Daniel Martingano OMS I Microcirculation Ronald Januchowski, D.O. Gentleman’s Review Daniel Martingano OMS I

Objectives Describe the regulation of regional blood flow by the arterioles Describe the balance between hydrostatic and osmotic forces under normal and abnormal conditions Describe the lymphatic circulation Explain the roles of diffusion, filtration and pinocytosis in transcapillary exchange Apply the concepts above to analyze a patient scenario

Components of Microcirculation Arterioles = resistance Key players in modifying vessel radius via smooth muscle contraction or relaxation Venules = capacitance Capillaries = exchange of gas, water, solutes

Capillary Transport Direct diffusion transport through endothelium Follows Fick’s Law Gases and lipid soluble materials Bulk Flow through Intercellular clefts Important in renal glomerular capillaries (kidneys) Water, ions, glucose Contraction of cells increases movement Filtration through fenestrations Pinocytosis through endothelium (vesicular transport) Slower, but ideal for larger molecules

Case A 54 year old female with a history of heart failure and malnutrition presents 2 hours after a bee sting. She notes swelling in her legs, worse than normal. She also is developing some mild shortness of breath. What’s going on? What would be your treatment?

Physical Factors Affecting Exchange at the Capillaries Hydrostatic pressure Oncotic pressure Permeability of the capillary wall Lymphatics

Net Driving Force NDF = (PC-PI)-σ(πC-πI) σ = resistance based on protein type (most often albumin) Pc = Capillary Hydrostatic Pressure Pi = Tissue (interstitial) Hydrostatic Pressure πC = Capillary Oncotic Pressure πI = Tissue (interstitial) Oncotic Pressure Hydrostatic capillary (and interstitial) pressures Pc – capillary hydrostatic pressure is most affected by changes in venous pressures (vs. arterial pressures) Oncotic capillary (and interstitial) pressures σ=Reflection coefficient – indicates permeability related to proteins influencing the oncotic pressure (0 to 1 – freely permeable to impermeable) Why is there a change from filtration to reabsorption from one end of the capillary to the other?

Net Driving Force When NDF>0, filtration to the interstitial space occurs Hydrostatic pressure (PC-PI) will be greater than oncotic pressure When NDF<0, reabsorption from the interstitial space to the capillary occurs Oncotic pressure σ(πC-πI) will be greater than hydrostatic pressure

Starling Equation = Fluid flux – JV JV = KF∙A∙NDF An increase in any factor will lead to an increase in exchange KF is the filtration constant Barrier physical properties Intrinsic to membrane types Fenestrated () vs. continuous () capillaries Can be influenced by substances such as histamine Increase filtration constant by making membrane more permable A is surface area for exchange Can be dynamic (recruitment of vessels) Jv – amount of fluid filtered or reabsorbed per time Kf – filtration constant A – surface area for exchange NDF – net driving force (positive or negative)

Capillary Types Capillaries from different beds may differ in permeability Within limits capillaries may increase their permeability based on local conditions E.g. increased venous pressure or damage may increase filtration rate Types of Capillaries Continuous – tight, seen in muscle, skin, lungs, and CNS Fenestrated – moderately permeable, seen in GI and Kidney Sinusoidal – very permable, seen in sleep, bone marrow, lymph nodes These are functional definitions. There are other classifications. What’s important here is that capillaries form different beds may differ in permeability. Within limits capillaries may increase their permeability based on local conditions. For example increased venous pressure may increase the filtration rate. Damage within a capillary bed may allow greater filtration. Continuous – muscle, skin, lung, CNS Fenestrated caps – exocrine, renal, intestine Discontinuous – liver, spleen, bone marrow

Relative Permeabilities Substance Molecular Weight Permeability Water 18 1.00 NaCl 58.5 0.96 Urea 60 0.8 Glucose 180 0.6 Sucrose 342 0.4 Inulin 5,000 0.2 Myoglobin 17,600 0.03 Hemoglobin 68,000 0.01 Albumin 69,000 0.001 Data from Pappenheimer JR: Passage of molecules through capillary walls. Physiol Rev 33:387, 1953.

Fluid Balance Capillary filtration and absorption are almost equal (Starling Equilibrium) There is a net filtration across the capillary beds ~2ml/min or 3 L/day for a 70 kg person Lymphatics usually will return this to the general circulation Excess will cause edema

Factors Precipitating Edema Capillary hydrostatic pressure (Pc) Determined by arterial and venous pressures and resistances Arterioles main determinant Increases can lead to increased filtration Caused by increased arterial or venous pressure Increases in venous pressure have a greater effect What factors change hydrostatic pressures in the capillaries?

Factors Precipitating Edema Tissue hydrostatic pressure (Pi) Normally close to 0 Ranges from -4 to 1 mmHg Decreased will increase filtration Influenced by Compliance of surrounding tissue Lymphatic Pump OMT utilizes lymphatic pump to decrease tissue hydrostatic pressure and reduce edema What factors change hydrostatic pressures in the tissues? What organs or sites have limitations to compliance (and therefore can have large increases in hydrostatic pressure with small increases in volume)?

Factors Precipitating Edema Capillary Oncotic Pressure (πC) Decrease caused by decreased protein concentration in blood leads to an increase in filtration Mostly due to the protein albumin More fluid accumulates in the interstitial space as a result A decrease in albumin due to complications such as nephrotic syndrome, protein malnutrition, and liver failure results in decreased oncotic capillary oncotic pressure Capillary oncotic pressure is increased with increases in protein concentration in the blood e.g. dehydration What causes the change increase along the course of the capillary? What factors change oncotic pressures in the capillaries?

Factors Precipitating Edema Tissue Oncotic Pressure (πi) Mainly depends on permeability of capillary An increase in tissue oncotic pressure favors filtration Most often associated with inadequate lymphatic function Conditions resulting in increased tissue oncotic pressure proinflammatory mediators (histamine, bradykinin) damage to capillary structure (burns, trauma)

Factors Precipitating Edema

Back to the case… What are the patient’s medical concerns? Anaphalaxis -> histamine release -> increased capillary permeability -> increased tissue oncotic pressure Malnutrition -> decrease in capillary oncotic pressure -> increased filtration -> increased edema Heart Failure -> venous pooling -> increased capillary hydrostatic pressure -> increased filtration -> increased edema

Back to the case… How are each of these related to causing edema? Edema occurs when the volume of the interstitial fluid exceeds the capacity of the lymphatics’ ability to return it to circulation Each pathology of the case results in conditions favoring filtration which serve to exacerbate edema What would be treatments we would use?

Treatments Diuretics Cardiostimulatory medicines (ionotropic agents) Decrease blood volume -> decrease venous pooling (usually seen in the context of heart failure) -> decrease capillary hydrostatic pressures -> decrease filtration -> allows edema to be cleared Cardiostimulatory medicines (ionotropic agents) Increase stroke volume -> reduce venous pooling -> decreased capillary hydrostatic pressure Elevation of feet Reduce gravity effect -> prevents venous pooling -> decrease capillary hydrostatic pressure Where in the “edema cycle” do each of these treatment options work?

Treatments Elastic compression hose Dietary changes Increased pressure on tissues -> increase tissue hydrostatic pressure -> decrease filtration -> reduce edema Dietary changes Correct malnutrition -> increase capillary oncotic pressure back to normal -> reduce edema

BREAK

The Lymphatics Accessory route for fluids return from the interstitial space Protein return from interstitial space Also involved in immune function

The Lymphatics Composed of endothelium with intercellular gaps surrounded by highly permeable basement membrane and are similar in size to venules Lymphatics in all body systems except: Brain Superficial skin Endomysium of muscles Bones

The Lymphatics Lymph fluid is similar composition of interstitial fluid Water Albumin (~2 g/dl) Larger molecules, fats, bacteria also travel in this system Aided by one-way valves and skeletal muscle contraction

Lymph Flow “Vasomotion” mainly dependent upon interstitial pressures Increased Flow with: Increased capillary hydrostatic pressure (↑Pc) Decreased capillary oncotic pressure (↓πc) Increased interstitial oncotic (↑πi) Increased permeability of the capillaries (↑πi) Sympathetic nerves can cause contraction

Lymph Flow Other factors influencing “Vasomotion” Terminal lymphatic capillaries Activity of the Lymph Pump Contraction of surrounding muscles Movement of body parts Pulsations of arteries near lymph vessels Compression of lymph from external objects / OMT Causing decrease in tissue hydrostatic pressure Ventilation

Lymph Flow Pumping action of lymphatics is thought to produce the negative tissue pressure Valves in the system prevent reverse flow Lower pressure initially up to 100 mmHg at the thoracic duct level

OMT and Lymph Flow Increase in lymphatic flow from use of abdominal and thoracic lymphatic pump

Obstructions to Lymphatic Flow There is a limit to lymphatic flow Tissue pressures > 17 mmHg  flow maximum reached Further increases in pressure will not result in increased flow As interstitial pressures increase, this will close off lymphatics in the area, thereby increasing edema in the interstitial space

Obstructions to Lymphatic Flow Elephantiasis (lymphatic filiariasis) Destruction of lymph system by worms Wucheria bancrofti worms transmitted by mosquitos

Question A 22 year old woman is hospitalized with a history of respiratory distress, fever and fatigue. History, physical and labs determine that she has a viral myocarditis. Over the next few days, she develops significant peripheral edema. What is the most likely cause of her edema? Decreased capillary permeability Decreased arterial pressure Increased plasma protein concentration Increased lymphatic flow Increased central venous pressure

Question An elderly woman complains of edema in her lower extremities. Which of the following would not be helpful in reducing the woman’s edema? Increasing tissue interstitial pressure by wearing compression stockings Elevating her feet as often as possible to reduce venous pressure Giving her a vasodilator drug to reduce precapillary resistance lowering capillary and venous pressures by reducing blood volume through the use of a diuretic drug

Question Your patient with heart failure is on digoxin (a cardiostimulator) to help with symptoms. What is the best explanation how digoxin will help with the heart failure symptom of peripheral edema? Increasing cardiac output will increase peripheral vasoconstriction Tachycardia will increase blood flow from the edematous limbs back to the heart Decreasing blood volume will reduce peripheral edema Increasing cardiac output will decrease hydrostatic capillary pressures Decreasing blood pressure will improve absorption at the capillary beds