Pathology Flashcards

Question 1

Q

Define Aetiology and Pathogenesis ?

Answer

A

Aetiology = the cause of disease

Pathogenesis = mechanism of how a disease develops

Question 2

Q

What are the seven different causes of cell injury ?

Answer

A

Causes of cellular injury

Hypoxia = reduced oxygen supply / heart respiratory failure, anaemia
Physiological agents = trauma, extreme cold, extreme heat and UV radiation
Chemicals, drugs, toxins = poisons arsenic, 1080
Infectious agents = viruses, bacteria, fungi
Immunological dysfunction = autoimmune disease, hypersensitivity (allergy)
Nutritional deficiencies/ imbalances = hypervitaminosis A, scurvey
Genetic disorders = haemophilia, von willebrand disease

Question 3

Q

Although the causes of cell injury are numerous the general mechanisms of injury are few identify these five mechanisms ?

Answer

A

The five mechanisms of cell injury

ATP depletion
altered protein synthesis
nucleus damage
membrane damage
cytoskeleton damage

Question 4

Q

Describe the mechanism of cellular injury ATP depletion ?

Answer

A

ATP depletion

mitochondria require oxygen to generate cellular energy
hypoxia is one of the most common and important causes of cellular injury - results in acute swelling

The mechanism

decrease oxidative phosphorylation and results in a decrease in ATP
decrease in ATP triggers a switch to anaerobic glycolysis
increase anearobic glycolysis
resulte in a decrease in glycogen stores and PH
decrease enzymatic activity
chromatin clumping
decrease in ATP causes a failure of K+/P+ pump influx of Na+, Ca2+ ions and cell and organelle swelling.
detachment of ribosomes from RER - reduced protein syntheiss and lipid deposition can occur

Excessive ATP depletion

severe disruption of cell membranes fragmentation
influx Ca2+
lysosome rupture and enzyme release
severe changes to the nucleus (pyknosis, karyorrhexis, karyolysis).

This eventually leads to cell death 2-24 hrs post injury - may still be reversible within the first 60 mins.

Question 5

Q

Describe the mechanism of Membrane damage in cellular injury ?

Answer

A

Membrane damage

the selective permeability barrier
cellular function due to loss of the structural base for enzymes/receptors
both the plasma membranes and organelle membranes can be damaged
cell injury membrane damage is similar to changes already described for ATP depletion

results in swelling if sevre proceeds to death

Question 6

Q

Describe free radicals and the three mechanisms by which they cause cellular damage ?

Answer

A

Free radicals

Common cause of membrane damage, highly reactive oxygen species cause lipid peroxidation

Free radicals have unpaired electrons and are oxidising agents

Mechanism

lipid peroxidation = of cell membranes (poluunsaturated fats) creates a chain reaction of free radical generation causing extensive membrane damage
DNA damage single strand breaks
Protein damage oxidation of amino acids

Oxidative stress = imbalance between free radical production and free radical scavenging.

Question 7

Q

What are the three main causes of membrane damage ?

Answer

A

Three main causes of membrane damage

Free radicals

common
highly reactive oxygen species cause lipid peroxidation
unpaired electrons highly unstable may injure cells

Direct damage

chemicals, bacterial toxins, viruses and immunological injury

Hypoxia

ATP depletion (impaired energy supply)
causes altered membrane permeability (Na+/K+ pump)

Question 8

Q

What are free radicals and describe three ways in which they cause cell damage ?

Answer

A

Free radicals

what

highly reactive oxygen species with unpaired electrons
O2-, H2O2, HO
continuously produced by biological systems
scavenging mechanisms - antioxidants
oxidative stress is caused by an imbalance between free radicals and antioxidants

Damage to cells

lipid peroxidation = oxidation of polyunsaturated fatty acids creating a chain reaction of free radical generation causing extensive cell membrane damage
DNA damage = cause single strand breaks
Protein damage = oxidation of amino acids

Question 9

Q

Identify the two types of reversible cell injury ?

Answer

A

There are two types of reversible cell injury

Hydropic degeneration
Fatty acid change

Question 10

Q

Describe hydropic degeneration ?

Answer

A

Hydropic degeneration

reversable cell injury
acute cell swelling due to fluid influx
injured cells are incapable of maintaining ion and fluid homeostasis
vacuolar degeneration
Hist cells at the interface of the normal and necrotic areas become pale, swollen and finely vacuolated

Question 11

Q

Describe fatty acid change ?

Answer

A

Fatty acid change

reversable cell injury
cell swelling due to lipid accumulation
occurs with hypoxic or toxic cell injury
frequently a more chronic change than hydropic degeneration

Seen most commonly in the liver - organ central to lipid metabolism (hepatic steatosis)

Question 12

Q

What is the role of calcium in irreversible cell injury ?

Answer

A

Calcium and irreversible cell injury

Calcium activates varous enzymes, proteases, ATPases and phospholipases resulting in

membrane damage
damage to cytoskelton
degradation of chromatin
degradation of proteins
decrease in ATP

Question 13

Q

At what point dose cell injury become irreversible ?

Answer

A

Irreversible cell injury is associated with a dritical change

severe damage to mitochondria no ATP production
severe damage to cell membranes
leakage of cellular contents
swelling and rapture of lysosomes
large amorphous bodies in mitochondria
influx of calcium into the cell
profound nuclear changes
all eventually leading to cell death

Question 14

Q

Identify a number of agents which may accumulate inside of cells ?

Question 15

Q

Identify the four mechanisms by which agents may accumlate within cells ?

Question 16

Q

Describe the four mechanisms in which lipids may accumulate ?

Answer

A

Accumulation of lipid within cells

Accumulation of triglycerides, cholesterol, choleserol esters and phospholipids in cells.

Varaible causes
decreased oxidation or use of FFA
impaired synthesis of apoprotein (not apoprotein is required to to transport lipid)
impaired ability to combine lipids and protein to form lipoprotein (rare)
impaired release (secretion of lipoproteins from the hepatocyte (uncommon)
common in liver, heart and skeltal muscle
hepatic lipidosus, hepatic steatosis

Question 17

Q

How do you recognise an accumulation of lipid within cells during hepatic steatosis ?

Answer

A

Lipid accumulation / hepatic steatosis

Grossly the liver will appear swollen slightly yellow with a greesy texture.

Histologically, the lipid vacuoles become sharply defined and displace the nucleus to one side.

Question 18

Q

What factors could lead to an accumulation of glycogen within cells, and describe the morphology ?

Answer

A

Glycogen

Glycogen is normally stored in the liver and muscle cells

Excess accumulation could result from

diabetes mellitus
excess corticosteroids
in glycogen storage disease, glycogen accumulates as a result of a defective enzyme

Accululation of glycogen appears

grossly the liver appears swollen, pale brown and mottled
Histologically irregular, clear vacuoles within the cytoplasm
PAS stain (periodic acid shift) glycogen stains bright pink +ve

Question 19

Q

How would you identify the accumulation of protein within a cell ?

Answer

A

Protein accumulation

Histologically proteins are eosinophilic
Russel bodies = cytoplasmic globules (retained immunoglobulins) found with a MOTT cell.

Question 20

Q

What is the difference between a exogenous and endogenous product accumulating within cells ?

Answer

A

Exogenous

from outside the body
substances eg minerals, lead

Endogenous

products of abnormal metabolism
eg lysosomal storage disease

Question 21

Q

Identify ?

Answer

A

Infectious agents -

viral inclusion bodies
may be intracellular or intracytoplasmic (or both) eg rabies, canine distemper, parvovirus, herpes etc
exogenous

Question 22

Q

Identify ?

Answer

A

Lead poisoning

Question 23

Q

Where would we see melanin in a Veterinary pathology setting ?

Answer

A

Melanin in pathology

Chronic injury / endocrine skin disease

hyperpigmentation of the skin
extra melanin pigment

Congenital melanosis

no clinical impairment

Neoplasia

melanoma / melanocytoma

Question 24

Q

Identify what is this cellular accumulation

Answer

A

Lipofuscin

observed in neurons, cardiac myocytes (post mitotic cells)
wear and tear pigment
often seen with aging - indicating the age of a cell
endogenous pigment
golden coulour

Question 25

Q

Identify this cellular accumulation ?

Answer

A

Haemosiderin

A intracellular storage complex - found mainly in macrophages

When do we observe Haemosiderin in pathology

when there is increased RBC red blood cell destruction ‘haemolysis’
chronic congestion
iron infections

Grossly = see a brownish tinge (eg lungs, bruised skin)

Histology = golden brown granules (Perl’s Prussian blue)

Question 26

Q

Differentiate between physiological and pathological adaptations of cells ?

Answer

A

Cell adaptations

Physiological adaptation

occur in normal body conditions
usually beneficial
eg pregnancy, building of muscle

Pathological adaptation

changes occur due to a disease condition
usually detrimental for the host
eg injury

Question 27

Q

The cellular response to an altered steady state is limited, how can these cells respond ?

Answer

A

Cell response to an altered steady state is limited

Reversable cell injury

return to normal function (once stress or injury ceases)
extent and duration of injury is not excessive

Adapt

to the changed conditions
can occur after sublethal persistant stress or injury

Irreversable cell injury

leads to cell death
occurs after severe or prolonged injury

The cellular response depends upon the extent, duration and cell type

Question 28

Q

Define stable, labile and permanent cell division ?

Answer

A

Cell division

Permanent

terminally differentiated
non dividing cells eg skeletal muscle, cardiac muscle and neurons

Stable

conditionally dividing cells
liver, kidney, endothelium of blood vessels, fibroblasts

Labile

constantly having to renew / mutiple via stem cells
skin, intestine, urogenital, lining of exocrine glands

Question 29

Q

Define hypertrophy, where is this likely to occur and why ?

Answer

A

Hypertrophy an increase in the size of cells.

size increases by an increase in the number and size of organelles
occurs in most organs and tissues
more common in permanent and stable cells - which undergo litle replication
eg striated and cardiac muscle

Question 30

Q

Define hyperplasia ?

Answer

A

Cellular adaptation

Hyperplasia = an increase in the number of cells

increased mitotic division implied
most common in labile cells that routinely proliferate and readily become hyperplastic
eg epithelium, GIT, glands

Question 31

Q

What stimuli could induce hypertrophy ?

Answer

A

The cellular adaptation of hypertrophy is stimulated by

Hypertrophy can occur in response to several different stimuli

mechanical or demand
pathological eg increased workload
hormonal eg oestrogen and pregnancy
compensatory loss of a paired organ or part of an organ
xenobiotic eg liver cells increase in size after chronic exposure to drugs

Xenobiotic = chemical substances which are foreign to animal life

Question 32

Q

Describe stimuli which would cause a hyperplasia response ?

Answer

A

Traditionally hyperplasia is divided into physiological and pathological responses

Physiological

hormonal eg pregnancy
compensatory

Pathological

excessive hormonal stimulation (endometrial hyperplasia)
chronic irritation

Question 33

Q

Define Atrophy ?

Answer

A

Atrophy

Decrease in size or amount of cells, tissue or an organ

occurs after normal growth has been reached
caused by a decrease in size and or number of cells as a result of gradual and continuous injury

Physiological atrophy also called ‘involution’

eg thymus with age, uterus atrophy post partuition

Question 34

Q

Describe the pathological causes of atrophy ?

Answer

A

The pathological causes of atrophy

Nutrient deficient - starvation, reduced blood supply
reduced workload - reduced skeletal muscle mass
disuse - limb immobilisation following injury
denervation - forelimb muscle atrophy after radial nerve paralysis
pressure - may cause atrophy of adjacent tissues
loss of hormonal stimulation - eg prolonged corticosteroid treatment

Question 35

Q

Define metaplasia ?

Answer

A

Cell adaptation metaplasia

Replacement of one cell type with another

it is not the transformation of individual cells
stem cells differentiate along a different path, and may eventually replace the original cell type
may be reversible in some cases, if the cause is withdrawn
can be preneoplastic - indicating an increased risk of neoplasia

Question 36

Q

Identify the causes of metaplasia ?

Answer

A

The cause of metaplasia

Usually an adaptive change to withstand an adverse environment

eg cigarette smokers, vitamin A deficiency in birds

Question 37

Q

Define hypoplasia ?

Answer

A

Hypoplasia

Not a true cell adaptation - due to abnormal development

Is the failure of an organ to attain its full size eg enamel

Question 38

Q

Define Aplasia ?

Answer

A

Aplasia

Not a cellular adaptation as it is due to abnormal development

Failure of an organ to develop

Question 39

Q

Define dysplasia ?

Answer

A

Dysplasia

Not a true cellular adaptation as it is due to abnormal cellular development

disorderly arrangemnet of cells which can cause abnormal architecture of a tissue/ organ
reflects abnormal cellular organsisation and development

eg hip dysplasia, chondrodysplasia (dwarfism)

Question 40

Q

Identify the four stages of wound healing ?

Question 41

Q

What is the difference between a granuloma, granulomatous and granulation tissue ?

Question 42

Q

Summarise the differences between acute and chronic inflammation ?

Question 43

Q

Describe four different scar types ?

Question 44

Q

Define the term neoplasia and tumor ?

Answer

A

Terms

Neoplasia = a new growth

an abnormal mass, composed of cells originally derived from normal tissues
uncoordinated and excessive growth
unresponsive to normal growth controls
persist after cessation of stimuli

Tumor = original meaning swelling

now associated with neoplasia or cancer
can be benign or malignant

Question 45

Q

Define the terms cancer and oncology ?

Answer

A

Terms

Cancer

common term for malignant tumors
Cancer is a collection of diseases characterised by
uncontrolled growth of cells
leading to an invasion of surrounding tissues and spread (metastasis) to other parts of the body

Oncology

study of tumors or neoplasm

Question 46

Q

What is meant by saying tumors are clonal ?

Answer

A

Tumors are clonal

The entire population of neoplastic cells within an individual tumor arise from a single cell that has acquired a genetic change.

clonal expansion - transformation of a normal neoplastic cell can be caused by

chemical, physical or biological agentsthat directly and irreversable alter the cells genome
characterised by the loss of some or all the cells specialised functions
aquisition of new biological functions

Tumors remain independant on the host for nutrition and blood supply

Question 47

Q

A tumor consist of what two components ?

Answer

A

A tumor consist of two components

proliferating neoplastic cells (paranchyma)
supportive stroma

made of blood vessels and connective tissue
tumor - stromal interactions modulate growth and differentiation

Question 48

Q

What factors determine the namming of a tumor ?

Answer

A

Tumor naming depends upon

whether the tumor is malignant or benign
also reflects the cell type of origin

Benign

end oma

Malignant

mesenchymal end sarcoma
epithelial end in carcinoma

Remember there are always exceptions to the rules

Question 49

Q

Differentiate between malignant and benign tumors ?

Question 50

Q

Provide the name of a benign tumor ?

Question 51

Q

Name a benign proliferation resembling blood vessels ?

Question 52

Q

Name a benign proliferation of adipocytes ?

Question 53

Q

Name a benign tumor of smooth muscle ?

Question 54

Q

Name abenign tumor of glandular epithelium ?

Question 55

Q

Name a host specific benign proliferation of skin : stratified squamous epithelium ?

Answer

A

papilloma

Question 56

Q

Name a benign proliferation of the mucosa stratified squamous epithelium ?

Question 57

Q

How would you name a malignant tumor of the epithelium or the mesenchymal tissue ?

Question 58

Q

How would you name a malignant proliferation of cells in the mesenchyma of the heart ?

Question 59

Q

Name a malignant proliferation of squamous epithelial cells ?

Answer

A

carcinoma (produce keratin)

produce central keratin pearls

Question 60

Q

Describe the mechanism which results in lipid accumulation in fatty change ?

Answer

A

Mechanism of fatty change

Excessive delivery of free fatty acids to the liver (GIT dietary excess)
Decreased oxidation of FFA (mitochondrial injury)
Impaired protein sysnthesis (apoprotein)

More uncommon

impaired ability to combine triglycerides and protein to form apoprotein
impaired release / secretion of lipoproteins from hepatocytes.

Question 61

Q

Identify the two processes responsible for the changes of necrosis ?

Answer

A

Mechanisms of necrosis

1) Denaturation of proteins

due to reduced PH in severely injured and dead cells

2) Enzymatic digestion of cell components

Autolysis self digestion by lysosomal enzymes of dead cells
Heterolysis lysosomal enzymes from immigrant leukocytes

Necrosis initiates an inflammatory response in adjacent tissues

Question 62

Q

Define postmortem autolysis ?

Answer

A

Postmortem autolysis

Cells that die along with the rest of the animal (somatic death)

Question 63

Q

Describe the histological changes observed in necrosis ?

Answer

A

Histology of necrosis

Cell nucleus

Pyknosis
Karyorrhexis
Karyolysis

Cell cytoplasm

increase eosinophilia (increased binding of eosin to denatured proteins)
Pale ghost like appearance (enzymatic digestion of cytoplasmic proteins)

Question 64

Q

Define pyknosis, karyorrhexis and karyolysis in necrotic cell change ?

Answer 49

A

Coagulative necrosis

Denaturation of proteins is the prominent process - therefore enzymes are unable to digest cellular components

Cell outline and archetecture intact.

Cytoplasm is uniformly eosinophilic (pink), nucleus may be pyknotic, karyorrhectic, karyolytic or absent.

often seen in hypoxic injury
often seen in kidney, liver and muscle (not brain)

Answer 50

A

Morphology of necrosis

requires 24-48 hrs to appear grossly
pale, soft
friable = (easily crumbled)
shrply demarcated from viable tissue by a zone of inflammation (histologically)

Necrotic tissue varies widely in appearance both grossly and histologically

Answer 51

A

Liquifactive necrosis

Cells are lysed and necrotic tissue is converted to a fluid phase.

final stages of brain parenchyma (large amounts of lipid and lytic enzymes)
pyogenic pus forming bacterial infections outside the CNS
centre of absesses or other collections of neutrophils

Answer 52

A

Caseous necrosis

Dead cells form friable, granular white/yellow mass : alike cottage cheese

often involve poorly degradable bacterial components
dystrophic calcification (central lesion)
cell outline is lost (architecture disrupted)
necrotic debris mostly composed of nuclear and cytoplasmic remnants of dead leukocytes
surrounded by granulomatous inflammation (macrophages)
fibrous connective tissue capsule

Answer 53

A

Gangrenous necrosis

Initial lesionis coagulation necrosis

Moist gangrene = contaminated saprophylytic bacteria putrefaction

Gas gangrene = tissue becomes infected with anearobic bacteria (Clostridium sp)

Dry gangrene = necrotic tissue dries out and becomes mummified extremeties eg frost bite, ergot, fescue toxin

Answer 54

A

Fat necrosis

Enzymatic necrosis of fat

activated pancreatic enzymes released during pancreatis or damage to pancreatic duct
destruction of surrounding tissue by lipases from pancrease
often get dystrophic calcification
traumatic when fat is crushed (pelvic canal in heifers)
idiopathic necrosis (unknown cause)

Answer 55

A

Dystrophic calcification

calcium salts depositied in tissue

deposition occurs locally in damaged, dying or dead tissue
occurs despite normal serum calcium levels
eg heart, skeletal muscle
significance it indicates previous injury
grossly looks white and has a gritty feel when incised

Basophilic blue fine granule dumps

Answer 56

A

Metastatic calcification

calcium salts deposited in tissue

deposition in otherwise normal tissue

secondary to hypercalcaemia
eg renal failure - calcium deposition
gastric mucosa, kidney, alveolar

Answer 57

A

Histological differences benign and malignant neoplasm

Differentiation

Rate of growth

Local invasion

Metastasis

Answer 58

A

Differentiation

the extant to which neoplastic cells resemble corresponding cells morphologically and functionally
poorly differentiated cells are a hallmark of malignancy
Anaplasia = lack of differentiation
cells display pleomorphism (marked different size and shape of cells)
large cell, irregular size and shape, hyperchromatic dark nuclei, multinucleated, disorganised

Answer 59

A

Growth rate differentiation

Benign

grow slowly
progressive growth
rare mitotic figures

Malignant

grow rapidly - often outgrow blood supply leading to necrosis
erratic growth (may appear slow)
OFTEN NUMEROUS MITOTIC FIGURES (in the process of division)

Answer 60

A

Local invasion for differentiation

Benign

remain localised to site of origin (discrete lesion)
well demarcated
cohesive, expansile growth
fibrous capsule

Malignant

progressive infiltration invasion and destruction of surrounding tissue
do not recognise anatomical boundaries
typically unencapsulated

Invasiveness is a reliable indicator of malignancy

Answer 61

A

Metastasis

Metastasis is the single most reliable hallmark of malignancy

M = when colonies of tumor cells take up residence at a distant site from the parent tumor - the neoplasm has migrated to another location

Answer 62

A

Pathways of metastasis

Direct seeding - transcoelomic spread in the body cavities / surfaces
Lymphatics - most carcinomas spread via the lymphatic system
Blood vessels - typical spread of sarcomas and also seen in carcinomas liver and lungs

For metastasis to occur the neoplasm must have the correct gene combination .

Answer 63

A

The mechanisms of invasion in metastasis

Detach - from main tumor mass - reduce cell to cell adhesion
Adhere and penetrate basement membrane
Invade extracellular matrix - adhere, migrate, degrade and remodel
Invade blood vessels lymph nodes (intravasation)
evade immune system cells - often form small tumor emboli with platelets
excit from vessel (extravasation)
colonise new site
stimulate new blood vessel growth angiogenesis ( to grow and thrive)

Answer 64

A

Tumour stromal interactions

Successful tumours can co-opt and adapt the environment to their own inferiors means
tumour cell and stroma interact in a variety of ways (wide range of signalling molecules; growth factors, cytokines, hormones and inflammatory mediators
modulate growth rate, differentiation state and behaviour of tumour cells (invasiveness, metastatic capability)

Scirrhous response (PDGF platelet derived factor)

some tumour cells release PDGF which stimulates proliferation of fibroblast, and increased production of collagen
often seen in epithelial cell tumours

Cytokine production

Some tumour cells induce stromal cells to produce cytokines which promote tumour proliferation or motility

Answer 65

A

The immune response to neoplasms

Neoplastic cells have antigen on their cell surface. These antigens are able to stimulate a immune response, and in some cases this response may lead to regression of the tumour.

However many cells evade the body’s immunosurveillance

antigen loss of tumour cell
class one MHC deficient tumour cell
immunosuppressive cytokines

Answer 66

A

Chemical response preformed vasoactive amines

Histamine

mast cells, basophils and platelets
increase muscous production and bronchial constriction
vasodilation and vascular permeability

Serotonins

platelets of mammals
important neurotransmitter
vasodilation and vascular permeability

Answer 67

A

Newly synthesised eicosenoids - chemical response in inflammation

Arachnidonic acid and metabolitesderived from cell membrane lipids - mediate many aspects of acute inflammation

Prostaglandins

endothelial cells, mast cells = vasodilation
fever, pain and increase in vascular permeability
act upon hypothalamus

Leukotrienes

vasoconstriction and increase vascular permeability
LTB4 potent chemotactic agent for leukocytes
however, an incrase in conc leads to vasodilation

Answer 68

A

Compliment cascade

Inflammation activates circulating complement proteins

synthesised by liver up of 25 complement proteins
activated by microbes, antibodies, endotoxins and venom

Function

form membrane attack complexes - perforate membranes of pathogens
when complement proteins become activated they become activated proteolytic enzymes
promote chemotaxis and opsonisation
enhance histamine release from mast cells
these in turn activate other compliment proteins resulting in powerful enzymatic amplification
the critical step is activation C3 (most abundant compliment protein)

Answer 69

A

Activation of the compliment cascade

Classical pathway

binding of CL to AB-Ag complexes

alternative pathway

binding of endotoxin or LPS

Lectin pathway

plasma manose binding lectin binds to CHOS on microbes activation CL

Answer 70

A

The kinin system

Activated by hageman factor 12

activated by secondary exposure of collagen or basement membrane, when endothelium is damaged

Bradykinin

vasoactive amine
vasodilation and increase in vascular permeability (endothelial cell contraction)
increases sensitivity to pain
Kallikreins - kininogens - bradykinin

Plays a role in blood pressure and inflammation via the production of bradykinin

Answer 71

A

Acute inflammation is a vasocentric process

characterised by marked vascular changes vasodilation, increased permeability and fluid exudation
exudation of fluid, plasma proteins
emigration of leukocytes

What is responsible for this marked vascular response

mast cell degranulation (BK, PGs and FR) causing vasodilation which in turn increases blood flow.

Answer 72

A

Genes of oncogenesis

Proto oncogenes

help regulate cell growth and differentiation
when modified in a way initiates or promotes neoplasia are then called oncogenes (promotors of autonomous cell growth RAS)

Tumour suppressor genes p53 (transcription up regulation)

the gene initiates cell cycle arrest at checkpoints
allows for time to repair DNA damage
many tumours have a mutation in p53, preventing cell arrest

Genes coding for DNA repair

tumours can regain the ability to replicate telomeres - immortality

Genes which code for DNA repair proteins

cells accumulate potentially mutagenic DNA damage

The development of neoplastic behaviour in a cell is complex, multi step process “stepwise development neoplasia”

Answer 73

A

The three steps of neoplasia development

Initiation

cell is primed by a non lethal, irreversible genetic change
appears morphologically normal
may remain quiescent for years

Promotion (high risk)

initiated cell expands to form a preneoplastic lesion or benign tumour
in response to stimuli called promoting agents
stimulate proliferation of mutated cells eg. hormones or drugs
not mutagenic effects are reversable

Progression

with further epigenetic or genetic alterations a malignant tumour arises from a sub clone
represents an irreversible change in the nature of the tumour
complex and poorly understood process

Answer 74

A

Angiogenesis

Continued growth of solid tumour cells absolutely depends on adequate blood supply

provides oxygen and nutrients to growing tumours
tumours induce angiogenesis via growth factors and other signalling molecules released from ECM - VEGF and FGF
blood vessels in tumours are tortuous, irregularly shaped, disorganised, leaky and unstable

Answer 75

A

Immune response to neoplasms

Neoplastic cell have antigens on the cell surface (proteins, glycoproteins, glycolipids)

These antigen elicit an immune response
the inflammation response dose not in general protect against neoplasia
macrophages, NK cells and cytotoxic T cells

Evasion of the immune response

antigen loss variant of tumour cell
class one MHC deficient tumour cell
immunosuppressive cytokines

Answer 76

A

Direct effects of neoplasia

A direct effect is when a tumour directly compromises the function of organs in which they arise

replace normal tissue of organs
cause pressure atrophy of adjacent tissue
compress adjacent blood vessels to cause ischaemia (blood restriction) and tissue necrosis
erosion of blood vessels can cause extensive haemorrhage
may rupture hollow organs such as the stomach, intestine or urinary bladder

Answer 77

A

Indirect effects of a neoplasm

Indirect and often remote effects caused by tumour cell products - known as paraneoplastic syndrome (occur in >70% of human patients)

cachexia
endocrinopathies
skeletal syndromes
vascular and haematologic syndromes
neurological syndromes
cutaneous syndromes

Answer 78

A

Cachexi

Many animals with cancer show notible weight loss and debility

loss of both muscle and fat
Aetiological complex - extra calories do not reverse the catabolic state
anorexia impaired digestion
nutritional demands of neoplastic tissues / nutrient loss of neoplasm
metabolic and endocrine derangements
humoral factor = TNF - alpha, interleukins IL-1 IL-6 and prostaglandins

Answer 79

A

Endocrinopathies

Due to an overproduction of hormones

hyperthyroidism due to thyroid neoplasia
Cushing’s disease (hyper-adrenocortism) due to pituitary or adrenal neoplasm

There are also a variety of non-endocrine neoplasms which produce hormonally active substances (ectopic hormone production)

hypercalcaemia or hypoglycaemia are frequently observed due to neoplasm
A wide variety of carcinomas/sarcomas result in the production of parathyroid hormone. Parathyroid hormone PTH removes calcium from bones, increases intestinal and kidney absorption causing hypercalcemia
Hypoglycaemia (low blood sugar) is seen with insulinomas - a functional neoplasm of the islet of Langerhans beta cells = results in incoordination, lethargy, weakness and seizures.

Answer 80

A

Hypertrophic osteopathy

Observed in cats and dogs

extensive periosteal new bone growth
occurs with a variety of neoplasms but frequently associated with neoplastic and non neoplastic space occupying thoracic lesions
the cause is not known - but presumed to be overproduction of growth hormone