Week 2

Question 1

Systemic Toxicity

Answer 1

Chemicals can cause local toxic effects (at site of contact); but more often,
toxic effects are observed at single or multiple sites distant from the entry site.

require both absorption of a toxicant and distribution by the bloodstream from its entry point to a distant site, where the deleterious effects are produced

Question 2

Target organs ranked in order of frequency for
exhibiting systemic toxicity are:

Answer 2

1. CNS
   2 circulatory system2. circulatory system
2. blood and haematopoietic system
3. visceral organs, such as the liver, kidney, and lung
   5 ki5. skin
4. muscle and bone – these are infrequent target

Question 3

Cellular Adaptations to Toxicity

Answer 3

When cells or tissues are damaged, the body attempts to adapt & repair or limit harmful effects. Often adaptive changes result in cells or organs that can’t function normally.
This imperfect adaptation is a pathological change – it has 3 basic types:
(1) Increase in cell activity; (2) Decrease in cell activity;
(3) Alteration in cell morphology (structure and appearance) or cell function

Question 4

Atrophy

Answer 4

is a decrease in the size &/or number of cells.
Tissue/organ may decrease in size if sufficient number of cells involved.
When cells atrophy, they have:
* reduced oxygen needs,
* reduced protein synthesis,
* decreased number & size of organelles.
Common causes of atrophy:
* reduced use of the cells,
* lack of hormonal or nerve stimulation,
* decrease in nutrition,
* a reduced blood flow to the tissue, &
* natural aging.
Example of atrophy: decrease in size of muscles and muscle cells in people with legs that are paralyzed, in a cast, or infrequently used (e.g. bed-ridden patients).

Question 5

Hypertrophy

Answer 5

Hypertrophy is an increase in size of individual cells.
* Frequently results in an increase in size of a tissue or organ.
* During hypertrophy, cell components increase in numbers with increased
functional capacity to meeting increased cell needsfunctional capacity to meeting increased cell needs.
* Generally occurs when the organ or tissue cannot adapt to an increased demand
by formation of more cells – commonly seen in cardiac and skeletal muscle cells, which do not divide to form more cells.
Common causes of hypertrophy:
* increased work or stress placed on an organ or hormonal stimulation.
Example of hypertrophy: is the compensatory increase in the size of cells in oneExample of hypertrophy: is the compensatory increase in the size of cells in one
kidney after the other kidney has been removed or is in a diseased state

Question 6

Hyperplasia

Answer 6

Hyperplasia is an increase in the number of cells in a tissue.
* Generally results in enlargement of tissue mass and organ size.
* Occurs only in tissues capable of mitosis (i.e. epithelium of skin, intestine, glands),
and not in cells that don’t divide (e.g. nerve and muscle cells).

Often a compensatory measure to meet an increase in body demands.
Examples of hyperplasia:
* A frequent response to tissue damage (wounds or trauma), where hyperplasia of
connective tissue (e.g. fibroblasts & blood vessels) contributes to the wound repair.
* A frequent response to toxic agents in many cases when the toxic stress is* A frequent response to toxic agents – in many cases, when the toxic stress is
removed, the tissue returns to normal.
* From hormonal stimulation, e.g. breast and uterine enlargement due to increased
estrogen production during pregnancy

Question 7

Metaplasia

Answer 7

Metaplasia: conversion from one mature cell type to another
* This cellular replacement process often occurs with chronic irritation & inflammation.
* Tissue becomes more resistant to external stress – replacement cells survive better.
* But usually results in a loss of function that was performed by the original cells

Question 8

Dysplasia

Answer 8

Dysplasia: abnormal cell changes or deranged cell growth.
* Cells are structurally changed in size, shape & appearance from original cell type;
cellular organelles also become abnormal.
* Common feature of dysplastic cells: larger nuclei & higher mitotic rate.
Causes of dysplasia:
* Chronic irritation and infection – reversible in many cases if the stress is removed; but may be permanent in other cases (a precancerous change)

Question 9

Anaplasia

Answer 9

Anaplasia: appearance of undifferentiated cells with irregular nuclei & cell structure with numerous mitotic figures.
* Frequently associated with malignancies (a grading criteria for aggressive cancer).
Example of an anaplastic carcinoma:
* Cell appearance has changed from highly-differentiated cell of origin to a cell type lacking normal characteristics of the original cell. Anaplastic cells have generally lost
normal cellular controls that regulate cell division & differentiation normal cellular controls that regulate cell division & differentiation.

Question 10

Neoplasia

Answer 10

Neoplasia: is basically a new growth of tissue;
commonly termed a “tumour”
* Two types of neoplasia:
benign and malignant

Question 11

There are 4 main final endpoints to cellular or biochemical toxicity

Answer 11

The tissue may be completely repaired
and return to normal.
* The tissue may be incompletely repaired, but is capable of sustaining its function with reduced capacity.
* Death of the organism, or the complete. Death of the organism, or the complete
loss of a tissue or organ (replacement therapy, e.g. insulin or organ transplant).
Neoplasm or cancers may result -> many can cause death, while others may
be cured by medical treatment

Question 12

two basic types of tissues

Answer 12

• parenchymal – containing the functional cells (e.g. squamous dermal cells, liver) hepatocytes & pulmonary alveolar cells).
• stromal – supporting connective tissues (e.g. blood vessels & elastic fibres)

Question 13

Repair of injured cells can be accomplished by:

Answer 13

(1) Regeneration of parenchymal cells, involving hyperplasia response:
– Labile cells routinely divide & replace cells with limited lifespan (e.g. epithelium)
– Stable cells usually have a long lifespan with a normally low rate of division, but
can rapidly divide upon demand (eg. hepatocytes)can rapidly divide upon demand. (e.g. hepatocytes)
(2) Repair and replacement by the stromal connective tissue, involving metaplasia
after damage to:
– Permanent cells that never divide, even when stressed or some cells die. (e.g. neurons, skeletal and cardiac muscle).