introduction to pathology

Question 1

what is pathology ?

Answer 1

• the structural, biochemical and functional changes in cells, tissues and organs that underlie disease

Question 2

what is the aetiology(etiology) of a disease ?

Answer 2

• aetiology of a disease is the cause of a disease

- the cause can be either genetic or acquired

Question 3

what is the cause of most diseases?

Answer 3

• most diseases have more than one cause and these can be a mixture of genetic and acquired factors

Question 4

what is pathogenesis ?

Answer 4

• what happens in cells between the initial cause and the development of the disease
• the sequence of events in cells and tissues in response to the causative agent from the initial event to the final manifestation of the disease

Question 5

what is cellular response to stress ?

Answer 5

when you stress a normal cell- two things can happen

• either cell adaptation (cell can still function )
• cell injury ( if stress stays for too long or if stress is extreme)- it is possible that injured cell can recover
• if cell is subject to severe progression than the cell is irreversibly injured
• this leads to cell death
• cells death can be two mechanism
  . Necrosis
  . Apoptosis

Question 6

what is the response of myocardium to stress?

Answer 6

• when you stress cardiac muscle so if you increase blood pressure- then heart will have to work harder- the heart tries to adapt to the high blood pressure by the cell size increasing
• increase in cell size leads to an increase in tissue size( hypertrophy)
• if high blood pressure stays around for a bit that is fine as cell can produce actin and myosin to cope
• if blood pressure stays high for too long then the cells become injured and cells can die
• you get infarct in the heart which is irreversible

Question 7

how can a cell adapt?

Answer 7

there are four things that can happen

• hypertrophy
• hyperplasia
• atrophy
• metaplasia

Question 8

what is hypertrophy ?

Answer 8

• increase in size of cells in response to stress

- the number of cells does not increase but the organ gets bigger

Question 9

what is an example of hypertrophy?

Answer 9

• skeletal muscle has limited capacity to replicate
• therefore in response to increased workload,
• cells produce more mitochondria , actin and myosin to keep up with the contraction
• the size of individual fibres increases and muscles grow larger

Question 10

what are the two effects of hypertrophy ?

Answer 10

hypertrophy can be both beneficial/physiological
e.g increased skeletal muscle size to improve function
uterus muscle increase in size during pregnancy

or pathological
e.g hypertrophy in the heart in the long run can affect how the heart pumps due to thickening of heart walls

Question 11

what is hyperplasia ?

Answer 11

• increased number of cells

- like hypertrophy , hyperplasia can be both physiological beneficial or pathological

Question 12

what are examples of pathological hyperplasia?

Answer 12

• all neoplasms/tumors
  e. g. granular cell tumour or oesophagus
• sebaceous hyperplasia- increase in number of cells in sebaceous glands around hair follicles
• push hair follicles out forwards

Question 13

what are examples of physiological hyperplasia?

Answer 13

• many of the hormonally induced changes of puberty
• increased in number of mammary gland cells during pregnancy to feed off spring
• the proliferative phase of wound healing
  . hyperplasia of fibroblast, vascular endothelial and epithelial cells are essential after injury to repair a wound

Question 14

what is atrophy?

Answer 14

• reduction in the size of an organ or tissue resulting from a decrease in cell size and/or decrease in cell number
• atrophy can be both physiologically beneficial pr pathological
• many of the atrophic changes during development are necessary for proper development

Question 15

what are examples of developmental ( beneficial/physiological) atrophy?

Answer 15

1. the hyaloid canal, which is empty after birth, contains the hyaloid artery in the foetus
   - during eye development lens forms before ciliary body is able to produce aqueous humour so lens is fed by the hyaloid artery
   - but you don’t want vascular network running through the vitreous and surrounding lens after birth as it will scatter a lot of light
   - before birth once you have adequate supply of aqueous being produce from ciliary body you no longer need these blood vessels so they undergo atrophy
2. non-ocular example of such atrophy might be the shrinkage of the thymus in adults
   - children have large thymus glands which are responsible for maturation of t-lymphocytes but as we age the size of thymus shrinks

Question 16

what are the causes of pathological atrophy?

Answer 16

• decreased workload (e.g. skeletal muscle atrophy when not used)
• denervation ( e.g. muscle wastes without nervous input)
• decreased blood supply ( e.g. tissue infract after ishaemia)
• inadequate nutrition ( e.g. anorexia)
• loss if endocrine stimulation ( e.g. changes after menopause)
• pressure ( e.g. benign tumour)

Question 17

what is metaplasia ?

Answer 17

reversible change of one cell type into another

e.g trachea is lined by simple columnar epithelium but when you smoke you induce stress into epithelial cells and the cells respond by changing into stratified squamous epithelium which is better able to withstand irritation

Question 18

what happens if cell cannot adapt?

Answer 18

• when cell cannot adapt, the cell becomes injured

- the injury may be reversible or the cell will die by necrosis or apoptosis

Question 19

what are the cause of cell injury ?

Answer 19

• hypoxia ( due to decreased blood flow, reduced cardiac output, co poisoning, anaemia, blood loss)
• physical agents( burn, trauma, electric)
• chemical agents( poisons, acids, drugs)
• infectious agents ( bacteria, fungi, viruses)
• immunological reactions
• genetic abnormalities ( causing for example abnormal cellular metabolism)
• nutritional imbalances ( e.g. cholesterol, anorexia)

Question 20

what happens following an injury ?

Answer 20

• the cell swells
• organelles also swells
• formation of membrane blebs
• ER detaches from ribosomes
• chromatic clumps

Question 21

what does the effect of an injury lead to ?

Answer 21

• decreased generation of ATP
• loss of membrane integrity
  . membrane blebs destabilise the membrane of the cell
• decreased protein synthesis this is because the ribosomes are no longer attached to ER and chromatic clumps
• cytoskeleton and DNA damage

Question 22

what happens if cellular injury is not too severe?

Answer 22

the cell can recover

Question 23

what happens if damage is irreversible?

Answer 23

i- f the damage is irreversible, the cell undergoes necrosis

- breakdown of plasma membrane , organelles and nucleus leakage of contents

Question 24

what happens in necrosis?

Answer 24

• plasma membrane disintegrates

- the integrity of the cell membrane is lost and contents leaks out

Question 25

what can happen due to necrosis ?

Answer 25

- an inflammatory response is triggered- neutrophils and leukocytes are stimulated to come into this area and clear up the mess - enzymes released by the dying cell itself and from inflammatory cells to digest cellular content

Question 26

what are dead cells characterised by ?

Answer 26

- dead cells are characterised by myelin figures which are phospholipid masses derived from the membrane and dilation of mitochondria with large amorphous masses

Question 27

what is other way cells can die ?

Answer 27

- via apoptosis

Question 28

what is apoptosis?

Answer 28

- much control form of cell death - doesn't involve other cells - doesn't trigger inflammatory response - can be regarded as cellular suicide ( programmed cell death )

Question 29

what happens in apoptosis ?

Answer 29

- cells shrinks - organelles become more tightly packed - nuclear chromatin condenses - membrane blebs form which continue to grow - blebs contain condensed organelles - the cell breaks up into apoptotic bodies as the whole cell starts to disintegrate - these are phagocytosed

Question 30

what is the difference between apoptosis and necrosis?

Answer 30

in apoptosis - the plasma membrane initially stays intact (no leakage of contents) - apoptosis does not initiate an inflammatory reaction - apoptosis can occur in physiological situations or it can be pathological

Question 31

what is physiological apoptosis ?

Answer 31

- widespread during embryological development inappropriate cells in the nervous system, synaptic connections between them are edited out - e.g development of CNS- you have 50% more neurons produced then you need so excess of neurons must die once all connectivity has been formed neurons die via apoptosis - retinal development . retinal cells develop in a specific order from multipotent precursor cells because you have no connection between cells as they are being produce there is no way of directing how many horizontal or ganglion cells you need until you got all rod cells being differentiated - any cell that hasn't integrated into synaptic network they are not needed , these cells go through apoptosis as they will be energy drain

Question 32

what are non-ocular examples of physiological apoptosis ?

Answer 32

- the breakdown of endometrial cells during the menstrual cycle - every month the endometrial increases its cell number , if you get to end cycle and you don't have fertilised egg , cells go through apoptosis - death of neutrophils once they have served their useful purpose ( phagocytosis ) during the inflammatory response

Question 33

what is pathological apoptosis ?

Answer 33

- occurs when a cell is damaged beyond repair due to disease or injury

Question 34

what is the advantage of using apoptosis rather than necrosis?

Answer 34

- you do not get a host reaction, limiting the damage

Question 35

what is example of pathological apoptosis ?

Answer 35

if cells DNA is damaged ( e.g. by radiation ) it may become unstable and the mutations may cause neoplasms , therefore the cell undergoes apoptosis

Question 36

what are the two pathways that can lead to initiation of apoptosis ?

Answer 36

- intrinsic pathway requires signalling through mitochondria - extrinsic pathway