Medical School · Year 1 · Cardiovascular · includes a quiz and discussion video

Lecture 8: Microcirculation and Lymphatics

Unit 1.7: Cardiovascular System

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the structure and function of the microcirculation
2. Explain the mechanisms of transcapillary exchange
3. Apply Starling forces to understand fluid movement
4. Describe the structure and function of the lymphatic system
5. Explain edema formation and its causes
6. Apply microcirculation concepts to clinical scenarios

Microcirculation Overview

The microcirculation comprises the smallest blood vessels—arterioles, capillaries, and venules—where the essential functions of the cardiovascular system are accomplished. While the heart provides the driving force and the large vessels distribute blood, it is in the microcirculation that oxygen and nutrients are delivered to cells and metabolic wastes are removed.

The components of the microcirculation form a functional unit. Arterioles, ranging from 10 to 100 micrometers in diameter, are the final resistance vessels controlling blood flow into the capillary bed. Metarterioles (10 to 20 micrometers) are transitional vessels that can serve as either thoroughfare channels or feeders to the capillary bed. Precapillary sphincters, small rings of smooth muscle at the entrance to individual capillaries, provide fine control over which capillaries are perfused at any moment. Capillaries themselves, only 5 to 10 micrometers in diameter (barely wider than a red blood cell), are the exchange vessels where diffusion, filtration, and absorption occur across a wall only one cell thick. Postcapillary venules (10 to 50 micrometers) continue the exchange function and are the primary site of white blood cell migration during inflammation. Larger venules (50 to 100 micrometers) collect blood for return through the venous system.

Capillary density varies enormously among tissues, closely matching their metabolic demands. The heart has extremely high capillary density, reflecting its constant high oxygen consumption. Skeletal muscle has moderate to high density that can increase functionally during exercise as previously unperfused capillaries are recruited. The brain has high density for its substantial metabolic needs. The skin has lower density, appropriate for its primarily thermoregulatory function. Cartilage and the cornea are essentially avascular, receiving nutrients by diffusion from adjacent tissues.

Under resting conditions, not all capillaries are perfused simultaneously. Precapillary sphincters open and close intermittently, creating vasomotion—the rhythmic opening and closing of capillary beds. When metabolic demand increases, more sphincters open, recruiting additional capillaries and increasing the surface area available for exchange.

The transit time of blood through a capillary—normally 0.5 to 1 second—is sufficient for complete equilibration of oxygen and carbon dioxide between blood and tissues. During exercise, transit time decreases as flow increases, but the simultaneously increased capillary surface area compensates, maintaining adequate exchange.

<image>Panel A: Vessel hierarchy showing arteriole (smooth muscle wall, 50 micrometers) branching into metarterioles giving rise to capillaries through precapillary sphincters, with capillary network as interconnected mesh (8 micrometers, single endothelial cell wall, RBC for scale). Panel B: Capillaries draining into postcapillary venules (20 micrometers with neutrophils migrating during inflammation) and collecting venules, with thoroughfare channels shown as direct arteriole-to-venule connections. Panel C: Vasomotion inset showing time-lapse of precapillary sphincters opening and closing with different capillaries perfused at different moments. Panel D: Table of capillary density by tissue (heart highest, skeletal muscle variable, brain high, skin moderate, cartilage avascular) with transit time graph showing 0.5-1 second oxygen equilibration.</image>

Capillary Structure

The capillary wall is structurally simple but functionally sophisticated, consisting essentially of a single layer of endothelial cells resting on a basement membrane.

The endothelial cells are flattened, with a central bulge where the nucleus is located. They are joined to one another by intercellular junctions whose tightness varies by capillary type. Endothelial cells are not passive barriers—they actively participate in exchange through transcytosis, synthesize vasoactive substances, regulate coagulation, and participate in inflammation. The basement membrane beneath the endothelium is a thin layer of extracellular matrix that provides structural support. Pericytes, contractile cells that wrap around the outside of some capillaries, may participate in regulating capillary blood flow.

Capillaries are classified into three structural types based on the continuity of their endothelium and basement membrane.

Continuous capillaries have a complete endothelium with tight junctions between cells and a continuous basement membrane. Substances cross primarily through the cells (transcytosis) or through small intercellular clefts. This type is found in most tissues, including skeletal muscle, skin, lung, and notably the brain, where especially tight junctions form the blood-brain barrier.

Fenestrated capillaries have pores (fenestrations) of 60 to 80 nanometers spanning the endothelial cells, usually covered by thin diaphragms. These pores greatly increase permeability to small solutes and water while still restricting proteins. Fenestrated capillaries are found where high rates of fluid exchange occur: the kidney (for filtration), intestine (for absorption), and endocrine glands (for hormone release).

Sinusoidal (discontinuous) capillaries have large gaps between endothelial cells and an incomplete or absent basement membrane. These permit the passage of proteins and even cells. They are found in the liver (where hepatocytes directly access blood constituents), spleen (for filtering blood), and bone marrow (where blood cells enter the circulation).

The blood-brain barrier deserves special mention. Cerebral capillaries have continuous endothelium with unusually tight junctions (formed by claudins and occludins), no fenestrations, few transcytotic vesicles, and a basement membrane reinforced by astrocyte foot processes that encircle the capillary. This arrangement strictly limits what enters the brain, protecting it from toxins and pathogens but also limiting drug delivery. Specific transporters allow essential substrates like glucose (via GLUT1) and amino acids to cross.

<image>Panel A: Continuous capillary with complete endothelial ring, tight junctions (magnified inset), continuous basement membrane, transcytotic vesicle, and intercellular cleft; location: muscle, skin, lung, brain. Panel B: Fenestrated capillary with circular pores (70 nm) covered by diaphragms (enlarged inset) and continuous basement membrane; location: kidney, intestine, endocrine glands. Panel C: Sinusoidal capillary with large gaps between endothelial cells, incomplete basement membrane, wide lumen accommodating blood cells; location: liver, spleen, bone marrow. Panel D: Blood-brain barrier showing tight junctions, continuous basement membrane, astrocyte foot processes, pericyte coverage, and specific transporters (GLUT1, amino acid transporters).</image>

Mechanisms of Transcapillary Exchange

Substances cross the capillary wall through several mechanisms, each suited to different molecular characteristics.

Diffusion is the predominant mechanism for gas exchange and small solutes. Driven by concentration gradients, molecules move from regions of higher to lower concentration. Oxygen diffuses from the high-concentration blood into the lower-concentration interstitium and then into cells. Carbon dioxide moves in the reverse direction. Fick's law describes diffusion: flux equals the product of diffusion coefficient, membrane area, and concentration gradient divided by membrane thickness. For lipid-soluble substances like oxygen, carbon dioxide, and anesthetics, the entire endothelial surface is available for diffusion, making exchange extremely rapid. Water-soluble substances primarily diffuse through intercellular clefts and fenestrations.

Bulk flow (filtration and absorption) describes the movement of fluid and dissolved solutes together through pores, driven by pressure gradients. When hydrostatic pressure exceeds opposing forces, fluid filters out of the capillary. When opposing forces predominate, fluid is absorbed back into the capillary. This mechanism is governed by Starling forces, discussed in detail below.

Transcytosis (vesicular transport) involves endocytosis of material on one side of the endothelial cell, transport of the vesicle across the cell, and exocytosis on the other side. This mechanism transports large molecules, particularly proteins, that cannot cross through pores or junctions. Albumin is transported by this mechanism. Transcytosis is relatively slow compared to diffusion.

Permeability varies dramatically by substance. Oxygen and carbon dioxide, being lipid-soluble, cross with extreme ease—the entire capillary surface is available. Water crosses rapidly through aquaporin channels and intercellular clefts. Small water-soluble molecules like glucose and amino acids cross via facilitated diffusion through specific transporters or through intercellular clefts. Small ions like sodium and chloride cross through intercellular clefts with moderate ease. Large proteins like albumin cross slowly via transcytosis, maintaining the crucial protein concentration gradient that generates oncotic pressure.

<image>Panel A: Diffusion showing O2 molecules moving from blood (high concentration) through endothelial membrane to interstitium and CO2 moving opposite direction with arrows through lipid bilayer indicating direct membrane passage and Fick's law equation. Panel B: Bulk flow showing fluid movement through intercellular clefts with direction determined by net Starling force (Pc - pi c vs. Pi - pi i). Panel C: Transcytosis showing albumin engulfed on blood side (endocytosis), transported in vesicle, and released on tissue side (exocytosis). Panel D: Permeability table by substance: O2/CO2 (very high, lipid diffusion), water (high, aquaporins/clefts), glucose (high, transporters), Na+/Cl- (moderate, clefts), proteins (low, transcytosis).</image>

Starling Forces and Fluid Exchange

The movement of fluid across the capillary wall is governed by the balance of hydrostatic and oncotic (colloid osmotic) pressures—the Starling forces, named for Ernest Starling who described them in 1896.

Four pressures determine net fluid movement. Capillary hydrostatic pressure (Pc) is the pressure exerted by blood within the capillary, pushing fluid outward. It is highest at the arteriolar end of the capillary (approximately 35 mmHg) and falls toward the venular end (approximately 15 mmHg) as blood flows through the resistance of the capillary bed. Interstitial hydrostatic pressure (Pi) is the pressure in the tissue space, which is slightly negative under normal conditions (approximately -3 mmHg) due to lymphatic drainage, and thus favors filtration. Capillary oncotic pressure (πc), generated primarily by plasma proteins (especially albumin), averages approximately 25 mmHg and acts to pull fluid into the capillary. Interstitial oncotic pressure (πi), generated by proteins that have leaked into the interstitium, averages approximately 8 mmHg and acts to pull fluid out of the capillary.

The Starling equation describes net filtration:

Net Filtration = Kf × [(Pc - Pi) - σ(πc - πi)]

where Kf is the filtration coefficient (reflecting permeability and surface area) and σ is the reflection coefficient (indicating how effectively the membrane excludes proteins; σ = 1 means complete impermeability to proteins).

The classic model proposed net filtration at the arteriolar end (where Pc exceeds the opposing pressures) and net absorption at the venular end (where Pc has fallen below the opposing pressures). However, modern understanding based on careful measurements suggests that most capillary beds have slight net filtration along their entire length. The excess filtered fluid is returned to the circulation by the lymphatic system rather than by capillary reabsorption.

At the arteriolar end, with Pc of 35 mmHg, Pi of -3 mmHg, πc of 25 mmHg, and πi of 8 mmHg, the net filtration pressure is approximately +21 mmHg (favoring filtration). At the venular end, with Pc of 15 mmHg, the net filtration pressure is approximately +1 mmHg (still slightly favoring filtration). The lymphatic system removes this filtered fluid, returning 2 to 4 liters per day to the circulation.

<image>Panel A: Capillary with four Starling force arrows: Pc (large outward, larger at arteriolar end), Pi (small inward from interstitium, slight negative), pi c (large inward, plasma oncotic pressure), pi i (small outward, interstitial oncotic). Panel B: Pressure profile showing Pc falling from 35 mmHg (arteriolar) to 15 mmHg (venular) with opposing forces constant, and calculation box showing net filtration pressure at each end. Panel C: Starling equation displayed with modern understanding showing slight net filtration along entire capillary length. Panel D: Lymphatics shown as blind-ended vessels with one-way valves collecting excess fluid and returning it to venous circulation.</image>

Factors Affecting Capillary Exchange

Changes in any of the Starling forces alter the balance between filtration and absorption, potentially causing edema if filtration exceeds the capacity of lymphatic drainage.

Increased capillary hydrostatic pressure increases filtration. This occurs with venous obstruction (deep vein thrombosis, venous insufficiency), heart failure (elevated venous pressure from cardiac backup), and gravitational effects (dependent edema in the legs after prolonged standing). Right heart failure elevates systemic venous pressure, causing peripheral edema. Left heart failure elevates pulmonary venous pressure, causing pulmonary edema.

Decreased plasma oncotic pressure reduces the force retaining fluid in the capillary, allowing increased filtration. This occurs when plasma protein concentration falls, most importantly with albumin loss (nephrotic syndrome) or decreased albumin synthesis (liver failure, malnutrition). Because albumin is the primary determinant of plasma oncotic pressure, hypoalbuminemia produces generalized edema.

Increased capillary permeability allows both fluid and proteins to leak into the interstitium. This increases Kf in the Starling equation and also raises πi as proteins accumulate in tissue, further promoting filtration. Burns, inflammation, sepsis, and allergic reactions all increase capillary permeability. The resulting edema is often protein-rich and can be massive (as in severe burns requiring enormous fluid resuscitation).

Lymphatic obstruction prevents the normal return of filtered fluid and protein to the circulation. Causes include surgical removal of lymph nodes (post-mastectomy lymphedema), radiation damage to lymphatics, parasitic infection (filariasis causing elephantiasis in endemic regions), and malignancy obstructing lymphatic channels. The resulting lymphedema is characteristically high in protein content and, unlike other forms of edema, is non-pitting.

Safety factors against edema help prevent tissue swelling under normal conditions. As fluid accumulates in the interstitium, interstitial hydrostatic pressure rises (reducing the driving force for further filtration), interstitial oncotic pressure falls (as proteins are diluted, increasing the opposing force), and lymphatic flow increases (removing the excess fluid more rapidly). These factors provide a considerable safety margin, so that significant edema develops only when Starling forces are substantially deranged or lymphatics are impaired.

<image>Panel A: Increased Pc showing heart failure with elevated venous pressure backing up to capillaries causing peripheral edema (legs) and pulmonary edema (lungs). Panel B: Decreased pi c showing nephrotic syndrome with albumin loss in urine and liver cirrhosis with decreased synthesis both causing generalized edema. Panel C: Increased permeability showing inflamed capillary with widened gaps, fluid and protein leakage, increased Kf and pi i causing protein-rich edema, with burns illustrated similarly. Panel D: Lymphatic obstruction from surgery, radiation, or filariasis causing non-pitting high-protein lymphedema, with safety factor graph showing Pi rising and pi i falling as interstitial volume increases.</image>

The Lymphatic System

The lymphatic system is a one-way drainage system that returns fluid and protein from the interstitium to the blood, plays a central role in immune function, and absorbs fats from the intestine.

Lymphatic vessels begin as blind-ended initial lymphatics in the tissues. These have a unique structure: the endothelial cells overlap loosely like shingles on a roof, anchored to surrounding tissue by filaments. When interstitial pressure rises, these filaments pull the overlapping cells apart, creating openings through which interstitial fluid—now called lymph—enters. When pressure falls, the overlapping cells close like one-way valves, preventing backflow.

Collecting lymphatics receive lymph from initial lymphatics and transport it toward the bloodstream. These vessels have smooth muscle in their walls and intraluminal valves similar to those in veins. The smooth muscle contracts rhythmically, propelling lymph forward (the lymphatic pump), while the valves ensure unidirectional flow.

Lymph nodes are specialized lymphoid organs interposed along lymphatic vessels. Lymph percolates through the node, where it is filtered of particulate matter and exposed to immune cells. Antigens carried in the lymph activate lymphocytes, initiating immune responses. The nodes also trap metastatic cancer cells, which is why lymph node involvement is important in cancer staging.

The lymph ultimately drains into the venous system. The thoracic duct, the largest lymphatic vessel, receives lymph from the left side of the head and neck, the left arm, and the entire body below the diaphragm; it empties into the venous system at the junction of the left internal jugular and subclavian veins. The right lymphatic duct drains the right upper body and empties into the corresponding right venous junction.

Under normal conditions, approximately 2 to 4 liters of lymph return to the circulation each day. This volume can increase dramatically (10 to 50 times) during inflammation, when capillary permeability and filtration increase markedly.

The lymphatic system serves critical functions. It maintains fluid balance by returning filtered fluid and protein to the blood. It maintains plasma protein concentration by returning leaked proteins. It transports absorbed fats from the intestine (as chylomicrons in the milky intestinal lymph called chyle). It provides immune surveillance, with lymph nodes serving as sites where antigens encounter lymphocytes and immune responses are initiated.

<image>Panel A: Initial lymphatics structure showing blind-ended vessels with overlapping endothelial cells, anchoring filaments, fluid entering through gaps when pressure rises, and collecting lymphatic with smooth muscle wall and intraluminal valves. Panel B: Lymphatic drainage pattern from initial lymphatics to collecting lymphatics with valves to lymph nodes (cross-section showing cortex, medulla, afferent/efferent vessels) to larger trunks. Panel C: Thoracic duct (draining most of body) and right lymphatic duct (right upper body) draining into venous system at internal jugular-subclavian junction, with flow mechanisms (smooth muscle contraction, external compression, respiratory pump). Panel D: Functions summarized: fluid balance (2-4 L/day), protein return (maintaining pi c), fat absorption (lacteals with chyle), and immune surveillance.</image>

Edema

Edema is the abnormal accumulation of fluid in the interstitial space, resulting from an imbalance between capillary filtration and lymphatic drainage.

Edema can be classified by mechanism as reflecting increased capillary hydrostatic pressure, decreased plasma oncotic pressure, increased capillary permeability, or lymphatic obstruction. It can also be classified by distribution as localized (affecting one limb or region) or generalized (affecting the whole body, typically most evident in dependent areas).

Increased capillary hydrostatic pressure causes edema when venous return is impaired. Local venous obstruction (from deep vein thrombosis or tumor compression) causes unilateral limb edema. Heart failure causes bilateral dependent edema: right heart failure causes peripheral edema, left heart failure causes pulmonary edema. The edema is typically low in protein content because the capillary barrier remains intact.

Decreased plasma oncotic pressure from hypoalbuminemia causes generalized edema. Nephrotic syndrome (loss of albumin through damaged glomeruli), liver failure (decreased albumin synthesis), and malnutrition (protein deficiency) are common causes. The edema is generalized because the oncotic pressure deficit affects capillaries throughout the body.

Increased capillary permeability allows protein-rich fluid to leak into the interstitium. Inflammation (whether from infection, injury, or autoimmune disease), burns, anaphylaxis, and sepsis increase permeability. The leaked protein raises interstitial oncotic pressure, further promoting filtration. Third-spacing in burns can sequester enormous volumes, requiring aggressive fluid resuscitation.

Lymphatic obstruction prevents the return of filtered fluid and protein. Post-surgical lymphedema (especially after mastectomy with lymph node dissection), radiation-induced lymphatic damage, and filarial infection (endemic in tropical regions, causing elephantiasis) are causes. Lymphedema is characteristically non-pitting because of its high protein content and eventual tissue fibrosis.

The physical examination distinguishes pitting from non-pitting edema. Pitting edema, where pressure leaves an indentation that slowly refills, is characteristic of edema from elevated hydrostatic pressure or decreased oncotic pressure. Non-pitting edema, where the tissue does not indent or quickly rebounds, is characteristic of lymphedema and myxedema (the mucopolysaccharide-rich edema of hypothyroidism).

Specific distributions provide clinical clues. Peripheral edema (legs, ankles, sacrum in bedridden patients) suggests right heart failure, venous insufficiency, or hypoalbuminemia. Pulmonary edema (with dyspnea, crackles on examination, and characteristic chest X-ray findings) suggests left heart failure. Ascites (fluid in the peritoneal cavity) suggests liver disease or malignancy. Periorbital edema is often seen with nephrotic syndrome and may be more prominent in the morning before gravitational redistribution.

<image>Panel A: Human figure with edema distributions: periorbital (nephrotic syndrome), pulmonary (left heart failure, dyspnea, crackles), ascites (liver disease), peripheral (right heart failure bilateral, DVT unilateral, hypoalbuminemia bilateral). Panel B: Pitting edema (finger pressure leaves persistent depression in low-protein edema) versus non-pitting edema (no indentation in high-protein lymphedema). Panel C: Edema mechanism table: increased Pc (heart failure, DVT), decreased pi c (nephrotic, liver failure), increased permeability (burns, sepsis), lymphatic obstruction (surgery, radiation, filariasis) with characteristic features. Panel D: Pulmonary edema showing alveoli filled with fluid, impaired gas exchange, and chest X-ray appearance (bilateral butterfly infiltrates).</image>

Special Circulations

Different organs have specialized microcirculatory features adapted to their particular functions.

The coronary circulation supplies the highly metabolically active myocardium. A unique feature is that most coronary flow occurs during diastole rather than systole, because myocardial contraction during systole compresses intramural vessels. The coronary circulation is primarily regulated by metabolic factors, especially adenosine, which is released when oxygen demand exceeds supply and causes vasodilation. Because oxygen extraction from coronary blood is already near-maximal at rest (approximately 70 percent), increased myocardial oxygen demand must be met by increased coronary blood flow rather than increased extraction. Autoregulation maintains constant flow over a mean arterial pressure range of approximately 60 to 140 mmHg.

The cerebral circulation supplies the brain, which despite being only 2 percent of body weight receives 15 percent of cardiac output due to its high metabolic demands. The blood-brain barrier strictly controls what enters the brain tissue. Cerebral blood flow is primarily regulated by carbon dioxide: increased PCO2 causes marked vasodilation (important in maintaining brain perfusion during hypercapnia) while decreased PCO2 causes vasoconstriction (the basis for hyperventilation to reduce intracranial pressure). Autoregulation maintains constant flow over a mean arterial pressure range of approximately 60 to 150 mmHg. Sympathetic innervation is minimal; local metabolic control predominates.

The pulmonary circulation differs fundamentally from the systemic circulation. It operates at low pressure (25/10 mmHg compared to 120/80 mmHg systemically) because the thin-walled alveolar capillaries cannot withstand high pressures. Pulmonary vascular resistance is only one-tenth of systemic resistance. A unique response is hypoxic pulmonary vasoconstriction: unlike systemic vessels that dilate in response to hypoxia, pulmonary vessels constrict. This response diverts blood away from poorly ventilated lung regions to better-ventilated regions, optimizing gas exchange. However, global hypoxia (as at altitude or in chronic lung disease) causes widespread pulmonary vasoconstriction and pulmonary hypertension.

The renal circulation is unique in having two capillary beds in series: the glomerular capillaries (where filtration occurs at high pressure) and the peritubular capillaries (where reabsorption occurs at low pressure). The glomerulus operates at a high capillary pressure (approximately 55 mmHg) to drive filtration. Autoregulation over a mean arterial pressure range of approximately 80 to 180 mmHg maintains constant renal blood flow and glomerular filtration rate. Regulation involves the myogenic response and the specialized tubuloglomerular feedback mechanism involving the macula densa.

The cutaneous circulation's primary function is thermoregulation rather than nutrition. The skin contains arteriovenous anastomoses (AVAs), direct connections between arterioles and venules that bypass the capillary bed. Opening AVAs during heat stress allows high blood flow through the skin for heat dissipation. Closing AVAs during cold exposure minimizes heat loss. Sympathetic innervation to cutaneous vessels is dense, allowing rapid adjustments in skin blood flow for temperature regulation.

<image>Panel A: Coronary circulation showing heart with graph demonstrating flow highest during diastole and falling during systole when myocardial contraction compresses vessels, with adenosine-mediated vasodilation. Panel B: Cerebral circulation showing brain with blood-brain barrier (tight junctions, astrocyte foot processes) and CO2 reactivity (increased CO2 vasodilation, decreased CO2 vasoconstriction). Panel C: Pulmonary circulation showing lungs as low-pressure system (25/10) with hypoxic pulmonary vasoconstriction diverting blood from poorly ventilated to well-ventilated alveoli. Panel D: Renal circulation showing two capillary beds in series (glomerular for filtration, peritubular for reabsorption) and cutaneous circulation with arteriovenous anastomoses for thermoregulation.</image>

Clinical Applications

Applying microcirculatory physiology illuminates the pathophysiology of common clinical conditions.

Heart failure causes edema through elevated venous pressure. Left ventricular failure causes blood to back up into the pulmonary veins, elevating pulmonary capillary hydrostatic pressure and causing pulmonary edema with dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Right ventricular failure causes blood to back up into the systemic veins, elevating systemic capillary pressure and causing peripheral edema, jugular venous distension, hepatomegaly, and ascites. Biventricular failure causes both. Treatment with diuretics reduces blood volume and capillary hydrostatic pressure; afterload reduction improves forward flow and reduces venous congestion.

Nephrotic syndrome causes edema through urinary protein loss. Damage to the glomerular filtration barrier allows albumin to leak into the urine (sometimes exceeding 3.5 grams per day). The resulting hypoalbuminemia reduces plasma oncotic pressure, promoting filtration throughout the body. The edema is characteristically periorbital (especially upon waking) as well as peripheral. Treatment addresses the underlying glomerular disease when possible and may include albumin infusion and diuretics.

Burns cause edema through capillary injury. Thermal injury damages capillary endothelium, dramatically increasing permeability. Protein-rich fluid leaks into the interstitium and onto wound surfaces. The volume loss can be massive in major burns, causing hypovolemic shock if not replaced. Fluid resuscitation formulas (such as the Parkland formula) estimate replacement needs based on burn surface area. The leaked protein raises interstitial oncotic pressure, perpetuating the edema.

Lymphedema results from impaired lymphatic drainage. Surgical removal of axillary lymph nodes for breast cancer staging or treatment can cause arm lymphedema. Radiation therapy damages lymphatics, often compounding surgical effects. Filarial infection (Wuchereria bancrofti) blocks lymphatics, causing massive lymphedema of the legs and genitalia (elephantiasis) in endemic tropical regions. Unlike edema from Starling force imbalances, lymphedema is high in protein and becomes progressively fibrotic, eventually becoming non-pitting. Treatment includes compression, manual lymphatic drainage, and in some cases surgery.

Ascites in liver disease involves multiple mechanisms. Portal hypertension from cirrhosis elevates capillary pressure in the splanchnic circulation. Impaired hepatic albumin synthesis reduces oncotic pressure. Sodium and water retention from RAAS activation (triggered by perceived hypovolemia from splanchnic pooling) expands plasma volume. The combined effects produce transudative ascites that may require repeated paracentesis.

<image>Panel A: Heart Failure showing left heart failure with elevated PCWP, pulmonary edema, dyspnea, orthopnea; right heart failure with elevated CVP, peripheral edema, JVD, hepatomegaly; treatment with diuretics and afterload reduction. Panel B: Nephrotic Syndrome showing leaky glomeruli with massive proteinuria, hypoalbuminemia, decreased pi c, generalized edema (periorbital, peripheral), and urine dipstick with heavy protein. Panel C: Burns showing capillary injury, increased permeability, protein-rich fluid loss, and fluid resuscitation formula (Parkland: 4 mL x %BSA x kg). Panel D: Lymphedema showing arm after mastectomy with progressive swelling and leg with filariasis elephantiasis showing massive non-pitting edema with compression therapy illustrated.</image>

Summary

The microcirculation comprises arterioles, capillaries, and venules, with capillaries serving as the exchange vessels. Three capillary types exist: continuous (most tissues, tight junctions), fenestrated (kidney, intestine, endocrine organs), and sinusoidal (liver, spleen, bone marrow).

Transcapillary exchange occurs via diffusion (gases, small solutes), bulk flow (governed by Starling forces), and transcytosis (large molecules).

Starling forces include capillary hydrostatic pressure (Pc, promoting filtration), interstitial hydrostatic pressure (Pi, slightly negative, promoting filtration), capillary oncotic pressure (πc, opposing filtration), and interstitial oncotic pressure (πi, promoting filtration). Net filtration equals Kf times [(Pc - Pi) - σ(πc - πi)].

The lymphatic system returns filtered fluid (2 to 4 liters per day) and protein to the circulation, maintains fluid balance, transports absorbed fats, and provides immune surveillance.

Edema results from increased Pc (heart failure, venous obstruction), decreased πc (nephrotic syndrome, liver failure), increased permeability (inflammation, burns), or lymphatic obstruction. Pitting edema suggests low protein content; non-pitting suggests lymphedema or myxedema.

Special circulations have unique features: coronary (diastolic flow, adenosine regulation), cerebral (blood-brain barrier, CO2 sensitivity), pulmonary (low pressure, hypoxic vasoconstriction), renal (two capillary beds in series), and cutaneous (thermoregulation via AVAs).

Key Terms

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