Pathology Flashcards
what is a risk factor
social or individual factor which increases the risk of development of a disease
what is aetiology
cause of a disease
what is pathogenesis
sequence of events from a health state to a clinical disease
what causes aging
- Genetic factors
- Environmental factors
- Manifestation of age related diseases
For cell integrity what must be highly functioning?
- DNA
- Cell membrane
- Energy production
- Protein synthesis
What is necrosis
Cell death that requires no energy
Patterns of necrosis
- Coagulative- proteins coagulate to preserve the cell outline
- Colliquative- necrotic material becomes sofened and liquefied (PUS), no cell structure remains
- caseous- cheese like eg TB
- Gangerous- Cell death by necrosis then infection on top of that
- Fibrinoid- fibre deposition
- Fat necrosis- fat cells die often due to trauma
what is apoptosis
cell death that requires energy- programmed cell death due to a stimuli. May be physiological or pathological. No inflammation.
causes of apoptosis
withdrawal of growth factors loss of matrix attachment viruses free radicals ionising radiation DNA damage (AIDs and neurodegenerative disorders increase apoptosis) (Neoplasia and auto-immune diseases decrease apoptosis)
what is p53
like a spell checker at G1 of the cell cycle, if a mistake is found the cell cycle is paused and p53 repairs it, if it cannot be fixed then p53 stimulates apoptosis
what causes cell aging
a progressive decline in the proliferation capacity and lifespan of the cell
biochemical and structural changes in cell aging
- mitochondrial abnormalities
- reduced ER
- disorted golgi apparatus
- accumualtion of lipofusion
- advanced glycation products
- abnormally folded proteins
- reduced capacity to undertake key biochemical processes
what happens to biochemical processes with cell aging?
they become less effective; decreased oxidative phosphorylation, decreased synthesis of key nucleic acids and proteins/enzymes and reduced capacity for nutrient uptake
What are telomeres
RNA- protein complex (DNA caps at chromosome ends TTAGGG)
What are the functions of teleomeres?
- ensure complete replication of the genome
2. protect coding sequences at the chromosome ends from damage
What is telomere shortening
incomplete replication of chromosome ends which leds to cell cycle arrest
telomere activity is greater in germ cells than in stem cells, why?
there is no telomere activity in somatic cells
what type of cells are suceptable to DNA damage?
- dividing cells
- abnormal sequence inherited by daughter cells and so is recognised as normal, so DNA repair mechanisms are by passed
- permenant cells are most resistant
what cells are highly succeptable to abnormalities
skin and hair cells as they have a high turn over
what cells are at low risk of abnormalities
cardiac and adult neurone cells as they have a low turn over
what can cause loss of membrane integrity
- failure of ion pumps
- disruption of membrane
- alteration of lipids
- cross linking of membrane proteins
what is a metabolic disorder
a defective enzyme leading to an increased substrate metabolite and a decreased product metabolism and therefore the rest of the molecules in the pathway are also decreased (may be inherited or acquired)
causes of an inherited metabolic disorder
autosomal recessive
Acute inflammation
neutrophils
vascular phase- dilatation and increased permability of blood vessels
exudative and cellular phase- fluid and cells escape from the permeabily venules
neutrophil accumulation in extracellular space
Intermediate inflammation
eosinophils
Acute–> Chronic
the agent causing inflammation isnt removed, recurrent episodes of acute inflammation
Chronic inflammation
macrophages, plasma cells, lymphocytes, fibroblasts
subsequent and ofter prolonged tissue reactions follow initial response. recurrance of acute inflam may lead to chronic
characteristics of inflammation
redness (erythema)- due to dilatation of the of blood vessels
Heat (calor)- increased blood flow
swelling- accumulation of fluid in extravascular space
pain- distortion of tissues
loss of function- inhibited by pain of swelling
what is the exudate fluid
a protein containing fluid (including immunoglobins)
What is fribrinogen
fibrin on contact with ECM, acutely inflammed organs are commonly covered in fibrin
neutrophil inflammation cascade
- margination
- adhesion
- chemotaxis
- chemical mediators
- recognition of micro-organisms
- suppuration
- abscess formation
- resolution
What occurs in the margination phase?
loss of intravascular fluid and increased plasma viscosity, allowing neutrolphils into plasma
What occurs in the adhesion phase?
surface adhesion molecules expression increased by:
- Complement C5a
- Leukotriene B2
- TNF
endothelial cell expression of adhesion molecules is increased by:
- IL1
- Endotoxins
- TNF
Transendothelial migration
Chemotaxis phase:
Locomotion oriented along chemical gradient
Chemical mediators:
Histamine- vascular dilation, released by mast cells, eosinophils, basophils and platelets. Stimulated by C3a, C5a and lysosomal proteins
Seratonin-increased vasular permeability, 5HT present in high concentration in platelets (serotonin receptors)
Chemokines- attract various leukocytes to site of inflammation
leukotrienes- Type 1 hypersensitivity reaction
Protiglandins- increase vascular permeability and stimulate platelet aggregation
Recognition of micro-organism phase:
not recognised until coated in opsonins (phagocyte marking)
- C3b (surface of an antigen, it can be recognized by phagocyte receptors that signal for phagocytosis)
- Fc fragment of IgG (This property allows antibodies to activate the immune system.)
- collectins (trigger elimination of a microorganism and activation of phagocytes)
Suppuration phase:
formation of pus- living and dead cells- neutrophilsm bacterial and cellular debris
Absecess formation:
tissue architecture destruction and abundant neutrophils after an episode of acute inflammation plus pus, surgically removed, unlikely to solve itself
resolution:
complete restoration of tissue to normal after episode of acute inflammation
name 2 chronic inflammation pathways:
- primary chronic inflammation
2. chronic inflammation secondary to acute inflammation
cells of chronic inflammation
- plasma cells
- lymphocytes
- macrophages
macroscopic appearance of chronic inflammation
- ulcer
- abscess cavity
- thickening of wall by fibrous tissue
- granulomas
- fibrosis
on contact with antigens whar do B and T lymphocytes do?
B lymphocyte- becomes a plasma cell
T lymphocyte- produces cytokines
What is repair of a cell?
angiogenesis followed by fibroblast proliferation and collagen synthesis
what cells have a high regenerative capacity?
hepatocytes and kidney cells
what cells have a love regenerative capacity?
cardiac and adult neurone cells
Name some irreversible cell damage:
- severe damage to cell membranes and mitochondria
- leakage of enzymes
- nuclear changes- ATP, cell membrane damage
Example of labile cell type?
In GI tract and bone marrow
these can proliferate to replace lost cells
Example of stabe cells?
heaptocytes and endothelium
these can proliferate to replace lost cells
Examples of permenant cells?
Neurones and skeletal cells
regeneration is not possible
What is a granuloma?
chronic inflammation, collection of macrophages
what is wound contraction?
when myofibroblasts act to minimise the volume of a wound but this can lead to stenosis or strictures
scarring:
injury to tissue–> formation of granulation tissue–> organisation (ie fibrosis)–> fibrous scar matures and contracts (collagen)
uclerated scar:
widely separated, prominent granulation tissue and prominent fibrosis
excessice scarring leads to..
hypertophic scar and keloid scarring
causes of a granulomatous disease:
- specific infections
- foreign bodies
- chemicals
- drugs
- idiopathic
what is differentiation
acquisition of a specialised function
what is hyperplasia
increase in cell number
amlodipine causes gingival hypertrophy
what is hyperplasia
increase in cell number
amlodipine causes gingival hypertrophy
what is hypertrophy
increase in cell size
what is atrophy
reduction in cell size and number in an organ that was normal size
what is hypoplasia
reduction in size of an organ that never fully developed to normal size
what is metaplasia
one type of cell becomes another form of cell in response to stress (site at risk of cancer)
eg barratts oesophagus
what is neoplasia
new growth, abnormal mass of tissue, growth of which exceeds and is uncoordinated with that of normal tissue
(monoclonal= derived from a single common ancestor)
Benign neoplasia:
- no necrosis
- nucleus: cytoplasm ratio normal
- minimal pleomorphism
- diploid
- adenoma
- papilloma
Malignant neoplasia:
- necrosis
- N:C ratio increased
- pleomorphic
- aneuploid
- carcinoma (cancer of epithelial cell)
- carcinoma in situ= not invading other tissues
- sarcoma- cancer of mesenchymal cell
what is dysplasia
disordered growth, pre-malignant process, abnormal cell changes
what is angiogenesis
formation of new, abnormal blood vessel, sucessfully growing tumours with develop ability to create own blood supply
what are metastasis?
formation of tumour implants that are discontinuous from primary lesion
routes:
- lymphatic= carcinoma
- haematogenous=sarcoma
what is the double hit hypothesis?
one working gene is enough. one faulty gene puts a person at increased risk. two faulty mutated genes will result in a functional problem
What is stepwise progession?
- initiation (1st mutation- basically how cancer is caused)
- promotion (further accumulation of mutations)
- persistence (unregulated abnormal growth, can beome malignant)
Malignant mutation examples:
RAS (GTP binding) eg. colon, pancreatic, bladder, renal and melanoma
Myc (nuclear transcription factor promoting DNA replication) eg. lymphoma, neuroblastoma, small cell carcinoma
P13K (most common mutated kinase in cancer, located in the nucleus at transcription) eg.haematological malignancies
causes of failure of ion pump…
1.structural defects
2. defective mitochondria
(causing disruption of ionic concentration and osmorailty)
Tumour suppressor functions
- inhibit cell proliferation
- stimulate cell death
What is P53 function
makes a protein that causes apoptosis in cells with DNA damage
BRCA 1 and 2 mutations
Breast cancer
cancer of the epithelium
carcinomas
cancer of the glands
adenoma (benign)
adenocarcinoma (malignant)
cancer of squamous cells
papilloma (benign)
sqaumous cell carcinoma (malignant)
Inherited metabolic disorders:
-autosomal recessive
Inherited metabolic disorders:
- autosomal recessive
- loss of function mutation
- gene encodes in metabolic pathway
Phenylketonuria:
deficiency of phenylalanine hydroxylase (an enzyme which converts phenylalanine to tyrosine) this then causes a build up of phenylalanine which causes brain toxicity and mental retardation. GUTHRIE TEST (phenylalanine free diet)
Complication of Phenylketonuria:
cant produce tyrosine so cant produce melanin so are fair skinned
cretinism:
deficiency of the enzyme that converts tyrosine into thyroid hormones
what is tyrosinosis?
the enzyme that converts tyrosine into homogenitisic
albinism:
deficiency of the enzyme that converts tyrosine into melanin
Alkaptonuria:
deficiency of the enzyme that breaks down homogenistic acid into carbon dioxide and water
Diabetes type 1:
insulin dependent: HLA linked. anti-islet antibodies form immune complexes with islet B cells causing islet cell destruction and failure of insulin secretion
Diabetes type 2:
non insulin dependent: target cell becomes unresponsive to the insulin being secreted
Risk factors of atheroma
- fam history
- male
- smoker
- obesity
- alchohol
- hypertension
- age
- diabetes
Pathogenesis of atheroma
fatty streak–> fibrofatty plaque–> proliferative atheroma–> complicated atheroma
causes of atheroma
endothelial injury–> response to injury–> macrophages and platelets agreggate–> lipid accumulation–> smooth uscle proliferation
complications of atheroma
- thombosis
- aneurysm
- dissection
- embolism
- ischaemia
Left ventricular hypertrophy
- increase LV load
- poor perfusion of organs
- interstitial fibrosis
- micro infarcts
- diastolic dysfunction
define thombus
solid mass of bloof formed in a blood vessel
Virchows triad:
vessel wall (loss of endothelial surface, inflammation) blood flow (stasis, turbulence) blood constituents (platelets, coagulation proteins, viscosity)
what are platelets
anucleated cell fragments, adherence properties and growth factors
what is an embolism
mass of material in vascular system, moving from its site of origin to lodge in the vessel of a distant site
Deep vein thrombus
Post op, bed bound, travel , unilateral leg swelling, oedema, pain
Pulmonary thromboemolism
sudden onset, life threatening, haemoptosis, breathlessness, cardiovascular collapse, cardiac arrest
Define infarction
Zonal necrosis due to sudden occlusion of blood supply, lack of nutrient and oxygen
senescence
non dividing state a cell goes into after a fixed number of cell divisions
Werners syndome
genetic abnormality assoc with defective SNA helicase
Progeria:
a rare genetic condition causing growth retardation in infancy with macrocelphaly and fast developing signs of old age- low life expectancy due to high risk of athersclerosis
neurogenerative disease
frontal and temporal lobe atrophy and compensatory ventricular dilation, formation of senile plaque and neurofibillary tangles all causing acceleration of normal aging process
osteoporosis
when bones decline in density
osteartheritis
degeneration of articular surfaces
hypoxic cell
ATPase pumps are shed due to reduced ATP consumption and ionic conc will be altered and cells swell with fluid intake
osteomyelitis
a chronic abscess which is extremely difficult to eradicate
histocyte
a macrophage present in connective tissue, mainly secretory function , little phagocytic function
