Necrosis and apoptosis/inflammation

Question 1

What is necrosis?

Answer 1

-Necrosis is defined as abnormal tissue death during life. -Necrosis is ALWAYS pathological and is accompanied by inflammation.
-Groups of cells are involved and they undergo swelling and lysis.
-Necrotic cells are phagocytosed by inflammatory cells.

Question 2

What are the different types of necrosis?

Answer 2

Coagulative (structured): most common form due to interruption of blood supply

Liquefactive: Occurs in the brain

Caseous: TB

Fat necrosis: Can follow direct trauma (e.g. in breast) or enzymatic lipolysis (pancreatitis)

Gangrenous necrosis: can be wet, dry or gaseous. Tissue appears green or black due to
haemoglobin breakdown

Question 3

What is apoptosis?

Answer 3

Apoptosis is the process of programmed cell death. Unlike necrosis, apoptosis produces apoptotic bodies that phagocytic cells remove before stimulating any inflammatory reaction

Question 4

What is the difference between apoptosis and necrosis?

Answer 4

Necrosis is ALWAYS pathological and is accompanied by inflammation.

Apoptosis is the process of programmed cell death. Unlike necrosis, apoptosis produces apoptotic bodies that phagocytic cells remove before stimulating any inflammatory reaction

Question 5

What is a neoplasm?

Answer 5

A neoplasm is an abnormal growth of tissue which displays:
Uncoordinated growth
Growth which exceeds that of the normal tissue
Growth which continues despite removal of the original stimulus
Note: The term neoplasm is synonymous with the term tumour

Question 6

How are neoplasms classified?

Answer 6

Can be divided into benign or malignant
Malignant neoplasms are then subdivided into primary or secondary

Question 7

How can neoplasms be classified according to cell type?

Answer 7

One cell type:
Epithelial: papilloma, adenoma, carcinoma
Mesenchymal: fibroma, lipoma, sarcoma
Lymphoma

More than one cell type from one germ layer:
Pleomorphic adenoma, fibroadenoma

More than once cell type from more than one germ layer:
Teratomas (can be benign or malignant)

Question 8

What is hyperplasia?

Answer 8

Hyperplasia is an increase in the size of an organ or tissue through an increase in the
NUMBER of cells. The cells are of normal size and morphology

Question 9

Can you give 2 physiological and 2 pathological examples of hyperplasia?

Answer 9

Physiological examples: Breast tissue during puberty, thyroid during pregnancy
Pathological examples: Benign prostatic hyperplasia, adrenals in Cushing’s

Question 10

What is hypertrophy?

Answer 10

Hypertrophy is an increase in the size of an organ or tissue through an increase in the SIZE of
the cells. The number of cells remains the same, as does the morphology.

Question 11

Can you give 2 physiological and 2 pathological examples of hypertrophy?

Answer 11

Physiological examples: Skeletal muscle with exercise, uterus in pregnancy
Pathological examples: Cardiomyopathy, thyroid in Graves’ disease

Question 12

What is a hamartoma and can you name some examples?

Answer 12

A hamartoma is a tumour-like malformation
-composed of a disorganised arrangement of different amounts of tissue normally found at that site
-It grows under normal growthcontrols.

Examples: Peutz-Jegher’s polyps of the bowel; haemangiomas; lipomas

Question 13

What is metaplasia and can you give some examples?

Answer 13

Metaplasia is a REVERSIBLE replacement of one fully differentiated cell type with another differentiated cell type.

Examples include:
-Barrett’s oesophagus secondary to GORD(Change from stratified squamous to columnar epithelium)
-Transformation zone of the cervix secondary to HPV (Change from columnar epithelium to
stratified squamous)

Question 14

What is dysplasia?

Answer 14

Dysplasia is disordered cellular development characterised by increased mitosis and pleomorphism but WITHOUT the ability to invade the basement membrane and metastasise.
Note: Severe dysplasia = carcinoma-in-situ

Question 15

Define the term pleomorphic

Answer 15

Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei

Question 16

What are carcinomas and sarcomas, and how do they typically spread? Are there exceptions?

Answer 16

A carcinoma is a malignant tumour of epithelial cells
A sarcoma is a malignant tumour of connective tissue
Carcinomas typically spread by the lymphatic route
Sarcomas typically spread by the haematogenous route
Note: An exception to this is follicular thyroid carcinomas which spread via the
haematogenous route

Question 17

What type of epithelium lines the oesophagus?

Answer 17

Stratified squamous

Question 18

What is metastasis?

Answer 18

Metastasis is the survival and growth of cells that have migrated from a malignant neoplasm to a site distant from the primary neoplasm

Question 19

What are the routes by which tumours spread? Which cancers spread via each?

Answer 19

Local invasion
Lymphatics – most carcinomas
Blood – sarcomas and follicular carcinoma of the thyroid
*Transcoelomic – carcinoma of the stomach, ovary, colon, pancreas
CSF – CNS tumours
Iatrogenic – Implantation/seeding during surgery/FNA/biopsy

*The spread into body cavities occurs by the seeding surface of the peritoneal, pleural,
pericardial or subarachnoid spaces

Question 20

What is acute inflammation?

Answer 20

Acute inflammation is the body’s stereotypical response to tissue injury. It is characterised
by:
Heat, pain, redness, swelling (calor, dolor, rubor, tumor)
+/- loss of function (functio laesa)
+/- secretions

Question 21

What are the stages of acute inflammation?

Answer 21

1. Vasodilation
2. Increased vascular permeability
3. Migration of white cells through the vessel walls
4. Phagocytosis
5. Either resolution or progression to chronic inflammation

Question 22

Name some chemical mediators that participate in acute inflammation

Answer 22

Vasoactive amines (histamine and serotonin)
Bradykinin
Complement cascade
Coagulation cascade and fibrinolytic system
Arachidonic acid metabolites (leukotrienes, prostaglandins, thromboxane A2)
Cytokines (Interleukins, TNF alpha)

Question 23

What is the complement cascade?

Answer 23

-Component innate immune system
-Cascade of proteins that result in formation of MAC–> can destroy bacteria or recruit other cells
-Two main arms to complement cascade:
–> Classical: consists of antigen-antibody complexes
–> Alternative: activated by contact with micro-organisms

The complement cascade is a component of the innate immune system. It consists of a
cascade of proteins that result in the formation of a membrane attack complex, which can
destroy invading bacteria or recruit other cells to the inflammatory response.
There are two main arms to the complement cascade: the classic pathway consists of antigenantibody complexes. The alternative pathway is activated by contact with micro-organisms.
Note: Knowing the complement cascade in any more depth would be of no benefit as it will
not be tested further than this in part B.

Question 24

What are the possible outcomes of acute inflammation?

Answer 24

Resolution
Progression to chronic inflammation
Organisation and repair culminating in scar formation
Death (meningitis is a good example)
Abscess formation (which may then drain spontaneously by means of a sinus)

Note: Remember the definitions.
An abscess is a collection of pus surrounded by granulation or fibrous tissue
A sinus is a blind-ended track lined by granulation tissue, which normally connects an abscess to the skin

Question 25

What is a sinus?

Answer 25

A sinus is a blind-ended track lined by granulation tissue, which normally connects an abscess to the skin

Question 26

What is an abscess?

Answer 26

An abscess is a collection of pus surrounded by granulation or fibrous tissue

Question 27

What is chronic inflammation?

Answer 27

Chronic inflammation is present where there is:
-active inflammation
-tissue injury
-healing

at the same time.

defined by the cells types present (macrophages and lymphocytes)

and typically has a longer time course than acute inflammation

Question 28

Can you name some examples of chronic inflammatory states

Answer 28

Persistent infection that evades host defence mechanisms e.g. TB, H. pylori
Endogenous agent e.g. gastric acid in PUD
Persistant or non-degradable toxin e.g. asbestos
Auto-immune diseases e.g. RA
Immunocompromise e.g. secondary to HIV or prolonged steroid use

Question 29

What is a granuloma?

Answer 29

A granuloma is a collection of epithelioid macrophages.

Question 30

What is granulomatous inflammation?

Answer 30

-Form of chronic inflammation characterised by presence of epithelioid macrophages
-Can fuse to form multinucleate giant cells (langerhan’s cells)
-These are sometimes present in granulomatous inflammation

Granulomatous inflammation is a form of chronic inflammation characterized by the
presence of epithelioid macrophages, called such as they resemble epithelial cells. These can
fuse to form multinucleate giant cells (Langhan’s cells) which are sometimes present in
granulomatous inflammation

Question 31

How can granulomatous inflammation be classified and can you give some examples?

Answer 31

It can be classified as caseating (e.g. TB) or non-caseating (e.g. sarcoidosis, Crohn’s disease)

Question 32

What is necrotising fasciitis?

Answer 32

-Aggressive infection that spreads from subcutaneous tissues to fascial planes
-Spreads rapidly along deep and superficial fascial planes, causing tissue necrosis
-Usually caused by synergistic polymicrobial infection (aerobes e.g. staph aureus, anaerobes e.g bacteroides)
-If monomicrobial usually due to haemolytic group A strep (strep pyogenes)

Question 33

Nec fasc risk factors

Answer 33

-Diabetes
-Alcohol excess
-CKD
-Immunocompromise