Mechanisms of ischemia development
The pathogenesis of ischemia is based on two fundamental processes. The first is a decrease in arterial blood inflow. This variant is realized through several mechanisms:
- Neurogenic: associated with impaired nervous regulation of vascular tone.
- Humoral: occurs when there is an excess of vasoconstrictor substances in tissues (angiotensin II, antidiuretic hormone, adrenaline, thromboxane $A_2$, prostaglandin F). It can also develop due to hypersensitivity of arteriolar receptors to these agents, for example, against the background of rising concentrations of calcium ions ($Ca^{2+}$) or sodium ($Na^{+}$).
- Physical (mechanical): creation of a barrier to blood flow. This can be external vessel compression (by a tumor, scar, edema, tourniquet) or internal obturation (by a thrombus, embolus, cell aggregate).
The second process is an increase in the consumption of oxygen and metabolic substrates. In this case, blood flow may even increase, but the organ's demand increases disproportionately more. A classic example is myocardial ischemia during emotional stress or a hypertensive crisis. An excess of catecholamines forces the heart to work harder, and although coronary blood flow increases, oxygen demand rises significantly faster. This leads to an anginal attack, and in severe cases, to an infarction.
How ischemia manifests
The clinical and morphological picture consists of macroscopic signs and alterations at the microcirculation level.
Externally, the ischemic area turns pale, its temperature drops, and its volume and turgor decrease. Arterial pulsation weakens, lymph formation and lymph drainage are suppressed. A visual decrease in the number and diameter of arterial vessels is determined.
Under the microscope, the following is observed in the vascular bed:
- Decrease in the diameter of capillaries and arterioles.
- Sharp slowing of blood flow velocity.
- Narrowing of the plasma zone near the vessel walls.
- Widening of the axial «cylinder» (erythrocytes and other formed elements accumulate in the center of the stream).
- Fall in the number of functioning capillaries.
Consequences and severity factors
The primary damaging factors in ischemia are hypoxia and the toxic accumulation of metabolic products, ions, and biologically active substances. They lead to the suppression of both specific (e.g., renal filtration) and nonspecific functions of the organ. Structural alterations range from reversible dystrophies to hypoplasia, atrophy, hypotrophy, and irreversible necrosis (infarction).
The scale of damage depends on several conditions:
- Rate of occlusion: the faster the blood flow is blocked, the more severe the consequences, as tissues do not have time to adapt.
- Vessel caliber: damage to large arteries causes more extensive ischemia.
- Tissue sensitivity: the brain, heart, and kidneys die the fastest, whereas bones, cartilage, and skeletal muscles possess low sensitivity.
- Significance of the organ: ischemia of vital centers threatens the death of the entire organism, whereas skin ischemia is compatible with life.
- Collateral circulation: the degree of development and speed of recruitment of collateral blood pathways.
Role of collateral blood flow
Collateral blood flow is the main compensatory mechanism saving tissues from death. This is a circulatory system through bypass vessels around and within the lesion zone.
Its activation is triggered by four factors:
- Pressure gradient: blood rushes from the high-pressure zone (before the stenosis) to the low-pressure zone (after the obstruction).
- Chemical factor: powerful vasodilators (adenosine, prostaglandins, kinins, acetylcholine) accumulate in the ischemic focus, dilating vessels.
- Nervous factor: local parasympathetic influences relieve vascular spasm.
- Anatomical factor: the initial density of the vascular network. According to the degree of development of arterial anastomoses, all organs are divided into three groups, which largely determines their survival during vascular catastrophes.
Briefly: answers to topical questions
What types is ischemia classified into according to its pathogenesis (mechanism of origin)?
According to the etiological mechanism and conditions of origin, ischemia is classified into four main types.
- Obturative — caused by partial or complete closure of the arterial lumen by a thrombus, embolus, or atherosclerotic plaque.
- Angiospastic — caused by reflex or organic spasm of arteries due to an increased tone of vasoconstrictors.
- Compressive — occurs due to the external compression of an artery by a scar, tumor, tourniquet, or edematous tissue.
- Redistributive — develops as a result of the redistribution of circulating blood volume into areas of hyperemia and a decrease in blood inflow to other anatomical regions.
What specific metabolic changes occur in cells during ischemic injury?
During ischemia, hypoxia and the accumulation of an excess of metabolites, ions, and biologically active substances in tissues develop primarily. Metabolic changes associated with O2 and metabolic substrate deficiency:
- Energy metabolism — suppression of tissue respiration, decrease in oxidation and phosphorylation processes, sharp drop in ATP levels; hypoxia leads to ATP and creatine phosphate deficiency in cells.
- Carbohydrate metabolism — activation of anaerobic glycolysis with the accumulation of lactate and the development of acidosis; acidosis subsequently inhibits glycolysis secondarily.
- Lipid metabolism in hypoxia — activation of lipolysis and inhibition of lipid resynthesis, leading to ketosis and worsening acidosis.
- Protein and nucleic acid metabolism in hypoxia — inhibition of nucleic acid synthesis and proteosynthesis, activation of proteolysis.
- Cellular consequences of ATP deficiency — impaired function of ion pumps, ion imbalance, and cellular hyperhydration.
To memorize the factors of ischemia severity, use the rule «R-C-T-S-C»: Rate of occlusion, Caliber of vessel, Tissue sensitivity, Significance of organ, Collaterals.
Class and exam questions
Why can myocardial ischemia occur during a hypertensive crisis if the blood pressure is high?
Due to the release of catecholamines, cardiac activity increases sharply. Blood inflow via the coronary arteries increases, but the myocardial oxygen demand grows to a substantially greater extent, creating an acute deficit.
Which substances cause humoral ischemia?
Powerful endogenous vasoconstrictors include angiotensin II, antidiuretic hormone (ADH), adrenaline, thromboxane $A_2$, and prostaglandin F.
What happens to blood flow at the microscopic level during ischemia?
Arterioles and capillaries narrow, blood flow slows down. The plasma zone near the walls becomes thinner, and the central axial stream of formed elements widens.
What else to study on this topic
- Classification of organs by the degree of collateral blood flow development
- Pathogenesis of ischemic cell injury (the role of hypoxia and metabolites)
- Features of skeletal muscle ischemia during physical exertion
- Two types of neurogenic mechanisms of ischemia development
- Influence of calcium and sodium ions on vascular wall sensitivity
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