Harrison's volume II

Cardiovascular

Blood vessel

- vascular ultrastructure

Capillary - consist of monolayer of endothelial cell, few layer of pericytes (smooth muscle) which does not
encompass the whole microvessel unlike vein and artery. Vein and artery contain 3 layers (tunica intima which
is layer of endothelial cell, media consisting of smooth muscle of which arteries can have few layers of smooth
muscle, and adventitia of which vein can have more adventitia compared to artery)

Figure 1: Capillary containing continuous endothelial and some pericyte

Figure 2: Vein and artery and their 3 layers

Adventitia consist of loose extracellular matrix with occassional fibroblast, mast cell and nerve terminals.
Larger arteries have their own vasculature, the vaso-vasorum which nourishes tunica media.

Endothelial cells serve to regulate entry of molecules and cells into tissues in a selective manner. The ability of
endothelial cells serve as a permselective barrier fails in many vascular disorders such as atherosclerosis and
HTN. Capillary leak also results in dysregulation of permselectivity occuring in pulmonary oedema.

Endothelium participates in local regulation of blood flow and vascular caliber through endogenous substances
auch as prostacyclin, endothelium derived hyperpolarizing factor, nitrous oxide. Prob with NO can cause
pathological vasoconstriction. Reactive oxygen species can impair NO and promote local oxidative stress.

Endothelial cell can express different classes of leucocytes and even in cases such as atherosclerosis. Also
dynamically regulates thrombosis and hemostasis.

When activated by inflammatory cttokines such as bacterial endotoxin or Ang II, endothelial cells can produce
major inhibitor of fibrinolysis, plasminogen activator inhibitor 1 (PAI-1). Promote local thrombus accumulation
rather than combat it.

Presentation of foreign histocompatibility complex antigens by endothelial cells in solid

organ allografts can trigger immunologic rejection.
Endothelial functions in health and disease
Homeostatic phenotype Dysfunctional phenotype
Vasodilatation Impaired dilatation, vasoconstriction
Antithrombotic, profibrinolytic Prothrombotic, antifibrinolytic
Anti-inflammatory Pro-inflammatory
Antiproliferative Proproliferative
Antioxidant Pro-oxidant

regulation of vascular smooth muscle - myosin, protein kinase A and G, calcium, sarcoplasmic reticulum etc.
Endothelium modulates vascular smooth muscle tone by NO, prostacyclin, endothelium-derived hyperpolarizing
factor which cause vasorelaxation and endothelin which causes vasoconstriction. Stimulated by mechanical
(shear stress, strain) and biochemical mediator.

Control of cardiac performance and output

Extent of shortening of heart nyscke and thereby stroke volume is dependent on:

a) length of muscle at onset of contraction ie preload b) tension muscle is called upon to develop during
contraction ie afterload c) the contratility of muscle ie extent and velocity of shortening at any given preload and
afterload

SV ∂ end-diastolic fiber length (preload)

SV ∂ 1/ afterload (arterial resistance) and 1/ inotropy

Afterload = load opposing shortening ie tension developed in teh ventricular wall during ejection. Determined
by aortic pressure as well as by volume and thickness of the ventricular cavity.

Laplace law = tension of fiber = intracavitary ventricular pressure & ventricular radius divided by wall thickness
so afterload for dilated cardiomyopathy is higher than normal heart. Conversely hypertrophied heart = reduce
afterload.

Determinants of stroke volume:

1. Ventricular preload

A. Blood volume B. Distribution of blood volume (body position, intrathoracic pressure, intrapericardial
pressure, venous tone, pumping action of skeletal muscles) C. Atrial contraction

2. Ventricular afterload

A. systemic vascular resistance B. Elasticity of arterial tree C. Arterial wall tension (ventricular radius,
ventricular wall thickness)

3. Myocardial contractility

A. intramyocardial Ca B. Cardiac adrenergic nerve activity C. Cardiac rate D. Cathecholamines E. exogenous

inotropic agents F. MI G. Myocardial cell death H. Alterations of sarcomeric and cytoskeletal proteins (genetic
or haemodynamic overload)_I. Myocardial fibrosis J. Chronic overexpression of neurohormones K. Ventricular
remodeling L. Chronic and/or excessive myocardial hypertrophy

Ejection fraction (ie ratio SV/EDV) = 67+-8%

Limitation of EF as a tool for cardiac function - lower EF or CO may be express in people with normal
ventricular function but reduced preload as in hypovolemia or increased preload such as acutely elevated arterial
pressure.

http://www.cvphysiology.com/Cardiac%20Function/CF025.htm
Diastolic function:influenced by extent and speed of myocardial relaxation which in turn is determined by the
rate of uptake of calcium by SR. The latter enhanced by adrenergic activation and reduced by ischaemia which
reduces ATP available for pumping calcium into SR. Stiffness of ventricular wall may impede filling (stiffness
increases with hypertrophy and consitions that infiltrate ventricle such as amyloid or by extrinsic constraint such
as pericardial compression). Ventricular filling assessed by continuously measuring velocity of flow across MV
using Doppler. Usually velocity of inflow is more rapid in early diastole than during atrial systle. But with mild
to moderate mpaired relaxation, rate of early diastolic filling declines while rate of presystolic filling rises.