Capillaries, Lymph and veins

Capillaries

• Primary site for exchange of gases, nutrients, water and waste

• Single cell endothelial cells

• Highest density of capillaries in tissues with oxygen consumption/exchange functions

  • Heart, skeletal, glands, brain

• Lowest density in cartilage and subcutaneous tissue

• Not all capillaries open simultaneously

  • Only 20% of caps are open at rest

  • Regulated by small arteries, arterioles and metarterioles

  • Metarterioles and precapillary sphincters are not innervated and regulated by metabolites

    • Build up of local metabolites will open/close precap sphincter, H+/CO2/Lactate

Metarterioles

Small arteriole that acts as a bypass to get blood form arteriole to venous circulation

 

Continuous capillary

• Intracellular junction, and coated pits

• No leakage

• "well seal"

• Junctions 10-15nm wide

• Blood brain barrier has tight junction, desmosomes

Fenestrated Capillaries

• Membrane-lined holes through the cell

• 20-100nm wide

• Closed by diaphragm

  • Found in intestine, glomerulus and exocrine

  • Need leakiness in glomerulus (kidney, nephron)

Sinusoidal (discontinuous) capillary

• Almost straight mixing between circulation and tissue

• Large gaps between cells

• 100-1000micrometers

• See in liver, bone marrow and spleen

• Facilitate cells entering/exiting circulation

Tight Junction

• Forms at the end of endothelial cells and prevent leakage from macromolecules from capillary

• Membranes are fused

Transcapillary Exchange Mechanism

1. Diffusion, most used mechanism

   1. Small uncharged molecules

      1. Water, small solutes, gasses

2. Filtration, second most used

   1. Leak across fenestrations

3. Bi-directional Vesicular transport

   1. Transcytosis of macromolecules (endo/exocytosis)

   2. Trans endothelial channels

Exchange is dictated by 2 factors

Diffusion and Starling Forces

Diffusion:

1.  Fick's law J = P A ([solute out] - [solute in])

   1. J = flux = quantity move per unit time, P = permeability coefficient, A = cap surface area

   2. Gases: direct diffusion across endothelial membrane

   3. Small solutes: through small pores and clefts

   4. Polar molecules: decreased permeability (poo lipid solubility)

   5. Large molecules: no diffusion 60kDA, remain in cap

Starling Forces

1. Fluid movement across cap occurs by bulk flow, convection

2. Starling forces dictate net fluid movement, hydrostatic and oncotic pressure

   1. Hydrostatic pressure difference: Pcap - Pintersitial but since interstitial is around 0, the difference in pressure is equal to Pressure in capillaries. Basically Blood pressure, higher BP means higher leakiness. Pressure that contributes to push out of capillaries, filtration

   2. Oncotic Pressure Difference: colloid oncotic pressure (by plasma proteins) that creates a pull of fluid back in, anti-filtration. Oncotic cap - oncotic interstitial, oncotic = sigma*R*T*(Ci-Co)

3. Net filtration pressure = Hydrostatic Pressure diff - Oncotic pressure difference

4. Idealized capillary balances filtration and absorption, actual net filtration pressure = 0.33mmHg causing 2-3L of fluid from blood to interstitial fluid

5. Renal glomerulus is example of  cap that mainly filters, interstitial mucosa mainly absorb

Factors that increase net filtration

• Pregnancy, capillary injury, severe burns and inflammation

  • More blood volume than plasma protein in pregnancy, lower oncotic pressure in pregnancy and severe burns

  • Inflammation increase leakiness and open caps

  • Capillary injury causes protein to escape, reduce colloid coefficient

• Dehydration and above decreases plasma protein concentration and lower oncotic pressure

• Standing increases venous pressure as blood pools in the legs

• Hypertension increase pre-capillary hydrostatic pressure

• Low oncotic pressure, higher venous pressure and high hydrostatic pressure increases interstitial fluid  causing edema

• High interstitial fluid can also be when capacity is exceeded, lack of circulation, gland are removed and lymph was blocked by tumors

 

Lymphatic

• Returns proteins and excess interstitial fluid to the bloodstream

• Has closed ends and valve-like inter-endothelial junctions instead of tight junctions

• Fine filaments anchor lymph caps to surrounding tissue, helps to regulate their permeability

  • As fluid increases in the interstitial space, interstitial hydrostatic pressure increases

    • This opens  flaps of endothelial cells open allowing interstitial fluid, proteins and cells to enter

    • Filaments attached to surrounding tissue stretch lymphatic walls and open more as tissue swells

    • Anchoring filaments hold the vessel in place and prevent collapse

Drainage Pathway

• From right side of head and neck drains into the right subclavian vein at its junction with the right internal jugular vein

• From left side of head and neck drains into the thoracic duct

• Lymph below the neck drains into left subclavian vein at junction with left internal jugular 

Lymphatic flow and regulation

2 phases:

Expansion

• Interstitial hydrostatic pressure is greater than lymphatic pressure, inter-endothelial valves open and interstitial fluid enter the initial (terminal) lymphatic

Compression

• Movement of tissue compresses lymphatic vessels, increases lymphatic pressure above hydrostatic and closes inter-endothelial valves

• Forces lymph downstream past secondary valve, valve within vessel

• Skeletal muscle compresses and pumps fluid along

Regulation of Lymphatic flow

• Interstitial pressure

  • Increase net efflux from capillaries increases interstitial pressure, increase lymphatic flow

• Compression forces

  • Skeletal muscle contractions propel lymph to central areas

• Myogenic tones

  • Stretch causes VSM cell contraction and constriction move lymph towards central areas

 

Lymph flow is slow and passive

• 2-3L per day

• Unidirectional and crucial to prevent edema

Pathology

• removal of lymph nodes during breast cancer treatment

  • Cause lymphedema, extensive swelling in hands, arm back, breast or trunk

• Elephantiasis:

  • Extensive swelling of lower half of body

  • Due to obstruction of lymph flow by

    • Parasitic round worm (filariasis)

    • Persistent contact with highly alkali soils (podoconoisis)

Veins

• Tunica intima: endothelial cell

• Tunica media: VSM cells

• Tunica adventitia: connective tissue and nerves

  • Less elastic

• Highly compliant and deformable, gives high capacitance

  • Change volume with little change in pressure = capacitance

  • Allows for venous pooling

  • 70% of blood is on venous side of circulation at rest

  • Helps cardiac output to meet metabolic demand

  • Veins has valve to ensure unidirectional blood flow

  • At low pressure, compliance is high and vein becomes fully rounded

Capacitance and Cardiovascular control

• Passive: passive changes in venous volume (flow changes)

• Active: active changes in venous volume (sympathetic vasoconstriction)

Sympathetic stimulation on Veins

• Increases active constriction of venous VSM

• Constriction of arteriole VSM

  • Decrease flow into vascular bed, decrease venous flow

  • Passive recoil/deformation of veins

• Decreased venous volume = increased venous return = increased cardiac output

Peripheral Capacitance Response

1. Arteriole constriction

2. Increase BP

3. Passive capacitance response, 100% in periphery

4. Increased venous return

5. Increased cardiac output: Frank Starling Law/ Length-tension relatoinship

Splanchnic Capacitance (in abdominal cavity)

1. Venule constriction

2. Empties capacitance reservoir

   1. Empties blood volume in splanchnic circulation

3. Increase venous return

4. Increased cardiac output

5. Arteriole constriction

Varicose Veins

• Venous valve back flux

• Symptoms

  • Heavy/aching legs

  • Ankle swelling

  • Skin discoloration (build up of metabolites)

• Complications

  • Predisposition to syncope (fainting)

  • Intolerance to standing

  • Eczema, dermatitis

  • Thrombophlebitis (lead to pulmonary embolism, deep vein thrombosis, stroke or myocardial infarction, blood clot forms)

• Treatment

  • Compression stockings

  • Elevation of legs

  • Anti-inflammatory/anti-coagulant drugs

  • Removal of the vein