Session 2 - Cell Injury 2

Question 1

Defintions of cell death (3)

Answer 1

Oncosis - Changes before death
Necrosis - Changes after death
Apoptosis - Programmed cell death

Question 2

What is necrosis?

Answer 2

Morphological changes following death largely due to action of enzymes
When plasma and organelle enzymes are damaged -> cell contents are released and inflammation is seen

Question 3

How long after death do necrotic changes develop?

Answer 3

4-12 hours

Question 4

What types of necrosis exist? (4)

Answer 4

Coagulative
Liquefactive (Colliquitive)
Caseous
Fat

Question 5

When is coagulative necrosis seen?

Answer 5

When protein denaturation is the dominant feature -> leads to solidity of dead cells
Most common (ischaemia) e.g. pancreas
Forms a ghost outline (only seen for a few days before acute inflammation)

Question 6

When is liquifactive (colliquitive) necrosis seen?

Answer 6

When the release of active enzymes, partiularly proteases, is the dominant feature of dead cells -> dead tisse tends to liquefy
When there is large numbers of neutrophils (abscesses) -> therefore bacterial infections
Seen in brain due to poor stromal support

Question 7

When is caseous necrosis seen?

Answer 7

Seen in infections (especially TB)
Amorphous debris appearance (looks cheesy macroscopically)
Associated with granulomatous inflammation

Question 8

When is fat necrosis seen?

Answer 8

Seen in destruction of adipose tissue
Most common after acute pancreatitis -> during inflammation there is release of lipases
Free fatty acids can react with calcium to from chalky deposits (visible on x-rays and macroscopically)
Can occur after direct trauma to fatty tissue (differential for breast cancer)

Question 9

What is gangrene in terms of necrosis?

Answer 9

It is NOT a necrosis - describes necrosis visible to naked eye
Can be dry (coagulative) or wet (liquefactive) (wet can lead to septicaemia)
Can be see most commonly in ischaemic limbs

Question 10

What is infarction in terms of necrosis?

Answer 10

It is NOT a necrosis - it is a cause of necrosis, most often ischaemic. e.g. death by ischaemic necrosis is an infarct

Question 11

What causes infarctions?

Answer 11

Thrombosis or embolism
external compression of vessel
twisting of vessels

Question 12

What is a white infarct?

Answer 12

White (anaemic) infarct - occurs in solid organs after occlusion of an end artery -> prevents haemorrhaging
e.g. heart, spleen, kidneys
white appears as coagulative necrosis histologically

Question 13

What is a red infarct?

Answer 13

Red (haemorrhagic) infarct - occurs due to:
dual blood supply (collateral)
numberous anastomoses
loose tissue
previous congestion (more blood than usual)
raised venous pressure (transferred to capillary bed)

Question 14

What determines the consequences of an infarct?

Answer 14

Alternative blood supply?
How quickly ischaemic occured
How vulnerable a tissue is to hypoxia
Oxygen content of the blood

Question 15

What is apoptosis?

Answer 15

Programmed cell death - can be physiological -> occurs when cells are no longer needed, damaged and in embryogenesis.

Question 16

Features of apoptosis - light microscope

Answer 16

Shrunken
Eosinophilic
Chromatin condensation
Pyknosis
Karyorrhexis

Question 17

Features of apoptosis - electron microscope

Answer 17

Cytoplasmic blebbing
Fragentation into membrane bound apoptotic bodies
No leakage of cell contents (therefore no inflammation)

Question 18

Describe the intrinsic apoptosis pathway

Answer 18

Triggered by DNA damage, withdrawal of growth factors or hormones.
p53 detects and triggers increased mitochondrial permeability -> cytochrome C is released.
Cytochrome C intereacts with APAF1 and caspase 9 to form an apoptosome which activates caspase 3

Question 19

Describe the extrinsic apoptosis pathway

Answer 19

Triggered by death ligands (TRAIL and Fas) which bind to death receptors (TRAIL-R) which activates downstream caspases.
Both intrinsic and extrinsic meet at the downstream caspase activation and cause degradation -> apoptotic bodies form, and induce phagocytosis.

Question 20

What prevents cytochrome c release from mitochondria?

Answer 20

BcI-2

Question 21

When do we see abnormal cellular accumulations?

Answer 21

When metabolic processes become deranged - often with sublethal or chronic injury

Question 22

What abnormal cellular accumulations are there?

Answer 22

Normal cellular constituents e.g. water, lipids, proteins, carbohydrates
Abnormal substances (exogenous or abnormal endogenous products of metabolism)
Pigments

Question 23

What lipid accumulations are there?

Answer 23

Steatosis (fatty change) - accumulation of TAGs. Often seen in liver (fat metabolism)
Caused by alcohol, diabetes, obesity and toxins.
In mild cases no effect on cell function.

Cholesterol - accumulates in SMC and macrophages in atheroma. Also seen in hyperlipidaemia (xanthoma, xantholasma, corneal arcus)

Question 24

What protein accumulations are there?

Answer 24

Mallory’s hyaline - seen in hepatocytes in alcholic liver disease - they are altered keratin filaments

Incorrectly folded a1-antitrypsin

Question 25

What exogenous pigments are there?

Answer 25

- carbon/coal dust - inhaled and phagocytosed macrophages in lung tissue - seen as blackened lung tissue or blackened peribronchial lymph nodes - tattoos - [igments phagocytosed by macrophages within the dermis

Question 26

What endogenous pigments are there?

Answer 26

- lipofusin - brown pigment seen in aging cells (signs of ROS injury) - Haemosiderin - derived from haemoglobin - yellow/brown and contains iron (often seen as a bruise). Can be seen in haemolytic anaemias, blood transfusions and haemochromatosis (increased absorption of dietary iron). Can result in severe liver, heart and pancreas damage. - Bilirubin - bile pigment - yellowing of the skin in haemolytic anaemia or abnormal liver function

Question 27

What is calcification and what types of calcification are there?

Answer 27

Abnormal deposit of calcium salts in tissues | Dystrophic or Metastatic

Question 28

What is dystrophic calcification?

Answer 28

Occurs in an area of dying tissue, atherosclerotic plaques, damaged heart valves and TB lymph nodes. No abnormality of calcium metabolism or serum calcium concentration. Causes organ dysfunction.

Question 29

What is metastatic calcification?

Answer 29

``` Calcium is deposited in normal tissue in hypercalcaemia -> asymptomatic. Four causes: More PTH Destruction of bone Vit D disorder Renal failure ```

Question 30

Describe cellular aging

Answer 30

As cells age, they accummulate damage. Also can accumulate lipofuscin and abnormally folded proteins. Replication ability declines - repilicative senscense. This is due to telomeres shortening. (germ cells and stem cells have telomerase which maintains telomere length - cancer cells produce telomerase)

Question 31

What are the major effects on the liver by alcohol? (3)

Answer 31

Fatty change - steatosis - hepatomegaly (reduced transport of fat out of cells) Acute alcholic hepatitis - alcohol and its metabolites are toxic -> focal hepatocyte necrosis, formation of Mallory bodies and neutrophilic infiltrate - can cause fever, liver tenderness and jaundice. (usually reversible) Cirrhosis - 10-15% of alcholics - hard, shrunken liver appears histologically as micronodules of tegenerating hepatocytes surrounded by bands of collagen. Irreversible and sometimes fatal

Question 32

Who are more susceptible to paracetamol overdose? (4)

Answer 32

Alcoholics Malnourished people People on enzyme inducing drugs HIV positive or AIDS patients

Question 33

How to determine when to prescribe NAC?

Answer 33

4 hours after overdose serum concentration of paracetamol is measured and plotted. 24 hours later INR is measured (PT) to assess liver damage. (liver produces clotting factors). When PT increases its indicative of liver damage.

Question 34

What does aspirin do?

Answer 34

Acetylates platelets cylcooxygenase and prevents thromboxane A2 production. -> petechaie may be present Aspririn also stimulates the respiratory centre which results in respiratory alkalosis - compensatory acidosis occurs. Aspirin then contributes to acidosis via lactate, pyruvate and ketone body production. Can see GI bleeding in acute erosive gastritis.