1 - Cellular pathology

Question 1

pathology

Answer 1

the scientific study of causes and effects of disease

Question 2

Pathological processes

Answer 2

• Adaptation - may result in abnormal cell growth
• Cell death - lack of adaptation
• Abnormal cell growth - such as metaplasia or dysplasia or neoplastic growth
• Healing - stimulated by a pathological stress such as physical injury, collagen deposition in scar tissue
• Genetic and immune factors - affect a cell/organ ability to adapt to environmental stresses leading to different susceptibilities to disease

Question 3

Normal cell structure and function

Answer 3

• Functional units of living organisms
• Human body is a clone of 10^13 cells
• Adaptable to changing environment
- within physiological limits

Question 4

Regulation of Metabolic Function

Answer 4

• Fasting - fatty acids mobilised from adipose tissue
• Calcium lack - calcium mobilised from bone matrix
• Liver enzymes induced to metabolise drugs

Question 5

Pathological stimuli cause cellular stresses

Answer 5

• Osmotic stress (water and electrolyte/salt concentrations)
• temperature stress
• oxygen / energy deprivation
• Injury, infection
• any disruption of homeostasis…

Question 6

cell stress response

Answer 6

decreased activity from ‘housekeeping’ genes (normal structural proteins)
increased activity from Cell stress genes (cell-organising/ protective functions)
e.g. heat shock proteins (HSPs), NF-kB, AP-1
-> high degree of evolutionary conservation
-> essential to cell survival

Question 7

Protection in times of cellular stress

Answer 7

• Heat shock proteins (HSPs) act as chaperones: protect proteins, assist refolding, prevent protein aggregation
• Ubiquitin – targets protein for destruction by specific proteases (proteasome)
• Chronic stress = visible aggregates of constituents known as inclusion bodies e.g. Lewy body in nerve cells

Question 8

Adaptive response during cell stress

Answer 8

• Alterations in metabolism and structure
• Improves survival in adverse environment
• Inability to adapt may result in cell death
• Cells vary in their ability to survive

Question 9

Physiological adaptive responses

Answer 9

Morphological change – metaplasia, Restitutive Wound Healing
Increased cellular activity
Decreased cellular activity – cell/tissue atrophy

Question 10

Hyperplasia

Answer 10

increase in number of tissue cells due to increased cell division, e.g. endometrial lining during menstrual cycle

Question 11

Hypertrophy

Answer 11

increase in size of existing cells, matched by increase in functional capacity e.g. skeletal muscle fibres of athletes

Question 12

Colonic epithelial hyperplasia

Answer 12

The normal colon has a smooth lining of single layer epithelial cells and short crypts.
Epithelial hyperplasia increases the number of cells present resulting in deeper crypts.

Question 13

Prostate hyperplasia

Answer 13

Benign prostatic hyperplasia (BPH) 
• 20% of males age 40 
• 70% at age 60
• 90% at 80
• Hyperplasia of prostate cells 
• BPH not risk factor or precursor for prostatic carcinoma

Question 14

Transient hyperplasia

Answer 14

useful defence and repair mechanism

- allows increase functional capacity

Question 15

Persistent hyperplasia

Answer 15

increased risk of mutation, survival/uncontrolled growth

Question 16

Irreversible cell damage

Answer 16

Leads to pathological death
• Apoptosis (programmed cell death)
• Necrosis
Cell targets include:
• Cell membranes
• Mitochondria
• Cytoskeleton
• Cellular DNA

Question 17

Apoptosis

Answer 17

Responsible for elimination of unwanted/damaged cells
Four phases:
1) Induction/signalling - anti-apoptotic proteins Bcl-2
2) Effector - ‘point of no return’ = mitochondrial permeability
3) Degradation - proteases (caspases) = morphology
4) Phagocytic - cell fragments are engulfed and removed

Question 18

Apoptosis is a normal cell process

Answer 18

• Intestinal cell turnover
• Immune system – removal of autoreactive immune cells
• Embryogenesis and development
- larval forms & evolutionary background

Question 19

Apoptosis as a pathological disease

Answer 19

• Under-active pro-apoptotic pathways and/or over-active anti-apoptotic pathways can promote cancer

Question 20

Necrosis

Answer 20

Triggers: any acute stressor e.g. metabolic stress, hypoxia, absence of nutrients, trauma
Common molecular mechanisms that result in necrosis:
• Reduction in ATP  swelling of internal membranes (‘cloudy swelling’), reduced biosynthesis
• Increased cytosolic calcium (Ca++) = activate protein kinases, phospholipases
• Reduction in ability to scavenge ROS (reactive oxygen species)
• Plasma membrane integrity and cytoskeleton compromised
• Cells swell, lyse and burst

Question 21

Examples pathological stimuli that cause necrosis

Answer 21

• Hypoxia - reduction or absence of normal oxygen supply to an organ
• Specific chemical agents - carbon tetrachloride (CCl4) or paracetamol
• Hypoxia = death of an area of tissue = INFARCTION
Myocardial Infarction = Heart attack
Cerebral infarct & brain necrosis

Question 22

Hypovolaemic shock

Answer 22

• Reduction in blood available for the heart to pump
Loss of blood - Haemorrhage
Loss of plasma - severe burns
Loss of sodium and intravascular water

Question 23

Symptoms of hypovolaemic shock

Answer 23

• restlessness and confusion
• pale, cold, sweaty skin
• rapid, weak pulse and low blood pressure
• drowsy and confused, may comatose
• multiple organ failure = Death

Question 24

Cellular effects of hypovolaemia

Answer 24

• Inadequate cardiac output -> reduction in oxygen supply ->Switch to anaerobic metabolism ->
• Increase in metabolic waste products e.g. lactic acid, CO2
• Loss of Na+/K+ pump = Cellular swelling
• Long term – insufficient energy supply ->
  Cellular necrosis

Question 25

Response to hypovolemic shock (body)

Answer 25

• Increase respiratory rate and blood glucose
• Increase in heart rate and vasoconstriction
• Release of postaglandins and hormones eg Adrenaline

Question 26

Response to hypovolemic shock (clinical)

Answer 26

• Deal with cause
• If <25% blood volume lost = restored by compensatory mechanisms; i.v. infusion of fluids
• If >25% blood volume lost = blood/plasma transfusion

Question 27

Ischaemia

Answer 27

Reduction or absence of normal oxygen supply to an organ

Question 28

Hypoxia

Answer 28

Reduction in circulating blood volume

Question 29

Hypovolaemia

Answer 29

Inadequate blood supply

Question 30

Apoptosis vs. Necrosis

Answer 30

Shrinking of cytoplasm vs Swelling of cytoplasm
Condensation of nucleus vs Swelling & disintegration of organelles
Blebbing of plasma membrane, maintains integrity vs Loss of plasma membrane integrity
Formation of membrane-bound vesicles vs Loss of membrane integrity
Tightly regulated process vs Loss of ion homeostasis
Energy (ATP) dependant – does not occur at 4oC vs Passive process - occurs at 4oC
Very little inflammatory response vs Cell contents release = Inflammatory
response

Question 31

Gel electrophoresis (apoptosis)

Answer 31

Non-random degradation of DNA = ladder pattern on agarose gel electrophoresis

Question 32

Gel electrophoresis (necrosis)

Answer 32

Random digestion of DNA = smear on agarose gel electrophoresis