Pathology Flashcards
Thrombosis
formation of a solid mass from blood constituents in
an intact vessel in a living person
1st stage of thrombosis
platelet aggregation. 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
+ive or -ive feeback loop- platelet aggregation
postive
2nd stage of thrombosis formation
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
why dont 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
How does smoking cause thrombosis
cigarette smoking causing endothelial cell injury (change in vessel wall and change in blood flow over the injured/absent cells)
How to prevent risk of thrombosis in hospital?
early mobilisation after operation, low dose subcutaneous heparin
How does aspirin reduce the risk of thrombosis?
aspirin inhibits platelet aggregation
How does COVID cause thrombotic events?
Causes changes in clotting factors that causes thrombosis, leading to micro-thrombi in vessels
Embolus
mass of material in vascular system that becomes stuck in a vessel, blocking it
Most common embolus
Thrombus, ie DVT in legs breaking off and embolising through the large veins and right side of the heart to the lungs
Less common causes of embolus
- air (be careful with pressurised systems of intravenous fluids/blood especially in infants and children)
- cholesterol crystals (from atheromatous plaques)
- tumour
- amniotic fluid (rare in pregnant women with precipitate labour)
- fat (severe trauma with multiple fractures)
Effects of thrombosis or embolus
Reduction in blood flow, causing reduction of O2 to surrounding cells, leading to ischemia
Ischaemia
a reduction blood flow to a tissue without any other implications
Infacrtion
reduced blood flow, leading to cell death
Why are certain organs less prone to infarction
dual arterial supply so are much less susceptible to infarction:
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
Resolution
- initiating factor removed
-tissue undamaged or able to regenerate
Repair
- initiating factor still present
-tissue damaged or unable to regenerate
-replacement of damaged tissue by fibrous tissue
Can the liver regenerate?
Yes! as long as not too much liver is removed so the patient dies of liver disease
Why don’t alcoholics livers regenerate?
Initiating factor constantly present due to constant alcohol abuse, so repair occurs not resolution
Why can lungs regenerate after lobar pneumonia
Pneumocytes can regenerate, no damage to alveoli walls
Does repair or resolution occur after severe COVID?
If alveoli walls are damaged as a result severe covid, repair occurs in lungs
Most superficial skin wound
Abrasion- only removed top layer of epidermis, basal cells still present
Healing by 1st intention
Edges of skins brought together, reduces risk of infection. Fibrinogen first brings skins together, then collogen strengthens and epidermis reforms
Healing by secondary intention
sides of the wound are not opposed, therefore healing must occur from the bottom of the wound upwards
Cells that can regenerate
- hepatocytes (liver)
- pneumocytes (lungs)
- all blood cells
- gut epithelium
- skin epithelium
- osteocytes (bones)
Cell that don’t regenerate
- myocardial cells
- neurones
Man aged 30 takes a large overdose paracetamol overdose and doesn’t come to hospital for 2 days. He spends a few days on ITU with liver failure but then recovers.
What will be happening in his liver -
resolution or repair?
resolution, Only overdose once, so provided he doesn’t die of liver damage, his liver should regenerate
A child aged 3 falls off a climbing
frame onto his hand, he fractures his
clavicle. He has his arm in a sling for
4 weeks and is very good about
keeping it in the sling
What will be happening in his
clavicle - resolution or repair?
Resolution- provide child keeps arms in sling as osteocytes regenerate
Atherosclerosis
accumulation of fibrolipid plaques in systemic (as opposed to pulmonary) arteries
Risk of Atherosclerosis
narrowing of arteries reduces the blood flow to important areas e.g. myocardial infarction in the heart
Risk factors of atherosclerosis
- hypertension
- hyperlipidaemia (too many lipids (fats) in your blood)
- cigarette smoking
- poorly-controlled diabetes mellitus
higher in more social deprived areas
Do you find atheroslcerosis in the pulmonary arteries
No, blood pressure is lower
Current atherosclerosis theory
Endothelial cell damage theory
* endothelial cells are delicate
* easily damaged by cigarette smoke, shearing forces at
arterial divisions, hyperlipidaemia, glycosylation products
* cumulative damage leads to endothelial ulceration, microthrombi, eventual development of established atherosclerotic plaques
How does hypertension lead to atherosclerosis
Shearing forces on endothelial cells
How does smoking lead to atherosclerosis
Free radicals, nicotine and CO damage endothelial cells
How does diabetes lead to atherosclerosis
Superoxide anions and glycosylation products damage endothelial cells
How does hyperlipidaemia lead to atherosclerosis
direct damage to endothelial cells
Atherosclerosis feedback loop
Positive feedback loop. Damage to endothelium, leads to thrombi healing over, causes increased narrowing, higher BP, causes more damage…
Complications of atherosclerosis
Consequences of blocked pluming, occlusion of blood vessel leading to ischemia and possibly infarction
Apoptosis
Programmed individual cell death.
What causes apoptosis?
DNA damage detected, cell triggers a series of proteins which lead to the release of enzymes (caspases) that auto digest the cell
Importance of apoptosis for healthy function
- Development - removal of cells during development e.g. interdigital webs
- Cell turnover - removal of cells during normal turnover e.g. cells in the intestinal villi at the tips, to be replaced by cells from below
Apoptosis in disease
- Cancer - cells in tumours often don’t apoptose when they would have been expected to which results in increase in the tumour size and accumulation of genetic mutations. Often this is due to mutations in the P53 gene so the p53 protein can no longer detect DNA damage and instigate apoptosis.
- HIV - the HIV virus can induce apoptosis. It can induce apoptosis in CD4 helper cells which reduces their numbers enormously to produce an immunodeficient state.
Necrosis
Traumatic cell death- wholesale destruction of large numbers of cells by some external factor
Apoptosis vs Necrosis
Apoptosis is programmed cell death. Necrosis is traumatic cell death by external factor
Clinical Example of Necrosis
- Infarction due to loss of blood supply e.g. myocardial infarction, cerebral infarction, avascular necrosis of bone
- Frostbite
- Toxic venom from reptiles and insects
- Pancreatitis
Spina bifida occulta
Missing a spinus process, wouldn’t notice unless CT scan performed
Meningocele
Outpouring sac filled with fluid, n can need to be fixed by surgery, minor disability can occur
Myelomeningocele
Outpouring sac containing spinal cord, leads to paralysis
Congenital
Present at birth, not always genetic ie club foot
Inherited
Caused by an inherited genetic abnormality
Chromosomal Abnormalities
Incorrect number of chromosomes inherited, ie downs syndrome, 3 chromosome 21’s inherited
Medellin Inheritance
Single gene mutation causes problem
Autosomal inheritance
On paired chromosome except sex chromosomes
Autosomal dominace
Only one dominant allele needed to express problem
Autosomal recessive
2 recessives alleles needed to express problem
Polygenetic Inheritance
Variation in several genes lead to increased risk of problem
Acquired
Caused by non-genetic environmental factors
Are inherited diseases always congenital?
No, ie Huntington’s disease
Can acquired disease be congenital?
Yes, ie fetal alcohol syndrome
hypertrophy
increase in size of a tissue caused by increase in size of the constituent cells, usually occurs organs when cells cannot divide, ie skeletal and cardiac muscle
hyperplasia
increase in size of a tissue caused by an increase in number of constituent cells, usually occurs in organs that can regenerate, ie gut, skin, smooth muscle ect
Common conditions caused by hyperplasia
prostate enlargement as a result of smooth muscle hyperplasia
endometrial hyperplasia, often as a result of hormone imbalance
Atrophy
decrease in size of a tissue by a decrease in number of constituent cells and/or a decrease in their size
Common atrophy conditions
Cerebral atrophy can be a result of Alzheimer’s
Muscle atrophy, can be a result of lack of use after immobilization
Optic atrophy
Metaplasia
change in differentiation of a cell from one fully-differentiated type to another fully-differentiated cell
Common metaplasia condtions
Bronchi of smokers, ciliated columnar epithelium to squamous epithelium
Barrett’s oesophagus, squamous epithelium to columnar epithelium as result of regular stomach acid exposure
Dysplasia
imprecise term for the morphological change seen in cell in the progression of becoming cancer, can be used to refer to a developmental abnormality
What is found at the end of chromosomes?
Telomeres, region of repetitive DNA
Common conditions associated with aging
Dermal elastosis, osteoporosis, cataracts, dementia, sarcopenia, deafness
Dermal elastosis
Skin aging, wrinkling, due to cross linking of proteins
Cataracts
Protein cross linking in eye lens leading to them becoming opaque
Osteoporosis
Increased bone reabsorption, leading to weaker, more brittle bones, more common in woman after the menopause due to hormone imbalance
Sarcopenia
Decrease in muscle mass with age, mobility problems (falls, getting up and around) after after losing a lot muscle
Deafness
Loss of hair cells in cochlea, these cells do not regenerate
Features of acute inflammation
Redness, heat, swelling, pain, loss of function
Key cells involved in acute inflammatory process
Neutrophils, multi-lobular nuclease
NSAIDS
Non-steroidal anti-inflammatory drugs
Common side effect of chronic NSAID use
Gastritis. NSAIDs diminish protective mucin secretions. They also cause exfoliation of the surface epithelium. This results in damage to the surface epithelium, eliciting an acute inflammatory response
Most common Bacteria that causes gastritis
Helicobacter pylori
Common signs of sepsis
High temp, HR is fast, BP is low, Confusion
Chronic inflammation, causes and cells associated
May be a progression from acute inflammation. May represent a primary disease process. Lymphocytes, macrophages, plasma cells and eosinophils are associated with chronic inflammation
Granuloma
Aggregate around cause of inflammation of epithelioid histocytes (tissue resident macrophages)
How does chronic inflammation lead to cancer?
Chronic inflammation> Metaplasia> Dysplasia> Carcinoma in situ> Invasive Carcinoma
Why does chronic inflammation cause cancer?
-Inflammation causes cellular changes and immune responses to repair damaged tissue → cell proliferation @ site of injury
-Inflammatory response becomes chronic → ↑ cell proliferation and ↑ risk of the development of mutations
-Chronic inflammatory cells (especially macrophages) generate high levels of reactive oxygen and nitrogen species to fight infection → release of mutagenic agents
-Inflammatory cells also release factors that interfere with regulation of cell replication exacerbating tumourgenesis
Conditions when chronic inflammation plays a key role
-Myocardial fibrosis (post MI)
-Atheroma development
-Multiple sclerosis (macrophages break down myelin)
Is osteoarthritis an inflammatory disease?
NO, inflammation plays a small role in disease pathogenesis. Primarily degenerative disease
Can basal cell carcinomas of the skin metastases?
No
Name of a malignant tumour of striated muscle
Rhabdo myo sarcoma
Is it common for liposarcomas to metastasise to bone?
No
Common bone metastases
Breast, lung, prostate, renal cell and thyroid cancer
Name of benign tumour of glandular epithelium
Adenoma
UK screening programs, types of cancer
Breast cancer, colorectal cancer and cervical cancer
Name of benign tumour of fat
Lipoma
Name of malignant tumour of glandular epithelium
Adenocarcinoma
Can ovarian cancer spread in the peritoneum
Yes, if it breaches the ovarian cavity
Why does leukemia cause a large range of symptoms?
WBC circulate round the body and so will any tumour of WBC, hence can spread easily causing many symptoms
Why do lymph nodes need to be removed when treating certain carcinomas?
Carcinomas can spread to the lymph nodes that drain the site of carcinomas so need to be removed to ensure as many tumours as possible have been taken out
Ways carcinomas can spread
-Invade nearby structures
-Through lymph nodes
-Through blood to bone
Steps for breast cancer treatment
- Diagnosis breast cancer
- Check has it spread to the axilla via lymph nodes, if yes axillary node need to be removed with breast cancer
- Check has it spread to the rest of the body ie bone scan or CT scan, if yes systemic treatment needed (chemo)
- If no to 3, Surgery need to remove breast cancer either with or without axillary clearance
- Radiotherapy to remove any remaining micro metastases
- Further adjuvant treatment depending on breast cancer pathology
Is a patient definitely cured if a tumour has been completely excised?
No, micro metastases could still be present
Adjuvant treatment
Extra treatment given after surgery
Tumour
Any abnormal swelling ie neoplasm, inflammation. Hypertrophy and hyperplasia
Neoplasm
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells with persists after the initiating stimulus has been removed
Lesion
area of abnormal tissue
Malignant-benign spectrum
Not always binary, some neoplasms are borderline so can present as benign or malignant but act as the opposite
Structure of neoplasms
Neoplastic cell (derived from nucleated cells) are supported by a stroma (a connective tissue framework which provides mechanical support and nutrition)
What does central necrosis of neoplasm show?
Neoplasm is growing so quickly that blood supply is unable to provide nutrients to the centre of the neoplasm
Tumour angiogenesis
Essential to growth, how a tumour forms a blood supply to provide its self with nutrients, tumour unable to grow via simple diffusion
Classification of neoplasms
Benign, borderline and malignant
Benign neoplasms
-Localised, non-invasive
-Slow growth rate
-Low mitotic activity
-Close resemblance to normal tissue
-Circumscribed or encapsulated, well defined
Histology of benign neoplasms
-Nuclear morphometry (shape) often normal
-Necrosis rare
-Ulceration rare
-Growth on mucosal surface usually exophytic (grow outward beyond the surface epithelium from which it originates)
Can benign neoplasms be harmful?
Yes, they can put pressure on adjacent structures, obstruct flow, produce hormones, transform to malignant neoplasm and anxiety for patient
Malignant neoplasms
-Invasive
-Metastases
-Rapid growth rate
-Variable resemblance to normal tissue
-Poorly defined or irregular border
Histology of malignant neoplasms
-Hyperchromatic (stain more deeply than normal) and pleomorphic (changes shape) nuclei
-Increased mitotic activity
-Necrosis and ulceration common
-Growth on mucosal surfaces and skin often endophytic (tending to grow inward into tissues in fingerlike projections from a superficial site of origin)
Why are malignant neoplasms harmful?
-destruction of adjacent tissue
-mets
-Blood loss from ulcers
-obstruct flow
-produce hormones
-paraneoplastic effects (disorders that occur when the immune system has a reaction to a cancerous tumour)
-anxiety and pain
Papilloma
Benign neoplasm of non-glandular non-secretory epithelium, prefix with cell type origin
Carcinoma
-Malignant epithelial neoplasm
-Prefix with epithelial cell type e.g. urothelial carcinoma
-Carcinomas of glandular epithelium are adenocarcinomas
Adenoma
-Benign neoplasm of glandular or secretory epithelium
-Prefix with cell type of origin, e.g. colonic adenoma, thyroid adenoma
Anaplastic neoplasm
Cell type of origin cannot be determined, typically poor prognosis
Teratoma
congenital (present prior to birth) tumor formed by different types of tissue. Teratomas in newborns are generally benign
Papilloma
Benign neoplasm of non-glandular non-secretory epithelium
How do decided a prefix for a neoplasm?
Depends on behavioural classification and cell type
Adenocarcinomas
Carcinomas of glandular epithelium
What is cell type origin of Lipoma?
adipocytes
What is cell type origin of Chondroma
cartilage
What is cell type origin of Osteoma
Bone
What is cell type origin of Angioma
Vascular
What is cell type origin of Rhabdomyoma
striated muscle
What is cell type origin of Leiomyoma
smooth muscle
What is cell type origin of Neuroma
nerves
What is cell type origin of Liposarcoma
adipose tissue
What is cell type origin of Rhabdomyosarcoma
striated muscle
What is cell type origin of Leiomyosarcoma
smooth muscle
What is cell type origin of Chrondrosarcoma
cartilage
What is cell type origin of Osteosarcoma
bone
What is cell type origin of Angiosarcoma
blood vessels
Carcinogenesis
The transformation of normal cells to neoplastic cells though permanent genetic alterations or mutations
Applies to malignant neoplasms
Carcinogenic vs Oncogenic
Both agents known or suspected to cause tumours
Carcinogenic = cancer causing
Oncogenic = tumour causing
Classes of carcinogens
Chemical, Viral, Ionising and non-ionising radiation, Hormones, parasites and mycotoxins, Miscellaneous
Host Factors
Ethnicity, Diet / Lifestyle, Constitutional factors (age, gender etc), Premalignant lesions, Transplacental exposure
conventional chemotherapy
- not selective for tumour cells
– except that they might be dividing faster - usually hits normal cells which are dividing
– myelosuppression
– hair loss
– diarrhoea
What type of tumour is conventional chemotherapy most effective for treating
good for fast dividing tumours
– germ cell tumours of testis
– acute leukaemias
– lymphomas
– embryonal paediatric tumours
– choriocarcinoma
What type of tumour is conventional chemotherapy less effective for treating
not so good for slower dividing tumours
– most other tumours
targeted chemotherapy
exploits some difference between cancer cells
and normal cells to target drugs to the cancer
cells
– more effective
– less side effects
Methods for differentiating tumours
Gene arrays, proteomics, tissue microarrays
