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2. • Grays anatomy 40th edition.
• Guyton an Hall textbook of Medical Physiology 12th edition
• Cunningham’s Manual of practical Anatomy. 15th edition
Vol.3 Head & Neck and Brain.- G. J. Romanes
• K. Sembulingam – textbook of physiology -3rd edition
• Wheater’s Functional Histology.

3. • Molecular characterization of lymphatic endothelial
cells
– Simona Podgrabinska , Pascal Braun , Paula Velasco, Bryan Kloos,
Michael S. Pepper , David G. Jackson, and Mihaela Skobe
– PNAS December 10, 2002 vol. 99 no. 25 16069–16074
• Characteristics of lymphatic endothelial cells in
physiological and pathological conditions
– R.C. Ji -- Division of Morphological Analysis, Department of Anatomy,
Biology and Medicine, Oita University Faculty of Medicine, Oita, Japan
– Histol Histopathol (2005) 20: 155-175

4. • At the end of the seminar the learner should
be able to know about :
– Lymph and constituents of lymph
– The lymphatic system
– Lymphatic vessel & capillary
– Functions
– Significance
– Lymphatic capillaries & Its special feature

5. • WHAT IS LYMPH ?
• A transparent, usually slightly yellow, often
opalescent liquid found within the lymphatic vessels,
which is collected from tissues in all parts of the
body and returned to the blood via the lymphatic
system.

6. • The body contains three main kinds of fluid:
– Blood,
– Tissue fluid,
– Lymph.
• The blood consists of the
– Blood cells,
– Plasma(fluid portion)

7. • The body contains three main kinds of fluid:
– Blood,
– Tissue fluid
– Lymph.
• When the plasma, without its solid particles and
some of its dissolved substances, seeps through the
capillary walls and circulates among the body
tissues, it is known as tissue fluid or interstitial fluid.

8. • The body contains three main kinds of fluid:
– Blood,
– Tissue fluid
– Lymph.
• When this fluid is drained from the tissues and
interstitial spaces, and collected by the lymphatic
system, it is called lymph.

10. • On an average, about 1/10 of the fluid from the
arterial ends of blood capillaries flows among the
cells; enters the lymphatic capillaries instead to
reabsorb back in the venous ends of the blood
capillaries.
• The total quantity of all this lymph is normally only
2 to 3 liters each day

11. • Constituents:
– It is about 95 per cent water;
– The remainder consists of plasma proteins
and other chemical substances contained in
the blood plasma, but in slightly smaller
percentage than in plasma.
– Its cellular component consists chiefly of
lymphocytes.
water
95%
Plasma
protein
and cells
5%

12. water
95%
Protein
Lipid
Carbohydrates
Amino acids
Nonprotein
Nitrogenous
substances
Electrolytes

13. •Constituents:
• Protein
• The lymphatic system represents an accessory route
through which fluid can flow from the interstitial
spaces into the blood.
• Lymphatics can carry proteins and large particulate
matter away from the tissue spaces.
• Neither of which can be removed by absorption
directly into the blood capillaries.

14. •Constituents:
• Protein
• This return of proteins to the blood from the
interstitial spaces is an essential function without
which we would die within about 24 hours.

15. •Constituents:
• Protein :
»For protein lymphatics is extremely
important because
»high molecular weight (proteins)
hamper its absorption from the
tissues in any other way,
» Although they can enter the
lymphatic capillaries almost
unimpeded.

16. •Constituents:
• Protein :
• Concentration:
• Most tissues in our body
– In interstitial fluid = 2 g/dl,
– lymph flowing from these tissues is near this value.

17. •Constituents:
• Protein :
• Concentration:
• Conversely
• lymph formed in the liver = 6 g/dl (app)
• lymph formed in the intestines = 3 to 4 g/dl (app)
• Because about two thirds of all lymph normally is
derived from the liver and intestines.

18. •Constituents:
• Protein :
• Concentration:
• The thoracic duct lymph, which is a mixture of lymph
from all areas of the body, usually has a protein
concentration of 3 to 5 g/dl.

19. •Constituents:
• Protein :
• Concentration:
• Lymph protein concentration is undergoing continuous
changes depending on the
– Capillary Filtration Rate.
• capillary hydrostatic pressure
– it changes at various body positions

20. •Constituents:
• Protein :
• Concentration:
• Lymph protein concentration is undergoing continuous
changes depending on the
– Metabolic rate of tissues
(muscular activity, temperature)
• Leads to increasing the number of dilated
capillaries (increase in filtration surface area).

21. •Constituents:
• Protein :
• Concentration:
• Concentration in lymph ∞ 1
mol. wt. of
protein
• The larger the molecule the less of it is in lymph
(molecular sieving mechanism).

22. •Constituents:
• Protein :
• Concentration:
• The mean concentration and lymph to serum ratio
(L/S) of some immune proteins in normal lymph
estimated in 24h collected samples are:
• Total protein mean concentration : 3.5 g%
(0.5 during fast walking and 3.8 during night rest).
• L/S= 0.39

23. •Constituents:
• Protein :
• Concentration:
• The mean concentration and lymph to serum ratio
(L/S) of Albumin in normal lymph estimated in 24h
collected samples are:
• Total protein mean concentration : 1.7-3.2 g%
• L/S= 0.13-0.48

24. •Constituents:
• Protein :
• Concentration:
• Levels of individual proteins are arranged according
to molecular weight :

25. •Protein Mean conc.
in lymph
Mean conc.
in serum
Lymph
conc./ Serum
conc.
•Alpha-1-
glycoprotein
0.22 gm%, 0.6-1.2 mg/mL L/s = 0.45
•Prealbumin 0.12 gm% 16-35 mg/mL L/s = 0.35
•Haptoglobin 0.15 gm% 36-195 mg/dL L/s = 0.17
•Beta-lipoprotein 1.11 gm% L/s = 0.2
•Igm 0.23 gm%. 65-132 mg/dL L/s =0.08

26. Protein Mean conc. in
lymph
Mean conc. in
serum
Lymph conc./
Serum conc.
Complement
components:
•C3 0.191 gm%, 8.8-252 mg/ml L/S= 0.21
•C1q. 0.034 gm% 276(+/- 25)
mg/L
L/S= 0.15

27. Protein Mean conc. in
lymph
Mean conc. in
serum
Lymph conc./
Serum conc.
Cytokines
levels:
•TGF β 12 mg/ml, 20-58 ng/ml L/S =1.0
•IL1 β 3.9 pg/ml, 16.5 pg/ml L/S =1.4
•IL6 8 pg/ml, L/S =1.4
•VEGF-C 262 pg/ml, 91.85 pg/ml L/S =1.1

28. •Constituents:
• Lipid :
»The components of lymph lipoproteins are
derived mostly from plasma lipoproteins,
»which cross endothelium by filtration and
possibly also by transcytosis

29. •Constituents:
• Lipid :
• Fasting lymph contained few VLDL and relatively
more lipid in HDL form than in LDL form.
• Lymph also have a higher absolute concentration of
total glycerol in the lipoprotein- free fraction than
same that of plasma.

30. •Constituents:
• Fats:
• After a fatty meal, thoracic duct lymph sometimes
contains as much as 1 to 2 % fat.
• Carbohydrates :
• Glucose level of lymph is usually same as that of
the plasma.
• Electrolytes :
• Ca+ & K+ ion are less; Cl- & HCO3
-
ion are higher
as compare to plasma.

31. •Constituents:
• Amino acids :
• Lymph have amino acid constituents same as that
of the blood serum.
• But usually their concentration are low as compare
to the blood plasma.

32. •Constituents:
• Amino acids :
• Several studies shows that normal amino acid
concentration is higher in blood than in lymph
except for
• Glutamic acid
• Metheonine
• Lysine

33. •Constituents:
• Amino acids :
• But in case of any allergic condition or sensitization
the concentration of amino acids in lymph increases
(except cystine)
• Most highest increase in the concentration is found
in the level of Aspartic acid (more than 10 times.)

34. • All regions of head and neck contains a rich supply
of lymphatics.
• Origin : it is arise from the tissue spaces as
meshwork of delicate vessels.
• Of the estimated 450 lymph nodes in the body-
approximately 60-100 are located in head and neck
region

35. • The lymph nodes and the lymph vessels together
constitutes the lymphatic system.
• Lymph vessels form minute channels which carry
lymph to the lymph nodes.

36. • So the lymphatic system includes
– Lymph
– Lymphatic capillaries & vessels
– Lymph nodes
– Extra nodal Lymphatic organs
• MALT; GALT; BALT
• Thymus
• Spleen
• Tonsils

37. • All these components help to achieve the functions
of the lymphatic system.
– draining of interstitial fluid,
– transportation of lipids,proteins etc.
– fighting infection (immune response).
• They all have a unique one-way structure that
allows interstitial fluid in but not out and also
maintain the unidirectional flow.

38. • Lymphatic capillaries & vessels :
• They are the smallest vessels of the network.
• They are microscopic and have a blind end (Cul-de-
sacs).

39. Lymphatic capillaries & vessels

40. Lymphatic capillaries & vessels

41. • Lymphatic capillaries & vessels:
• Lymphatic capillaries are similar to those of the
blood capillaries, i.e. lined by a single layer of flat
endothelium but they are more permeable because
of fenestrated “porous” endothelium.

42. • Lymphatic capillaries & vessels:
• There are anchoring filaments which extend out
from the lymphatic capillary, attaching lymphatic
endothelial cells to the surrounding tissue.

43. • Lymphatic capillaries & vessels :
• So if there is an accumulation of fluid in an area, the
resulting swelling will cause anchoring filament to be
pulled,

44. • Lymphatic capillaries & vessels :
• Results in opening up of the fenestra wider to
enable them to absorb the excess fluid more rapidly.

45. • Lymphatic capillaries & vessels :
• The lymphatic capillary endothelial cells also contain
a few contractile actomyosin filaments.
• And have been observed to cause rhythmical
contraction of the lymphatic capillaries in same way
as that of small blood vessel and large lymphatic
vessels.

46. • Lymphatic capillaries & vessels :
• Lymphatic capillaries Present in all tissues of the
body except in the

47. • Lymphatic capillaries & vessels :
• The lymphatic capillaries then form lymphatic
vessels, which are larger than capillaries and opens
into lymph nodes.

48. • Lymphatic capillaries & Vessels :
• The Lymph vessels that carry lymph towards lymph
node are referred to as afferent and those that
transport it away from a node are called efferent
vessels.

49. • Lymphatic capillaries & vessels :
• Motion pictures of exposed lymph vessels, show
that when a collecting lymphatic or larger lymph
vessel becomes stretched with fluid.
• The smooth muscle in the wall of the vessel
automatically contracts.

50. • Lymphatic capillaries & vessels :
• Furthermore, each segment of the lymph vessel
between successive valves functions as a separate
automatic pump.
• This fills the subsequent segment, and a few
seconds later it, too, contracts.

51. • Lymphatic capillaries & vessels :
• This process continuing all along the lymph vessel
until the fluid is finally emptied into the successive
lymph node / blood circulation.
• This lymphatic pump can generate pressures as
great as 50 to100 mm Hg.

52. • Lymphatic capillaries & vessels :
• In addition to the pumping caused by intrinsic
intermittent contraction of the lymph vessel walls,
many external factor that intermittently compresses
the lymph vessel also can cause pumping.

53. • Lymphatic capillaries & vessels :
• In order of their importance, such factors are:
– Contraction of surrounding skeletal muscles
– Movement of the parts of the body
– Pulsations of arteries adjacent to the lymphatics
– Compression of the tissues by objects outside
the body

54. • Function of Lymphatics in different parts of body :
• Gastro intestinal tract :-
• Almost all of the fats absorbed from the intestinal tract are
not carried in the portal blood but instead are absorbed into
the intestinal lymphatics and then conducted to the
systemic circulating blood by way of the thoracic duct.
• Bypassing the liver.

55. • Function of Lymphatics in different parts of body :
• Pulmonary system :-
• “Negative Pressure” in Pleural Fluid is always required on
the outside of the lungs to keep them expanded.
• Provided by negative pressure in the normal pleural space.
• The basic cause of this negative pressure is pumping of fluid
from the space by the lymphatics

56. • Function of Lymphatics in different parts of body :
• Pulmonary system :-

57. • Function of Lymphatics in different parts of body :
• Brain :-
• Brain is devoid any true lymphatics.
• Therefore, perivascular spaces, act as a specialized
lymphatic system for the brain.

58. • Function of Lymphatics in different parts of body :
• Brain :-

59. • Clinical significance of Lymphatic vessels:
• Lymphatic Blockage Causes Edema
• lymphatic blockage  plasma proteins leak into the
interstitium  have no other way to be removed  Rise in
protein concentration  raises the colloid osmotic pressure
of the interstitial fluid Draws even more fluid out of the
capillaries. SEVERE EDEMA

60. • Clinical significance of Lymphatic vessels:
• Cause for blockage of lymphatics:
– Infections of the lymph nodes; e.g- Filaria nematodes
– Certain types of cancer.
– After surgery in which lymph vessels are removed or
obstructed.
• For example, large numbers of lymph vessels are
removed during radical mastectomy.

61. • Clinical significance of Lymphatic vessels:
• Cause for blockage of lymphatics:
– Impaired removal of fluid from the breast and arm areas
and causing edema and swelling of the tissue spaces.
– A few lymph vessels eventually regrow after this type of
surgery, so that the interstitial edema is usually
temporary.

63. Special features of Lymphatic vessels and capillaries :
• The lymphatic microvasculature is uniquely adapted for the
continuous removal of interstitial fluid and proteins and is an
important entry point for leukocytes and tumor cells.
• Specialized functions of lymphatics suggest differences
between the lymphatic and blood vascular endothelium.

64. Special features of Lymphatic vessels and capillaries :
• Although endothelial cells (EC) of lymphatic capillaries have
many properties in common with the endothelium of blood
vessels.
• They also have distinct structural characteristics reflecting
their specific functions.
• However, the extent to which the two cell types differ is still
unclear, and few molecules that are truly specific to
lymphatic endothelial cells have been identified to date.

65. Special features of Lymphatic vessels and capillaries :
• Morphologically lymphatic and vascular endothelium cells
differs as
Lymphatic endothelium Vascular endothelium
Endothelium cells are loosely arranged Endothelium cells are closely arranged
Lack basement membrane (not well
defined)
Basement membrane well defined
Lack mural cells Mural cells is present
Numerous invagination and cytoplasmic
vesicle are present
Invagination and cytoplasmic vesicle not
frequently present
Overlapping intercellular junction is seen
(button junction)/ desmosomal like
structure
Adherens junction and tight junction type

66. Special features of Lymphatic vessels and capillaries :
• Morphologically lymphatic and vascular endothelium cells
differs as
Lymphatic endothelium Vascular endothelium
Connected to E.C.M by fine strands of
Elastin fibers- Anchoring fibers
Absent
Valves are present Absent
Contain actinomyosin filaments in it cause
its contraction
Pericytes does this action

67. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic endothelium cells shows several
positive markers of lymphatic vessels
– VEGFR-3
– VEGF-C and VEGF-D (the tyrosine kinase receptor for vascular
endothelial growth factor)
– PODOPLANIN (a glomerular podocyte membrane mucoprotein)
– PROX-1,(the homeobox gene product that is involved in
developmental regulation of the lymphatic system)
– LYVE-1 (a hyaluronan receptor)

68. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic and vascular endothelium cells
differs as
Lymphatic endothelium Vascular endothelium
•At intercellular junction it have
epithelial desmosomal junctions type
component like
•Plakoglobin
•Desmoplakin
Absent
That are usually found to be associated
with VE-Cadherin
Not found with VE- Cadherin
Pletlet endothelium cell adhesion molecule
( PECAM-1 ) present
Absent

69. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic and vascular endothelium cells
differs as
Lymphatic endothelium Vascular endothelium
Distinct Expression Patterns of Vascular Markers in Lymphatic and Blood Vasculature.
•LYVE-1+; is a hyaluronan receptor
(exclusively)
•PAL-E+; a specific blood vascular
marker.
In contrast, CD31 is detected in all vessels,
Levels were lower in the LYVE-1+ve
endothelium
Levels are high in LYVE-1 - ve
endothelium
CD34- ve CD34 +ve

70. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic and vascular endothelium cells
differs as
Lymphatic endothelium Vascular endothelium
Distinct Expression Patterns of Vascular Markers in Lymphatic and Blood Vasculature.
Expression of
Smooth muscle-actin absent
Expression of
Smooth muscle-actin present
A marker of mural cells

71. Special features of Lymphatic vessels and capillaries :
Selective expression of vascular markers in human skin vasculature.
Double immunofluorescent staining for LYVE-1+ (red) and a
PAL-E+ a marker of blood vessels (green), in a 50-m thick section of human
foreskin
•Arrows point to the lymphatics;
•Arrowheads point to blood vessels;
•Dots indicate dermal-epidermal junction

72. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic and vascular endothelium cells
differs as
(B–D) Fluorescent staining for LYVE-1+(red), CD31+ (green),
or both together (merged), respectively, demonstrates that
all LYVE-1+ vessels are also CD31+.

73. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic and vascular endothelium cells
differs as
(E and F) Double-staining for CD34+ (red) and PAL-E+(green)
revealed identical expression pattern in blood vessels (E),
Whereas LYVE-1+ lymphatic vessels (green) do not express CD34 (F)

74. Special features of Lymphatic vessels and capillaries :
• At Molecular level lymphatic and vascular endothelium cells
differs as
(G and H) Smooth muscle actin (red) was colocalized with PAL-E (green)
in blood vessels (G) but absent from LYVE-1+ vessels (H).
•Arrows point to
the lymphatics;
•Arrowheads point
to blood vessels;