Year three: Pathology: Blood Vessel Diseases:
Lecture 1: Introduction, congenital anomalies and hypertensive vascular disease: February 2018. By Dr. Ehsan.Objectives:
Discuss the clinical importance of congenital anomalies of blood vessels.
Recognize the main cells of blood vessels and their response to injury.
Discuss the pathogenesis of hypertensive vascular disease, clinical importance and morphological changes.
Define arteriosclerosis and their types.
Vascular disorders are responsible for more morbidity and mortality than any other human disease. Although the most clinically significant lesions typically involve arteries, venous diseases also occur.
Vascular pathology results in disease via two principal mechanisms:
(1) Narrowing (stenosis) or complete obstruction of vessel lumens, either progressively (e.g., by atherosclerosis) or precipitously (e.g., by thrombosis or embolism).
(2) weakening of vessel walls, leading to dilation or rupture.
The Structure and Function of Blood Vessels (read in the text book)
Vessel development, growth and remodeling:
Three major processes characterize blood vessel formation and remodeling:
1- Vasculogenesis: formation of blood vessels during embryogenesis.
2- Angiogenesis: or neovascularization, new blood vessel formation in mature organism.
3- Arteriogenesis: remodeling of existing arteries in response to chronic changes in pressure or flow, occur due to effect of factors from the endothelial cells and smooth muscle cells.
Congenital anomalies:
Berry aneurysm.Arterio-venous fistula.
Fibromuscular dysplasia.
1-Berry aneurysm:
It is a developmental disease, occurs in cerebral vessels, and when rupture may has a fatal intracerebral hemorrhage.
2-Arterio-venous fistula:
It is an abnormal direct connection between arteries and veins that bypass the capillaries. Causes:
1- Developmental defects (arteriovenous malformation-AVM).
2- Rupture of an arterial aneurysm into an adjacent vein.
3- Penetrating injuries that involve the walls of adjacent artery and vein.
4- Inflammatory necrosis of adjacent artery and vein.
Clinical presentation and Complications:
If there is short-circuit, there will be an increase in the blood from the arterial to the venous side, results in volume overload on the heart that may end in heart failure.
Also if there is rupture, ends with destructive hemorrhage (as in the AVM of the brain).,
3- Fibromuscular dysplasia:
Is the focal irregular thickening of the walls of the medium and large muscular arteries, including renal, carotid, splanchnic, and vertebral vessels,
The cause is unknown but can be of developmental cause.
Irregular intimal and medial thickening cause luminal stenosis, and aneurysm.
Vascular wall cells and their response to injury:
Endothelial cells: is critical for maintaining vessel wall homeostasis and circulatory function.Activated VECs express adhesion molecules, produce cytokines, and chemokines, growth factors, vasoactive molecules that result either in vasoconstriction or vasodilation.
It express also major histocompatibilty complex molecules, procoagulant and anticoagulants and a variety of other biologically active products.
Function of VECs:
Maintain a non thrombogenic blood tissue interface.
Modulate vascular resistance.
Metabolize hormones.
Regulate inflammation.
Affect the growth of other cells, as smooth muscle cells.
Endothelial activation inducers:
Cytokines and bacterial products lead to inflammation and septic shock.
Hemodynamic stresses and lipid products critical to the pathogenesis of atherosclerosis.
Advanced glycosylation end products in D.
Viruses complement components and hypoxia.
Endothelial dysfunction:
Altered features and status of cells that impairs vasoreactivity, or induces a surface that is thrombogenic or abnormally adhesive to inflammatory cells.
Responsible for initiation of thrombus formation, atherosclerosis and the vascular lesions of hypertension, and other disorders.
Endothelial cell properties and functions. (table in the book)
Vascular smooth muscle cells:
It has a role in normal vascular repair and pathologic processes as atherosclerosis. Also has a great capacity to proliferate and synthesize collagen, elastin and proteoglycans, and elaborate growth factors, and cytokines.
It has a role in vasoconstriction and dilation. Promoted by: PDGF, endothelin-1, thrombin, FGF, Gamma I, and IL-1.And inhibited by heparan sulfate, nitric oxide, TGF-Beta.
Intimal thickening- response to vascular injury:
Vascular injury -with endothelial cell loss or even just dysfunction- stimulates smooth muscle cell growth, and associated matrix synthesis that thickens intima.
Injury heal by neointima.
Filling endothelial cells origin from adjacent uninjured area or circulatory precursors.
Neointima is thick.
Neointimal smooth muscle cells:
Thicker than normal.
Don’t contract but capable for dividing.
Heal with time but leave a thick intima.
Persistent and recurrent insult result in narrowing, as atherosclerosis.
Not always pathologic.
Hypertensive vascular disease:
Is a sustained diastolic pressure greater than 89 mmHg or a sustained systolic pressure in excess of 139 mm Hg.
The mechanisms that result in hypertension remain largely unknown in most individuals.
Causes of HT: Essential and secondary HT.
Essential HT: is multifactorial, resulting from combined effects of multiple genetic polymorphisms and interacting environmental factors. It comprises 95 % of all cases, and is compatible with long life, and with no serious complications if treated properly.
While secondary HT is caused by renal, endocrine, cardiovascular and neurologic diseases.
(table in the book- for revision)
Accelerated HT:
A small percentage, perhaps 5%, of hypertensive persons show a rapidly rising blood pressure that, if untreated, leads to death within a year or two, called accelerated or malignant HT characterized by severe Ht (systolic above 200 mm Hg, diastolic above 120 mm Hg).
Regulation of normal BP:
It is a function of cardiac output and peripheral vascular resistance; these two variables are influenced by multiple genetic, environmental and demographic factors. (Age, gender, body mass index, and diet especially salt intake).
1- Cardiac output:
It is dependent on blood volume, which is greatly influenced by sodium. Increase with high heart rate, increased contraction, and increased blood volume in increased aldosterone secretion.
2- Peripheral resistance:
The major factor is increased angiotensin II, increased catecholamines, increased thromboxane, increased endothelin and increased alpha adrenergic factors lead to HT. All of these are vasoconstrictors; normally there is balance with the vasodilators causing normal vascular tone, with the role of kidney.
3- Role of kidney:
Renin-angiotensin system:
Renin is secreted from the juxtaglomerular cells, in fall of blood pressure. It converts plasma angiotensinogen (from liver) to angiotensin I. By angiotensin converting enzyme (endothelial cells) converted to angiotensin II.
Is a powerful BV constrictor and stimulate secretion of aldosterone (salt retention).
vascular relaxing substances:
Including nitric oxide and prostaglandins.
sodium reabsorption in case of low BP:
(By effect of low glomerular filtration).
natriuretic factors:
These peptides are secreted from atria and ventricles, in response to volume expansion and inhibit sodium reabsorption in distal tubules and cause sodium excretion and diuresis.
Mechanisms of essential HT:
Results from interactions of mutations or polymorphisms, at several loci, that influence blood pressure with a variety of environmental factors.Rarely there is single gene mutation affect aldosterone metabolism and result in increase secretion of aldosterone.
Effects of vasoconstrictors and other mentioned factors in regulation of BP.
TABLE 11-2 -- Types and Causes of Hypertension (Systolic and Diastolic) (book)
Pathogenesis of secondary HT:
Renal hypertension:
Renal artery stenosis causes decreased glomerular flow and pressure in afferent arteriole of the glomerulus. This:
1- Induces renin secretion, initiating angiotensin II mediated vasoconstriction, and increased vascular resistance.
2- Increase sodium reabsorption, blood volume increase and HT.
Vascular pathology in HT effects:
Accelerate atherosclerosis.
Degenerative changes in the walls of large and medium arteries that can lead to:
Aortic dissection and cerebrovascular hemorrhage.
Morphology:
Hypertension is associated with two forms of small blood vessel disease: hyaline arteriolosclerosis and hyperplastic arteriolosclerosis.
1- Hyaline arteriolosclerosis
The vascular lesion: arterioles showa a homogeneous, pink, hyaline thickening of the arteriolar wall with loss of the native structural details and this is associated with narrowing of the lumen.
Pathogenesis : Occur from leakage of plasma proteins through injured and increased smooth muscle cell matrix synthesis in response to chronic hemodynamic stress.
This condition is also encountered in:
Elderly whether normotensive or hypertensive, but it is in hypertensive individuals, it is more severe and more generalized.
In Diabetics as part of the characteristic diabetic microangiopathy.
Nephrosclerosis is hyaline arteriosclerosis in kidneys of patients with chronic hypertension, lead to narrowing of arteries causing diffuse impairment of renal blood supply and causes glomerular scarring.
2- Hyperplastic arteriolosclerosis:
Is related to malignant hypertension.
Morphologically: the vessels show “onion-skin lesions” which is concentric, laminated thickening of the arteriolar wall with progressive narrowing of the lumen.
These consist of smooth muscle cells with thickening and reduplicated of the basement membrane and fibrinoid deposits and vessel wall necrosis (necrotizing arteriolitis) particularly in the kidneys.
Arteriosclerosis:
Mean hardening of the arteries: This is thickening and loss of elasticity of arterial walls and thus leading to sclerosis.
There are three distinctive morphological variants:
Arteriolosclerosis.
Monckeberg medial sclerosis (medial calcific sclerosis): are calcific deposits in muscular arteries of persons above 50 years, with patent lumen and of no clinical significance.
Atherosclerosis: the most frequent and important type.