BL 23 Flashcards
Learn the major lymph nodes, lymph tissues and lymph organs
Remember that bone marrow is part of this system!
Organisation of the lymph system, what are the main components of it?
- Lymph
- Lymphatic vessels
- Lymphoid tissues and organs
- Cells contained within the tissues and organs
Description of lymph (what does it contain, it’s pH etc)
A thin fluid that resembles plasma (pH 7.4)
• Lower amounts of protein in lymph compared to plasma
What is chyle?
- Lymph that arises in the GI tract
- White, cloudy substance
- Contains fats and dissolved lipids – Chylomicrons and fat soluble vitamins
How much lymph is produced each day?
Approximately 3-5 litres produced (recycled) each day
Describe lymphatic capillaries structure
- Overlapping endothelial cells. The overlapping endothelial cells have gaps between them (don’t have tight junctions)
- they are blunt ended
- sit in and around blood capillaries in capillary beds
- Fluid enters from capillary bed into the lymph
- Collagen reticular fibres hold the lymph capillaries together (also called anchoring fibres)
- Valves ensure uni-direction of flow
How does lymph move through the lymph capillaries, lymph trunks and lymph ducts? Which direction does lymp flow in the body?
• Direction of lymph flow: Like veins, lymphatic vessels are arranged into superficial and deep (deep to the deep fascia) - Flow is superficial to deep
• Lymphatic vessels tend to lie adjacent to cardiovascular vessels (capillaries, arteries and veins). Pulsations of adjacent ateries also help properl lymph along.
• In the limbs, the deep lymphatics pass through muscles where contraction aids lymph movement
• Larger lymphatic vessels (ducts and trunks), contain smooth muscle cells in their walls e.g. in the abdomen or thorax
- Contraction of smooth muscle is an important contributor to lymph flow at these sites
Does increasing physical activity increase or decrease flow of lymph?
Increases it
Are they are lymphatic vessels in the CNS?
No, there are no lymphatics in the CNS
What is the process called that helps move lymph along the lymph vessels?
Lymphangion compression by local veins and arteries propels the lymph
How does lymph enter the lymph capillary?
- The fluid accumulates in the interstitial space inside tissues after leaking out through the cardiovascular capillaries
- This increases the pressure in the interstitial space.
- The fluid enters the lymphatic capillaries by leaking through the minivalves located in the junctions of the endothelium
Draw out a small mindmap showing how the lymph system links to the cardiovascular system and the ‘progression of lymp vessels’
Comparison of lymphatic capillary to veins
- Low pressure system
- Valves present
- (BUT) no cells (normally)
pic is taken at at 45 degree angle so can see the lymphatic valve. Also can see the vein full of cells
Do lymphatic trunks and ducts still have valves?
Yes they do, the valves are fibrocartilaginous!
What is the cisterna chyli?
The cisterna chyli receives the lymphatic drainage in the abdomen, just posterior to the aorta. It passes through the aortic hiatus of the diaphragm, where it continues as the thoracic duct.
When lymphatic capillaries join together they become…
…trunks
How much ducts are in the body and what are their names?
2 ducts in the body:
Right lymphatic duct
Thoracic duct
What is the role of the lymph ducts?
A lymphatic vessel that empties lymph into one of the subclavian veins
How is lymph drained? (all details including ducts, viens, regions of the body etc)
- Upper right quadrant (above the ambivilus) drained by the right lymphatic duct into the right subclavian vein/internal jugular vein
- Rest of the body: drained by the thoracic duct into the left subclavian vein/internal jugular vein
Capilliaries -> ____ -> ____ -> ____ -> ____
Where else does lymph pass through? (filtering component)
Lymph nodes
How many lymph nodes are in the body?
600-700
Which lymph nodes are the most clinically important?
- Axillae (armpits)
- Neck (cervical)
- Groin (Inguinal)
Lymph node structure (basic structure)
- Shaped like a kidney
- Each node has multiple afferent lymphatic vessels - that enter via the convex surface
- A single efferent lymphatic vessel - that leaves via the concave hilum (concave surface is called the hilum)
(lots of lymph capillaries enter the node, only one lymph trunk leaves the node) - Each lymph node has a feeding artery and draining vein that also enter and leave via the hilum (node’s own blood supply)
- Capsule: this is the browny/yellow colour in the diagram, it is made of connective tissue. It’s extensions are called trabeculae
- Cortex is split into two: out cortex and inner cortex (inner cortex is also called the paracortex)
- Inner portion is called the medulla
Lymph node structure cont. (more detail of the cortex)
- Lymphatic Follicle: In outer cortex of the lymphatic follicle, B lymphocytes are in the lymphatic follicle. Macrophages and follicular dendritic cells are also present in the outer cortex (reticular cells also present).
Actively dividing B-lymphocytes are in the centre of the follicle, they undergo mitotic division and the follicle becomes large. The outer part of the lymphatic follicle is not stimulate B cells. As the B cells in the centre of the follicle are dividing, they have loose structure of chromatin so the centre appears lighter under the microscope, the B cells on the outside which aren’t proliferating are in resting phase, there chromatin is condensed. - Germinal centre - this is the actively dividing B cells in the centre of the lymphatic follicle.
- Inner cortex: T cells. Macrophages and dendritic cells are also present in the inner cortex.
Blood flow is in the germinal centres, as the way the lymphocytes reach the germinal centres is through blood vessels - Medulla is the innermost layer of the lymph node and contains large blood vessels, sinuses, and medullary cords. The medullary cords contain antibody-secreting plasma cells, B-cells, and macrophages.
Journey of lymph through the lymph node
Afferent lymphatics -> subcapsular sinuses -> trabecular sinuses -> medullary sinuses -> efferent lymphatics
- Afferent lymphatics: carry lymph to the lymph node from peripheral tissues. The afferent lymphatics penetrate the capsule of the lymph node on the side opposite the hilum
- The afferent vessels deliver lymp to the subcapsular space, a meshwork of reticular fibres, macrophages and dendritic cells. Dendritic cells are important for initiation of the immune response.
- Lymph next flows into the outer cortex, which contains B cells within germinal centres that resemble those of lymphoid nodules
4, Lymph then flows through lymph sinuses in the deep cortex, which is dominated by T cells
- Lymph continues into the medullary sinus at the core of the lymph node. This region contains B cells and plasma cells.
- Efferent lymphatics have the lymph node at the hilium. These vessels collect lymph from the medullary sinus and carry it toward the venous circulation.
Journey of lymph through lymph node… (diagram to show this)
What connective tissue in lymph nodes?
- Reticulin (collagen 3) (in the capsule and it’s extensions)
How do the immune cells interact in the lymph node?
- Dendritix cell is bringing the bacterium to the macrophage cell
- It presents the bactera to the macrophage that engulfs it
- The macrophage then engulfs the pathogen and produces the antigen-antibody complex
- The dendritic cell present the antigen, whilst T cells come in and are activated
- Activated T cells are passed through the septum into the B cell zone
- This leads to B cells secreting plasma cells
- The plasma cells leave through the efferent lymphatic vessels and start making antibodies
Antibodies then find the bacterium and destroy it
What is the role of follicular dendritic cells?
Follicular dendritic cells cause proliferation of B cells and B memory cells
What type of white blood cell needs antigens to be presented to it?
- T lymphocytes do not recognise antigens (they need to be presented to the antigen)
- B lymphocytes do recognise antigens
How do macrophages, T lymphocytes and B lymphocytes all interact?
APC - means antigen presenting cells
- APC (e.g. the macrophage) interact with T cells
- T cells are presented to the antigen
- T cells then put antigens on their surface
- The specific B cell will recognise it
- The B cell makes an antibody against this antigen
- Antibody interacts with the pathogen
Big difference between B cells and T cells (where they attack)
B cells attack outside the cells
T cells attack inside the cells
Summary of lymph nodes - number of lymph nodes in the body, main role, structure, how lymphocytes enter, how dendritic cells enter, how many cells 1 dendritic cells can activate
- There are about 600 to 700 lymph nodes in the human body
- Serve as ‘filters’ as lymph percolates on its way to the vascular system - traps antigen, processes antigen and macrophage presents processed antigen to T cells
- Repository of macrophages, B cells and T cells that work together to produce an inflammatory response (macrophages, neutrophils) followed by an immune response (B cells, plasma cells, T cells) • Each node has afferent lymphatic vessels that enter via the convex surface and efferent lymphatics that leave via the hilum
- Each lymph node has a feeding artery and draining vein that enter and leave via the hilum
- The majority of lymphocytes enter lymph nodes via the feeding artery (a few in lymph) and the majority leave in the efferent lymphatics
- Most dendritic cells enter with pathogens within lymph
- 1 dendritic cell can activate 1000+ cells
What does lymphadenopathy mean?
Enlarged lymph node
Give reasons for lymphadenopathy?
• As lymph nodes fight infection, the germinal centres fill with increasing numbers of lymphocytes causing the lymph nodes to swell
-> Can cause considerable pain
• Cancers can metastasise to lymph nodes via the afferent lymphatics to also cause swelling
• Lymphoma (malignancy of the lymphoid tissue itself) often presents with lymphadenopathy
-> Hodgkin’s and non-Hodgkin’s lymphoma (need to know names, but no more detail than this)
Where does lymphadenopathy occur?
• Lymphadenopathy can occur in all the nodal regions or affect lymphatic organs
What type of cells are Langerhan cells?
Dendritic cells
Name some lymphatic organs
- Thymus – in the mediastinum
- Bone marrow – red marrow of bone (see lectures # 15 and 16)
- Spleen – left side of abdomen (posterior to stomach)
- Tonsils – in the oropharynx and nasopharynx
- Vermiform Appendix – lower right quadrant of abdomen
- Payer’s patches – under the mucosal membrane of small intestine
Thymus - location
- superior mediastinum
- is fully formed and functional at birth
- involutes after puberty by late teens, is mostly fat
- gradually gets smaller as we age and turns into adipose tissue
Thymus - structure
Similar to lymph node (but no hilium), it has a cortex and medulla
Thymus - Function
• Maturation of bone marrow derived stem cells into immunocompetent T cells (helps T cells become immuno-competent)
Thymus - the type of fibres, diagram
- Capsule and septa made mainly of reticulin/reticular fibres in fairly dense ECM
- Changes in the thymus associated with myasthenia gravis – leads to Myasthenia crisis - inability to swallow because of weakened muscles
- in the diagram - can see germinal centres etc
What happens to the thymus with age?
Hyperplasia of adipose cells with age
Spleen - Location
Largest lymphatic organ, very rich blood supply!
- Inferior to diaphragm
- Posterior to stomach is fully formed and functional at birth
Spleen - Structure
• Similar to lymph node but separated into white pulp (full of lymphocytes) and red pulp (full of erthrocytes)
Spleen - Function
- The spleen filters blood in the same way that lymph nodes filter lymph
- It has functions in both the immune and haemopoietic systems
Functions of the spleen - Immune functions and where this part is position
Immune functions
• Antigen presentation by APCs (macrophages)
• Activation and proliferation of B and T lymphocytes, production of antibodies
• Removal of macromolecular antigen from blood (macrophages do this)
WHITE PULP - this is situated in the medulla region
Functions of the spleen - Haemopoietic function
- Removal and destruction of old, damaged and abnormal erythrocytes and platelets
- Retrieval of iron from erythrocyte haemoglobin
- Erythrocyte storage - after erythrocytes are formed in the bone marrow, can then come and stay in the red pulp
RED PULP - around the outside (cortex)
The spleen - Clinical correlates
- What notable things are linked to the spleen?
The spleen has a very rich blood supply and it has a very thin capsule, it is also relatively fragile and not large quantities of connective tissue
• A ruptured spleen can easily lead to death through exsanguination
• Surgeons often remove the spleen (e.g. trauma)
What is a splenectomy?
Removing the spleen
- The liver and bone marrow can take over the removal and destruction of ageing red blood cells
- Splenectomy increases the risk of infection by encapsulated bacteria (e.g. meningococcus) and malaria,
Splenomegaly
Enlargement of the spleen
- Enlarges in response to localised infection (just like lymph nodes)
- Enlarges in response to systemic infection (glandular fever, malaria, septicaemia)
- Can enlarge to 10x its normal size
What does a ruptured spleen look like?
Top left picture, shows ruptured spleen and lots of blood
Tonsils - location
- Oropharynx (oral cavity) and nasopharynx (nasal cavity)
- Fully formed and functional at birth
- Affected mostly in childhood
- Together constitute Waldeyer’s ring
Tonsils - Structure
Nodules reside inferior to surface invaginations (crypts)
Tonsils - Function
- Prevents pathogen ingress through oral and nasal routes
- Prevents pathogen ingress through aural route (adenoids)
- Crypts increase surface area (for protection of underlying tissues)
Tonsils - clinical correlates
- What causes the swelling? Processes to get to the swelling?
- Surface epithelia have numerous microfold (M-Cells) • Present antigens to underlying immune cells
- Swelling due to B-cell and T- cell proliferation (increase in B and T cells means the tissue swells)
What do swollen palatine tonsils look like?
What do swollen lingual tonsils look like?
What do swollen adrenoids look like?
Image taken with a tube up through the nose
Vemiform appendix - Location
• Inferior to and attached to caecum (ascending colon) (initial part of the ascending colon)
Vemiform appendix - Structure
Nodules reside inferior to surface invaginations (crypts)
Many M-fold cells in epithelial surface
C in pic is referring to crypts
Vemiform appendix - Function
- Prevents pathogen ingress through GI routes (?)
- Prevents pathogen ingress arriving from ileum
- Crypts increase surface area
What does an INFLAMMED appendix look like?
Payer’s patches - Location
• Inferior to and attached to side of ileum
ONLY ON ONE SIDE OF THE LUMEN
Peyer’s patches - Structure
Nodules reside inferior to surface domes
Many M-fold cells in epithelial surface
Peyers patches - Function
Prevents pathogen ingress through digestion
Functions of the lymphatic system - Summary - 4 major functions
1. Fluid balance
• Most of the interstitial fluid is returned to the circulation by this route
2. Transport of fats and fat-soluble vitamins
• Quickest way to send lipid soluble materials from the digestive system to the venous circulation
3. Defence against invading pathogens and disease
• Lymph nodes and other lymphatic organs filter the lymph to remove microorganisms, parasites, foreign particles and [cancer cells]
• ‘Visiting’ T and B lymphocytes and macrophages – motel system
4. Storage of and destruction of aged erythrocytes • The spleen is responsible for this role – liver can take over after splenectomy
Clinical correlates - cancer and lymphoedema (brief explaination of both)… for one of them, need to talk about the sentinel lymph node
More detail for all later
• Sentinel lymph nodes:
- First node to receive lymph from area of a primary tumour
• Primary lymphoedema
- Usually congenital
• Secondary lymphoedema
- Usually medical intervention or immobility
- Occasionally parasite or infections
What is the sentinel lymph node?
• Sentinel lymph nodes:
- First node to receive lymph from area of a primary tumour
How does cancer metastasise? (spread over the body)
- Through newly produced vasculature (angiogenesis and vasculogenesis)
- Through interstitial space (through interstitum)
- Through lymph
Which cancers metasise particularly via lymph?
- Malignant melanoma
- Breast cancer
- Endometrial cancer
How does the cancer ‘prepare’ the lymph, so the lymph can then ‘support’ it when it arrives?
- Tumour cells send out protein vesciles which interact with myeloid cells in the lymph nodes
- this makes the lymph node starting making matrix etc, it does this so when the cancer cell does move, it has the environment in which it can grow. Cancer cells therefore interact with lymphocytes to create a new tumour site
Sentinel lymph nodes in cancer detection
First set of lymph nodes that swell
• Axilla or pectoral in breast cancer – frozen section whilst in theatre (‘old hat’)
• Presence of malignant epithelial cells - mastectomy (this is an operation to remove the breast)
An example where sentinel lymph nodes are used in cancer detection
- Inject a blue dye into the tumour
- The blue dye is able to move through to the nearest lymph node
- When it gets into the lymph node, we use fluorography
- Blue dye is where the cancer cells are
- Surgeons will then go in and remove the lymph node and everywhere with the blue dye as possible
*Therefore, the primary tumour and sentinel lymph nodes are removed. Must leave some lymph nodes behind to drain this area.
Lymphoedema - Primary (causes of this)
Inherited conditions (primary) or mutations. Runs in familes.
Congenital (Milroy’s disease)
• Onset within 2 years
• Cause: mutated FLT4 gene (VEGF-r)
• Small or missing endothelial cells in vessel wall (so don’t get the lymph vessels in the vessel wall, poor movement around the body)
Praecox (Meige’s disease)
• Onset 2- 35 years (familial: 1 in 3)
• Cause: currently unknown
Tarda
• Onset after 35 years
• Cause: currently unknown
Lymphoedema - Secondary (causes)
Neoplasia
• Pelvic masses (pelvic lymph nodes get inflammed or enlarged and stop the flow or fluid from the lower limbs)
• Infiltration of lymph node
Surgery (happens quite a lot!)
• Node involvement
• Accidental (removal of too much lymph nodes, then tissues can’t drain properly, or removal by mistake)
Radiotherapy
• Nodal fibrosis – obstruction of vessel (radiotherapy to remove cancer. Radiotherapy may also damage lymph nodes nearby = fibrosis causes obstruction to the vessel)
Autoimmune Disease
• Rheumatoid arthritis
• Eczema
Infections
• Cellulitis – infection of the lymphatics system leading to obstruction of vessel
• Filariasis – parasitic worm that invades and survives in the lymphatic vessels (parasitic worm blocks the vessel, so stops the lymph from flowing)
Lymphoedema - what is this?
Long term condition - that causes the swelling of the body’s tissues. It can affect any part of the body, but usually develops in upper and lower limbs. It develops when the lymphatic system doesn’t work properly.
Pic of cellulitic, primary - tarda and secondary - filariasis
Cellulitis - infection within the lymphatic system
Second pic - can see necrosis due to poor blood supply
Lymphoedema - Treatments
Lympha Press system - messaging the limb, moving the lymph fluid away from periphery back into the body
Improvement of symptoms - but no known cure
