Pathology Flashcards
What does VINDICATE stand for?
V – Vascular I – Infectious/inflammatory N – Neoplastic D – Drugs/toxins I – Intervention/iatrogenic C – Congenital/developmental A – Autoimmune T – Trauma E – Endocrine/metabolic
What is an example of vascular pathology?
Blood vessels- inflammation, clot, blockage
what is neoplasia?
New growth
What is iatrogenic?
Caused by doctor
Describe adaptation?
Increased demand- hyperplasia, hypertrophy
Decreased demand-atrophy
Altered stimulus- metaplasia
What is hyperplasia?
Increase in cell number
-response to external stimulus
What does hyperplasia result in?
Will regress on withdrawal of stimulus
Increased organ volume
Describe hormonal hyperplasia?
Puberty- breast tissue
Pregnancy- hyperplasia of lining of uterus
When does compensatory hyperplasia occur?
After loss of tissue
Where does compensatory hyperplasia occur?
Liver
Bone Marrow
Describe the mechanism of hyperplasia?
Production of increased growth factors- locally or from distant site. Hormone may be a growth factor itself.
Increased growth factor receptors
Switch on genes encoding growth factors and cell cycle regulators to promote new cell growth.
Describe hormonally induced pathological hyperplasia?
Excess oestrogen- endometrial hyperplasia and abnormal bleeding
Prostatic hyperplasia in response to androgens
What happens in lymph nodes as a result of infection?
Hyperplasia
Is hyperplasia reversible?
Yes, reverse on withdrawal of stimulus
What is the risk of hyper plastic tissue?
Risk site for development of cancer
What is hypertrophy?
increase in cell size
Not cell number
When does hypertrophy occur?
In conjunction with hyperplasia
In isolation in non-dividing cells e.g. cardiac myocytes, skeletal muscle
In response to mechanical stress
When does hypertrophy of cardiac myocytes become pathological?
When heart can no longer function and requires more than is supplied
Muscle becomes less functional
Results in HF
What is atrophy?
Reduction in cell size
What are examples of physiological atrophy?
Embryological structures
Uterus after parturition
What can pathological atrophy be a result of?
Decreased workload
Malnutrition
Describe pathological atrophy?
Loss of inervation
Loss of function after nerve supply is removed
What causes atrophy in the brain?
Blocked blood supply
In association with atherosclerosis
Ageing (also in heart)
What causes atrophy of the kidneys?
Pressure
Due to endogenous or exogenous structures
Describe the mechanism of atrophy?
Reduced cellular components
Protein degradation
Digested in lysosomes and degraded in many cases by ubiquitin proteasome pathway
Which hormones promote atrophy?
Glucocorticoids
Thyroid hormone
Which hormones oppose atrophy
Insulin
Define metaplasia
Reversible change from one mature cell type to another
What does metaplasia represent
Change in signals delivered to stem cells causing them to differentiate down a different line
What is metaplasia in response to?
Cytokines (chemical messengers, growth factors and other chemicals in the cells microenvironment)
Noxious stimuli
What is squamous metaplasia a result of?
Response to injury
what is the risk of metaplasia?
Metaplastic site is at risk for cancer development
Which metaplasia cancer is common in the lung?
Squamous cell
Which metaplastic cancer is common in the oesophagus?
Adenocarcinoma (glands)
What does stress on cells cause?
Adaptation
What are the causes of inflammation?
Infection Trauma Foreign bodies Immune reaction Necrosis
What is the response to injury?
Vascular changes
Cellular changes
Chemical mediators
Morphologic patterns
Describe vascular changes in response to injury?
Changes in flow and vessel caliber
Vasodilation
First involves arterioles and then capillary beds
What mediates vascular changes?
Histamine
Nitric oxide
What are the clinical manifestations of vascular changes?
Increased heat (calor)
Redness/erythema (rubor)
What are the cellular changes in response to injury?
Stasis White cell margination Rolling Adhesions Migration
What are selectins?
Expressed on a variety of white cells and bind cell adhesion molecules (CAMs) on endothelial surface
What are integrins?
Over 30 types
Bind to vessel walls, cell matrix and other cells
What increases selectin expression?
Histamine and thrombin
What increases endothelial cell expression of VCAM and ICAM?
TNF and interleukin 1
What is the role of chemokines?
Chemokines from the site of injury bind to proteoglycans on endothelial cell surface
What is the role of proteoglycans?
Increase the affinity of VCAMs and ICAMs for intergrins
What happens in increased vascular permeability?
Leaky vessels- loss of protein
Change in osmotic pressure
Water follows protein- swelling (tumour)
What causes Endothelial contraction?
Histamine, bradykinin, substance P, leukotrienes
What causes leaky vessels
Endothelial contraction Direct injury White cells Transcytosis New vessel formation
What causes direct injury to vessels?
Toxins
Burns
What do white cells do to vessels?
Self harm
What is transcytosis mediated by?
VEGF
What forms new vessels?
VEGF
What is chemotaxis?
Cells follow a chemical gradient
What causes chemotaxis?
Bacterial components
Complement
Leukotrienes
Cytokines- interleukins
What are the three phases of phagocytosis?
Recognition and attatchment
Engulfment
Killing and degradation
What is responsible for recognition and attachment?
Mannose receptors
(Bacterial surface glycoproteins and glycolipids contain terminal mannose residues)
Scavenger receptors
Opsonins
What does not contain mannose receptors?
Mammalian glycoproteins and glycolipids do not
What are opsonins?
Coating proteins making bacteria stand out
Include components of the complement cascade as well as IgG
What vesicle is formed during engulfment?
Phagosome
What is it called when a phagosome joins with lysosome?
Phagolysosome
What is responsible for killing and degradation?
Reactive oxygen species
NADPH oxidase- oxygen gains an electron from it and becomes superoxide
Reactive nitrogen species
Nitric oxide synthase combines NO with superoxide and produces ONOO
Many other cytotoxic granules
What are the five pillars of inflammation?
Heat Redness Swelling Pain Loss of function
Define rubor?
Redness
> Increased perfusion. Slow flow. Increased permeability of vessels.
Define calor?
Heat
> Again – increased perfusion, slow flow rate, increased vascular permeability
Define tumour?
Literal translation- swelling
Due to vascular changes
Define Dolor?
Pain
Mediated by prostaglandins and bradykinin
What are the microscopic changes in inflammation?
Neutrophils -polymorph Many lobes to nucleus Granulocyte Phagocytic and cytotoxic abilities
