Local Hormones: Inflammation And Anti-inflammatory Agents

Question 1

What is inflammation?

Answer 1

Inflammation is the body’s defence response to invasion.

Question 2

What is invasion in terms of defender and inflammation?

Answer 2

Invasion refers to pathogens that are disease causing and allergens which doesn’t necessarily cause a disease.

Question 3

What are the 5 signs of inflammation?

Answer 3

1. calor which means warmth which indicates a increase in blood flow.
2. Rubor which means redness which is another indicator of increases blood flow.
3. Dolor which means pin, this is due to the activation of sensory nerves.
4. Tumor means swelling which is caused by post capillary permeability.
5. Function laws means loss off nction and this could be also due to pain/injury.

Question 4

Which system caused inflammation?

Answer 4

Both innate and adaptive immune systems.

Question 5

What is chronic inflammation?

Answer 5

Chronic inflammation occurs over a long time, so long that it causes tissue damage.

Question 6

What is the time scale of inflammation?

Answer 6

When inflammation starts mediators get released with micro vascular changes taking place. Mediator release last until the end where as micro vascular 24hours after it starts, which is also shorter after cell accumulation and systematic effects starts. Cell accumulation and and system effects end right before the end. Repair and healing occur in the last two days.

Question 7

What is micro vascular changes?

Answer 7

Increased blood flow.

Question 8

What are the systemic effects of inflammation?

Answer 8

Fever, increased leukocyte a and vascular changes:

Question 9

What are the beneficial effects of inflammation?

Answer 9

Entry of antibodies, fibrin formation and stimulation of immune response.

Question 10

During inflammation increased vascular permeability allows antibody to enter the extravascular space, what does it do?

Answer 10

These antibodies either lead to lysis of microorganism through participation of complement or to phagocytosis by opsonisation.

Question 11

What are the effects of fibrin formation?

Answer 11

Fibrin formation from exuded fibrinogen from the blood may impede the movement of microorganisms, trapping them. This also assists it for phagocytosis.

Question 12

How does fluid drainage lean to induction of immune response?

Answer 12

Fluid drainage from the site of inflammation exudate into the lymphatic duct allows particles and soluble antigens to reach the local lymph nodes where immune response is induced.

Question 13

What are harmful effects of inflammation?

Answer 13

Tissue damage, swelling and inappropriate inflammation/immune response

Question 14

How does inflammation cause tissue damage?

Answer 14

Collage base, elastase and other protease can degrade normal tissue result in tissue damage.

Question 15

What are the local hormones of inflammation?

Answer 15

They are autocoids, it is released for local actions and inactivated afterwards to minimise systemic effects

Question 16

What is histamine synthesised by and from what?

Answer 16

Synthesised from histamine amino acid by histamine decarboxylase.

Question 17

What are the local hormones of inflammation?

Answer 17

They are autocoids, it is released for local actions and inactivated afterwards to minimise systemic effects

Question 18

What is histamine synthesised by and from what?

Answer 18

Synthesised from histamine amino acid by histamine decarboxylase.

Question 19

What is histamine metabolised by?

Answer 19

INMT - Imidsole-n-methyltransferase and diamine oxidase.

Question 20

What is histamine synthesised and released from?

Answer 20

1. Mast cells, mast cells express receptors for IGE, C3a and c5a on cell surface in connective tissues.
2. Basophils in blood.
3. Neurones in brain
4. Histaminergic cells in gut

Question 21

whitch events trigger histamine release?

Answer 21

Histamine is released by allergic reactions via igE

Production of complement agents c3a, c5a

Insect stings

Trauma

These are all done via a rise of calcium ions

Question 22

What inhibits histamine release?

Answer 22

Stimulation of beta - adenoreceptors

Question 23

There are four types of histamine receptors, where and they and what do they do?

Answer 23

H1 is found in smooth muscles, endothelium and the CNS. It is a Gq receptor with pip2 production and generation of DAG/IP3.

H2 is found in parietal cells to increase gastric secretions, it is also found in the heart. It acts via cAMP using Gs protein and stimulate PKA

H3 is found in neuronal pre synaptic terminals and it cause a decrease in cAMP using Gi.

H4 is found in basophils, bone marrow and gut, it also acts via Gi to decrease cAMP levels

Question 24

What happens when you stimulate H1 receptors?

Answer 24

In cause dilation if arteries to decrease total peripheral resistance, it also increase permeability to post capillary venules which decrease blood volume.

In non-vascular smooth muscles it causes contraction such as in the airway and the gut.

H1 receptor causes Algeria, so it cause stimulation of sensory nerves which lead to pin, itching and sneezing.

Question 25

What are the effects of H2 receptor?

Answer 25

H2 receptor can be found on the heart to increase in heart rate in the event of low blood pressure due to H1 activation.

H2 receptor also increase gastric acid secretions

Question 26

What are the most important clinical roles of histamine?

Answer 26

Acute inflammation (H1) and gastric secretion (H2)

Question 27

Acute inflammation causes the triple response, what is it?

Answer 27

The triple response is flare, flush and wheel

Question 28

What does the antidromic impulses do?

Answer 28

Antidromic impulse release neuropeptides which cause vasodilation that is distant from the site of irritation - the flare response

Question 29

What is the orthodontic response

Answer 29

This is when histamine stimulate afferent fibres, it stimulate nerve impulse towards the spinal cord and the dorsal root ganglion and then pass antidromically down the other branches of sensory nerves.

Question 30

What is the role of C-fibre in inflammation?

Answer 30

C-fibre is involved in a axon reflex, wth it pain stimuli not only lead to sensitisation of pain but it also induce the release of substance P locally

Question 31

What is the role of substance P?

Answer 31

Substance P increase inflammation by causing histamine release and dilation of vessels.

It is also involved in the flare response.this is due to oedema from capillaries, it induce and increase in vascular permeability the other the help of histamine which cause fluid to become leaky as well as plasma proteins from capillaries.

Question 32

What are the 3 generation of H1 antagonists? What do they do?

Answer 32

1st gen, mepyramine, diphenhydramine and promethazine.

2nd and third gen - terfenadine and fexofenadine.

Terfenadine is a pro drug with potential cardiac arrhythmia action in high concentrations, these are increased with grape fruit juice, fexofenadine is a non toxic metabolite of terfenadine.

Question 33

Side effect of H1 antagonists?

Answer 33

Minor inflammatory reactions from things like insect bites, but it produce no significant result in asthma.

First generation are sedative and cause drowsiness. They can also have anti muscarinic actions e.g. Atropine like effects of blurred vision and constipation.

Question 34

What are H2 antagonists

Answer 34

They are cimetidine and ranitidine.
They reduce gastric acid secretion for treatment of duodenal and gastric ulcers and Zollinger-Ellison syndrome.

It increase INMT activity so there are more rapid breakdown of histamine.

It can also aide mental confusion and dizziness, tiredness and diarrhoea

Question 35

What causes the generation of bradykinin?

Answer 35

The activation of:

 - hageman factor and the production of plasma kallikrein 
 - production of lysylbradykinin by tissue kallikrein
 - action of cellular protease in kin in formation.

Question 36

What is the pharmacological effect of bradykinin?

Answer 36

It cause pain, increase vascular permeability and vasodilation. T is a potent vasoactive peptide as it cause contraction in smooth muscle such as the gut and bronchus and is chemotactic to leukocyte a to defend the body against infections.

It can be metabolised via kinases such as ACE, amino peptides P and carboxypeptidase.

Question 37

What are the effects of kinins?

Answer 37

Blood coagulation, regulation of BP and blood flow via RAAS, cellular proliferation and growth, angiogenesis, apoptosis, inflammation, production of NO, mobilisation of AA by endothelial cells and vasodilation and vascular permeability.

Question 38

Where do we get 5-HT from?

Answer 38

Platelets release it and endothelial cells of gastrointestinal tract secret it. It mediate gut movements.

The brain also release it which is useful for cognition, aggression, mating, feeding, sleep, pain, vomiting and regulation of behaviour.

Question 39

What are the inflammatory action of 6-HT

Answer 39

Serotonin stimulate mast cell adhesion and migration, it enhances the inflammatory reaction of skin, lung and gut. Serotonin promotes inflammation by increasing the number of mast cells at the site of tissue injury.

Serotonin and synergies in with TXA2 to stimulate platelet activity and vasoconstriction.