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Файл:Pathophysiology of breathing and cardiovascular pathology. Educational and methodological manual
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Topic 2. Vascular pathophysiology
Topic 2
VASCULAR PATHOPHYSIOLOGY
Training objectives:
Vascular tone impairment is one of the leading pathogenetic
factors underlying most cardiovascular diseases (Fig. 7). Knowledge of the main mechanisms of its regulation, the causes leading to
their breakdown, as well as the patterns of its disorders that are
forming, which play a role in the pathogenesis of vascular disorders, are of important theoretical interest for future doctors, because they are basic in understanding the essence of this group of
diseases.
Fig. 7. Mechanisms of blood pressure regulation
As a result of studying the topic, students must:
— have an idea of main regularities of vascular tone regulation,
types of its disturbance and main nosological forms of vascular
system pathology;
— know the main causes and mechanisms of the development
of acute and chronic hypotension, arterial hypertension, essential
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Pathophysiology of breathing and cardiovascular pathology
hypertension, atherosclerosis, theories explaining the pathogenesis
of atherosclerosis, leading pathomorphological changes in the vascular wall in this disease;
— be able to correctly interpret the main clinical and laboratory, as well as experimental data in order to determine certain types
of vascular pathology;
— have the skill of pathophysiological analysis of clinical situations indicating the pathology of the vascular system, formulate a
conclusion on the possible causes and mechanisms of its development,
differentiate the main nosological forms of vascular pathology.
Pathogenesis of essential arterial hypertension
Classification of arterial hypertension (AH) by the predominant increase in BP.
1. Systolic — mainly ↑ SBP in normal or reduced diastolic BP,
caused by increased heart function, which is observed in hyperthyroidism, insufficiency of heart valves.
2. Diastolic — mainly ↑ DBP (due to spasm of arterioles and ↑
total peripheral resistance (TPR)).
3. Systolic-diastolic — ↑ stoke volume and TPR.
Classification of AH according to changes in hemodynamics.
1. Hyperkinetic type of AH — ↑ cardiac output, TPR is little
changed.
2. Eukinetic type of AH — ↑ TPR, cardiac output changes little.
3. Hypokinetic — sharply ↑ TPR and decreases cardiac output.
Microcirculatory changes are considered both a cause and a
consequence of hypertension, especially in diastolic and sisto-diastolic forms, which are caused either by volumetric overload (mainly associated with renal mechanisms, as shown in a special lesson)
or by general peripheral hypertension. Increasing resistance. Peripheral vascular resistance is controlled mainly at the level of small
arteries and arterioles, whose vascular tone is regulated by many
factors, including:
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Topic 2. Vascular pathophysiology
• sympathetic nervous system (SNS) (Fig. 8);
• humoral factors (mainly of endothelial origin);
• local autoregulation.
Fig. 8. Pathogenesis of the complications of hypertension
1. Role of SNA.
Pathogenetic treatment.
1. Low-dose diuretic therapy is effective and reduces the risk of
stroke, coronary heart disease, congestive heart failure and overall
mortality (most often thiazides, loop diuretics in combination with
potassium sparing diuretics).
2. Activation of SNS, angina pectoris, and past myocardial infarction are indications for prescribing Adreno blockers β. However, β-blocker therapy is associated with symptoms of depression,
fatigue, and sexual dysfunction. These side effects should be taken
into account when evaluating the effectiveness of treatment.
3. Calcium channel blockers can be divided into dihydropyridines (e.
g. nifedipine, nimodipine, amlodipine) and non-dihydropyri-
dines (verapamil, diltiazem). Both groups reduce peripheral vascular resistance, but verapamil and diltiazem have negative inotropic
and chronotropic effects. Calcium channel blockers are often combined with β — Adreno blockers, diuretics, and/or ACE inhibitors.
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Pathophysiology of breathing and cardiovascular pathology
4. ACE inhibitors are increasingly being used as first-line therapy. They have relatively few side effects and contraindications,
except for bilateral renal artery stenosis.
5. Because angiotensin II stimulates AT1 receptors that cause
vasoconstriction, angiotensin AT1 receptor antagonists are effective antihypertensive drugs. Losartan, valsartan and candesartan
are effective and cause cough to a lesser extent than ACE inhibitors.
6. Natriuretic peptides play a role in vascular tone control and
interact with the renin-angiotensin-aldosterone system (Fig. 9, 10).
By inhibiting their degradation, peptidase inhibitors make these naturally occurring peptides more effective, thereby reducing vascular resistance.
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Fig. 9. Renin-angiotensin-aldosterone system
Topic 2. Vascular pathophysiology
Fig. 10. Mechanism of action of renin
7. Inhibitors of central adrenergic receptors are agonists of α
2-adrenoreceptors and agonists of imidazoline I 1 receptor. Methyldopa is both a false neurotransmitter and a 2-adrenergic α agonist.
Clonidine and dexmedetomidine are agonists of centrally lo-
cated α 2-adrenergic receptors.
Both clonidine and dexmedetomidine make blood circulation
more stable, reduce the release of catecholamines in response to
stress, and cause sedation, so dexmedetomidine is now used for sedation in intensive care units.
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Pathophysiology of breathing and cardiovascular pathology
All antihypertensive drugs should act by reducing cardiac output, peripheral vascular resistance, or both.
2. Humoral factors (mainly of endothelial origin).
The endothelium can respond to physical and chemical signals
by producing a wide range of factors that regulate vascular tone,
cell adhesion, thromboresistance, smooth muscle cell proliferation,
and vascular wall inflammation. These factors include nitric oxide
(NO), reactive oxygen species, endothelin 1, Ang II, bradykinin,
and several other growth factors.
Endothelial production of NO by the endothelial isoform of
NO synthase (eNOS) is controlled by receptor-mediated mechanisms (acetylcholine, bradykinin, serotonin, substance P, adenosine
diphosphate) and an increase in intravascular pressure. Endothelial
dysfunction is characterized by reduced NO availability due to a
change in the balance between production and NO degradation.
3. Role of local autoregulation.
Local autoregulation and remodeling of arterioles: myogenic
tone is an integral property of vascular smooth muscle cells. An
increase in transmural pressure causes stretching and, following it,
contraction of smooth muscle cells of the vascular wall regardless
of neural or humoral influences. This response protects the distal
capillaries from increasing BP, but also causes an increase in overall peripheral resistance that supports an increase in systemic BP
values. Initially, microvascular adaptation has a positive effect, but
prolonged exposure to elevated BP causes rearrangement of
smooth muscle cells and the extracellular matrix. These structural
changes, known as internal remodeling, cause the lumen to narrow
and increase the ratio of wall thickness to lumen, representing the
earliest form of hypertensive lesion of target organs.
Reduction in the spatial density of microvascular networks has
been described in both experimental models and in patients with
hypertension. Microvascular rarefaction seems to be an extreme
consequence of functional microcirculatory changes: pronounced
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Topic 2. Vascular pathophysiology
vasoconstriction causes reversible closure of arterioles (functional
rarefaction), followed by their anatomical disappearance. The decrease in the availability of NO observed in patients with AH is
considered one of the most important triggers of functional and
structural vacuum of capillaries. Evidence suggests that NO deficiency may alter the response to vascular growth factors (including
vascular endothelial growth factor) and reduce maturation and mobilization of endothelial progenitor cells in the bone marrow. These
changes may impair angiogenesis and contribute to the reduction
of microvascular blood flow (Fig. 11).
Fig. 11. Vascular insufficiency
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Pathophysiology of breathing and cardiovascular pathology
In large arteries, the aging process is characterized by deep remodeling of the vascular wall, which is associated with increased
collagen deposition and rupture of elastin fibers. There is a decrease in the availability of endothelial NO, an increase in vascular
oxidative stress and the development of inflammation.
Causes of secondary arterial hypertension
1. Renal (parenchymal or vascular):
• Renal artery stenosis;
• Renal failure;
• Polycystic kidney disease;
• Glomerulonephritis;
• Hypertensive nephrosclerosis.
2. Cardiovascular:
• Aortic coarctation.
3. Tumors:
• Pheochromocytoma;
• Neuroblastoma;
• Wilms tumor;
• Adrenal adenocarcinoma.
4. Endocrine:
• Hyperthyroidism;
• Cushing's disease;
• Congenital adrenal hyperplasia;
• Primary hyperaldosteronism.
5. Neurological:
• Guillain-Barré syndrome;
• Increased intracranial pressure.
6. Other reasons:
• Systemic arteritis (Schönlein-Genoch syndrome);
• Sleep Apnea (Table 1).
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Topic 2. Vascular pathophysiology
Table 1
Etiology of hypertension
Risk Factors for Hypertension
Unregulated factors Regulated factors
Increasing Age Sedentary lifestyle
Family history Metabolic syndrome
Dietary Factors
• Increased fat intake
• Increased sodium intake
• Inadequate potassium intake
• Inadequate calcium intake
Laboratory data
• Elevated blood glucose levels
• Elevated total cholesterol
• Elevated triglyceride levels
• Lowering high-density lipids (HDL)
• Elevated low-density lipid (LDL) levels
SITUATIONAL TASKS
Clinical case №
1
Patient K., 42 years old, was admitted to the clinic with complaints of headache, general weakness. In the urine — protein, red
blood cells. Residual blood nitrogen — 30 mmol/l. Blood pressure
(BP) — 200/100 mm Hg.
Question: Characterize the state of vascular tone and justify
the pathogenesis of developing changes.
Answer: the patient has hypertension, which is confirmed by
increased BP and headache complaints. The presence of protein
and red blood cells in the urine, as well as an increase in residual
nitrogen in the blood, indicate kidney pathology. Therefore, we are
talking about symptomatic arterial hypertension of renal origin.
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Pathophysiology of breathing and cardiovascular pathology
Clinical case №
2
Patient S., 45 years old, presents complaints of weakness, rapid
fatigue, insomnia, frequent headaches, periodically with bouts of
dizziness and nausea. Such attacks are associated with a change in
weather. The skin is pale, the limbs are cold to the touch. Respiratory rate — 18 per minute, heart rate — 75 beats/min, blood pressure — 100/60 mm Hg.
Electrocardiogram unchanged.
Question: Characterize the state of vascular tone and justify
the pathogenesis of developing changes.
Answer: in this case, we are talking about pathological hypotension. Hypotension is confirmed by reduced BP, the presence of
complaints of poor health (as opposed to physiological), data from
an objective examination. Due to the lack of a history of any past
or existing somatic diseases, it should be assumed that the patient
has primary, not secondary (symptomatic), hypotension. Its pathogenesis is complex. It is believed that it can develop against the
background of autonomic dystonia with a predominance of the
tone of the parasympathetic department of the autonomic nervous
system.
Clinical case №
3
Patient B., 16 years old. After taking blood from the vein, there
is a pronounced pallor of the skin, cooling of the limbs. Pupils are
narrowed, do not respond to light. Breathing is superficial, the frequency of respiratory movements is 10 per minute. The pulse of
weak filling is 52 beats/min. Blood pressure — 80/40 mm Hg.
After 1 minute, the patient regained consciousness. Skin color
returned to normal.
Question: Characterize the state of vascular tone and justify
the pathogenesis of developing changes.
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