1. Microcirculation and Lymphatic System
Prof.Dr. Ümmühan İşoğlu-Alkaç
İ.Ü. İstanbul Tıp Fakültesi
Fizyoloji Anabilim Dalı
YU Medical Faculty,

3. Microcirculation and the Lymphatic System3

6. Structure of the microcirculation and capillary system
The arterioles are highly muscular …
Metarterioles (the terminal arterioles) do not have a continuous muscular coat, but smooth muscle fibers encircle the vessel at intermittent points
Precapillary sphincter between the metarteriole and capillary
The venules are larger than the arterioles and have much weaker muscular coat
Local conditions of the tissues and regulation of blood flow 6

7. Structure of the microcirculation and capillary system7

9. Structure of the capillary wall
Total thickness of the capillary wall is only about 0.5 µm, m2 , 4-9 µm, funct.cell:20-30 µm 9

10. Special types of pores and certain organs
In the brain, junctions between the capillary endothelial cells are mainly “tight” junctions that allow only extremely small molecules such as water, O2, CO2 for passage
In the liver, the opposite is true.
The pores of the gastrointestinal capillary membranes are midway between those of the muscle and liver
In the glomerular structure of the kidney, there are small oval windows on the capillary walls called “fenestrae” (fenestrated capillaries) 10

11. Liver, Bone Marrow, Spleen

12. Flow of Blood in the Capillaries- Vasomotion
Blood usually does not flow continuously through the capillaries
It flows intermittently every few seconds or minutes
This phenomenon is called “vasomotion”
The most important factor to affect the degree of openning and closing of the metarterioles and precapillary sphincters is the oxygen concentration
Average function of the capillary system… 12

14. Exchange of water, nutrients and other substances between the blood and interstitial fluid
Diffusion through the capillary membrane: the most important means for transport of substances between the plasma and interstitial fluid
Lipid soluble substances can diffuse directly through the cell membranes of the capillary endothelium (e.g. O2 and CO2)
Water-soluble, non-lipid-soluble substances diffuse only through intercellular pores in the capillary membrane (e.g. water molecules, Na ions, Cl ions and glucose)
Effect of concentration difference on net rate of diffusion through the capillary membrane 14

15. Exchange of water, nutrients and other substances between the blood and interstitial fluid15

16. Effect of molecular size on passage through the pores
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 16

17. The Interstitium and Interstitial Fluid
Interstitium and interstitial fluid (12 lt, ~1/6¨, mmHg)
Two major types of structures
Collagen fiber bundles
Proteoglycan filaments
Proteoglycan filaments: 98% hyaluronic acid and 2% protein
“Gel” in the interstitium: because of large number of proteoglycan filaments, it is difficult for fluid to flow easily through tissue gel
Interstitial fluid is the same as plasma except it contains low concentrations of proteins
Formation of edema… (%1 free fluid) 17

18. The Interstitium and Interstitial Fluid18

19. Fluid filtration, hydrostatic and oncotic pressures
The hydrostatic pressure in the capillary tends to force fluid and its dissolved substances through the capillary pores into the interstitial spaces
Conversely, colloid osmotic pressure (oncotic pressure) of the plasma proteins tends to cause fluid movement by osmosis from the interstitial spaces into the blood
This oncotic pressure prevents significant loss of fluid volume from blood
Lymphatic system and recovery of proteins from the interstitial space 19

20. Fluid filtration, hydrostatic and oncotic pressures
Starling Powers:
The hydrostatic pressure
Kolloid osmotic pressure (oncotic pressure) 20

21. Capillary hydrostatic pressure (Pc)
Four primary hydrostatic and colloid osmotic forces determine fluid movement through the capillary membrane
Capillary hydrostatic pressure (Pc)
Interstitial fluid (hydrostatic) pressure (Pif)
The capillary plasma colloid osmotic (oncotic) pressure
Interstitial fluid colloid osmotic (oncotic) pressure 21

22. Net filtration pressure
The net filtration pressure is positive, under normal conditions 22

23. Capillary and Interstitial Hydrostatic Pressures
Capillary hydrostatic pressure:
Arterial end of capillary: 30 mmHg
Venous end of capillary: 10 mmHg
Interstitial fluid (hydrostatic) pressure:
The true interstitial fluid pressure is negative, averaging about -3 mmHg
Pumping by the lymphatic system is the basic cause of negative interstitial pressure 23

24. Plasma Colloid Osmotic (Oncotic) Pressure
Proteins in the plasma cause oncotic pressure
Non-permeability of plasma proteins
Normal values: plasma oncotic pressure of normal human plasma is about 28 mmHg
19 mmHg of this is caused by molecular effects of dissolved proteins and 9 mmHg by Donnan effect (i.e. Osmotic pressure caused by Na, K and other cations held in the plasma by proteins)
About 80% of plasma oncotic pressure results from Albumin, 20% from globulin and almost none from fibrinogen 24

25. Interstitial Fluid Colloid Osmotic (Oncotic) Pressure
Although size of the usual capillary pore is smaller than the molecular sizes of the plasma proteins, this is not true for all pores. Therefore, small amounts of proteins leak into the interstitial space
Presence of these proteins cause interstitial fluid oncotic pressure (8 mmHg) 25

26. Exchange of Fluid Volume Through the Capillary membrane
The average capillary pressure at the arterial ends of the capillaries is 15 to 25 mmHg greater than at the venous ends.
Because of this difference, fluid filters out of the capillaries at the arterial end, but it is reabsorbed at the venous end. 26

27. Analysis of the forces causing filtration at the arterial end of the capillary
Forces tending to move fluid outward:
  Capillary pressure (arterial end of capillary) 30
  Negative interstitial free fluid pressure 3
  Interstitial fluid colloid osmotic pressure 8
    total outward force 41
Forces tending to move fluid inward:
  Plasma colloid osmotic pressure 28
Summation of forces:
  Outward
  Inward
    net outward force (at arterial end) 13

28. Analysis of reabsorption at the venous end of the capillary
Forces tending to move fluid inward:
  Plasma colloid osmotic pressure 28
    total inward force
Forces tending to move fluid outward:
  Capillary pressure (venous end of capillary) 10
  Negative interstitial free fluid pressure 3
  Interstitial fluid colloid osmotic pressure 8
    total outward force 21
Summation of forces:
  Inward
  Outward
    net inward force 7

29. Starling Equlibrium for Capillary Exchange
Mean forces tending to move fluid outward:
  Mean capillary pressure
17.3
  Negative interstitial free fluid pressure
3.0
  Interstitial fluid colloid osmotic pressure
8.0
    total outward force
28.3
Mean force tending to move fluid inward:
  Plasma colloid osmotic pressure
28.0
    total inward force
Summation of mean forces:
  Outward
  Inward
    net outward force
0.3

30. Net Filtration Outward forces: 28.3 mmHg Inward forces: 28 mmHg
This slight excess of filtration is called net filtration: 0.3 mmHg
2 ml / min in the body
Abnormal imbalance of forces at the capillary membrane
If the mean capillary pressure rises above 17 mmHg, the net force increases.
As a result fluid will accumulate in the interstitial space and edema will result.
Conversely, if the capillary pressure falls very low, net reabsorption of fluid will occur and blood volume will increase… 30

31. arterial end

32. venous end

33. Vasodilatator theory
According to this theory, greater the rate of metabolism or the less the availability of oxygen or some other nutrients to the tissue, the greater the rate of formation of vasodilatator substances
Adenosine, CO2, adenosine phosphate compounds, histamine, K ions and H ions
Importance of adenosine in local vasodilatation 33

34. Oxygen lack theory for local blood flow control
Vasomotion, metarteriole and precapillary sphincter
Smooth muscle requires oxygen to remain contracted 34

35. Lymphatic System

36. Lymphatic System: Overview
Consists of two semi-independent parts
A meandering network of lymphatic vessels
Lymphoid tissues and organs scattered throughout the body
Returns interstitial fluid and leaked plasma proteins back to the blood
Lymph – interstitial fluid once it has entered lymphatic vessels

37. Lymph vessels from lower parts of the body – Thoracic Duct
Lymphatic System
Exceptions for the lymphatic system: superficial portions of the skin, central nervous system, endomyosium of muscles and bones.
But even these tissues have prelymphatics through which interstitial fluid can flow
Lymph vessels from lower parts of the body – Thoracic Duct 37

38. Lymphatic System
Lymph from the left side of the head, left arm, and parts of the chest also goes into thoracic duct
Lymph from right side of the head, right arm, and parts of the thorax enters the right lymph duct which empties into the venous blood at the right side (juncture of jugular vein and right subclavian vein) 38

39. Lymphatic System: Overview

40. 40

41. Lymphatic Capillaries
Similar to blood capillaries, with modifications
Remarkably permeable
Loosely joined endothelial minivalves
Withstand interstitial pressure and remain open
The minivalves function as one-way gates that:
Allow interstitial fluid to enter lymph capillaries
Do not allow lymph to escape from the capillaries

43. Lymphatic Capillaries
* Total quantity of lymph is normally only 2-3 liters/day
* This lymph is continually absorbed from the tissues by lymphatic capillaries and returned to the blood circulation

44. 44

45. Lymphatic Vessels
A one-way system in which lymph flows toward the heart
Lymph vessels include:
Microscopic, permeable, blind-ended capillaries
Lymphatic collecting vessels
Trunks and ducts

46. Lymphatic Capillaries
During inflammation, lymph capillaries can absorb:
Cell debris
Pathogens
Cancer cells
Cells in the lymph nodes:
Cleanse and “examine” this debris
Lacteals – specialized lymph capillaries present in intestinal mucosa
Absorb digested fat and deliver chyle to the blood

47. Rate of Lymph Flow
Any factor increasing interstitial fluid pressure also increases lymph flow. Such factors include
Elevated capillary pressure
Decreased plasma colloid osmotic pressure
Increased interstitial fluid colloid osmotic pressure
Increased permeability of the capillaries
Maximum lymph flow rate 47

48. Lymphatic Pump
Intrinsic intermittent contraction of the lymph vessel walls
External factors:
Contraction of surrounding skeletal muscles
Movement of parts of the body
Pulsations of arteries adjacent to the lymphatics
Compression of the tissues by objects outside the body
The lymphatic pump becomes very active during exercise 48

49. The lymphatic system lacks an organ that acts as a pump
Lymph Transport
The lymphatic system lacks an organ that acts as a pump
Vessels are low-pressure conduits
Uses the same methods as veins to propel lymph
Pulsations of nearby arteries
Contractions of smooth muscle in the walls of the lymphatics

50. Lymphatic Pump Primary factors that determine the lymph flow:
Interstitial fluid pressure
Activity of the lymphatic pump 50

53. Interstitial Protein Concentration, Fluid Volume and Pressure
The lymphatic system plays an important role in controlling
protein concentrations in the interstitial fluid
volume of interstitial fluid
interstitial fluid pressure
Significance of negative interstitial fluid pressure as a means for holding the body tissues together
Different tissues of the body are held together by connective tissue fibers
Skin sliding over the back of the hand and face
It acts partially as a vacuum pump
In its absence, edema develops. 53

54. Lymph Nodes Their two basic functions are:
Filtration – macrophages destroy microorganisms and debris
Immune system activation – monitor for antigens and mount an attack against them

55. Structure of a Lymph Node