner
- Ionising electromagnetic radiation=leukaemia and solid tumours
Chemical carcinogen examples
- Hydrocarbons
- Amines
- Nitrosamines
- Azo dyes
Infectious carcinogen examples (oncogenic viruses)
- Epstein-Barr virus (EBV)=Burkitt’s Lymphoma
- Human papillomavirus (HPV)=Cervical cancer
- Hepatitis B virus=hepatocellular carcinoma (liver)
- human herpesvirus-8=Kaposi sarcoma
- Helicobacter pylori (bacterium)=gastric cancer and lymphoma
Barrett’s Oesophagus
Epithelial lining of the oesophagus converts from stratified squamous to columnar (change of normal oesophageal tissue lining to that which resembles the lining of the small intestine)
Metaplasia in the cervix
- Endocervix is lined with columnar epithelium and the ectocervix is lined with stratified squamous epithelium
- At puberty/during pregnancy, the cervix expands and exposes the fragile columnar epithelial lining of the endocervical canal to the harsher more acidic environments in the vagina
- Causes metaplasia from columnar to stratified squamous
Cause of Barrett’s Oesophagus
Acid reflux
Treatment to reverse pathological metaplasia in Barrett’s Oesophagus
PPI’s (proton pump inhibitors) which inhibit acid production
Reversal of the physiological metaplasia in the cervix
Cervix contracts and closes up
Properties of cells in the dysplastic stage
High nuclear-cytoplasmic ratio, increased mitoses, genetic abnormalities of cancer, do not invade through the basement membrane
Define necrosis
Confluent cell death associated with inflammation
Define apoptosis
Programmed cell death of single cells, not associated with inflammation
Define necroptosis
- Programmed cell death associated with inflammation
- Energy dependent
- Halfway between necrosis and apoptosis
- many causes such as viral infection
- generally occurs in pathological circumstances
Features of a bruise (contusion)
- blunt trauma injury
- occurs alone when the skin remains intact or can be associated with other injuries
- Occurs more easily where the skin is lax
- Factors effecting bruising include coagulation state and fragility of blood vessels
- Can take hours or days to form
- It is possible to bruise after death
- Bruises can be present in patterns and deep bruising can occur which is never seen on the skin surface
- don’t age bruise but can describe the colour
Features of an abrasion
- can occur before or after death
- caused by either a tangential force (force acting on the moving body in the direction of a tangent to the path of the body) or vertical force
- tangential force may be distal skin tag whereas the vertical force has no distal skin tag
- example of friction burn, whip, stamp etc
Features of a laceration
- will pass through the full thickness of the skin=deep and will bleed
- common where the skin can be compressed between the force and the underlying bone
- Rare over soft, fleshy areas like the buttocks and breasts
- Margins are ragged with crushing and bruising
- bridging fibres arch across the skin defect
- flaying=where a tangentially applied force leads to a horizontal laceration
- example of hammer, fall etc
Features of a cut or stab wound
- Caused by an object with a sharp or cutting edge (typically a knife but it can be any material such as broken glass etc)
- Edges of the wound are clean, defined and well demarcated(can distinguish the limits of the wound)
- Minimal injury to the surrounding tissue
- Information about weapon type can be gained from analysis of the wound (do not overinterpret though)
Causes of cell injury
G=genetic defects
I=infectious agents (bacteria, viruses, multicellular parasites)
N=nutritional imbalances
C=chemical agents (includes iatrogenic injury which is cell injury resulting from the drugs/medication that the doctors give)
H=hypoxia (oxygen deprivation)
A=aging
P=physical agents (eg: gunshot wound, trauma etc)
I=immunological reactions (autoimmune disease where the body attacks itself as in conditions such as rheumatoid arthritis)
Factors affecting the cellular response to injurious stimuli
- type of injury
- duration of the injury (how long the injury is sustained)
- the severity of the injury
Factors affecting the consequences of an injurious stimuli
- type of cell (some cell types are naturally more resistant to injury than others such as in the example of bone, fat, the brain and the heart to oxygen deprivation=differing metabolic requirements)
- The cell’s status (more vulnerable to various agents if in the process of dividing)
- adaptability (does the cell have particular adaptations it can undertake)
- The genetic makeup of cells
List the four intracellular mechanisms/systems which are vulnerable to cell injury (systems are linked so damage to one, will impact the others)
- cell membrane integrity
- ATP generation
- protein synthesis
- integrity of the genetic apparatus
What occurs before the morphological changes (structure, shape or form) of the cell are observed?
Cell death and before cell death we see loss of cellular function
- Often, the loss of cellular function kills a patient before the morphological changes take place in the cell
- You might not observe anything at post mortem because it is the loss of function which has killed the patient before cell injury
Why do multiple secondary effects rapidly occur from cell injury to the vulnerable systems listed?
Structural and biochemical components of a cells are so integrally related
Features of necrosis
- death of cells stimulates the cellular reaction of inflammation
- not just single cells (areas of cells)
- not energy dependent
- always pathological and associated with diseased states
Features of apoptosis
- active cell death and hence energy dependent (requires ATP hydrolysis)
- can be physiological as well as pathological
- not associated with inflammation (no bystander damage)
- normal part of an organism’s growth and development
Key differences between necrosis and apoptosis
- energy
- inflammation
- state (pathological or physiological)
- apoptosis is often in response to mild injury whereas necrosis is in response to severe injury
Causes of apoptosis
- Embryogenesis
- deletion of auto-reactive T cells in the thymus
- hormone dependent physiological involution (eg: shedding of endometrium in each menstrual cycle)
- cell deletion in any proliferating populations
- a variety of mild injurious stimuli that causes irreparable DNA damage that triggers cell suicide pathways
Define coroner
- Independent judicial officer of the crown (employed by the queen) who has a statutory duty to investigate the circumstance of certain categories of death for the protection of the public
- only in court room with jury if patient died in police custody etc
- reported by most junior doctor of the firm
- investigates death and how it occurred
Extracellular fluid quantity, composition and respective ratios
-19L
-blood plasma, interstitial fluid and transcellular fluid
3L:15L:1L
-45% of the total body water content
Intracellular fluid quantity
- 23L
- 55% of the total body water content
Aetiologies of oedema
- increased hydrostatic pressure
- salt and water retention
- decreased plasma oncotic pressure
- inflammation
- lymphatic obstruction
Define oedema
Abnormal increase in the interstitial fluid (increase in fluid in the interstitium)
Which factors govern the interstitial fluid flow?
- hydrostatic pressure
- plasma oncotic pressure
- endothelial permeability
Define thrombosis
Abnormal blood clot formation in the circulatory system
Types of cerebral oedema
- vasogenic
- cytotoxic
Main symptom of pulmonary oedema
Dyspnoea (difficulty breathing=shortness of breath)
Prevalence of death from malignant tumours
- many do not cause death
- especially in the incidence of skin cancers=common occurrence in most populations (SCC, BCC)
Why do malignant tumours not always result in death?
- in the example of skin cancers and hence BCC, they tend to remain localised and NEVER metastasise
- Still invades locally to give malignancy
BCC
- Basal cell carcinomas
- invade locally (invasive) to give malignancy
- never metastasises so do not result in death
- easy cure by local treatment
- common for patients living in sunny areas
Top common cancers in terms of causing death
breast/lung
Why can some benign tumours kill?
-behaviour is not benign although it is histologically
- location in a critical area (particularly the brain)
- hormonally active synthesising and pumping out excessive hormone amounts
Define hamartomas
- localised benign overgrowth of one more mature cell types
- Do not represent cytological abnormalities
- way the cells are organised(architecture) has abnormalities
Define heterotopias
- normal tissue being found in parts of the body where they are not normally present
- cause of a tumour
Primary description of a neoplasm
- cell origin
- tissue they are derived from
Secondary description of a neoplasm
-benign or malignant
Benign glandular tumour
epithelial neoplasms
Adenoma
Benign squamous tumour (epithelial neoplasms)
Squamous epithelioma or papilloma
Benign transitional tumour (epithelial neoplasms)
Transitional papilloma
Malignant glandular tumour (epithelial neoplasms)
Adenocarcinoma
Malignant squamous tumours (epithelial neoplasms)
Squamous cell carcinoma
Malignant transitional tumours (epithelial neoplasms)
Transitional cell carcinoma
What does the suffix ‘oma’ mean?
a benign tumour except in the instance of malignant lymphoma, malignant melanoma, hepatoma and tetratoma
Smooth muscle benign tumour (connective tissue neoplasm)
Leiomyoma
Smooth muscle malignant tumour (connective tissue neoplasm)
Leimyosarcoma
Bone benign tumour (connective tissue neoplasm)
Osteoma
Bone malignant tumour (connective tissue neoplasm)
Osteosarcoma (osteogenic sarcoma)
Lymphocyte benign tumour (haematological neoplasm)
Extremely uncommon
Lymphocyte malignant tumour (haematological neoplasm)
Lymphoma
Bone marrow benign tumour (haematological neoplasm)
Extremely uncommon
Bone marrow malignant tumour (haematological neoplasm)
Leukaemia
Features of a successful cancer screening programme
1) the condition is an important health problem
2) treatment is possible
3) facilities for diagnosis/treatment are available
4) recognisable latent or early symptomatic stage
5) suitable test or examination
6) test is acceptable to the population
7) natural history understood
8) agreed policy on which patients to treat
9) cost-effective
10) case finding should be a continued process
What happens to normal cells for cell injury to occur?
- respond to injurious stimuli (stress which is harmful)
- stress exceeds the adaptive capability of the cells
What happens to normal cells for cell adaptation to occur?
- Stressed by increased demand/increased load
- cells remain in an equilibrium (steady state) but work in the new adapted state
Recall the two types of cell injury
- Lethal (produces cell death)
- Sub-lethal (injury does not amount to cell death=injury which does not kill the cell/organism)
Recall the two types of sub-lethal cell injury
- Reversible (within certain limits, the cell can return back to normal)
- Irreversible (progress to cell death)
Define infarction
Tissue death due to ischaemia
In what instances might cell death occur?
- stress is too severe
- prolonged/persistent stress
Trophy
Growth
Plasia
Development
Physiological effects
- Result of a normal stressor
- Occurs in healthy people
Pathological effects
- Result of an abnormal stressor
- Associated with diseased states
Causes of hypertrophy
- Increased functional demand
- specific hormonal stimulation (as seen in pregnancy)
Example of hormonal stimulation as a cause of hypertrophy
-tumour of the parathyroid secreting TSH (thyroid stimulating hormone) causing an enlargement of the thyroid gland
Recall the two causes of physiological hyperplasia
- Hormonal (eg: oestrogen causes wave of proliferation of the endometrium=inner lining of the uterus)
- Compensatory (eg: tissue previously lost)
Cause of pathological hyperplasia
- excessive hormonal or growth factor stimulation
- observed in cancer(tremendous hyperplasia because of high cell proliferation)
Why is cell membrane integrity important?
- intrinsic to the viability of the cell
- interface between the cell and its surrounding environment
- distinguishes self from non-self
- problems if functionality is broken
Why is ATP generation important?
- immediate energy source of the cell
- maintaining cell membrane integrity
Why is protein synthesis important?
- growth, repair and homeostasis
- synthesis of carrier proteins in the cell membrane for the process of active transport
- requires ATP generation and intact genetic apparatus
What happens if the DNA of the cell is damaged?
- neoplasms
- problems with cell division
- impacted protein synthesis
Example of the four intracellular systems linking with each other
- to maintain cell membrane integrity, you require energy in the form of ATP
- ATP generation is a metabolic pathway requiring substrates and enzyme systems, with the enzymes being proteins
- Require ATP generation and genetic apparatus integrity for protein synthesis
Define fatty changes
- fat accumulation within cells (fatty globules)
- example in alcoholics where we see fat accumulation within liver cells due to the metabolic demands placed on the liver from the alcohol consumption
Define ballooning
- cell membrane damage stopping pumps working and therefore, the gradient cannot be maintained leading to fluid leaking in
- example in liver cells from alcohol consumption
Coagulative necrosis
- substance changes but the shape of the molecule does not
- tissue retains structure after coagulation but nuclei are gone with inflammatory cells present
- tissue can still be recognised
- example of myocardial infarction
Liquefactive necrosis
- tissue is broken down leaving a space which gets filled with fluid
- area is totally liquefied
- empty space so identification is only from cells surrounding it
- example of old cerebral infarct
Caseous necrosis
-form of granulomatous inflammation
characteristic ‘cheesy’ appearance
-often associated with pulmonary tuberculosis
-necrotic area becomes granular making it caseous
-tissue cannot be recognised from structure
Fat necrosis
- characterised by the breakdown of fat cells (by lipase release or trauma)
- release of lipases digest the fat and hydrolyse the triglycerides into free fatty acids and glycerol
- free fatty acids combine with calcium in extracellular fluid to give calcium fat salts which deposit
- associated with acute pancreatitis
- also due to significantly severe fat trauma
Mechanism of apoptosis
- cell implodes on itself
- nucleus shrinks
- parts of the cell break off but cell membrane is never ruptured meaning no inflammation
- apoptotic cells and fragments under phagocytosis by macrophages
Mechanism of necrosis
- enzymatic digestion
- leakage of cellular contents
- dead cells attract inflammatory cells
Purpose of apoptosis
-injury is too severe or repair systems are lacking (cell cannot repair itself)
Percentage of deaths reported to the coroner?
45%
Consent for hospital autopsy?
- Consent obtained from next of kin/relatives
- with relevant consent, any material can be taken
Consent for coroner’s autopsy?
- no need because we are investigating the cause of death
- wishes of family must however be considered
- material can only be taken if it needed to help find the cause of death
What is the death certificate data used for?
- epidemiology
- gives accurate morbidity and mortality data to monitor the nation’s health, allocate appropriately the limited quantity of resources and funds in the health sector and to detect any environmental risks
How is an autopsy conducted?
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Features of the death certificate
- filled in for any death
- taken to the Registrar by the family
- Scrutinised, examined and corrected before registration of death is possible
Layout of death certificate
1a) Immediate cause of death (always filled in)
1b) Predisposing factor
1c) Predisposing factor
2) Other factors which contribute but do not directly lead to death
- 1c leads to 1b and 1b leads to 1a
- it is possible to have two 1a’s (occurs more in older people)
3 main causes of death in young people
- drugs and alcohol
- trauma
- congenital conditions
Coronary artery disease
- 75% of deaths handled by medical examiners in the USA
- 50% die suddenly
- 25% die without any preceding history or warning
- cardiac arrhythmia is the usual mode of death (irregular heartbeat)
- Severe coronary artery atherosclerosis is the most common anatomical finding
- If the stenosis (abnormal narrowing) observed is more than 75%, death can occur
- usually occurs in 2 or more of the major blood vessels
- Other findings include myocardial scarring, coronary artery thrombosis and acute or subacute myocardial infarction
- If arrhythmia is the mechanism of death the diagnosis is one of exclusion, full autopsy must be conducted and severe coronary atherosclerosis must be the major finding. (In such cases, 1a is stated as ischaemic heart disease)
Hypertensive heart disease
- Usually accompanied by coronary artery atherosclerosis
- Cardiomegaly (enlargement of the heart) with symmetrical left ventricular hypertrophy
- acute cardiac arrhythmia tends to be the usual cause of death
Other cardiac causes of sudden unexpected death
- cardiomyopathy (disease of the heart muscle)
- myocarditis (inflammation of the myocardium)
- floppy mitral valve
- structural abnormalities (eg: bridging)
- conduction abnormalities (eg: long QT syndrome)
- aortic stenosis (usually calcific)
Ruptured aortic aneurysm
Ruptured aortic aneurysm associated with atherosclerosis and hypertension
Non-traumatic subarachnoid haemorrhage
- Commonly due to berry aneurysms in the intracranial arteries
- 90% of these berry aneurysms are silent until rupture
- Affects 2%-4% of adults
- 2/3 of individuals are symptomatic between 40 and 65 years old
Intracerebral haemorrhage
- type of stroke called a haemorrhagic stroke
- this type of stroke accounts for 10%-30% of all strokes (relatively uncommon)
- Most common cause of hypertension
Respiratory system
- Pulmonary embolus
- Asthma
GI tract
- not usually unexpected causes of death
- Bleeding oesophageal varices
- Bleeding ulcers
- Pancreatitis
Drugs and alcohol
- Alcohol can be a cause of sudden, unexpected death in alcoholic patients
- Alcohol is often associated with gastrointestinal problems
- Often alcohol related damage pairs with drug use
- Both associated with 1% of deaths reported to the coroner
Trauma
-can be self induced or caused by others
Other CNS causes of sudden, unexpected death
Epilepsy
