Lymphatic System Flashcards
Function of lymphatic system
The body’s cleansing anddrainage system as well as being a transport route for immune cells and fat.
consists of lymphatic vesselsoperating as a one-waydrainage system(containinglymph) and the lymphoid organs (the roleof which is mainly in hostdefence).
Anatomy of lymphatic system
One way drainage system
Tissue fluid absorbed by initial lymphatics- blind ending lymphatic capillaries to become lymph
Lymph flows in small streams and to bigger channels to lymph nodes
Where is lymph collected and where does it exit the lymphatic system?
Largest lymph vessels collect it from both peripheral (superficial) and central tissues
Lymph draining channels converge on thoracic duct + lymph exits system here to enter great veins of neck
What are lymphoid organs?
Lymphoid organs/tissuesare organized structures within the lymphatic system that support immune responses through lymphocyte production or activationand are important for host defence
What are the primary lymphoid orgas=ns?
Thymus and Bone Marrow
They generate lymphocytes from immature progenitor cells. (responsible for production and maturation of lymphocytes)
What are the secondary lymphoid organs?
Lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT)
where lymphocytes are activated
What are the tertiary lymphoid organs?
acquired loose lymph node-like immune cell clusters in tissues
Develop in response to inflammation
What is the difference in function between the reticuloendothelial system (RES) and the lymphoid organs?
The RES is responsible for phagocytosis and the removal of organic and inorganic material from blood and tissues
The lymphoid organs are responsible for immunity and specifically the production and activation of lymphocytes in order to generate immune responses to microbes
What are the 2 types of lymphatic vessel?
- Initial lymphatic- absorbs fluid and material
2. Collecting lymphatic
Passage of lymph down upper limb
Initial lymphatics generates lymph -> travels downstream through arm to lymph glands in axilla
What type of vessel are collecting lymphatics?
Contractile - have smooth muscle
Also have valves
Lymphatic capillaries vs collecting vessels
Initial lymphatics:
blind ended
no SM
incontinuous basement membrane
Collecting vessels:
SM coverage
luminal valves
basement membrane
What do lymphatic vessels form from?
Cardinal vein (MAIN)
and mesenchymal stem cells
Development of lymphatics
Lymphatic endothelial cells (LECs)
differentiate from venous endothelial cells on the cardinal vein
Expansion and maturation
of LECs proceed via growth factors and specific lymphatic genes
To form lymph sacs
Further expansion and differentiation
produces mature initial
and collecting lymphatics
How do lymphatic vessels work?
Initial lymphatics are passive structures dependent on alternating changes in surrounding tissue hydrostatic and oncotic pressures to drive fluid (and proteins and cells) into and along the vessels
process:
nitial- delicate vessels dependant on pressure changes for lymph formation and transport, pressure wave compresses initial lymphatic w lymph -> empties it and send fluid downstream to collecting vessel
once emptied it can open due to recoil generated by anchoring filaments outside of endothelial cells
recoil generates pressure difference between inside and outside lymphatic = neg pressure inside encouraging fluid to move from tissue into initial lymphatic through gaps between endothelial cells (primary valves)
fluid flows through lymphatic -> equilibirum -> flat valves close and nothing happens until another pressure wave comes along and cycle repeats
How do collecting lymphatics work?
Collecting lymphatics receive lymph
from initial lymphatics and actively
pump lymph towards the lymph node.
Internal valves ensure flow is in one direction
Each section of collecting lymphatic
between two valves, known as a lymphangion, contracts like an individual heart
collecting lymphatics have valves- section between valves that contracts independently- lymph enters section (lymphangion) distends vessel aka muscle relaxes and section fills
then filling point reached -> valve closes and muscle contracts, valve to next section opens and so lymph passes along towards lymph node
this is why lymph can be pumped up a leg against gravity
Process of lymph drainage- when is muscle involved?
Raised interstitial fluid pressure drives tissue fluid into initial lymphatics during relaxation of skeletal muscle.
Next wave of muscle contraction compresses full initial lymphatic and drives lymph drainage downstream towards collecting lymphatics.
Smooth muscle contractions of collecting lymphatics pump lymph towards lymph nodes
Lymph drainage without pumping collecting lymphatics depends on passive effect of skeletal muscle contractions and compression
Main role of lymphatic system
Controls tissue and plasma volume homeostasis
Controls immune cell trafficking and adaptive immunity
Facilitates fat transport
Tissue fluid is drained predominantly by the…
lymphatic NOT venous reabsoprtion
In the steady state all vascular filtrate/interstitial fluid drains via the lymphatic with only periods of transient reabsorption directly back into the blood circulation.
The clinical significance of this new physiology is that all chronic oedema represents lymphatic failure. If one accepts that the composition of lymph in pre-nodal lymphatics is not significantly different from interstitial fluid one could argue that chronic peripheral oedema is no different from lymphoedema (peripheral swelling with accumulation of lymph in the tissues due to inadequate lymph drainage).
Microvascular filtration is governed by what?
Starling principle of fluid exchange
In capillary fluid exchange what acts as a regulator?
The subglycocalyx acts as a regulator or stabiliser for filtration so
the default position is no reabsorption
Revised Starling principle includes interstitial forces as well as hydrostatic and osmotic pressures
Subglycocalyx- plasma proteins held and control osmotic pressure outside of blood and so gradient is controlled by it, acts as a regulator
Process of pitting oedema
Tissue (interstitial) fluid is drained predominantly by the lymphatic and not by venous reabsorption
Blood capillary plasma filtrate becomes interstitial fluid and then lymph. The capillary filtration fluid is the lymph load
Oedema develops when lymph load exceeds lymph drainage
Lymph drainage is the rate limiting step for all oedema and so any chronic oedema is, in principle, a lymph drainage problem
Venous hypertension increases lymph load (fluid filtration from blood capillaries)
Venous oedema occurs when lymph load exceeds lymph drainage for a period of time
Lymphoedema occurs when the dominant fault is with the lymph drainage
Process of pitting oedema
Tissue (interstitial) fluid is drained predominantly by the lymphatic and not by venous reabsorption
Blood capillary plasma filtrate becomes interstitial fluid and then lymph. The capillary filtration fluid is the lymph load
Oedema develops when lymph load exceeds lymph drainage
Lymph drainage is the rate limiting step for all oedema and so any chronic oedema is, in principle, a lymph drainage problem
Venous hypertension increases lymph load (fluid filtration from blood capillaries)
Venous oedema occurs when lymph load exceeds lymph drainage for a period of time
Lymphoedema occurs when the dominant fault is with the lymph drainage
Lymphatics in immune system
Antigen arrives at lymph node and presents to dendritic cells in lymph which then presents to B and T cells –> generates immune response
From lymph node mature B lymphocytes leave bone marrow and T lymphocytes to infection
A tender lymph gland indicates immune response to infection
Lymphatics and fat absorption
Intestinal lymphatics absorb fat
Lacteals - in walls of intestine, absorb fat as lymph and fatty lymph called chyle
Moves downstream through lymphatic vessels to lymph glands where its surveyed for unwanted materials -> goes to collecting point below diaphragm for distribution to organs
If absorption doesn’t happen = protein losing enteropathy (fat malabsorption)
gut becomes inflamed and loses fluid + protein –> diarrhoea
Label the lymph node
Why is an efficient lymphatic system is needed to overcome Covid-19 infection
Lymph vessels absorb the microbes responsible for an infection
and transport them to lymph glands for acquired immunity.
It is in lymph glands where immune cells become sufficiently developed to produce the specific resources to fight an infection such as Covid.
Secondary lymphoid organs
Filters where foreign invaders like microbes are captured and lymphocytes activated
eg lymph nodes, tonsils, Peyer’s patches of small bowel,
MALT (mucosa-associated lymphoid tissue)
spleen
How can lymphatics attract immune cells to site?
CCL21 can attract cells containing CCR7 (receptor) on immune cells
Why does pulmonary oedema occur in heart failure?
Raised pulmonary venous pressure causing increased amounts of interstitial fluid which is not sufficiently cleared by lymph so congesting the lung.
This interstitial oedema spills out into the alveoli and interferes with O2 exchange
Tissue fluid homeostasis
the blood vessels supply fluid, and the lymph drains it away
Tissue fluid is formed from plasma escaping through the blood vessel wall
Tissue (interstitial) fluid drains predominantly as lymph and NOT by venous reabsorption
Left sided heart failure does what to pulmonary capillary pressure? And how does it lead to oedema?
The lung generates lymph even though
pulmonary capillary pressure (10mm Hg)
is much lower than plasma COP (25 mm Hg).
Pulmonary capillaries are in a filtration state because pulmonary interstitial protein concentration is high (70% of plasma). The COP gradient is therefore lower than the Hydraulic pressure gradient.
Left sided heart failure increases pulmonary capillary pressure, increasing filtration. Unless lymph drainage increases accordingly, oedema occurs in lung parenchyma.
Overflow of increased interstitial fluid into alveoli and impairment of O2 exchange
Recommended staging investigation for breast cancer
Sentinel lymph node biopsy
Preferential spread of cancer?
Via lymphatics
Diseases where lymphatic dysfunction involved
Respiratory disease: Asthma, Chronic airways disease
CVS : Hypertension, Plasma volume homeostasis, Atherosclerosis
CNS: Glaucoma, Dementia
Infection: HIV, cellulitis, TB
Immunity: Organ rejection, autoimmunity, wound healing
GI: Crohn’s disease
Cancer Metastases
Obesity
Pitting oedema
Indicates an excess of interstitial fluid
Results from too much fluid filtration from blood vessels overwhelming lymph drainage
or
too little lymph drainage
When plasma ultrafiltration (lymph load) exceeds lymph drainage for a sufficient period of time oedema develops
Venous oedema
Varicose veins or venous engorgement e.g. heart failure, creates high venous pressure and increased microvascular fluid filtration into tissues.If lymph drainage adequate oedema can be avoided
Lymphoedema
Lymphoedema is a chronic swelling due to lymph drainage failure
Lymphoedema occurs when the dominant fault is a failure of lymph drainage with no increase in capillary filtration (normal lymph load) e.g. breast cancer related lymphoedema, elephantiasis
Primary lymphoedema
Primary lymphoedema is due to an inborn, presumed genetic, fault in lymph drainage. Basic science research in the form of genetic studies of patients’ DNA has opened up our understanding of the causes of primary lymphoedema. Identification of mutations in a specific gene provides a cause and a diagnostic test as well as revealing how that gene fault causes the disease. Understanding the mechanism of the disease provides guidance for new treatment.
eg. Milroy Disease due to mutations in the VEGFR3 gene
(Vascular Endothelial Growth Factor Receptor 3 Gene)
Cellulitis
Cellulitis is a common complication of impaired lymph drainage and is often recurrent.
Impaired immune cell trafficking causes a failure to eradicate the infection
Recurrent cellulitis always means a problem with lymph drainage. Up to 50% lymphoedema patients suffer at least one attack of cellulitis
3 lymph function failures causing certain diseases
Lymphoedema arises from a failure of lymph drainage which can be due to damage from external causes or inborn from genetic faults.
A failure of immune cell trafficking leads to infections particularly cellulitis
Disordered lymphatic fat transport can lead to intestinal malabsorption and excess peripheral fat deposition
