Collateral circulation

# Collateral circulation

## Overview
Collateral circulation is a network of blood vessels that provide a bypass or alternate conduit of blood flow in tissue. These specialized blood vessels are naturally present in tissue and undergo adaptive growth and development in response to ischemia. The main function of collateral vessels is to provide an alternate pathway for nutrient and oxygen supply in the case of stenosis or obstruction of the main artery.

## Classification
Rentrop devised a grading system to assess the filling of collateral arteries. 
- Grade 0: no visible filling of any collateral channels
- Grade I: collateral filling of branches of the vessel to be dilated without any dye reaching the epicardial segment of that vessel
- Grade 2: partial collateral filling of the epicardial segment of the vessel being dilated
- Grade 3: complete collateral filling of the vessel being dilated.
Collateral circulation can be classified on the basis of size. 
- CC0: no continuous connection between donor and recipient artery.
- CC1: continuous, threadlike connection. The diameters of collaterals are 0.3 mm.
- CC2: continuous, small side branch-like size throughout its course. The estimated diameter of CC2 0.4 mm.

## Pathophysiology
There are four stages in the development of mature collateral blood vessels from collateral microvasculature.
- Phase 1 lasts for approximately two days following stenosis or obstruction of the main artery by an embolus. The stenosis of the main artery results in diversion and increase blood flow through small collateral blood vessels. This increases the circumferential diameter of small collateral vessels and augments sheer stress on its walls. The increased stress on the vessel wall causes activation of the Nf-kb gene.  There is an increased expression of adhesion molecules on endothelial cells which attracts monocytes at the site of the blocked blood vessels. The monocytes from the bone marrow start accumulating at the extracellular site of collateral vessel formation. The main distinguishing features of this phase is an increase in the permeability of the blood vessel and the transformation of smooth muscle and endothelial cells in the proliferative phase.
- In the second phase, there is an infiltration of monocytes followed by the release of various cytokines including matrix metallopeptidases, tumor necrosis factor-alpha, platelet-derived growth factors, and vascular endothelial growth factors. There is controlled digestion of extracellular matrix and internal elastic lamina. The cytokines also promote increased proliferation of vascular smooth muscles and endothelial cells.
- In phase three, there is a maturation of smooth muscle cells in uniform circular layer with increase synthesis of elastin and collagen and formation of the cell to cell contacts. This results in the formation of a large-caliber blood vessel.
- In phase four, there is dissolution and reduction of small collateral vessels in which there is less blood flow. The collateral vessels which have more flow of blood enlarges and forms mature blood vessels while smaller collateral vessels regress due to decreased flow of blood. 

## Blood flow in Collaterals
Collateral blood vessels are communicating vessels that bridge two main arteries. There is bidirectional blood flow in it with the minimal flow in the midpoint of the vessel. This results in low resistance blood flow with reduced incidence for thrombosis. 

## Benefits of Collateral Circulation
Circle of Willis is a primary collateral vessel in the brain. Anterior and posterior communicating artery serves as a connection between the internal carotid and posterior cerebral artery. It provides blood flow if there is obstruction at any site at the circle of Willis. Collateral circulation is a protective adaptive response to restore blood flow in the hypoxic region due to stenosed blood vessels. A slowly developing plaque gives sufficient time for the development and maturation of collateral blood vessels. A study showed an increase in angiographic collaterals from 66% to 75% three to six hours after the onset of symptoms. There was also a reduced incidence of cardiogenic shock in patients with collateral vessels which further proved the protective role of collateral circulation. 

## Drawbacks of Collateral Circulation

### Coronary steal syndrome
In situations of increased blood flow to heart i.e. administration of vasodilators like nitrates or exercise, the resistance to blood flow to collaterals is less compared to the obstructed artery. This results in enhanced blood flow through collateral vessels and further compromises blood flow through the stenosed artery. The supply of oxygen and nutrients to the hypoxic area of the heart is worsened exacerbating angina clinical symptoms. 

### Re-stenosis of the main artery
In a percutaneous intervention at the site of a coronary stent, there is a competition of anterograde blood flow through the main coronary artery and retrograde flow via a stenosed artery. This results in resistance to blood flow, with a slow velocity of blood flow. It causes a cascade of reactions including platelet aggregation, endothelial proliferation, and thrombus formation which results in restenosis of the vessel.