Pathology Flashcards
What does VINDICATE stand for?
- Vascular
- Infectious/Inflammatory
- Neoplastic
- Drugs/toxins
- Interventions/Iatrogenic
- Congenital/developmental
- Autoimmune
- Trauma
- Endocrine/metabolic
What are the main categories for response to injury?
- vascular changes
- cellular changes
- chemical mediators
- morphological patterns
What are the vascular changes that happen in response to injury?
vasodilation in the arterioles then capillary beds which is mediated by histamine and nitric oxide and results in rubor and calor
What are the cellular changes that can happen in response to injury?
stasis whit cell margination rollin adhesions migration
What does vasodilation do to normal blood flow?
causes white cell margination as blood no longer flows centrally
What are the two types of cell adhesion molecule and what do they do?
selectins: expressed on endothelial cell surface
integrins: bind to walls, matrix and other cells
What hormones cause the inflammatory response and what do they cause?
histamine and thrombin from inflammatory cells increase selection expression, TNF and IL1 which increases endothelial cell expression of VCAM and ICAM
What effect do the chemokine from the injury site have?
bind to proteoglycans on cell surface which increases affinity of VCAMs and ICAMs fro integrins
How does swelling happen?
leaky vessels leading to loss of protein so change in osmotic pressure so water moves out causing swelling
What is chemotaxis?
cells following a chemical gradient and moving along it
What are the steps of phagocytosis?
- recognition and attachment
- engulfment
- killing and degradation
What happens in the recognition and attachment phase of phagocytosis?
- bacteria have terminal mannose receptor residues in glycoproteins and glycolipids (mammals don’t)
- scavenger receptors
- opsonins (complement and IgG)
What happens in the engulfment has of phagocytosis?
- arms are pseudopods
- phagosome forms and joins with lysosome to make phagolysosome
What components are involved in the killing and degradation phase of phagocytosis?
reactive oxygen species (NADPH oxidase)
reactive nitrogen species (nitric oxide synthase)
What are the five pillars of inflammation?
rubor- redness with increased perfusion, slow flow and increased vessel permeability
tumor- swelling due to vascular changes
dolor- pain mediated by prostaglandins and bradykinin
calor- heat with increased perfusion, slow flow and increased vessel permeability
functions laesa- loss of function
What cell is also called a polymorph?
neutrophil due to many lobes
these are granulocytes with phagocytic and cytotoxic abilities
What is the major cell involved in acute inflammation?
neutrophil
What are the factors that determine what happens after acute inflammation?
- site of injury
- type of injury
- duration of injury
What is resolution?
- complete restoration of tissue to normal after removal of inflammatory components
- minimal cell death
What does the tissue need to have resolution after inflammation?
- fast delivery of white cells
- removal of injurious agent
What is suppuration?
pus neutrophils bacteria inflammatory debris abcsess
When does organisation happen?
if there is necrosis, fibrin, poor blood supply or damage beyond the basement membrane
How do erosions and abrasions heal?
there is an intact basement membrane so it will heal with complete resolution
What is granulation tissue?
hole is infiltration by capillaries then myofibroblasts which deposit collagen and smooth muscle cells
What does scarring and fibrosis cause?
patch job with loss of function
skin will be less mobile and stretchy
What happens when the liver gets overwhelmed by fibrosis?
cirrhosis leading to liver failure
Who is chronic inflammation favoured?
suppuration, scarring, empyema, persistence of injury so foreign material, infectious agent so virus or autoimmune such as transplant rejection
What are the cells of chronic inflammation?
- lymphocytes (small round blue cell)
- macrophages
What are granulomas?
balls of macrophages including foreign bodies that can be endogenous (keratin, bone, crystals) or exogenous (talc, asbestos, suture) eg TB mycobacterium
What is caseous necrosis from?
tuberculous granulomas
What happens when they is no ATP?
increased K+ (causes swelling), Ca2+ pump fails so increased Ca2+
What does increased Ca2+ cause?
- ATPase
- phopholipase (membrane damage)
- proteases (membrane and cytoskeleton damage)
- endonuclease (DNA damage/breakdown)
- mitochondrial permeability (release pro death factors)
After how long does cell death occur?
20 minutes
What happens when cell begin to die?
1) cells shrink (pyknotic), become red, nucleus shrinks and becomes dark and marginal contraction bands appear
2) cell contents leaked, complement cascade and acute inflammation
3) vasodilation, m flow slows, white cell margination, rolling, parementing, diapedesis, chemotaxis and phagocytosis
What is coagulative necrosis and where does it occur?
happens in cardiac tissue
ghost outline before neutrophils can remove them
What is restitution?
gradual progressive scarring as macrophages are replaced by fibroblasts that lay down collagen, this is complete at 6 weeks
What is hyperplasia?
enlargement of an organ caused by an increase in reproduction rate of cells
What is hypertrophy?
enlargement of an organ due to an increased size of cell
What is atrophy?
decrease in the size of cell
What is metaplasia?
reversible transformation of one differentiated cell type to another
What is cell division caused by?
production of more growth factors or more growth factor receptors
What actions can growth receptors have?
- intrinsic tyrosine kinase activity
- 7 transmembrane G-protein-coupled receptors
- receptors without intrinsic kinase activity
What controls each stage of the cell cycle?
cyclin dependent kinases which are activated by cyclins A, B, D and E
What happens in G1?
- cell gets bigger with increased protein synthesis
- CDK4 activated by cyclin D
- CDK4 phosphorylates Rb (retinoblastoma protein)
What does Rb do in G1?
binds to E2F to stop cell division but when it is phosphorlyated by CDK4 cell division occurs readily
What happens in the synthesis phase?
- E2F initiates DNA replication
- increases levels of cyclin A which activates CDK2
- promotes DNA replication
- after S phase, there will be two copies of every gene
What happens in G2?
second growth phase so cell gets bigger and there is more protein synthesis
What does p53 do?
checks cell for mistakes, pauses, repairs and then progressed or causes the cell to commit suicide
(cancer avoids these checks)
What are telomeres?
TTAGGG repeats at the end of chromosomes that limit divisions
What causes hyperplasia?
- an external stimulus which will stop when stimulus does
- can be physiological or pathological (by hormones)
What is hyperplastic tissue at risk of?
development of cancer
What is the mechanism of atrophy?
- reduced cellular component
- protein degradation
- digested in lysosomes
What substances increase or decrease atrophy?
glucocorticoids and thyroid increase atrophy
insulin decreases atrophy
What is cancer?
uncontrolled cell proliferation and growth that can invade other tissues
What is neoplasia?
new growth that is not is response to a stimulus- it can be benign, premalignant or malignant
Where does malignancy occur in relation to the epithelium?
the malignancy goes beyond the basement membrane
What is metaplasia?
the reversible change from one mature cell type to another mature cell type
How does metaplasia occur?
change in signals sent to stem cells so they differentiate down a different line which can be in response to cytokines, growth factors or other chemicals
What does thermal or chemical injury do to the bronchial epithelial surface?
changes it to squamous epithelium
What is the epithelium in the bladder?
transitional but changes to squamous with injury
What is metaplastic tissue at risk of?
becoming cancerous
What does hyperplasia need to occur?
can be autonomous and not need a stimulus
What is dysplasia?
disordered growth with abnormal cells where growth is not in response to a stimulus and there is no invasion beyond the basement membrane
What is carcinoma in situ?
dysplasia affecting the whole epithelium which is the last stage before invasion
What are the Weinberg hallmarks of cancer?
- metastasis
- replicative immortality
- angiogenesis
- resist cell death
- sustained proliferative signalling
- evade growth suppressors
What is BRCA?
mutations in a tumour suppressor gene
What is the double hit hypothesis?
one working gene is enough and two are needed to be faulty for a problem to occur
What are initiators?
initiators cause long lasting genetic damage but must be followed by a promoter
What are promoters?
there require initiators to cause damage
What cancers does smoking cause?
small cell lung
head and neck
bladder
cervical
What are aflatoxins?
cause a p53 mutation
What does radiation cause?
pyrimidine dimers in DNA
How can chronic inflammation cause cancer?
causes lymphomas as so much replication can cause errors
What must a cancer cell do to sustain growth signals?
- grow without stopping
- avoid homeostatic controls
- growth receptors (with or without intrinsic tyrosine kinase activity and 7 transmembrane G protein-coupled)
- Myc promotes growth
- P13K is commonly mutated
What must a cancer cell do to have a loss of growth inhibition?
- stops tumour suppressors
- stopping p53 checking for mistakes
How does p53 check for mistakes?
- senses DNA abnormality at G1
- pauses cell cycle
- increases levels of p21 (CDK inhibitors)
- repair or apoptosis
How do cancer cells have unlimited replicate potential?
reactivate telomerase to get more telomeres
How do cancer cells resist apoptosis?
bcl-2 binds Bak/Bax so stops death
How do cancer cells induce angiogenesis?
upregulation of vascular endothelial growth factor
How do cancer cells evade inflammatory response?
over expression of PD-L1 which inhibits T cell proliferation
What does an inflammatory response do the cancer?
helps body fight it
How do cancer cells activate invasion and metastases?
chew up surrounding tissue
increase expression of matrix metalloproteinases
What is atrophy?
physiological or pathological reduction in cell size
What is necrosis?
always pathological death that requires no energy
What is coagulative necrosis?
preserves cell outline and dead cells are consumed by enzymes eg cardiac muscle
What is liquefactive necrosis?
leaves no cell structure, pus, associated with localised infections eg in the brain
What is caseous necrosis?
TB, granulomas with central necrosis, ZN positive
What is apoptosis?
programmed cell death in response specific signals
requires energy
can be physiological
What is pathological apoptosis due to?
injury vasodilation chemotherapy viral infection cancer
What is the extrinsic pathway for apoptosis?
- death cell receptors initiated
- TNF or fas
- Fas recognises self
- TNF induces apoptosis with inflammation
What is the intrinsic pathway for apoptosis?
- mitochondrial
- anti-apoptic molecules removed form membrane
- these are replaced with Bax/Bak
- increased leakiness in mitochondria so caspases so cytochrome C
How does apoptosis occur?
- pyknosis
- chromatin condensation
- cytoplasmic blebs
- macrophages
What is cellularly ageing caused by?
- oxidative stress due to free radical damage
- accumulation of metabolism by-products
What is a polymorph?
neutrophil
What is a monocyte/histiocyte?
macrophage
What is suppuration?
involves necrosis, phagocytosis, abscess and neutrophils but not lymphocytes
What steps of inflammation are the fibroblasts in?
the later stage
What does homogenous tissue look like?
one area that looks the same as another
What is the classification of encapsulated slow growing lesions?
benign
What does heterogenous tissue look like?
all areas look different and there is haemorrhage and necrosis
What is an ideal nucleus:cytoplasmic ratio?
a low ration is good and a high ratio is seen in malignancy
What does differentiation say about a cell?
well differentiated cells are normal and poorly differentiated cells can be malignant as they look nothing like they are supposed to
What is pleomorphism?
all cells look different
What is hyperchromasia?
is dark staining nuclei due to more DNA
What is mitoses?
a high mitotic count which is common in malignancy
What is a tumour of the epithelium called?
carcinoma
What is mesenchymal related to?
connective tissue
What is a tumour of the glands called?
adenoma or adenocarcinoma
What is a tumour of the squamous cells called?
papilloma or squamous cell carcinoma
What is a tumour of the bladder called?
transitional cell carcinoma
What is a tumour of the connective tissue called?
mesenchyme sarcomas
What is a tumour of the fat called?
lipoma or liposarcoma
What is a tumour of the bone called?
osteoma or osteosarcoma
What is a tumour of the cartilage called?
enchondroma or chondrosarcoma
What is a tumour of the skeletal muscle called?
rhabdomyoma or rhabdomyosarcoma
What is a tumour of the smooth muscle called?
leiomyoma or leiomyosarcoma
What is a tumour of the nerve called?
meurofribome or shwannoma is benign
malignant peripheral nerve sheath tumour
What is a tumour of the vessels called?
haemangioma or angiosarcoma
What is a freckle?
ephelis
What is a mole?
naevus
What is a malignant lesion of the skin called?
melanoma (exception to the nomenclature rule)
What is the word for how far the cancer has spread?
stage
What is the word for how differentiated the cells are?
grade
well differentiated = low grade
poorly differentiated = high grade
What is cachexia?
weight loss in cancer due to tumour and TNF which increase metabolism
What are paraneoplastic syndromes?
result from the tumour but aren’t directly related- can be due to increased Ca2+ or decreased Na+
What are examples of paraneoplastic syndromes?
osteoarthropathy
skin rash
fever (pyrogens)
pyrexia
Why are cancer patients susceptible to infection?
tumours can evade and suppress immune system
What is the difference between blood colts and thrombosis?
blood clots are extravascular
thrombosis is intravascular
What are the features of the intrinsic coagulation cascade?
factor XII activation
measured with PT
What are the features of the extrinsic coagulation cascade?
starts with tissue factor
measured with APTT
What are the consequences of increased calcium ions?
ATPase phospholipase proteases endonuclease mitochondrial permeability
