1. Ahmad Shihada Silmi Msc, FIBMS IUG Medical Lab. sciences Dept
Kinin system
Ahmad Shihada Silmi Msc, FIBMS
IUG
Medical Lab. sciences Dept

2. Introduction
All the following physiological processes are activated in a cascade-like manner:
Complement
Kinin generation
Blood coagulation
Fibrinolytic system
They interact with one another and with various cell membrane proteins.

3. The kinin interaction System
Pre-Kallikrein
Kallikrein
Kininogen HMWK, LMWK
Kinin e.g. Bradykinin
F XIIa
F XII
Surface
Fibrinolytic Pathway
Plasminogen
Plasmin
Complement Activation
Clotting Cascade (intrinsic pathway)
Effects
vascular smooth muscle relaxation
Increased permeability of blood vessels  Oedema
Pain
Interaction with clotting cascade
Interaction with fibrinolytic cascade
Interaction with complement cascade

4. Kinin system It's the second important-forming system.
It's product is Bradykinin.
Bradykinin functions:
Increase vascular permeability.
Vasodilatation.
Hypotension.
Pain.
Contraction of smooth muscles.
Activation of arachidonic acid.
Blood pressure homeostasis and renal function.

5. Bradykinin Receptors
B1 & B2 receptors that present on the membrane of many cell types including:
Vessel endothelial cells
Smooth muscle
Nerve cells
Synovial lining cells
Bradykinin interaction with receptor causes the release of a variety of cytokines that alter cellular function.

6. Proteins of the kinin cascade
Hagaman factor.
Factor XI.
Prekallikrein.
High-molecular-weight kininogen.

7. Physiology of kinin system
Factor XI circulate as a complex with HMWK in a molar ratio of 2:1.
Prekallikrein circulate in a complex with HMWK in a molar ratio of 1:1.
Hagaman factor circulates as an uncomplexed single-chain protein.

8. Steps in kinin activation
On interaction with a negatively charged surface such as:
In-vitro: glass (experimently)
In-vivo: lipid A of gram-negative bacterial endotoxin.
hageman is cleaved & activated (αHFa).
αHFa can activate more Hageman factor to produce more αHFa.

10. Steps in kinin activation
αHFa can interact with XI-HMWH and activate XI to factor XIa activate the intrinsic coagulation cascade.
αHFa can also interact with HMWK-prekallikrein complex and activate PK to K.
To facilitate activation of PK and XI, HMWK is bound to the surface near Hageman factor (XII)

11. Steps in kinin activation
Active Kallikrein cleave HMWKto release Bradykinin.
Bradykinin has a short half-life and attacked by carboxypeptidase N enzyme to form des-arg-bradykinin which has few vascular effects.
Des-arg-bradykinin is cleaved by angiotensin-converting enzyme (ACE) to form inactive peptide.

12. Plasma inhibitors of kinin generation
The principal inhibitors are:
C1 inhibitor (major inhibitor for K & XII).
α2 macroglobulin (2nd for K & XII).
α1 proteinase (major inhibitor for Xia).

13. Low molecular -weight Kininogen
Tissue kallikrein can activate LMWK to lysylbradykinin (kallidein) which undergoes the same degredation pathway as does bradykinin.

14. Functions of kinin in disease
Both bradykinin & lysylbradykinin contribute with the following diseases:
Rhinitis
Asthma
Pancreatitis
Synovitis
Hereditary angioedema