Introduction to clinical sciences (brief) Flashcards
Acute inflammation
Initial and often transient series of tissue reactions to an injury. Lasts hours-days
List 5 causes of acute inflammation
- Physical agents (trauma, radiation, UV)
- Biological agents (bacteria, virus)
- Chemicals (acid, alkali)
- Autoimmune disease (hypersensitivity)
- Tissue necrosis
Clinical features of acute inflammation and reason for them
- Redness - blood vessel dilatation
- Swelling - oedema due to increased vascular permeability
- Heat - increased blood flow
- Pain - stretching of tissue due to oedema
- Loss of function
Cells present in acute inflammation
Neutrophil polymorphs
Lymphocytes, fibroblasts, macrophages, mast cells & eosinophils (allergy)
Chemical mediators of vascular dilatation
Histamine, prostaglandin E2, nitric oxide, PAF, VIP
Chemical mediators of vascular permeability
Immediate: Histamine
Prolonged: Bradykinin, nitric oxide, C5a, PAF, leukotriene B4
Chemical mediators of neutrophil adhesion to endothelium
IL-1, IL-8, C5a, leukotriene B4, TNF-a
Chemical mediators of neutrophil chemotaxis
Leukotriene B4, IL-8
Outcomes of acute inflammation
- Resolution
- Suppuration
- Organisation
- Progression to chronic inflammation
Constituents of pus
Living, dead and dying neutrophils and bacteria, cellular debris, lipid globules
Abscess
Walled off collection of pus
Ulcer
Break in skin or mucous membrane that fails to heal
Chronic inflammation
The subsequent and prolonged tissue reactions to injury (lasts months-years)
Cells that predominate in chronic inflammation
Lymphocytes, plasma cells, macrophages
Causes of chronic inflammation
- Primary chronic inflammation (autoimmune, agents resisting phagocytosis, granulomatous inflammation)
- Transplant rejection
- Progression from acute
Clinical features of chronic inflammation
- Chronic ulcer
- Chronic abscess
- Granulomatous inflammation
- Fibrosis
Granuloma
Aggregation of epithelioid histiocytes. Form when the body attempts to wall off a foreign agent but fails to eliminate it.
Epithelioid histiocytes
Cells with large vesicular nuclei, elongated shape and plentiful eosinophilic cytoplasm. Arranged in clusters
Granulomatous inflammation
Form of chronic inflammation characterised by granuloma formation
Gliosis
Fibrosis in the brain
Keloid
A thick scar that grows massively - more collagen released and excessive fibroblast proliferation
Abrasion
Top layer of cells scraped off (underlying tissue fine), scab forms and then is sloughed off
Healing by 1st intention
- Incision sutured, weak fibrin joins the edges
- Coagulated blood forms scab
- Capillaries proliferate to bridge gap and fibroblasts secrete collagen
- Strong collagen join - scar formation
Healing by 2nd intention
- Damage too extensive to join sides together
- Phagocytosis removes debris
- Granulation tissue forms, organisation, early fibrous scar
Atheroma
Accumulation of materials in vessel wall (lipids, cholesterol), causing restriction of blood flow
Constituents of an atheroma
Cholesterol, platelets, macrophages, foam cells, smooth muscle cells, collagen, elastin
Tx for atheroma (preventative)
Low dose aspirin = 75mg (anticoagulant)
Atherosclerosis
Disease characterised by atherosclerotic plaques in the intima of large/medium sized arteries, causing narrowing of lumen. Predisposes thrombosis
Risk factors of athersclerosis
- Increasing age
- High LDL cholesterol diet
- Hypertension
- Familial history
- Male
- Poorly controlled diabetes
- Smoking
- Alcohol
Process of atherosclerosis
- Endothelial damage due to irritants (cigarette toxins, HTN etc.)
- LDL accumulates in damaged endothelium
- Monocytes attracted to site of damage, transform into macrophages and phagocytose LDL
- LDL filled macrophages die and become foam cells (release cytokines to attract more monocytes)
- Foam cell presence stimulates smooth muscle cells to invade and secrete collagen and elastin - forms fibrous cap
Thrombosis
Process by which a solid mass of blood constituents is formed within an intact vascular system during life
Thrombus
A solid mass of blood constituents in a vascular system
Virchow’s triad
Predisposing factors for thrombosis:
- Change in blood flow
- Change in blood constituents
- Change in vessel surface
Process of thrombosis
Epithelium damaged - collagen exposed so extrinsic coagulation cascade activated (and subsequently intrinsic). Platelets aggregate and fibrin mesh forms. This can cause a larger plaque to form.
Outcomes of thrombus formation
- Breaks down
- Changes to scar tissue
- Recannulisation/ revascularisation
- Embolus
- Occludes vessel and causes infarction
Embolus
Solid mass in the blood carried through circulation until it gets stuck and blocks a vessel. Most commonly pulmonary embolism from DVT
Infarction
Ischaemic death of tissue due to inadequate oxygen supply
Ischaemia
Reduction in blood flow to a tissue or part of the body caused by constriction or occlusion of blood vessels supplying it
Apoptosis
Programmed cell death
Which enzymes causes apoptosis
Caspases
Which factors reduce/enhance apoptotic inducing factors
Bcl-2 family reduces
Bax-Bax dimers enhance
Factors inhibiting apoptosis
- Growth factors
- Extracellular matrix
- Sex steroids
Factors inducing apoptosis
- Viruses
- Ionising radiation
- Growth factor withdrawal
- Free radicals
Necrosis
Traumatic cell death characterised by loss of plasma membrane integrity and bioenergetic failure
Some causes of necrosis
Thrombi, emboli, ischaemia and subsequent infarction
Disease involving necrosis
Avascular necrosis of the femoral head, scaphoid fracture, caseous necrosis (seen in TB)
Hypertrophy
Increase in size of tissue by an increase in the size of constituent cells
Pathological example of hypertrophy
Left ventricular hypertrophy
Hyperplasia
An increase in size of tissue by increase in number of constituent cells
Physiological example of hyperplasia
Endometrial hyperplasia in the uterus during pregnancy
Pathological example of hyperplasia
Enlarged prostate
Atrophy
Decrease in size of tissue caused by reduction in constituent cell size/number
Physiological example of atrophy
Thymus atrophy after puberty
Pathological example of atrophy
Alzheimer’s disease
Metaplasia
A fully differentiated cell changing to another fully differentiated cell type
Pathological example of metaplasia
Barrett’s oesophagus - squamous epithelium changes to columnar epithelium as a result of excessive stomach acid exposure
Dysplasia
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer
5 general effects of ageing
- Deafness - hair cell loss
- Osteoporosis - lack of oestrogen, vit D, calcium in early life
- Cataracts - UV damage resulting in cross-linking of proteins in the eye
- Sarcopenia - loss of skeletal muscle
- Dermal elastosis - less collagen and elastin in the skin
Neoplasm
Lesion resulting from autonomous, abnormal growth of cells which persists after the initiating stimulus has been removed
2 classifications of neoplasms
Behavioural
Histological
Benign tumour
Non invasive, well defined, close histological resemblance to parent cell
Malignant tumour
Invasive, irregular border, hyperchromatic & pleomorphic nucleus, poor resemblance to parent cell
Benign tumour of non-secretory, non-glandular epithelial cells
Papilloma
Benign tumour of secretory or glandular epithelial cells
Adenoma
Malignant tumour of non-secretory, non-glandular epithelial cells
Carcinoma
Malignant tumour of secretory or glandular epithelial cells
Adenocarcinoma
Benign tumour of connective tissue
Cell origin + oma
Malignant tumour of connective tissue
Cell origin + sarcoma
Benign tumour morbidity
- Pressure on adjacent structures
- Obstruction of flow of fluid
- Excessive hormone production (thyroid)
- Tranformation to malignant tumour
Adipose tissue tumour
Lipoma/sarcoma
Cartilage tumour
Chondroma/sarcoma
Striated muscle tumour
Rhabdomyoma/sarcoma
Smooth muscle tumour
Lieomyoma/sarcoma
Vascular tumour
Angioma/sarcoma
Bone tumour
Osteoma/sarcoma
Melanocyte tumour
Melanoma
Mesothelial cell tumour
Mesothelioma
Lymphoid cells tumour
Lymphoma
Unknown cell type tumour
Anaplastic
Teratoma
Germ cell tumour made up of one or more germ cell layers (endoderm, mesoderm, ectoderm)
Blastoma
Neoplasm composed of embryonic cells derived from the blastema of an organ/tissue
Tumour angiogenesis
Recruitment of blood vessels into a tumour
Carcinogenesis
Transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
Oncogenic
Tumour causing
Lesion
Localised abnormality
Tumour
Any abnormal swelling
Metastasis
Malignant tumour spread from site of origin to form secondary tumours at distant sites
Process of metastasis
- Primary tumour vascularised
- Tumour cells detach
- Intravasation (enter blood vessels)
- Evasion of host defences (e.g. natural killer cells)
- Adhere to endothelium
- Extravasation
- Growth and vascularisation of secondary tumour
TNM system of tumour grading
Tumour size
Number of lymph node metastases
Metastases (anatomical extent)
Microinvasive carcinoma
Cancer cells invade the basement membrane
Enzymes that a tumour uses to invade tissue
Proteases, matrix metalloproteinases, collagenase, cathepsin D, urokinase-type plasminogen activator
Pathways for metastasis
Lymphatics, blood vessels
Cancers that usually metastasis to bone
- Breast
- Thyroid
- Lung
- Kidney
- Prostate
Gatekeeper genes
Prevent apoptosis (BRCA1/2)
Caretaker genes
Repair DNA
p53
RB1
