Ella Kulman ICS

define inflammation

a local physiological response to tissue injury

what is an advantage of inflammation?

inflammation can destroy invading microorganisms and can prevent spread of infection

what is a disadvantage of inflammation?

can produce disease and lead to distorted tissues with permanently altered function

4 outcomes of inflammation

1. resolution
2. suppuration
3. organisation (scar tissue formation)
4. progression onto chronic inflammation

give 6 causes of acute inflammation

1. microbial infections (bacteria/viruses)
2. chemicals
3. physical agents (trauma/burns/frostbite)
4. hypersensitivity reactions (TB)
5. bacterial toxins
6. tissue necrosis

what does viral infection result in?

cell death due to intracellular multiplication

what does bacterial infection result in?

release of exotoxins (involved in the initiation of inflammation) or endotoxins

5 cardinal signs of inflammation

1. redness (rubor)
2. swelling (tumor)
3. pain (dolor)
4. heat (calor)
5. loss of function

how can acute inflammation be diagnosed histologically?

by looking for the presence of neutrophil polymorphs

give 3 endogenous chemical mediators of acute inflammation

1. bradykinin
2. histamine
3. nitric oxide

what are 4 systemic effects of acute inflammation?

1. fever
2. feeling unwell
3. weight loss
4. reactive hyperplasia of the reticuloendothelial system

what cells are involved in chronic inflamation?

macrophages and plasma cells (B and T lymphocytes)

what cell can form when several macrophages try to ingest the same particle?

multinucleate giant cell

give 4 causes of chronic inflammation

1. primary chronic inflammation
2. transplant rejection
3. recurrent acute inflammation
4. progression from acute inflammation

give examples of primary chronic inflammation

1. infective substances having resistance to phagocytosis (eg TB/leprosy)
2. endogenous materials (eg uric acid crystals)
3. exogenous materials (eg asbestos)
4. autoimmune diseases (eg chronic gastritis, RA etc)
5. other chronic inflammatory diseases (eg chronic inflammatory bowel disease)

in which type of inflammation would you see neutrophil polymorphs?

acute inflammation

what are some macroscopic features of chronic inflammation

1. chronic ulcer
2. chronic abscess cavity
3. granulomatous
4. fibrosis

what is granulation tissue?

composed of small blood vessels in a connective matrix with myofibroblasts (important in healing and repair)

define granuloma

an aggregate of epithelioid histocytes

give an example of a granulomatous disease

TB, leprosy, crohn's disease and sarcoidosis

the activity of what enzyme in the blood can act as a marker for granulomatous disease

angiotensin converting enzyme

what is the difference between resolution and repair?

resolution is when the initiating factor is removed and the tissue is able to regenerate, in repair the initiating factor is still present and the tissue is unable to regenerate

5 types of cells capable of regeneration

1. hepatocytes
2. osteocytes
3. pneumocytes
4. blood cells
5. gut and skin epithelial

name 2 cells incapable of regeneration

1. myocardial cells
2. neuronal cells

define an abcess

acute inflammation with a fibrotic wall

define thrombosis

formation of a solid mass from blood constituents in an intact vessel in the living

give 2 reasons why thrombosis formation is uncommon

1. laminar flow
2. non sticky endothelial cells

what are the 3 factors that can lead to thrombosis formation?

1. change in vessel wall
2. change in blood constituents
3. change in blood flow

define embolus

a mass of material (often a thrombus) in the vascular system that is able to become lodged in a vessel and block it

define ischaemia

decreased blood flow

define infarction

decreased flow with subsequent cell death

why are tissues with an end arterial supply more susceptible to infarction?

they only have a single arterial supply and so if this is interrupted then infarction is more likely

give 3 examples of organs with a dual arterial supply

1. lungs (bronchial arteries and pulmonary veins)
2. liver (hepatic arteries and portal veins)
3. some areas of the brain around the circle of willis

what complication can occur if ischaemia is rectified?

re-perfusion injury can occur due to the release of waste products

what are the consequences of an arterial embolus?

it can go anywhere - so could be stroke, MI, gangrene etc

what are the consequences of a venous embolus?

it will reach the vena cava then the pulmonary arteries and become lodged in the lungs, causing a pulmonary embolism (decreased lung perfusion)

through which blood system does an embolus have to travel to result in a pulmonary embolism?

venous system

what common drug can be used to prevent thrombosis?

aspirin

define atherosclerosis

inflammatory process characterised by hardened plaques in the intima of a vessel wall

is atherosclerosis more common in the systemic or pulmonary circulation?

systemic because its higher pressure (endothelial damage theory)

what are the 3 main components of an atheromatous plaque?

1. lipids
2. fibrous tissue
3. lymphocytes

give 5 risk factors for atherosclerosis

1. smoking
2. hypertension
3. hyperlipidaemia
4. uncontrolled diabetes mellitus
5. lower socioeconomic status

what can be done to prevent atherosclerosis?

reduce risk factors and take low dose aspirin regularly

what theory is considered the primary cause of atherosclerosis?

endothelial cell damage

why can cigarette smoking lead to atherosclerosis?

releases free radicals, nicotine and CO into the body which all damage endothelial cells

why can hypertension lead to atherosclerosis?

high BP = greater force exerted on the endothelial cells which can lead to damage

define apoptosis

programmed cell death of a single cell

what is the role of p53 protein?

it looks for DNA damage, if damage is present p53 switches on apoptosis

what protein can switch on apoptosis if DNA damage is present?

p53 protein

give an example of a disease where there is a lack of apoptosis and why

cancer - mutations in p53 mean cell damage isn't detected

give an example of a disease where there is too much apoptosis

HIV

define necrosis

unprogrammed death of a large number of cells due to an adverse event

give 3 examples of events that can lead to necrosis

1. frost bite
2. avascular necrosis
3. infarction

define hypertrophy

increase in size of a tissue due to an increase in the size of its constituent cells

define hyperplasia

increase in the size of a tissue due to an increase in the number of its constituent cells

define atrophy

decrease in tissue size due to either decreased cell size or number of cells

define metaplasia

a change in differentiation of a cell from one fully differentiated type to another (eg fibrous tissue to bone or mucosal epithelia changing)

give an example of a disease that demonstrates metaplasia

barrett's oesophagus - the cells at the lower end change from stratified squamus to columnar

define dysplasia

morphological changes seen in cells in the progression to becoming cancer (cells become more 'jumbled up')

why can excision be a cure for basal cell carcinoma?

because BCC doesn't metastasise

what is the standard treatment for leukaemia and why?

chemo - leukaemia is systemic so can't be excised

give an example of 5 carcinomas that can spread to bone

1. breast
2. kidney
3. lung
4. prostate
5. thyroid

give an example of a carcinoma that can spread to the axillary lymph nodes

breast carcinomas

why is adjuvant therapy (used after primary treatment like surgery to prevent reoccurence) often used to treat carcinomas?

micrometastes are possible even if a tumour is excised and so adjuvant therapy is given to suppress secondary tumour formation

for what kind of carcinomas would targeted chemo be most effective against?

slower dividing tumours, like lung/colon/breast

what kind of drugs can be used in targeted chemo?

monoclonal antibodies (MAB) and small molecular inhibitors (SMI)

what 3 mechanisms do tumour cells use to evade host immune defence in the blood?

1. platelet aggregation
2. adhesion to other tumour cells
3. they shed surface antigens so as to 'distract' lymphocytes

give an example of a malignant tumour that often spreads to the lung

sarcoma (via vena cava → heart → pulmonary arteries)

give an example of carcinomas that can spread to the liver

colon, stomach, pancreatic via the portal vein

what causes the pain associated with acute inflammation?

1. stretching and distortion of tissues due to oedema and pus under high pressure in an abscess cavity
2. chemical mediators (eg bradykinin and prostaglandins) are also known to induce pain

what is the main source of histamine?

mast cells - histamine is stored in granules in their cytoplasm

what is the role of tissue macrophages in acute inflammation?

they secrete chemical mediators that attract neutrophil polymorphs

what is the role of the lymphatic system in acute inflammation?

lymphatic channels dilute and drain away oedematous fluid, therefore reducing swelling. antigens are also carried to lymph nodes for recognition by lymphocytes

what is the major role of neutrophil polymorphs in acute inflammation?

phagocytosis

define carcinogenesis

a multistep process in which normal cells become neoplastic cells due to mutations

what percentage of cancer risk is environmental/genetic?

85% environmental
15% genetic

5 host factors that can affect cancer risk

1. race
2. diet
3. constitutional factors (gender/age)
4. premalignant conditions
5. transplacental exposure

what causes skin cancer?

Exposure to UV light

what occupation makes people more susceptible to bladder cancer caused by aromatic amine exposure?

people who work in the rubber/dye industry

define neoplasm

an autonomous, abnormal, persistent new growth

what is a neoplasm composed of?

neoplastic cells and stroma

what is essential for neoplasm growth?

angiogenesis

what does a neoplasm release in order to initiate angiogenesis?

vascular endothelial growth factors

why does necrosis often occur in the centre of a neoplasm?

the neoplasm grows quickly and outgrows its vascular supply

what is the behavioural classifications of neoplasms?

benign, malignant or borderline

what are complications of benign neoplasms?

1. pressure on adjacent structures
2. obstruction to flow
3. transformation into malignant neoplasms
4. anxiety

what are complications of malignant neoplasms?

destroy surrounding tissue, blood loss due to ulceration, pain, anxiety

define carcinoma

malignant epithelial neoplasm - malignant tumour of epithelial tissue

define sarcoma

malignant connective tissue neoplasm

what is an adenoma?

benign tumour of glandular epithelium

what is a papilloma?

a non-glandular benign tumour

what is a leiomyoma?

benign smooth muscle neoplasm

what is a neuroma?

a benign neoplasm of nerves

what is a chondrosarcoma?

malignant neoplasm of cartilage

what is a lipsarcoma?

malignant neoplasm of adipose tissue

what is a melanoma?

malignant neoplasm of melanocytes

what is a lymphoma?

malignant neoplasm of lymphoid cells (immune cells)

what is a mesothelioma?

malignant neoplasm of mesothelial cells

is a carcinoma/sarcoma with a close resemblance to normal tissue classified as well differentiated or poorly differentiated?

well differentiated - these types of neoplasms are low grade and have a better prognosis

describe innate immunity

non-specific, instinctive, present from birth, first line of defence (eg cough reflex, mucus, enzymes and oils in tears)