Hydrostatic and osmotic pressure are opposing factors that drive capillary dynamics.
Describe hydrostatic pressure and osmotic pressure, the factors of capillary dynamics
- Capillary exchange refers to the exchange of material from the blood into the tissues in the capillary.
- There are three mechanisms that facilitate capillary exchange: diffusion, transcytosis and bulk flow.
- Capillary dynamics are controlled by the four Starling forces.
- Oncotic pressure is a form of osmotic pressure exerted by proteins either in the blood plasma or interstitial fluid.
- Hydrostatic pressure is a force generated by the pressure of fluid on the capillary walls either by the blood plasma or interstitial fluid.
- The net filtration pressure is the balance of the four Starling forces and determines the net flow of fluid across the capillary membrane.
- proteinuria: Excessive protein in the urine, a condition which can alter the net filtration pressure altering flow of fluid across the capillary wall.
- hydrostatic pressure: A pressure generated by fluid on the walls of the capillary, usually forcing water out of the circulatory system.
- net filtration pressure: The balance of the four Starling forces that determines the net flow of fluid across the capillary membrane.
- oncotic pressure: A form of osmotic pressure exerted by proteins in a fluid that usually tends to pull water into the circulatory system.
Capillary exchange refers to the exchange of material between the blood and tissues in the capillaries. There are three mechanisms that facilitate capillary exchange: diffusion, transcytosis, and bulk flow.
Capillary Exchange Mechanisms
Diffusion, the most widely-used mechanism, allows the flow of small molecules across capillaries such as glucose and oxygen from the blood into the tissues and carbon dioxide from the tissue into the blood. The process depends on the difference of gradients between the interstitium and blood, with molecules moving to low-concentrated spaces from high-concentrated ones.
Transcytosis is the mechanism whereby large, lipid-insoluble substances cross the capillary membranes. The substance to be transported is endocytosed by the endothelial cell into a lipid vesicle which moves through the cell and is then exocytosed to the other side.
Bulk flow is used by small, lipid-insoluble solutes in water to cross the the capillary wall. The movement of materials across the wall is dependent on pressure and is bi-directional depending on the net filtration pressure derived from the four Starling forces that modulate capillary dynamics.
The four Starling forces modulate capillary dynamics.
- Oncotic or colloid osmotic pressure is a form of osmotic pressure exerted by proteins in the blood plasma or interstitial fluid.
- Hydrostatic pressure is the force generated by the pressure of fluid within or outside of capillary on the capillary wall.
The net filtration pressure derived from the sum of the four forces described above determines the fluid flow into or out of the capillary. Movement from the bloodstream into the interstitium is favored by blood hydrostatic pressure and interstitial fluid oncotic pressure. Alternatively, movement from the interstitium into the bloodstream is favored by blood oncotic pressure and interstitial fluid hydrostatic pressure.
Transcytosis is a process by which molecules are transported into the capillaries.
Describe the process of transcytosis in capillary exchange
- Transcytosis is the process by which various macromolecules are transported across the endothelium of the capillaries.
- Due to this function, transcytosis can be a convenient mechanism for pathogens to invade a tissue.
- transcytosis: The process whereby macromolecules are transported across the interior of a cell via vesicles.
Transcytosis, or vesicle transport, is one of three mechanisms that facilitate capillary exchange, along with diffusion and bulk flow.
Substances are transported through the endothelial cells themselves within vesicles. This mechanism is mainly used by large molecules, typically lipid-insoluble preventing the use of other transport mechanisms. The substance to be transported is endocytosed by the endothelial cell into a lipid vesicle which moves through the cell and is then exocytosed to the other side. Vesicles are capable of merging, allowing for their contents to mix, and can be transported directly to specific organs or tissues.
Due to the function of transcytosis, it can be a convenient mechanism by which pathogens can invade a tissue. Transcytosis has been shown to be critical to the entry of Cronobacter sakazakii across the intestinal epithelium and the blood-brain barrier.
Listeria monocytogenes has been shown to enter the intestinal lumen via transcytosis across goblet cells. Shiga toxin secreted by entero-hemorrhagic E. coli has been shown to be transcytosed into the intestinal lumen. These examples illustrate that transcytosis is vital to the process of pathogenesis for a variety of infectious agents.
Transcytosis in Pharmaceuticals
Pharmaceutical companies are currently exploring the use of transcytosis as a mechanism for transporting therapeutic drugs across the human blood-brain barrier. Exploiting the body’s own transport mechanism can help to overcome the high selectivity of this barrier, which blocks the uptake of most therapeutic antibodies into the brain and central nervous system.
Bulk Flow: Filtration and Reabsorption
Capillary fluid movement occurs as a result of diffusion (colloid osmotic pressure), transcytosis, and filtration.
Explain the process of filtration and reabsorption in capillaries
- Bulk flow is a process used by small lipid-insoluble proteins to cross the capillary wall.
- Capillary structure plays a large role in the rate of bulk flow, with continuous capillaries limiting flow and discontinuous capillaries facilitating the greatest amount of flow.
- When moving from the blood to the interstitium, bulk flow is termed filtration.
- When moving from the interstitium to the blood, bulk flow is termed re-absorption.
- The kidney is a major site of bulk flow where waste products are filtered from the blood.
- filtration: In bulk flow, this refers to the movement of proteins or other large molecules from the blood into the interstitium.
- reabsorption: In bulk flow, this refers to the movement of proteins or other large molecules from the interstitium into the blood.
Bulk flow is one of three mechanisms that facilitate capillary exchange, along with diffusion and transcytosis.
Bulk Flow Process
Bulk flow is used by small, lipid-insoluble solutes in water to cross the the capillary wall and is dependent on the physical characteristics of the capillary. Continuous capillaries have a tight structure reducing bulk flow. Fenestrated capillaries permit a larger amount of flow and discontinuous capillaries allow the largest amount of flow.
The movement of materials across the capillary wall is dependent on pressure and is bidirectional depending on the net filtration pressure derived from the four Starling forces.
When moving from the bloodstream into the interstitium, bulk flow is termed filtration, which is favored by blood hydrostatic pressure and interstitial fluid oncotic pressure. When moving from the interstitium into the bloodstream, the process is termed reabsorption and is favored by blood oncotic pressure and interstitial fluid hydrostatic pressure.
Modern evidence shows that in most cases, venular blood pressure exceeds the opposing pressure, thus maintaining a positive outward force. This indicates that capillaries are normally in a state of filtration along their entire length.
The Kidneys and Bulk Flow
The kidney is a major site for bulk flow transport. Blood that enters the kidneys is filtered by nephrons, the functional unit of the kidney. Each nephron begins in a renal corpuscle composed of a glomerulus containing numerous capillaries enclosed in a Bowman’s capsule. Proteins and other large molecules are filtered out of the oxygenated blood in the glomerulus and pass into Bowman’s capsule and the tubular fluid contained within. Blood continues to flow around the nephron until it reaches another capillary-rich region the peritubular capillaries, where the previously filtered molecules are reabsorbed from the tubule of the nephron.
Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium, and then the transport of these substances from the interstitium into the bloodstream