ICS Pathology Flashcards
Define Inflammation
Local physiological response to tissue injury
In what ways can inflammation be beneficial?
- Destruction of invading microorganisms
- Walling off an abscess cavity
In what ways can inflammation be harmful?
- Over-reaction to stimulus
- Autoimmune diseases
- Abscesses can act as space-occupying lesions in the brain
- Fibrosis
Define acute inflammation
Initial and transient series of tissue reactions to injury
Define chronic inflammation
Subsequent and/or prolonged tissue reactions following initial response
Steps of acute inflammation
- Initial reaction
- Vasodilation
- Vascular leakage of protein-rich fluid
- Neutrophil polymorph recruited
- Outcomes
Outcomes of Acute Inflammation
- Resolution
- Suppuration (formation of pus e.g. abscess)
- Organisation
- Chronic Inflammation
Acute Inflammation causes
Microbial Infections Hypersensitivity reactions Physical agents Chemical Bacterial toxins Tissue necrosis
Appearance of Acute Inflammation
Rubor - Redness
Calor - Heat
Tumor - Swelling
Dolor - Pain
What cells are required for histological diagnosis of inflammation?
Neutrophil polymorphs
Describe Neutrophil Polymorphs
Contain cytoplasmic granules full of bacteria-killing enzymes. Usually die at scene of inflammation. Attracts macrophages.
Describe Macrophages
Phagocytic properties, ingesting bacteria and debris. Last weeks to months, can present antigen to lymphocyte
Describe lymphocytes
Live for years, attract other inflammatory cells, immunological memory etc.
Describe endothelial cells in areas of inflammation
Become sticky so inflammatory cells stick to them, become porous to allow inflammatory cells into tissues.
Describe fibroblasts in inflammation
Long-lived, form collagen in areas of chronic inflammation and repair.
Example of Acute Inflammation
Acute Appendicitis
Example of Chronic Inflammation
Tuberculosis
Treatment for acute inflammation
RICE
Aspirin
Ibuprophen (NSAIDs)
Analgesics
What is a granuloma?
A collection of epithelioid histocytes (macrophages) - a small area of inflammation
What is granulation tissue?
Important component of healing and comprises small blood vessels in a connective tissue matrix with myofibroblasts
What are the two types of autopsy and how common are they?
Hospital autopsies - 10%
Medico-legal autopsies - 90% (coronial or forensic)
What types of deaths are referred to coroners?
- Natural
- Iatrogenic
- Unnatural
Causes of Chronic Inflammation
Primary chronic inflammation (most common)
Transplant rejection
Progression from acute
Recurrent episodes of acute
Is a granuloma a form of acute or chronic inflammation?
Chronic (type IV hypersensitivity)
What is Rheumatoid Arthritis?
Inflammatory arthritis with granulomatous features with no overt cause
Define resolution of an injury
Initiating factor removed and tissue is undamaged or able to regenerate
Define repair of an injury
Initiating factor still present, tissue damaged and unable to regenerate. Usually results in fibrous scarring.
Lobar Pneumonia
Affects 1 lung lobe. Alveoli filled with polymorphs. Pneumocytes can regenerate so can be resolved.
Lung damage in COVID
Interstitial pneumonia, alveolar walls cannot regenerate so fibrosis occurs.
Describe healing of abrasions
Abrasion -> scab formed -> epidermis growing out from adnexa protected by scab -> thin confluent epidermis -> final epidermal regrowth
Describe healing of skin by 1st intention
Incision causes little damage to surrounding tissues. two sides brought together and healing can proceed quickly.
Incision -> exudation of fibrinogen -> weak fibrin joint -> epidermal regrowth and collagen synthesis -> strong collagen joint
Describe healing of skin by 2nd intention
Tissue loss injury, granulation tissue forms -> organisation -> early fibrous scar -> scar contraction
What is granulation tissue?
Loops of capillaries supported by myofibroblasts. Actively contracts to reduce wound size.
Examples of cells that DO regenerate
- Hepatocytes
- Pneumocytes
- All blood cells
- Gut epithelium
- Skin epithelium
- Osteocytes
Examples of cells that DON’T regenerate
- Myocardial cells
- Neurones
What is fibrosis in the brain called?
Gliosis
Why are blood clots rare?
Laminar flow
Endothelial cells aren’t sticky when healthy
Define thrombosis
Solid mass of blood constituents formed within vascular system
Steps of thrombus formation
- Damage to endothelial cells exposes collagen
- Platelets begin to stick to exposed collagen – platelet aggregation
- Red blood cells get trapped within aggregating platelets
- Clotting factors join the RBCs and platelets, clotting cascade forms fibrin which is deposited and forms a clot
- Positive feedback loop -> can end up causing a thrombus – blocking the artery
What can reduce risk of thrombosis?
Low-dose aspirin
Causes of thrombosis
- Changes in vessel wall
- Changes in blood flow
- Changes in blood constituents
What is an embolism?
Process of a solid mass in the blood being carried to a place where it gets stuck
Types of embolus
- Broken off thrombus (most common)
- Air
- Tumour
- Amniotic fluid
- Fat
What happens if an embolus enters the venous system?
Travels to the vena cava and lodges in pulmonary arteries
What happens if an embolus enters the arterial system?
Can travel ANYWHERE downstream of entry
Define ischaemia
Reduction in blood flow to tissue without other implications
Define infarction
Reduction in blood flow causing lack of nutrients to tissue causing tissue death
What is an end artery supply
Organ that only receives blood supply from 1 artery (problematic with thrombus)
Examples of organs with multiple arterial supplies
Lungs
Liver
Brain
What is in a plaque?
- Fibrous tissue
- Lipids (cholesterol)
- Lymphocytes
Is atherosclerosis found in low or high pressure systems?
High pressure systems e.g. systemic arteries
Risk factors of atherosclerosis
Age, smoking, hypertension, poorly-controlled diabetes, hyperlipidaemia
Formation of atheroma
Endothelial damage causes thrombus formation, endothelial cells grow over thrombus and this happens a lot causing build up.
What can be used to prevent platelet aggregation?
Low-dose aspirin
Complications of atherosclerosis
Cerebral infarction, MI, gangrene, carotid atheroma, aortic aneurysms, peripheral vascular disease
What is apoptosis?
Programmed cell death to get cells no longer functioning
Process of apoptosis
Nucleus condenses, cell shrinkage, cell breaks into apoptotic bodies
Trigger of apoptosis
DNA damage in dividing cells
Apoptosis in disease
Cancer (too little)
HIV (too much)
What are the effector molecules of apoptosis?
Caspases
What is necrosis?
Traumatic cell death of functioning cells
Causes of necrosis
Disease, injury or blood supply
Clinical examples of necrosis
- Toxic spider venom
- Frostbite
- Cerebral Infarction
- Avascular necrosis of bone
- Pancreatitis
Define Hypertrophy
Increase in tissue size due to increase in size of constituent cells
Define Hyperplasia
Increase in tissue size due to increase in number of cells
Define Atrophy
Decrease in size of tissue caused by decrease in constituent cell number OR size
Define Metaplasia
Change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type (reversible)
Define Dysplasia
Morphological changes seen in cells in the progression to becoming cancerous
What occurs to telomeres as we age?
Telomeres get shorter after each cell division – limiting the amount of division that can occur
Dermal elastosis in ageing
Accumulation of abnormal elastic in dermis. Result of prolonged exposure to UV light (causing cross-linking)
Osteoporosis in ageing
- Loss of coupling in the bone remodelling process – due to increased bone resorption or decreased bone formation due to a lack of oestrogen
- Can cause osteopenia
- Bone matrix mineralised as usual but trabeculae thinned
- Leads to hypercalciuria
Cataracts in ageing
- Result of the formation of opaque proteins within the lens resulting in loss of lens elasticity
- UV-B light causes protein cross-linking
Senile dementia in ageing
Plaques and neurofibrillary tangles occur in brain
Sarcopenia in ageing
Decreased GH, decreased testosterone, increased catabolic cytokines
Deafness in ageing
Hair cells cannot divide/regenerate so cannot recover once damaged
Pathology of Basal cell carcinoma
Only invades locally, never metastasises - local excision = cure
Basic pathology of Leukaemia
Malignant tumour of WBCs so circulates, so needs a systemic treatment e.g. chemotherapy
Where can carcinomas spread?
- Lymph nodes draining site of carcinoma
- Bone (breast, prostate, lung, thyroid and kidney)
- Rest of the body
Breast cancer care plan
- Core needle biopsy to confirm
- Axillary nodes ultrasound (then biopsy)
- CT scan/radio nucleotide scan of rest of body
- Surgery
What is adjuvant therapy?
Extra treatment given after surgical excision to eliminate micro-metastases
What can oestrogen-receptor positive breast cancers be combated with?
Anti-oestrogen therapy
Define carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
Define oncogenic
tumour causing
Define carcinogenic
cancer causing (only malignant neoplasms)
Why are carcinogens hard to identify?
Long latent periods, complexity of environment, ethical issues with research
Occupational cancer risks
Lung cancer - smoking
Bladder cancer - aniline dye and rubber
Scrotal cancer - chimney sweeps
5 classes of carcinogens
Chemical Viral Ionising and non-ionising radiation Hormones, parasite and mycotoxins Misc.
What percentage of cancer risk is inherited
15% (rest is environmental)
How long is the latent period typically between exposure and cancer?
VERY LONG
Define neoplasm
o A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
What makes up neoplasms?
Neoplastic cells and stroma
What cells are present in the stroma of a neoplasm?
Fibroblasts
Tumour angiogenesis
Blood supply growth to tumour, needed for growth. Malignant neoplasm too fast so has central necrosis.
Characteristics of a benign neoplasm
- Localised
- Non-invasive
- Grow slowly (low mitotic activity)
- Close resemblance to normal tissue
- Necrosis and ulceration rare
- Nuclei often normal looking
How can benign neoplasms cause morbidity/mortality
Pressure on adjacent structures, hormone production, transformation into malignant, anxiety
Characteristics of a malignant neoplasm
- Invasive and can metastasise
- Rapid growth rate
- Variable resemblance to normal tissue
- Poorly defined or irregular border
- E.g. prostate cancer, squamous cell carcinoma
- Hyperchromatic and pleomorphic nuclei
- Increased mitotic activity
- Necrosis and ulceration common
- Encroach upon and destroy surrounding tissues
Suffix of all neoplasms
-oma
What do you call a benign tumour of non-glandular or secretory epithelium?
Papilloma
Name of benign tumour of glandular/secretory epithelium
Adenoma
Name of malignant epithelial neoplasm
Carcinoma
Name of carcinoma of glandular epithelium
Adenocarcinoma
Benign connective tissue neoplasm
Lipoma Chondroma Osteoma Angioma Leiomyoma Rhabdomyoma Neuroma
Malignant connective tissue neoplasms
Sarcoma
What is an anaplastic tumour?
Cell-type of origin is unknown
Exceptions to neoplasm naming rules (long list)
Granuloma Tuberculoma Melanoma Mesothelioma Lymphoma Burkitt's lymphoma Ewing's sarcoma Grawitz tumour Kaposia's sarcoma Teratoma Blastomas Mixed Tumours APUDomas Carcinosarcoma
Example of granulomatous inflammation
Chron’s disease
Chronic inflammatory process never going through acute stage
Infectious mononucleosis
Pattern of differentiation of metaplastic cells in bronchi of smokers
Ciliated columnar to squamous
What is a carcinoma in situ?
A malignant epithelial neoplasm that has not yet invaded through the original basement membrane
Define invasive carcinoma
A carcinoma that has breached the original basement membrane. Needs proteases and cell motility
Define metastasis
A malignant tumour spreads from its primary site to produce secondary tumours at distant sites.
Steps of the metastatic cascade
- Detachment
- Invasion through basement membrane
- Intravasation
- Evasion of host immune defence
- Extravasation
- Growth at metastatic site
- Angiogenesis
Routes of metastasis
Haematogenous - blood
Lymphatic
Trans-coelomic - pericardial and peritoneal cavities
Tumours which commonly metastasise in the lungs
Sarcomas and any common cancers
Tumours which commonly metastasise in the liver
Colon, stomach, pancreas and carcinoid tumours of intestine
