Objectives:  be able to compare and contrast the circulatory system of specific organs with regard to vascular structure, regulation of blood flow, and organ function.

Companion Reading:  Chapter 38 Pulmonary Circulation; Pulmonary Edema; Pleural Fluid, pp. 444-451; Chapter 62 General Principles of Gastrointestinal Function - Motility, Nervous Control, and Blood Circulation, pp. 724-726. In: Textbook of Medical Physiology, 10th ed., A.C. Guyton & J.E. Hall, eds., W.B. Saunder: St. Louis, 2000

Two circulatory systems, those of the lung, and the gut will be presented, contrasting specific organ circulations and delineating how the structure of the circulatory system complements the organ function using the basic principles outlined in the BIOPHYSICS OF THE CIRCULATION lecture.  Other circulations worth considering are the

heart, which must provide high flow and efficient extraction in a non-constant milieu,
kidney, as the archetypical example of vascular beds in series,
uterine, where the vasculature turns over on a monthly basis and which has the capacity to increase blood flow by 16-fold during pregnancy,
brain, which maintains a tight barrier and a high flow system to deliver O₂ and glucose, and
skin, wherein the circulatory system is involved in the regulation of heat exchange, and
fetal.

I. Pulmonary Circulation

A. Functions of the Pulmonary Circulation:

1. Gas exchange: The chief function is the delivery of a thin film of blood to the terminal respiratory units for the exchange of gases.

a. Thin barrier: The small distance separating the alveolus and the blood at the capillary level facilitates the diffusive transfer of O₂ and CO₂.
b. Large surface area: Actually the largest exchange surface in the body: the capillary bed is 85-95% of the total alveolar surface.  The theoretical maximum area is 122 m².  Several factors determine how much of the vasculature is perfused at any one time.

2. Venous filter: the fine meshwork of capillaries vessels trap emboli and large particles and keep them from reaching the coronary or systemic vasculature.  Pulmonary exchange will occur with only half of the conducting system and vessels.  How the lung disposes of emboli is not yet known.
3. Left ventricular reservoir: pulmonary vessels contain 450 to 900 ml of blood; over half in readily distensible veins.  Since these are an extension of the left atrium, they act as a blood reservoir, supplying blood to the left ventricle and maintaining output, even if the left ventricular pump falls behind a few beats.
4. Pharmacological modification of a wide variety of potent short lived, circulating substances occurs in the microvessels of the lungs.
5. Fluid absorption capacity of the lungs (absorbing fluid from the alveoli into the pulmonary capillary blood) is of primary importance in clearing the lungs at birth and in maintaining a "dry lung".

B. Comparison of the Pulmonary and Systemic Circulations:

1. Structure/Function: The lung is characterized by LOW pressure, LOW resistance and HIGH flow.  Lung vessel morphology reflects these conditions.

a. Distensibilityvessels have thin walls and are highly distensible.
b. Pulmonary Artery is shorter than the aorta and much thinner.  Pulmonary arteries are also thinner than systemic counterparts and contain less VSM (thus less capacity to contract) and have less elastin (less damping).
c. Pulmonary Veins  are thinner than systemic and have little VSM.
d. Pulmonary Capillaries are sandwiched between the alveoli so blood flows through them like a sheet.  This provides a large, but thin, surface area for exchange.  Capillary endothelium are the site of production, modification, and metabolism of a wide variety of vasoactive materials.

2. Low Pressure: Pulmonary vascular pressures are much lower than systemic.  Pulmonary arterial pressure = 25 mmHg; pulmonary venous pressure = 5 mmHg; mean pressure in the lungs of ~15 mmHg.  Least arterial pressure is 5-8 mmHg so the total A-V pressure gradient is about 10 mmHg.  Mean capillary pressure in the lung is closer to P_v: about 10 mmHg.
3. High Flow: All of cardiac output goes through the lungs.
4. Low Resistance: Given lung blood flow = CO and low arterial pressure (1/5 systemic), the pulmonary resistance must be much less than systemic.  With exercise, CO may rise 2-3 times but inflow pressure to the lungs rises only slightly.  THUS, pulmonary resistance must be less to start with and capable of sustaining further decreased as blood flow increases.

C. Pulmonary Pressures and Effects on Regional Blood Flow

1. Effect of Height (gravity) on Pulmonary Pressures: Vascular pressure varies with vessel size and position in the lung.

a. Standing: Gravity influences hydrostatic pressure.  Vascular pressure is greater at the bottom of the lung than at the top.  At the top, pressure equals the inlet pressure of the pulmonary artery minus the height of the blood column from the inlet to the top. (Figure 1)
b. Lying down lessens the pressure gradients.
Implications: As pulmonary arterial pressure is relatively low, hydrostatic effects due to gravity have significant effects on blood flow and driving pressures.

2. Effect of Height and Pressure on Blood Flow.  Blood flow patterns in the lung a grouped into 3 zones.  The contribution of any one zone to total pulmonary blood flow is a function of alveolar, arterial and venous pressures.

a. Zone A: P_alv > P_alv > P_ven:   When this zone exists, it is at the top of the lungs.  It is created by positive pressure ventilation.  Because pressure in the alveoli is higher than the vascular pressures the vessels collapse (pulmonary vessels are thinner than system) and there is no blood flow in zone A.
b. Zone B: P_art > P_alv > P_ven: In this zone vessels are open along their length until vessel pressure = Palv.  The venous end of the vessels are shut.  Intermittent flow, though, does occur as blood accumulates at the arterial end and pushes through down the hydrostatic gradient. "Waterfall" effect.
c. Zone C: P_art > P_ven > P_alv: Vessels in zone C are patent at all times because vascular pressures exceed alveolar pressure along their entire length.  Resistance in this region is determined by the difference between pulmonary artery and vein.  Since this difference remains constant throughout zone C, there appears no reason to find regional difference in blood flow in the zone.  In actual fact this is not the case: the transvascular distending pressure increases with distance down the zone with arterial and venous pressure increase and alveolar pressure remaining constant.  Progressive increases in distending force alters geometry of the vessels and decreases resistance to blood flow.

3. Relationship between changes in Cardiac Output and Pulmonary Circulation:
Given that the pulmonary vessels are highly distensible, large changes in blood flow can be accommodated.  In heavy exercise CO can rise to 4-7 fold above normal. 3 mechanisms that keep the lungs from "blowing out" are to

a. Increase the number of open capillaries (open zone 1 (if present) use more of zone 2)
b. Distend the capillaries that are open (increase r thereby markedly decreasing R), and
c. Increasing pulmonary arterial pressure (Why? What does this do??)

II. Splanchnic Circulation: is the blood supply to the GI tract, liver, spleen and pancreas.  An example of two large capillary networks that are partially in series with each other.  The small splanchnic arterial branches supply capillary beds in the GI tract, spleen and pancreas.  From these capillary beds the blood flows into the hepatic portal vein which supplies most of the blood to the liver.  In addition the hepatic artery feeds the liver.

A. Intestinal:  The celiac, superior mesenteric and inferior mesenteric arteries supply the GI tract.  The superior mesenteric artery, the largest branch of the aorta, carries 10% of CO.

1. Anatomy:  The flow of blood in the venules and capillaries of the microvillus is opposite to that in the main arteriole.  Forms counter current exchange system that permits O₂ diffusion from arterioles to venules.  At low flows a large fraction of O₂ will be shunted into the venules without supplying the mucosal cells at the villus tip.  This meets the high demand for oxygen by the cells in the center of the villus.  This is a precarious architecture as extensive necrosis in the intestinal villi can occur during zero flow when oxygen delivery is interrupted to the cells at the tip. As you will find out from the GI lectures, epithelial turnover in the villi is extremely high to maintain a patent barrier between the intestinal lumen and the villus contents, thus metabolic demands are high and cessation of blood flow leads to loss of barrier function.

2. Autoregulation not as pronounced as in kidney and heart.  In this bed primary mechanism shown to be metabolic.  Adenosine rises 4-fold with brief arterial occlusion: in this bed ADO potent vasodilator and may be primary mediator of autoregulation. K⁺ and Osm may also be important.

3. Functional hyperemia:  Eating food increases intestinal blood flow.  GI hormone secretion contributes to hyperemia.  Absorption of food affects blood flow.  Undigested food has no vasoactive influence; whereas several products of digestion (constituents of chyme, glucose & fatty acids) are potent vasodilators.

4. Sympathetic Stimulation leads to cessation of blood flow to the gut via profound arteriolar constriction.  This allows for redistribution of blood flow during systemic sympathetic stimulation.  Constriction, though, is not prolonged.  With time the vessels dilate despite the presence of sympathetic constrictors.  This occurs because of the generation of metabolic dilators (see  The Capillary exchange lecture  TVII. Summary: Coordinated Control of blood and tissue transport) and receptor down regulation leading to "sympathetic escape".

B. Hepatic: blood flow to the liver is normally about 25% of CO.

1. Anatomy:  Flow from portal vein and hepatic artery: portal vein ~75%.  Portal vein blood comes from the GI capillary beds and thus much O₂ already extracted.  Hepatic artery provides other 25% with fully O₂-saturated blood.  Thus 3/4 of O₂ used by liver derived from hepatic arterial blood.  Small branches of portal vein & hepatic artery give rise to terminal portal system: terminal vessels enter the acinus of the liver (functional units) at their center.  The capillary network of the liver are the sinuses that radiate towards the periphery of the acinus where they connect with the terminal hepatic venules.  Blood from the venules drains into the hepatic veins which are tributaries of the inferior vena cava.

2. Hemodynamics: mean portal vein pressure ~10 & hepatic artery ~90 mmHg.

a. Pressure in sinusoids:  Vessels upstream of hepatic sinusoids greater than that of downstream vessels and in sinusoids pressure is only  2-3 mmHg above hepatic veins.  The ratio of pre- to post-sinusoidal resistance in the liver is greater than is the ratio of pre- to post-capillary resistance for almost any other bed.  The outcome is that vasoactive drugs usually have very little effect on the pressure in the sinusoids.  This then has little effect on fluid exchange.

b. Influence of hepatic venous and central venous pressure:  conversely, though, if pressure and/or resistance is changed in the hepatic veins  the effect is transmitted directly into the sinusoids and has a profound effect.  Case when central venous pressure is raised include congestive heart failure: plasma water transudes from the liver into the peritoneal cavity leading to ascites.

3. Regulation of flow

a. Reciprocal interplay:  Blood flow lowered in one system observe increase in the other: but not quite one for one compensation.

b. No autoregulation: as portal venous pressure is raised, flow rises: resistance either remains constant or decreases in portal venous system.  Hepatic artery, though, does auto regulate.  Portal vein smooth muscle is phasic and generates spontaneous contractions.

c. Constant O₂ consumption:  because O₂ extraction very efficient.  As rate of O₂ delivery varied liver compensates by altering the fraction of gas extracted from the blood.

4. Capacitance (Volume storage) function: Liver contains ~15% of total blood volume of the body.  During hemorrhage, for example, up to half of the hepatic blood volume released.  In humans this is a major blood reservoir.

That's all folks.