Histamine & Histaminic receptors

Platelet aggregation REF: Robbin’s pathology 7^th edition page 63

Preformed histamine is present in mast cell granules and is released by mast cell degranulation in response to variety of stimuli. In humans histamine causes:

1. Arteriolar dilatation
2. Increased permeability of venules (however constricts large arteries)
3. Via binding to H1 receptor on endothelial cells

All of the above

Vasodilation is the most important vascular effect of histamine in humans.

It involves both H1 and H2 receptors distributed throughout the resistance vessels in most vascular beds.

Histamine’s effect on small vessels results in efflux of plasma protein and fluid into the extracellular spaces and an increase lymph flow, causing edema.

The gaps between endothelial cells also may permit passage of circulating cells recruited to tissues during the mast cell response.

In the epidermis, it causes itch; in the dermis, it evokes pain, sometimes accompanied by itching.

• A localized red spot within a few seconds and reaches a maximum in 1 minute.               
• A brighter red flush, or “flare,” extending around 1 cm developing more slowly.             
• A wheal that is discernible in 1-2 minutes.

The initial red spot results from the direct vasodilating effect of histamine (H1 receptor–mediated NO production).
The flare is due to histamine-induced stimulation of axon reflexes that cause vasodilation indirectly.
The wheal reflects histamine’s capacity to increase capillary permeability (edema formation).

All of the statements given above are true about histamine.

Ref: Textbook of Medical Physiology By Guyton and Hall, 11th Edition, Pages 285, 450, 480, 797; Ganong’s Review of Medical Physiology, 22nd Edition, Page 107; KDT, 6th Edition, Pages 151-53

C i.e. Histamine

Ans. is ‘a’ i.e., Histamine

o Formation of endothelial gaps in venules, i.e. immediate transient response is the most common mechanism causing increased vascular permeability in acute inflammation.

o Mediators involved in this mechanism are :-

i) Immediate (more important) : Histamine, bradykinin, leukotrienes, neuropeptide substance P. Somewhat delayed : IL-1, TNF, IFN-y

Ans. is ‘a’ i.e., Mast cells

Mast cells and basophils

• Mast cells and basophils are important inflammatory cells.
• They precipitate in both acute & chronic inflammation.
• Basophils circulate in the blood, whereas mast cells reside and mature in tissues.
• They are the most important cells in immediate hypersensitivity and are also the most important source of histamine.
• Other secretions are : Serine proteases, Carboxypeptidases, Glycosidoses, Proteoglycans, Sulfatases.

Ans. is ‘a’ i.e., Histamine

Vasoactive amines

• The two amines are especially important because they are present in preformed stores in cells and are therefore among the first mediators to be released during inflammation. These are ‑

1. Histamine

• It is widely distributed in tissues, the richest source being the mast cells.
• It is also found in basophils and platelets.
• It is the principal mediator of immediate transient phase of increased permeability.
• It causes

1. Increased vascular permeability
2. Vasodilatation
3. Smooth muscle contraction.

2. Serotonine (5-hydroxy tryptamine)

• Serotonin is present in platelets and enterochromaffin cells.
• It is also present in mast cells of rodents, but not humans.

Biological effects of serotonin are same as histamine..

Ans. is ‘d’ i.e., Platelet aggregation

Ans. is ‘c’ i.e., Histamine

Mast cells

o Mast cells are bone marrow derived cells.

o They are found predominantly near blood vessels and nerves and in subepithelial sites, where local immediate hypersensitivity reaction tend to occur.

o Mast cells have cytoplasmic membrane-bound granules that contain a variety of biologically active mediators. o These granules are referred as metachromatic granules.

o Mast cells are central to the development of immediate hypersensitivity.

Ans. B i.e. Anti-allergic

H₁ antagonist is a histamine antagonist of the H₁ receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions.

Ans. is ‘c’ i.e., Histamine

Ans. is ‘b’ i.e., Histamine

Triple response (Lewis triple response)

When a pointed object is stroked very firmly over the skin, a characteristic 3 part response develops. Its feature are :‑

1) Red reaction (red line) is due to transient capillary engorgement (vasodilation) caused by histamine released from damaged tissue. Histamine relaxes precapillary sphincter thus leads to capillary dilatation.

2) Flush or flare is spreading of redness beyond the injury (red line). It is due to arteriolar dilation mediated by axon reflex (may be an indirect effect of histamine).

3) Wheal is local edema and elevation of skin due to increased permeability of capillaries and post capillary venules with consequent extravasation of fluid. Capillary permeability is increased due to histamine and other mediators.

Ans. is ‘a’ i.e., Histamine

Ans:D.)All of the Above.

The condition shown in the image is Angioedema

Angioedema

• It is the swelling of deep dermis, subcutaneous, or submucosal tissue due to vascular leakage.
• Acute episodes often involve the lip, eyes, and face however, angioedema may affect other parts of body, including respiratory and gastrointestinal (GI) mucosa. Laryngeal swelling can be life-threatening.
• Angioedema is a result of the fast onset of an increase in local vascular permeability in subcutaneous or submucosal tissue.
• Histamine and bradykinin are the most recognized vasoactive mediators known to be critical in the pathologic process of angioedema.
• Hereditary angioedema (HAE), angiotensin-converting enzyme (ACE) inhibitor–induced angioedema, and certain idiopathic angioedemas are examples of bradykinin-mediated angioedema.
• C1-INH is a serine protease that is involved in the regulation of bradykinin. Low levels of this protease (either hereditary or acquired) results in unchecked activation of the kallikrein-kinin system, which leads to the overproduction of bradykinin

Ans. b. Histamine release due to local injury to mast cells

• In Lewis Triple Response, redness when skin is scratched with a pointed object is seen due to histamine release due to local injury to mast cells

Lewis Triple Response

• Lewis triple response is a three-part response to blunt injury.
• It consists of the red reaction, wheal and flare.

Lewis Triple Response

Red reaction

• Red reaction appears at the site of injury within 10 seconds°.
• Due to dilation of pre- capillary sphincters by histamine and  polypep aged skiff^,.

Wheal

• Wheal is local edema due to increased    permeability   of the   capillaries with conse- quent extravasation of fluid°
• Occurs due to histamine or histamine-like substances released from local mast cells°.

Flare response

• Flare response is a spread‑ ing redness is due to arte‑ riolar dilatation produced by the axon reflee

Ans. is ‘a’ i.e., Histamine 

• Formation of endothelial gaps in venules, i.e. immediate transient response is the most common mechanism causing increased vascular permeability in acute inflammation.
• Mediators involved in this mechanism are :-
• Immediate (more important) : Histamine, bradykinin, leukotrienes, neuropeptide substance P.
• Somewhat delayed: IL-1, TNF, IFN-y