Features
Features:

Product Tour >

Edraw AI >

Paid Plans:

Individuals >

Business >

Eduaction >
Resources
Blog

History

How-tos & Tips

Discovery

Biography

Business Analysis

Examples

AI concept Map

Free AI Mind Map Generator

Onenote Mind Map

Bcg Matrix Examples

Nike Marketing Strategy

Unilever SWOT Analysis

Make Mind Maps in Google Docs

Guide

FAQs

What's New

Resource Center
Templates
All Templates

Brain Storming Templates

Strategy and Planning Templates

Project Management Templates

Product Management Templates

Human Resources Templates

Agile Workflow Templates

Marketing Templates

Education Templates

Fun and Games Templates

User Gallery
Download
Pricing
Enterprise

MindMap Gallery Medical ischemia reperfusion injury

Medical ischemia reperfusion injury

This is a mind map about ischemia-reperfusion injury, including concepts, influencing factors, causes, cardiac ischemia-reperfusion injury, mechanisms, etc.

Edited at 2023-12-18 17:05:48

PlotWizard

Recent works View more works>>

Medical ischemia reperfusion injury

PlotWizard

Recent works View more works>>

Recommended to you
Outline

Ischemia-reperfusion injury (IRI)

※The mechanism

Increased reactive oxygen species – initiating factors

increase mechanism

Reactive oxygen species (chemically active oxygen-containing substances)

type

Oxygen free radicals (general name for atoms, atomic groups or molecules with unpaired electrons in their outer orbits)

hydrogen peroxide

singlet oxygen

Reactive nitrogen

lipid free radicals

The mechanism of increased reactive oxygen species

Increased formation of xanthine oxidase (XO)

During ischemia, ATP is reduced, calcium pump dysfunction occurs, intracellular Ca²⁺ increases, and Ca²⁺-dependent protease is activated to convert XD (xanthine dehydrogenase) into XO

During hypoxia, ATP production decreases, decomposition increases, and it is metabolized into hypoxanthine.

After reperfusion, a large amount of O₂ is provided. The large amount of hypoxanthine accumulated during ischemia generates xanthine under the action of XO and releases superoxide anions. Under the action of XO, xanthine continues to be converted into uric acid and also releases oxygen free radicals.

Respiratory burst of neutrophils (PMNs)

Under normal circumstances, neutrophils consume increased oxygen during phagocytosis and produce oxygen free radicals through the NADPH/NADH oxidase system to kill pathogenic microorganisms.

During ischemia and hypoxia, more white blood cells chemotactically infiltrate into the ischemic tissue. During reperfusion, a large amount of O₂ is supplied and oxidized into more oxygen free radicals through the NADPH/NADH oxidase system (respiratory burst is aggravated).

Increased mitochondrial single electron reduction

mechanism

During ischemia and hypoxia, ATP production decreases and the sodium pump becomes imbalanced, causing the intracellular sodium ion concentration to increase. Then Na-Ca exchange increases calcium ions, causing the cytochrome C oxidase system to become dysfunctional.

During reperfusion, oxygen molecules are reduced by single electrons to generate oxygen free radicals

Under ischemic and hypoxic conditions, the activity of antioxidant enzymes decreases and the generation of oxygen free radicals increases.

Features

Decreased activities of antioxidant enzymes such as SOD, glutathione catalase, and catalase

Enhanced autooxidation of catecholamines

Excites the sympatho-adrenomedullary system and produces catecholamines

compensatory regulation

After reperfusion, a large amount of O₂ is supplied, and a large amount of oxygen free radicals are generated under the action of monoamine oxidase

Enhanced inducible NOS expression

Endothelial cell nitric oxide synthase (eNOS)

Exists in endothelial cells to catalyze the synthesis of a small amount of NO - a protective factor that maintains vascular function

Inducible nitric oxide synthase (iNOS)

Exists in macrophages, neutrophils, etc. - produces large amounts of NO when stimulated (toxic side effects)

It is activated during reperfusion and its expression is up-regulated.

Decreased reactive oxygen species scavenging ability

Enzymatic antioxidant system, non-enzymatic antioxidant system (low function)

Low molecular scavenger - vitamins A, C, E, GSH

Enzymatic scavengers - SOD, CAT

Reduced reactive oxygen species (ROS) scavenging Increased generation

The damaging effects of free radicals

Enhanced biomembrane lipid peroxidation

Intracellular Ca2 overload

DNA breaks and chromosomal aberrations

Protein deformation and reduced enzyme activity

Induces the production of inflammatory mediators

promote apoptosis

damaging effect

Enhanced membrane lipid peroxidation

Destroy the normal structure of the membrane - the liquidity and fluidity of the membrane are reduced, and the permeability is increased

Damage to cell membrane - inactivation of membrane receptors, allosteric ion channels, changes in enzyme activity

Disruption of lysosomal membrane - lysosomal release

Damage to mitochondrial membrane - ATP production↓

Disruption of sarcoplasmic reticulum – intracellular calcium overload

Indirectly inhibits membrane protein function

Indirectly inhibit calcium pump, sodium pump and Na⁺—Ca²⁺ exchange system → Cytoplasmic Na⁺, Ca²⁺↑ - cell swelling and calcium overload

Inhibits the coupling of receptors, G proteins and effectors to affect signal transduction

Promote the generation of free radicals and other active substances

Protein denaturation and reduced enzyme activity

Enzyme, ion channel, receptor dysfunction

Destroy the active center of enzyme - sulfide group

Destroy the lipid microenvironment necessary for enzyme activity

Cross-linking between proteins forms polymers

Amino acids that attack the active center of enzymes

Can activate some enzymes

intercellular matrix destruction

Degradation of hyaluronic acid and cross-linking of collagen lead to loose matrix and reduced elasticity

Destroy nucleic acids and chromosomes

Base modification, DNA fragmentation, DNA cross-linking

Calcium Overload – Common Pathways

concept

Abnormal increase in intracellular Ca²⁺ content caused by various reasons, leading to cell structure damage and functional and metabolic disorders

The mechanism of increased production (mainly increased inflow rather than decreased outflow)

Abnormal Na⁺-Ca²⁺ exchange (main route of calcium entry into cells during calcium overload)

direct activation

During ischemia and hypoxia, ATP decreases, sodium pump activity decreases, and intracellular sodium concentration increases.

During reperfusion, reactive oxygen species decrease the activity of the sodium pump, and intracellular Na⁺↑ activates the reverse exchange of sodium and calcium, causing the outflow of sodium ions and the influx of calcium ions to overload calcium.

indirect activation

During hypoxia, anaerobic metabolism causes H⁺↑, acidosis

During reperfusion, the blood flow takes away the high concentration of H⁺ in the interstitial fluid, while the intracellular H⁺ concentration is still very high → the transmembrane H⁺ concentration gradient difference↑ activates the H⁺-Na⁺ exchange protein, allowing Na⁺ to be internalized The efflux of H⁺ then secondary activates Na⁺-Ca²⁺ exchange, increasing the calcium concentration and causing calcium overload.

Increased catecholamines (stress)

Acts on α₁ receptors, activates the PLC conduction pathway, and decomposes PIP₂ to generate IP₃ and DG

IP₃ acts on the sarcoplasmic reticulum and promotes Ca²⁺ release

DG activates PKC, promotes H⁺-Na⁺ exchange, and then promotes sodium and calcium exchange, increasing intracellular calcium concentration.

Acts on β receptor→AC→cAMP, activates PKA, promotes phosphorylation of L-type calcium channels, and causes calcium ion inflow

biofilm damage

Increased cell membrane permeability

Increased permeability to calcium ions; generates oxygen free radicals, aggravating damage; increased calcium concentration destroys membrane phospholipids, further increasing permeability to calcium, causing an increase in intracellular calcium concentration

Mitochondria and sarcoplasmic reticulum damage—cytoplasmic calcium ion concentration↑

Mitochondria - Insufficient ATP production and insufficient calcium pump energy supply

Sarcoplasmic reticulum - Inhibition of calcium pump function, decreased ability to take up Ca²⁺

mitochondrial dysfunction

ATP decreases; ROS generation increases; oxidative phosphorylation is inhibited and ATP decrease worsens

Mechanisms causing reperfusion injury

mitochondrial dysfunction

Calcium overload stimulates the mitochondrial calcium pump to take up calcium ions and increase ATP consumption.

Calcium salt deposition affects electron transport and oxidative phosphorylation, reducing ATP production

Mitochondrial permeability transfer pore (MPTP) opening

Rapid decrease in membrane potential and decoupling of electron transport

Oxygen free radicals are generated in large quantities

Cytochrome C release→caspase3→apoptosis

Mitochondrial calcium release →activation of proteases and phospholipases →cell necrosis

Activates multiple calcium-dependent degradative enzymes

Phospholipase → Phospholipid breakdown

Protease → membrane and skeleton, protein destruction

ATP hydrolase→ATP↓, H⁺↑

XO→ROS↑

Endonuclease →chromosome damage

Promote the generation of oxygen free radicals

Damaging effect of white blood cells – key reasons

The mechanism of leukocytosis during ischemia-reperfusion

Increased chemokines - initiating factors

Ischemic tissue cell damage

Phospholipid breakdown

Increased white blood cells secrete inflammatory factors with chemotactic effects

Increased production of cell adhesion molecules—major factor

During ischemia-reperfusion, VEC/neutrophils→adhesion molecules increase

The mechanism by which leukocytes mediate ischemia-reperfusion injury

No reflow phenomenon

Concept: After a period of ischemia, the local tissue resumes blood flow and cannot be recanalized, and the ischemic area cannot be fully perfused.

①Cell swelling

②VEC swelling

③Microvascular permeability↑

④Myocardial cell contracture

⑤Microvascular spasm and blockage

Block microcirculation

Granulocytes aggregate in microvessels, causing capillary blockage and increased perfusion resistance.

Uncontrolled inflammatory response

Releases active oxygen and various particulate components

cardiac ischemia-reperfusion injury

ischemia-reperfusion arrhythmia

Oxygen free radicals and calcium overload cause increased calcium influx, forming early afterdepolarization and delayed afterdepolarization after AP.

Catecholamines stimulate alpha receptors and increase cardiomyocyte autonomy.

Electrolyte imbalance after reperfusion significantly reduces the ventricular fibrillation threshold, shortens the myocardial refractory period, and causes atrial fibrillation or ventricular fibrillation.

Electrolyte imbalance and different degrees of myocardial damage cause heterogeneity in AP duration and cause reentry excitement.

myocardial stunning

After ischemia-reperfusion, it takes a while for myocardial contractility to recover, and a period of "low-function state" occurs, which is reversible myocardial dysfunction.

Microvascular stunning—decreased coronary responsiveness to vasodilatory substances

Ischemia-reperfusion injury prevention and treatment

Eliminate the cause of ischemia and control reperfusion conditions

Antioxidant and free radical scavenger

Protect biofilm and improve energy metabolism of ischemic tissue

Inhibit the production of inflammatory mediators, anti-leukocyte therapy

Reduce intracellular calcium overload and regulate vascular tone

Ischemic preconditioning and postconditioning mobilize the body’s endogenous adaptive protective mechanisms

Carry out endurance exercise to improve tolerance to ischemia-reperfusion injury

Cause of occurrence (reperfusion of tissues and organs on the basis of ischemia)

Systemic: shock microvasospasm is relieved

Tissues and organs: organ transplantation, reattachment of severed limbs

After recanalization of a certain blood vessel

Influencing factors

length of ischemia time

Long or short, IRI is less likely to occur

Different species have different ischemia tolerance times

Different organs tolerate ischemia for different times

state before tissue ischemia

People with abundant or easy to form collateral circulation after ischemia are less likely to develop IRI

Organs with changes in functional status before ischemia are prone to IRI, while those with preconditioning before ischemia are less likely to develop IRI.

The higher the aerobic level, the more likely IRI is to occur

Conditions for reperfusion

IRI is less likely to occur when infusing low temperature, low pressure, low flow rate, low pH, low sodium, and low calcium solutions

※concept

After blood perfusion is restored to ischemic tissues and organs, not only are they unable to restore their normal functions and structures, but they instead aggravate their dysfunction and structural damage.