Week 5 - Lymphatic System and Associated Disorders Flashcards
Outline the different types and functions of:
c) Supporting cells
produce a connective tissue stroma (‘blanket’) for lymphoid tissues and organs
What clinical features may be associated with splenomegaly?
If portal hypertension… varicose veins, ascites
NOT SURE??
Use the following headings to compare and contrast Hodgkin’s and non-Hodgkin’s lymphoma
b) Likelihood of extranodal involvement
HL - extranodal lymphoid involvement is uncommon
NHL - extranodal lymphoid involvement is common, and features reflect affected organs
How would you introduce the spleen in the setting of a lab exam (structure/function/location)?
- Structure = largest lymphoid organ, roughly the size of a clenched fist and shaped as an ovoid.
- Location = found within the left hypochondriac region or LUQ behind stomach; it is roughly deep to ribs 9-11 and rests on the left colic flexure
- Function = BREWRI Blood filter (macrophages remove debris, foreign matter)
Reservoir (blood, platelets, monocytes)
Erhthropoiesis (involved in production of RBC)
When needed, spleen contracts and releases these substances into the circulation
Recycles by-products of RBC breakdown
Immunity (site for lymphocyte proliferation, surveillance and response)
What strategies can be used to manipulate the human microbiome?
- human nutrition
- antibiotics
- microbial supplementation (probiotic)
Describe the functions of lymphoid tissue
- proliferation site for lymphocytes
- surveillance point for lymphocytes and macrophages
Define microbiota
A collection of microbes
Differentiate a primary lymphoid organ from a secondary lymphoid organ. Provide examples.
Primary lymphoid organ - site of B and T cells maturation e.g. red bone marrow; thymus gland
Secondary lymphoid organ - site where mature B and T cells first encounter their antigens and become activated e.g. lymph nodes, spleen, tonsils, appendix
How would you introduce a lymph node in the setting of a lab exam (structure/function/location)?
Structure - gross structure is covered by dense fibrous capsule, compartmentalised by trabeculae and supported by a stroma of reticular connective tissue
Location - lymph nodes are widely distributed secondary lymphoid organs, clustered along lymphatic vessels
Function - house lymphocytes and macrophages; site of immune system activation; filtering of lymph (microorganisms, debris)
Use the following headings to compare and contrast Hodgkin’s and non-Hodgkin’s lymphoma
c) Compressive features
HL -
- occur secondary to nodal enlargement
- dysphagia, dyspnoea, engorged neck veins, neural compression
NHL -
- occur secondary to nodal enlargement
What name is given to the tumour formed in multiple myeloma?
Plasmacytomas
Provide examples of conditions that have been associated with (i) the GIT microbiome and (ii) the vaginal/urethral microbiome
GIT -
- dental cavities
- peptic ulceration
- obesity
- ulcerative colitis, Crohn’s disease
- irritable bowel syndrome
- sleep, mood, stress disorders
Vaginal and urethral microbiome -
- bacterial vaginosis
- recurrent UTIs
- susceptibility to infection during pregnancy
- pre-term birth
Outline the common sites for the development of plasmacytomas
Intraosseous plasmacytomas - vertebral column, ribs, skull, pelvis, femur, clavicle, scapula
May commonly spread to: lymph nodes, other bones, spleen, liver, kidneys, lungs
List three factors that can influence the flow of lymph
There are many factors affecting flow of lymph:
- rhythmic contraction of lymphatic vessels (thin layer of smooth muscles) and pulsations of nearby arteries
- intermittent pressure on lymphatic vessels (e.g. skeletal muscle contractions, movement of viscera)
- pressure changes in the thorax during respiration
- flow is almost negligible in an immobile limb
- effect of removing lymphatic vessels, leading to lymphoedema
Summarise the pathophysiology of glandular fever – including the progression of the disease and the body’s immune response
- EBV initially infects the oropharynx, nasopharynx and salivary epithelial cells
- later, extends into lymphoid tissues and B cells
Then.. Adaptive immune response:
- unaffected B cells produce antibodies against EBV
- cytotoxic T cells attack virus-infected B-cells directly
- enlargement of lymphoid tissues occurs due to proliferation of lymphocytes and removal of dead/damaged B cells
Define the term multiple myeloma
Lymphoid malignancy of the bone marrow, characterised by the uncontrolled replication of plasma (immunoglobulin-secreting) cells
Describe two functions of the lymphatic system
- circulatory function (returns fluid that has leaked from the vascular system to the blood; transports nutrients, hormones and wastes)
- immunity (lymphocytes housed within lymphoid organs are activated by immune responses; some lymphoid organs also contain macrophages, which engulf foreign material)
Differentiate diffuse lymphoid tissue from lymphoid follicles
- diffuse lymphoid tissue have a loose arrangement of lymphoid cells and reticular fibres; occur in most organs of the body e.g. lamina propria of the GIT
- lymphoid follicles ave a solid, spherical bodies consisting of tightly packed lymphoid cells and reticular fibres; form part of lymphoid organs; have germinal centres of proliferating B lymphocytes
Define glandular fever. How may the disease be transmitted?
Acute infection of B lymphocytes with Epstein-Barr Virus (EBV), also referred to as infectious mononucleosis
Transmitted through close personal contact - most commonly, saliva. i.e. mucosal secretions of the respiratory tract, genital tract, blood
Explain how dysbiosis can potentially lead to disease
Shifts a healthy microbiome to a disease-associated state
Disease can arise when…
- microbiome diversity increases at sites that normally have restricted diversity
- or when there is reduced diversity at body sites that usually have great diversity
The capsule of the spleen also contains elastin and collagen fibres. What ability do these fibres give to the spleen?
Ability to change in size - the spleen can enlarge when the body requires an increased proliferation of lymphocytes
NOT SURE ABOUT THIS ANSWER
Outline the different types and functions of:
b) Auxiliary immune cells
- Macrophages = phagocytosis, enhancement of inflammatory response, presentation of antigens to T cells
- Dendritic cells = present antigens to naive lymphocytes (initiates adaptive immune response)
Define pathogen
An organism that is detrimental to the host or causes disease
Identify common modes of transmission for human immunodeficiency virus
Predominantly through the exchange of body fluids (blood, semen), BUT not transmitted via formites
What clinical features are commonly associated with chronic leukaemia? How does the speed of progression of chronic leukaemia differ to that of acute leukaemia?
- there is an insidious onset of symptoms
- many patients are asymptomatic and diagnosed incidentally via routine blood test
- common initial symptoms include: splenomegaly, extreme fatigue, weight loss, night sweats, fever
speed of progression of clinical features is much slower in chronic versus acute leukaemia
Outline the pathophysiology of HIV
- Entry into cell
- HIV binds to CD4 receptor and chemokine co-receptor on the host cell
- viral envelope and cell membrane fuse
- HIV RNA injected into the host cell’s cytoplasm - Conversion of viral RNA
- HIV RNA converted to double-stranded DNA by the viral enzyme reverse transcriptase
- viral DNA is integrated into the host cell’s DNA by the viral enzyme, integrase - Dormancy
- if host cell is NOT activated, viral DNA remains dormant - Activation
- if host cell is activated by cytokines, the virus proliferates
- the viral enzyme protease modifies new virions - Host cell death
- release of new virions results in host cell lysis (necrosis)
- new virions free to infect other CD4-bearing cells
List five disorders that can result in splenomegaly
RIPLI is SPLENdid
Red blood cell disorders (where the body breaks down abnormal haemoglobin earlier than the normal 120 day period e.g. thalassaemia)
Infections (e.g. glandular fever, TB, syphilis, HIV)
Portal hypertension (e.g. cirrhosis, cardiac failure)
Lymphoid disorders (e.g. leukaemia, lymphoma, multiple myeloma)
Inflammatory conditions (e.g. rheumatoid arthritis, systemic lupus erythematosus)
Define the term lymphoma
Discrete, malignant tumours arising in the lymphatic system (cost commonly lymph nodes)
Define the term cisterna chyli. Where is it located and which vessels contribute to its formation?
It is an enlarged sac formed by the convergence of the lumbar and intestinal trunks (anterior to L1/2 vertebrae)
Outline the body regions drained by the thoracic duct and right lymphatic duct
Right lymphatic duct - Drains right upper limb and right side of head and thorax
Thoracic duct - Drains rest of the body
Explain how leukaemia is classified
Two classification:
- based on the predominant cell of origin (lymphoid or myeloid)
- based on degree of differentiation before the cells become malignant (acute = rapid growth of immature cells, chronic = slow growth of more differentiated cells)
Summarise the general pathway of lymphatic flow from the interstitial space back to the bloodstream
(near capillaries in tissue) Lymphatic capillaries - lymphatic collecting vessels - lymphatic trunks - lymphatic ducts - returns fluid to the venous system (right and left subclavian and internal jugular veins)
Use the following headings to compare and contrast Hodgkin’s and non-Hodgkin’s lymphoma
a) Nature of lymphadenopathy
Same: nodes are typically painless and discrete
Different:
HL - occurs in single or related group of superficial lymph nodes
NHL - usually originate in multiple sites - cervical, axillary, inguinal and femoral nodes commonly affected
HL - spread occurs to adjacent nodes
NHL - spread occurs to non-contiguous nodes
Define commensal
A colonising organism that is neither beneficial nor detrimental
Explain how a lymphadenopathy may be classified. Provide examples for each type of classification
Localised = present in 1 body area
E.g. dental or tonsillar infection (leads to cervical lymphadenitis)
Generalised = present in 2 or more non-contiguous nodal groups
E.g. gandular fever, lymphoma, leukaemia, neoplasia, HIV infection, tuberculosis
Use the following headings to compare and contrast Hodgkin’s and non-Hodgkin’s lymphoma
d) B symptoms and constitutional symptoms
HL -
- have prognostic significance
- unexplained fever, drenching night sweats, unexplained weight loss in preceding 6 months
NHL -
- can also exist
Define dysbiosis
A loss of balance within a microbial community
Valves are especially needed in lymphatic vessels to prevent backflow. Why is this the case?
Lymphatic system lacks a pump, therefore placing a reliance on valves to prevent backflow
Define probiotic
An organism that elicits health benefits to the host
Summarise the clinical features of multiple myeloma. Which features are especially relevant to osteopathic practice?
- often insidious for years
- bone destruction (bony pain, pathological fracture, hypercalcaemia = confusion, weakness, lethargy, thirst, constipation)
- marrow overcrowding (decreased immunity, anaemia)
- overproduction of light-chains (deposited in kidneys as amyloid protein = toxis)
- extraosseous plasmacytomas
- OLD CRABI = OLDer populations, Renal failure, Anaemia, Bony lesions, Infections
List the classes of anti-retroviral medications that can be used in the management of HIV infection.
For each class of medication, briefly describe its mechanism of action (refer to the slides on pathophysiology and pharmacology)
Entrance inhibitors - prevent fusion of HIV membrane with host cell
Reverse transcriptase inhibitors - prevents HIV RNA genome from becoming proviral DNA
Integrase inhibitors - prevents integration of provirus into host cell genome
Protease inhibitors - prevents assembly of virion core
Outline the stages of HIV infection, and associated clinical features
Stage 1: Acute Infection
- ~50% of infected people experience acute illness soon after initial exposure
- due to sudden increase of viruses in the host
- clinical features:
- *non-specific flu-like symptoms, including: fever, night sweats, fatigue, lymphadenopathy, sore throat, headache, photophobia, myalgia, arthralgia, diarrhoea, generalised maculopapular rash
- most symptoms subside in 1-3 weeks, although chronic lethargy, depression and irritability can persist
- HIV antibodies may not be detectable for some months, however, viral transmission is still possible
Stage 2: Chronic Infection (Clinical Latency)
- relatively symptom free +/- lymphadenopathy
- can be 2 months to 20 years before the onset of AIDS (median period is 10 years)
- virus multiplies but is only released sporadically
- CD4+ lymphoctyes gradually decrease
Stage 3: Acquired Immune Deficiency Syndrome
- AIDS can be diagnosed when various criteria are fulfilled
- most common diagnostic criterion met: CD4+ lymphocyte count of <200 cells/mcL
- AIDS-defining conditions
Where does the thoracic duct and right thoracic duct enter the venous system?
Right lymphatic duct - drains into right jugular, subclavian and bronchomediastinal trunks
Thoracic duct - drains into left internal jugular and left subclavian veins
Explain why trauma to the spleen can be potentially life-threatening
Due to the extensive blood supply within the spleen, and its predisposition to be punctured during rib fracture given its location, rupture can lead to extensive haemorrhaging and death.
Explain how lymphoma is classified. What characteristic cell is required for the diagnosis of Hodgkin’s lymphoma?
Traditional classification: Hodgkin’s lymphoma vs non-hodgkin’s lymphoma
Reed-Sternberg (RS) cell is involved in Hodgkin’s lymphoma - it is a distinctive neoplastic cell, that are large and binucleate. They secrete cytokines to promote tumour growth.
Define the term leukaemia
A malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leucocytes. These suppress the production of normal blood cells, leading to anaemia and other symptoms.
Outline the clinical features associated with acute leukaemia. Can you explain the pathophysiological origin of these features?
- rapid onset of symptoms (pts usually present within 3 months)
- proliferation of blast cells overcrowd bone marrow (suppressing formation of other blood cells)
- anaemia (decreased RBCs) = fatigue, pallor, weakness
- decreased immunity (decreased normal WBCs) = fever, mouth ulcers, recurrent infections
- bleeding tendencies (decreased platelets) = gum bleeding, epistaxis
- bone pain (marrow expansion)
- splenomegaly, hepatomegaly, lymphadenopathy (sequestration of blasts)
- non-specific features: anorexia, weight loss, muscle wasting
- nervous system infiltration: headache, vomiting, palsies, visual/auditory changes
What clinical features may be associated with glandular fever?
- long incubation period: 30-50 days
- classical symptoms include fever, sore throat, cervical lymphadenopathy, fatigue
- progression of disease: generalised lymphadenopathy, splenomegaly, heptamegaly (affects multiple glandular tissue)
- rare complications: ocular, cardiac, CNS involvement
List aetiological factors associated with lymphoma
Risk factors include:
- family history
- certain infections e.g. EBV, HIV
- obesity (adipose tissue possesses endocrine and metabolic properties, and have the ability to drive malignant processes)
- iatrogenic immunosupression (e.g. anti-rejection therapy)
- autoimmune conditions (RA, SLE)
- exposure to ionizing radiation or mutagenic chemicals
Describe the normal flow of lymph through a lymph node
- Lymph enters into the lymph node through numerous afferent lymph vessels (on convex side)
- Lymph moves through the subscapular sinus towards the medulla
- Flows occurs through medullary sinuses
- It exits via efferent lymph vessels located at the hilum (indented region on concave side)
Discuss the difference between red pulp and white pulp
White pulp is the site of immune function, composing 25% of tissue and where lymphocytes are suspended on reticular fibre
Red pulp is where RBC and blood-borne pathogens are destroyed, and compose 75% of tissue; there are huge numbers of erythrocytes and macrophages that engulf them
Differentiate the terms lymphadenopathy and lymphadenitis
lymphadenitis = lymphadenopathy + pain + other signs of inflammation
List aetiological factors associated with leukaemia
- exact cause is unknown, likely a complex interplay between environmental and genetic factors
- risk factors include:
- genetic factors
- exposure to cigarette smoke, benzene, ionising radiation
- certain infections (e.g. HIV_
- chemotherapy for the treatment of lymphoma, multiple myeloma, ovarian and breast cancer
- chronic myeloid leukaemia
Considering the functions of the spleen, what special precautions should a patient take post-splenectomy?
- take all precautionary vaccines prior to travelling to a different country
- take precautionary dose of antibiotics prior to travel
Outline the different types and functions of:
a) Lymphocytes
- T-cells = cellular adaptive immunity
- B-cells = humoural adaptive immunity
- Natural Killer cells = innate (non specific immunity)
Explain where immune cells are located within a lymph node (refer to the slide on histological structure)
- Cortex (germinal centres of proliferating B cells; T cells in transit; numerous dendritic cells)
- Medulla (contain numerous B and T cells)
- Lymph sinus (macrophages reside on reticular fibres)
The capsule of the spleen contains smooth muscle fibres. In which situations would this organ need to contract?
Smooth muscle fibres contract when the organ releases erythropoiesis into the blood stream when low levels are detected
Define microbiome
A collection of microbial genomes
