General Pathology Flashcards
Causes of cell injury
Oxygen deprivation - most common way to form reactive oxygen species (ROS), which damage lipids, proteins & DNA
Physical agents
Chemical agents
Infectious agents
Immunological reactions → excessive immune responses and autoimmunity.
Genetic changes (DNA mutation) → oncogenesis
Nutritional changes
Consequences of cell injury
Formation of ROS → highly damaging to cell contents
Loss of ATP → reduced cell function
Influx of Calcium into cell → causes activation of damaging cellular enzymes
Damage to cell memb causing loss of cellular content and leakage of lytic enzymes of lysosomes.
Protein misfolding/DNA damage → activation of pro-apoptotic enzymes.
Cell disorders
Hypertrophy
Increase in the size of cells → increase in size of tissue
Hyperplasia
Increase in number of cells in an organ (pathological)
Physical trauma: Linea alba (a type of frictional keratosis), denture hyperplasia, smoker’s keratosis
Endocrine involvement: Thyroid follicular hyperplasia - autoimmune → hyperthyroidism; Adrenal cortical hyperplasia - Cushing’s syndrome
Infection: viruses, fungi (hyperplastic candidasis)
Atrophy
Shrinkage in size of cell/organ by loss of cell substance
Metaplasia
Transition of one differentiated cell type to another
Reversible if stimulus is removed
Dysplasia
Disorderly proliferation - loss of uniformity of indiv cells and their orientation
Increased cell growth with decreased differentiation and atypical morphology.
Still same tissue
Reversible in early stages
Neoplasia
Abnormal, uncoordinated and excessive cell growth following dysplasia.
Irreversible even if stimulus is removed
Neoplasia
benign vs malignant
Continuous, unregulated replication -> unable to stop even when stimulus is removed
2 types of neoplasm:
Benign -> remains localised
Malignant -> lesion can invade and destroy adjacent structures and metastasise
Malignant
Benign
Metastasis potential
Yes, frequent
Never
Growth rate
Rapid
Slow
Direction of growth
Endophytic growth - growing into the tissue it originates from
Exophytic growth - grows out of where it originates from
Border
Poorly defined and irregular
Well-circumscribed and regular
Ulceration
Common, esp in lesions on mucosal surfaces
Rare
Histological resemblance to normal tissue
Often very poor
Often resembles normal tissue
Mitoses
Often present and atypical
Rarely present
Nuclear morphology
Usually abnormal; enlarged, hyperchromatic, irregular border and pleomorphic
Typically normal
Causes of neoplasia (after DNA damage, what happens)
Failure of tumour suppressor genes (eg p53)
Loss of protectory mechanisms against oncogenes
P53 - cell cycle arrest in G1-S, repairs damaged DNA prior S phase (DNA replication), triggers apoptosis if unreparable
Mutation of proto-oncogenes into oncogenes
Upregulates cell growth
Expression of telomerase - lengthens telomeres - prevents cells’ senescence and apoptosis
Define necrosis
Necrosis: unregulated form of cell death due to pathology, eliciting host inflammation, causing morphological changes by denaturation of intracellular proteins and enzymatic digestion.
Apoptosis vs necrosis
Apoptosis
Necrosis
Induction
Physiological or pathological stimuli
Pathological stimuli
Extent
Single cell
Groups of cells
Biochemical events
Energy-dependent fragmentation of DNA
Lysosomes intact
Impairment/cessation of ion homeostasis
Lysosomes leak lytic enzymes
Cell membrane integrity
Maintained
Lost
Morphology
Cell shrinkage
Apoptotic body formation
Cell swelling and lysis
Inflammation
No inflammation
Inflammation
Types of necrosis
Coagulative necrosis
Caused by ischaemia - lack of blood flow
Dry, hard and white cells
Tissue and cell architecture is preserved, but cells are anucleate
Necrotic cells are removed by phagocytes
Liquefactive necrosis
Caused by infection - bacteria, viruses, fungi, parasites
Bacteria enzymatic digestion of cells—further releases cell lysosomes which also contribute to digestion
Creamy yellow liquid
Inflammation stimulated
+ Production of pus (dead leukocytes)
Caseous necrosis
Caused by body inability to clear necrotic tissue
Granuloma formed: Collection of fragmented necrotic tissue, containing the foreign noxious stimuli
Yellow-white cheesy sphere, enclosed by clear border
Inflammation
- what is the purpose
- causes of inflamm
- Acute vs chronic
Purpose of inflammation - Protective mechanism
Remove infectious agents
Diluting toxins
Allow immune response to occur
Transport drugs and nutrients
Facilitate healing
Fibrin formation - barricade.
Causes:
Infectious agents
Hypersensitivity
Physical and chemical stimuli
Necrosis → releases lytic and damaging molecules
Acute
Chronic
Onset
Fast; minutes or hours
Slow; days
Cellular infiltrate
Mainly neutrophils
Monocytes/macrophages and lymphocytes
Tissue injury, fibrosis is:
Usually mild and self-limited
May be severe and progressive
Local and systemic signs
Prominent
Less
Characteristics of inflammation
Types of acute inflammation
Acute - develops within minutes or hours - lasts for a short duration
Exudation of plasma proteins and fluids
Emigration of leukocytes and neutrophils
5 Cardinal Signs of inflammation:
Redness - vasodilation → increase in blood flow → higher conc of RBCs
Oedema - release of chemokines increases permeability of blood vessels for extravasation → increase in interstitial fluid
Heat - increase in blood flow - water retains heat
Pain - prostaglandins sensitise free nerve endings, oedema causes pressure on free nerve endings
Loss of function - immobilisation from swelling
Serous inflammation
Exudation of cell-poor, protein-rich fluid into spaces created by injury
Eg in blisters/burns
Fibrinous inflammation
Fibrotic deposition, fibrin-rich coating over site
Large vascular leaks/local procoagulant stimulus
Increased vascular permeability -> fibrinogen passes out of blood → forms fibrin in the extracellular space
Could stimulate ingrowth of fibroblasts and blood vessels when not cleared → leads to scarring
Suppurative/Purulent inflammation
Abscess → production of pus (exudate consisting of neutrophils, necrotic cell debris, oedema)
Chronic inflammation
Chronic - failure of acute inflammation to clear the stimulus - recurrent acute inflammation . can be autoimmune disease
Infiltration of mononuclear cells -> Presence of lymphocytes and macrophages, plasma cells
Tissue destruction -> sustained inflammatory response
Recurrent cycles of injury and healing → connective tissue replacement → fibrosis
Granulomatous inflammation
Type of chronic inflammation characterised by groups of activated macrophages and thus T lymphocytes.
Formation of granuloma (collection of macrophages, T cells, plasma cells, neutrophils, and other cells) → body’s attempt to contain stimulus
Eg TB - TB grows within macrophages, is resistant to the humoral immune response
Pulpal inflammation - what is the pulp response to injury
Why is pulpal tissue so susceptible to death
Ability of pulp to resolve inflammation depends on
Severity, nature, duration of stimulus
Pulp response to injury:
Reparative dentine formation
Sclerosis of tubules
Fibrosis and reduced cellularity
Granulation tissue formation
Why is pulpal tissue so susceptible to death
Limited size of chamber
Concentrated stimulus
Low blood flow
Limited capacity for drainage, swelling, repair
Limitations of materials to treat
Periapical abscess development
Untreated pulp necrosis →
Tissue necrosis - pus formation - proteinaceous exudate -
Surrounded by acutely inflamed tissue - severe pain
Possible clinical outcomes:
1) Spread of abscess
Abscess spreads through buccal cortical bone or gingival tissue → sinus formation
Cellulitis formation - purulent discharge diffusely spread through soft tissues
2) Periapical granuloma formation
Chronic inflammation in PA tissues frm long-term abscess.
Granulation tissue + fibrous tissue
Wound healing
Primary intention
Primary intention
Edges of wound have no tissue loss, tissue is in apposition—stabilised in the same anatomic position
Small blood clot, small amt granulation tissue → not much space for granulation tissue to form (strong collagen join)
Minimal wound/scar contraction
Eg: well-repaired lacerations/incisions, well-reduced bone fractures
Wound edges joined by fibrin plug
Regrowth of basal layer of epidermis
Lysis of fibrin and re-epithelialisation
Restoration to intact skin
Wound healing
Secondary intention
Secondary intention
Tissue loss has occurred in a wound
More scar tissue -> causes contraction and slower compared to primary intention
More inflammation and larger blood clot
Eg extraction sockets, poorly reduced fractures, deep ulcers
Granulation tissue
Increased formation of BVs (angiogenesis)- supply tissue w O2 and nutrients for growth
VEGF
Degradation of extracellular matrix to make way for BV growth by MMPs
Macrophages - remove debris and damaged tissue
Fibroblasts + their products - form new CT
0-24h Formation of blood clot with underlying inflammation
2d-7d - Large defect filled by scab - exudate, fibrin clot
New blood vessels and fibroblasts (granulation tissue) grow from the dermis into fibrin
2wks - Reduced granulation tissue, Collagen laid down by granulation tissue fibroblasts, to restore integrity
1-2mths - Epithelial organisation - Maturation of collagen achieves structural integrity and allows regrowth of epidermis, wound contraction and decreased vascularity
