Cell Injury

Question 1

What can cause cell injury?

Answer 1

Hypoxia. 
Toxins. 
Physical agents: trauma, temp, pressure, electricity. 
Radiation. 
Microorganisms. 
Immune. 
Deficiencies.

Question 2

What is the difference between hypoxia and ischemia?

Answer 2

Hypoxia = decreased oxygen.

Ischemia = decreased blood supply

Question 3

Outline the 4 types of hypoxia

Answer 3

Hypoxaemia hypoxia = O2 arterial content low.

Anaemic hypoxia = decreased Hb ability to carry O2.

Ischaemic hypoxia = interrupted blood supply.

Histiocytic hypoxia = inability to utilise O2 due to disabled oxidative phosphorylation enzymes

Question 4

Explain how the immune system can damage body cells?

Answer 4

Hypersensitivity = secondary injury to vigorous immune reaction.

Autoimmune reaction = fail to distinguish self

Question 5

Which cell components are most susceptible to injury?

Answer 5

Cell membranes nucleus,
proteins,
mitochondria

Question 6

What happens at a molecular level during hypoxia

Answer 6

Lower O2 = lower oxidative phosphorylation = lower ATP

1) failure of Na K ATPase pump = ion gradient lost = ions pour in = cell swelling.
2) raised glycolysis = lower pH.
3) lower protein synthesis = lipid deposition

Question 7

Outline what occurs in prolonged hypoxia

Answer 7

Irreversible = massive influx of Ca2+ = activation of phospholipase, proteases, endonucleases

Question 8

Explain what free radicals are and how they cause damage

Answer 8

Single unpaired electron in an outer orbit = unstable configuration that will react with other molecules

mutagenic = carcinogenic, lipid peroxidation, autocatalytic chain reaction

Question 9

Name the 3 free radicals that are of particular biological significance in cells

Answer 9

OH (hydroxyl),

O2- (superoxide),

H2O2 (hydrogen peroxide)

Question 10

How are radicals produced?

Answer 10

Oxidative phosphorylation, inflam, radiation, contact with unbound metals, drugs/chemicals

Question 11

How does the body control free radicals

Answer 11

A, C, E vits donate electrons, metal carrier/storage proteins sequester iron/copper, enzymes neutralise

Question 12

What are heat shock proteins?

Answer 12

Aim to mend mis-folded proteins

Question 13

Describe the 3 ways injured/dying cells look like under a microscope

Answer 13

Pyknosis = irreversible condensation of nucleus chromatin

karyorrhexis = fragmentation of nucleus with chromatin distributed irregularly throughout cytoplasm.

karyolysis = dissolution of a cell nucleus

Question 14

Describe what injured/dying cells look like under an electron microscope

Answer 14

Can now visualise organelles: irreversible =

myelin figures (damaged cell membrane collection of fat), 
lysis of ER, 
mitochondrial swelling, 
rupture of lysosomes, 
nucleus pyknosis, 
karyolysis or karyorrhexis

Question 15

How can we diagnose cell death?

Answer 15

Testing cell function with uptake of dye, if alive = no dye due to impermeable cell membrane

Question 16

Define apoptosis, necrosis and oncosis

Answer 16

Apoptosis = controlled cell death non-random DNA cleavage.

Necrosis = morphologic changes that occur after a cell has been dead for a period of time.

Oncosis = cell death with swelling, DNA cleaved in random lengths

Question 17

What are the types of necrosis?

Answer 17

Coagulative: solid organs, protein denaturation.

Liquefactive: loose tissue, enzyme release = liquefaction of tissue.

Caseous: infections, structureless debris (cheese look).

fat necrosis: action upon fat by digestive enzymes, appear as white chalky deposits

Question 18

Define gangrene

Answer 18

Necrosis visible to the naked eye

Question 19

Define infarction

Answer 19

Necrosis caused by reduction in arterial blood flow

Question 20

Define infarct

Answer 20

Area of necrotic tissue as a result of low arterial blood supply

Question 21

What is the difference between wet and dry necrosis?

Answer 21

Dry = necrosis modified by exposure to air (coagulative necrosis).

Wet = necrosis by infection (liquefactive necrosis) (can be wet gas gangrene: presence of anaerobic bacteria that prod gas)

Question 22

What are the causes of an infraction?

Answer 22

Thrombosis, embolism, blood supply twisting: sigmoid colon or spermatic cord

Question 23

What is the difference between a thrombus and an embolism?

Answer 23

Thrombus: formation of a solid mass of blood within the circulatory system

Embolism: blockage of a blood vessel by solid, liquid or gas at a site distant from its origin

Question 24

How and why does infarcted tissue look different?

Answer 24

Can be white = occlusion of end artery in solid tissue.

Red = dual blood supply in loose tissue.

Question 25

Outline ischaemia-reperfusion injury

Answer 25

Damage can be worse if blood flow returns to a damaged but not yet necrotic tissue = prod of oxygen radicals, increased neutrophils so increased inflam, delivery of complement proteins

Question 26

When does apoptosis occur physiologically and pathologically?

Answer 26

Maintain a steady state, embryogenesis, cytotoxic T cells killing virus infected/neoplastic cells, damaged cells, GvsH disease

Question 27

Name the 3 stages of apoptosis

Answer 27

Initiation: activate caspases, execution, degradation and phagocytosis

Question 28

How is the intrinsic and extrinsic pathway resulting in apoptosis activated?

Answer 28

Intrinsic = p53, cytochrome C (released from mitochondria = activation of caspases). Extrinsic = TNFα (secreted by T killer cells)

Question 29

What can accumulate in a cell?

Answer 29

``` Water, electrolytes, lipids, carbs, proteins, pigments ```

Question 30

When do lipids accumulate?

Answer 30

= steatosis Alcohol, DM, obesity, toxins, when cholesterol cannot be eliminated by the liver

Question 31

In what conditions do proteins accumulate in cells?

Answer 31

Alcoholic liver disease, alpha1-antitrypsin def = accum in ER, not folded correctly

Question 32

When do pigments accum in cells?

Answer 32

Exogenous = Urban air pollutant and tattooing - phagocytosed by macrophages. Endogenous = haemosiderin, bilirubin

Question 33

Name an example of an accumulation of endogenous pigments?

Answer 33

Hereditary haemochromatosis: genetically inherited, increased absorption = accum of iron, often associated with liver/pancreas scarring

Question 34

What is accumulating in jaundice?

Answer 34

Bilirubin – breakdown prod of haem

Question 35

Outline the mechanisms of intracellular accumulation

Answer 35

Abnormal met, alteration in protein folding/transport, enzyme def, inability to degrade phagocytosed particles

Question 36

What are 2 the classification of calcified tissue?

Answer 36

Dystrophic: localised (abnormal Ca met/conc). Metastatic: generalised (hypercalcaemia secondary to disturbances in Ca met)

Question 37

What causes hypercalcaemia?

Answer 37

Increase PTH: primary = parathyroid hyperplasia/tumour, secondary = renal failure, ectopic = secretion of PTH-related protein by malignant tumours. Destruction of bone tissue: tumours, paget’s diseases (increased bone turnover), immobilisation

Question 38

What are the effects and lab diagnosis of excessive alcohol intake?

Answer 38

effects = liver cirrhosis, failure lab = AST, ALT, CRP, GGTP

Question 39

What is the presentation and lab diagnosis of Hep B?

Answer 39

pres = jaundice, fatigue, abdo pain, nausea/vomiting lab = serology, AST, ALT, LDH

Question 40

What is the lab diagnosis of acute pancreatitis

Answer 40

lipase, amylase

Question 41

Outline hereditary haemochromotosis

Answer 41

genetically inherited, increased absorption = accum of iron, often associated with liver/pancreas scarring pres = Fatigue, malaise, joint and bone pain, liver cirrhosis complications = organ damage treat = bloodletting, desferrioxamine: iron-chelating compound

Question 42

What is alpha-1 antitrypsin def?

Answer 42

pathophysiology = liver prod incorrectly folded alpha-1 antitrypsin = accum in ER pres = shortness of breath, wheezing, chackles complications = proteases in lung go unchecked = emphysema

Question 43

What is coal-workers pneumoconiosis?

Answer 43

Inhaled coal dust builds up, cannot be removed by the body = inflammation, fibrosis, necrosis pres = cough, dyspnea, lung function impairment complications = fibrosis, emphysema