Pathology Flashcards
What are the two types of autopsy?
- Hospital
2. Medico-legal
What percentage of autopsies are hospital autopsies and what percentage are medicolegal autopsies?
Hospital - <10%
Medico-legal - >90%
What is the purpose of hospital autopsies?
To confirm how the patient died for audits/teaching/governance/research
What do you need to perform a hospital autopsy?
- Family consent
- Medical certificate for the cause of death
What is the purpose of medico-legal autopsies?
These include coronial and forensic autopsies to determine cause of death.
Who performs autopsies?
- Histopathologists - hospital and coronial autopsies due to natural death, drowning, suicide, accidents, road traffic deaths, fire accidents, industrial deaths
- Forensic pathologists - coronial autopsies due to homicide, death in custody, neglect
What deaths are referred to the coroner?
Presumed natural - unknown cause and not seen by doctor 14 days leading up to death
Presumed iatrogenic - deaths which could be caused by doctor e.g. from operation, abortion
Presumed unnatural - accidents, industrial, homicide
Legislation surrounding autopsies?
Coroners act 1988
Coroners rules 1984 (and 2005 amendments)
Human tissue act 2004
What are the steps performed in an autopsies?
- History/scene - history of events leading to the death e.g. GP summary, police reports, medical reports
- External examination - identities, gender, jewellery, body habitus, modifications, injuries
- Digital autopsy - full body CT scan, if this doesnt determine death then evisceration occurs
- Evisceration - Y shape incision from neck to pubis. Body cavity is opened and organs are examined in situ
- Internal examination - heart/vessels, lungs/trachea/bronchi, liver/gall bladder/pancreas, spleen/thymus/lymph nodes, genitourinary tract, endocrine organs, CNS
- Reconstruction - organs are placed in a viscera bag and placed inside the body before being sewn up
Examples of cells which regenerate
- Hepatocytes
- Pneumocytes
- All blood cells
- Gut epithelium
- Osteocytes
- Skin epithelium
Examples of cells which don’t regenerate
- Myocardial cells
- Neurons
What is the difference between resolution and repair?
Resolution - Initiating factor is removed. It can only occur if the tissue is undamaged or can regenerate itself
Repair - Initiating factor is still present. It only occurs if tissue is damaged and is unable to regenerate itself.
Situations where regeneration occurs?
- Liver tumour resection
- Lobar pneumonia
- Skin wounds
What is the difference between skin abrasion and laceration?
In abrasion only the top layer of skin is removed whereas lacerations are deeper wounds where skin is breached.
How do abrasions heal?
Scab forms, epithelia proliferates/regenerates under the scab for protection
How do lacerations heal?
Healed by first or second intentions.
First intention - two surfaces of incision remain in contact, the wound fills with fibrin and collagen synthesis occurs filling the wound. Epidermal regrowth occurs.
Second intention - two surfaces from incision are not in contact forming a “hole”. Cells grow across the hole and loops of capillaries form. This leads to formation of granulation tissue.
Definition of laminar flow
Fluid flow in parallel direction with little disruption between layers
What are the three predispositions to a thrombus?
- Change in vessel wall - e.g. endothelial cell injury
- Change in blood flow - e.g. change from laminar to turbulent flow
- Changes in blood constituents - eg. thrombocythemia
Two means of preventing thrombosis:
- Aspirin/heparin
2. Leg stockings
What coagulation factors are fibrinogen, fibrin, prothrombin, thrombin?
Fibrinogen - I
Fibrin - Ia
Prothrombin - II
Thrombin - IIa
Definition of thrombosis
A solid mass of blood constituents formed within an intact vascular system during life.
What is a thrombus
Aggregation of platelets and red blood cells.
Definition of an embolus
A mass of material in the vascular system which is able to become lodged in thin vessels and block them
Definition of ischaemia
Reduction in blood flow
Definition of infarction
Reduction in blood flow resulting in cell death
Definition of end artery
An artery which is the only supply of oxygenated blood to tissue
3 examples of areas with a duel blood:
- Lungs
- Liver
- Parts of the brain
Why does a duel blood supply reduce risk of infarction?
If one artery becomes blocked, the tissue still has blood supply from the other artery.
What is a watershed area?
An area of tissue at the boundary of adjacent territories supplied by two different arteries. These areas do not receive much blood supply from either territory and are subject to infarction.
Why do watershed areas become infarcted?
In prolonged periods of low blood pressure or blood loss the area does not receive enough blood and therefore becomes infarcted.
An example of a disease caused by infarction of a watershed area?
Subendocardial myocardial infarction
What is reperfusion injury?
When an ischaemic area of tissue becomes rapidly perfused with oxygen leading to production of radical oxygen species.
In cardiopulmonary resuscitation, how do you try and avoid reperfusion injury?
Patients are cooled down to reduce metabolic rate.
What is atherosclerosis?
A disease in which plaque builds up in arteries.
Which vessels do atherosclerotic plaques occur?
High pressure vessels e.g. systemic vessels not pulmonary.
What is a fatty streak?
A precursor to an atherosclerotic plaque
What are the contents of a plaque?
- Fibrous tissue
- Lipids
- Lymphocytes
Risk factors of atherosclerosis:
- Cigarette smoking
- High blood pressure
- Poorly controlled diabetes
- Hyperlipidemia
What is the lipid insudation theory of causation in relation to atherosclerosis?
The theory that high lipid blood content leads to leakage of lipids between the endothelium through the artery wall. This theory is NOT true.
What is the endothelial cell damage theory of causation in relation to atherosclerosis?
Damage to endothelial cells leads to formation of small thrombi which are sealed within the vessel wall as the endothelium heals over it.
How does smoking, high blood pressure, poorly controlled diabetes and hyperlipidemia cause endothelial damage?
Smoking - increases blood content of free radicals/nicotine/carbon monoxide
High blood pressure - shearing forces of the blood
Poorly controlled diabetes - increases blood content of superoxide anions and glycosylation products
Hyperlipidemia - high lipid content directly damages endothelium
What are 3 complications of atherosclerosis?
- Cerebral infarction
- Carotid atheroma
- Myocardial infarction
- Aortic aneurysms
- Peripheral vascular disease
- Gangrene
Definition of apoptosis:
Programmed cell death
2 examples of DNA damage:
- single-strand break
- double strand break
- base alteration
- cross linkages
What does the p53 protein do?
“gate keeper of the genome”, it is the protein which can switch on apoptosis within cells.
Disease associated with not enough apoptosis?
Cancer
Why do elephants have a disproportionately low amount of cancers?
They have 20 copies of the p53 gene
Disease associated with too much apoptosis?
HIV - this virus binds to CD4 cells and stimulates apoptosis wiping out the T-lymphocyte population compromising the immune system
Definition of necrosis:
Traumatic cell death - mass amounts of cells wiped out by a sudden event/mass cell death
Examples/causes of necrosis:
- Toxic spider venom
- Frostbite
- Cerebral infarction
- Avascular necrosis of the femur/scaphoid bone
- Pancreatitis
What is the difference between congenital and inherited disease?
Congenital - present at birth e.g. foetal alcohol syndrome
Inherited - caused by an inherited genetic abnormality
What are two TYPES of inherited disease?
- Chromosomal abnormalities e.g. trisomy 21
2. Autosomal inheritance e.g. Huntington’s disease
What are the three types/categories of spina bifida?
- Spina bifida occulta
- Meningocele
- Myelomeningocele
What could be the effects of:
- too little growth hormone (mutation in growth hormone) before puberty
- too much growth hormone (pituitary adenoma) before puberty
- being abnormally short
2. being abnormally tall
Definition of hypertrophy
Increase in tissue size caused by an increase in the size of the constituent cells e.g. skeletal muscle growth
Definition of hyperplasia
Increase in tissue size caused by an increase in the number of constituent cells e.g. hyperplasia of the prostate
Definition of atrophy
Decrease in size of a tissue caused by either a decrease in size or number of constituent cells e.g. cerebral atrophy and dementia
Definition of metaplasia
Change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type e.g. Barrett’s oesophagus
Definition of dysplasia
Imprecise term for the morphological changes seen in cells in the progression of becoming cancer e.g. bronchial dysplasia within smokers
What is the pathology of ageing within cells capable of dividing?
A dividing cell is only capable of a finite amount of divisions as during the initiation of the DNA replication and division process a part of the telomere at the end of the chromosome is used up.
What is the pathology of ageing within cells which are not capable of dividing?
- Cross linking mutations of DNA or proteins
- Loss of calcium influx control
- Damage to mitochondrial DNA
- Peroxidation of membranes
- Free radical generation
- Accumulation of toxic by-products of metabolism
What are 5 examples of signs of ageing?
- Balding
- Dementia
- Deafness
- Cataracts
- Loss of teeth
- Hypertension/ischemic heart disease
- Osteoporosis
- Dermal elastosis
- Diverticular disease of the colon
- Prostatic hyperplasia
- Degenerative joint disease
- Ankle oedema from heart failure
What causes dermal elastosis?
UVB light causes cross-linking of collagen within the skin, decreasing their elastic properties.
What is osteoporosis?
Loss of bone matrix.
What causes cataracts?
UVB light causes cross-linking of crystalline protein within the lens.
What causes senile dementia?
Cortical atrophy, plaques and neurofibrillary tangles.
What is sarcopaenia?
It is the loss of muscle. It can occur as a result of decreased growth hormone, decreased testosterone, increased catabolic cytokines or immobility.
What causes deafness?
Damage to cochlear hair cells as they are unable to regenerate and proliferate.
What is inflammation?
The local physiological response to tissue injury
What are beneficial effects of inflammation?
Destroy invading microorganisms
Walling off abscess preventing infection spread
What are harmful effects of inflammation?
Abscess in brain may compress surrounding tissue
Fibrosis caused by chronic inflammation can permanently alter tissue function
Classification of inflammation
Acute inflammation - initial and often transient series of tissue reactions to injury
Chronic inflammation - subsequent and often prolonged tissue reactions following the initial response
Causes of acute inflammation
- Microbial infections (pathogenic bacteria, viruses)
- Hypersensitivity reactions (parasites, tubercle bacilli)
- Physical agents (trauma, ionising radiation, heat, cold)
- Chemicals (corrosive, acid, alkali, reducing agents)
- Bacterial toxins
- Tissue necrosis (ischaemic infarction)
Macroscopic appearances of acute inflammation
Rubor (redness) Calor (heat) Tumor (swelling) Dolor (pain) Loss of function
Ways to describe inflammation
- Serous
- Suppurative (purulent)
- Membranous
- Pseudomembranous
- Necrotising (gangrenous)
Process of inflammation following tissue damage
- Change in vessel calibre and flow
- Increase in vascular permeability (histamine, bradykinin, nitric oxide, C5a, leukotriene b4, platelet activating factor)
- Formation of cellular exudate (emigration of neutrophils and fluid to extracellular space)
What are neutrophils role in inflammation?
Ingest bacterium, encapsulating it in a phagosome (phagocytic vacuole), lysosomes fuse with the vacuole and digest the bacterium. Bacteria debris is released and lysosome is replenished.
What cells are involved in chronic inflammation?
- Macrophages (not neutrophils)
- Lymphocytes around vessles
- Multinucleate giant cells
- Fibroblasts
- Capillary endothelium
What causes chronic inflammation?
- Transplant rejection
- Progression from acute inflammation
- Recurrent episodes of acute inflammation
- Primary chronic inflammation
What are macroscopic features of chronic inflammation?
- Chronic ulceration
- Chronic abscess activity
- Thickening of the wall of a hollow viscus
- Granulomatous inflammation
- Fibrosis
What are microscopic features of chronic inflammation
- Enfiltrate consists of lymphocytes, plasma cells and macrophages
- Eosinophils may be present, neutrophils are scarce
- Macrophage amalgamation into multinucleate giant cells
- Evidence of tissue destruction alongside tissue repair
- Tissue necrosis
What is an epithelioid histocyte?
A phagocytic cell in connective tissue
What is a granuloma?
An aggregate of epithelioid histocytes
What is a histiocytic giant cell?
It is formed when particulate matter cant be ingested by one macrophage. Multiple macrophages attempt ingestion simultaneously and in this process their cell membranes fuse forming a multinucleated cell.
What are some specific giant cells and their histological appearance?
Langerhan’s giant cell - horseshoe arrangement of peripheral nuclei (seen in tuberculosis)
Foreign body giant cells - large cells with nuclei scattered in cytoplasm in relation to a foreign body
Touton giant cell - central ring of nuclei peripheral to a lipid material
What is Hashimoto’s disease?
Thyroiditis, inflammation/swelling of the thyroid gland due to an autoimmune response.
What is Spina bifida?
A disease caused by the failure of the neural tube to successfully fuse closed during embryonic development.
What are the three types of spina bifida?
- Spina bifida occulta - opened posterior vertebral body
- Meningocele - protrusion of meninges
- Myelomeningocele - protrusion and opened spinal cord
What are two other diseases which are caused by failure of tissue sealing during embryonic development?
- Cleft palette
- Ventricular septal defect
Define congenital and give an example of a congenital disease
Present at birth - club foot caused by insufficient amniotic fluid in the uterus
Define chromosomal disease and give an example
A diseases caused by a missing, extra or irregular positioning of a chromosome. An example is trisomy 21 - as beta amyloid is encoded on the 21 chromosome, an excess of this protein builds up in brains and causes dementia in people with Downs syndrome.
Define inherited disease
A disease caused by an inherited genetic abnormality
Define acquired disease
A disease caused by non-genetic environmental factors
What disease can cause excessive height?
Pituitary adenoma from excessive excretion of growth hormone. If this happens before fusion of growth plates, the patient will grow tall. If this happens after fusion, only their jaw and hands will continue to grow.
What disease can cause small height?
Genetic disorders which effect the growth hormone encoding sequence of DNA. This will inhibit growth hormone production and prevent growth.
What is Virchow’s triad of thrombosis?
The three factors which cause a thrombus:
- Vessel wall injury
- Change in blood constituents
- Change in blood flow
