GEP (Life Protection) Week 2 Flashcards

1
Q

How many vertebrates does the human body have, seperrate them into their sections and what is the strucutre inbetween the discs.

A
  • 33 vertebrae
    -7 cervical
    -12 thoracic
    -5 lumbar
    -5 sacral
    -4 coccygeal

-Intervertebral discs between vertebrae

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2
Q

What are the 4 natural curvature of the spine

A

Cervical lordosis
Thoracic kyphosis
Lumbar lordosis
Sacral kyphosis
-Kyphosis = concave anteriorly and convex posteriorly
-Lordosis = opposite

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3
Q

Name these anatomical areas on the vertebral

A
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4
Q

How many segments is the spinal cord broken down into and what is its function

A

Divided into 31 segments
-Each has a dorsal and ventral roots
-These combine to form mixed spinal nerves
Runs from Brain stem and ends at lower boarder of L1

Functions
Transmits nerve impulses to and from the brain
Mediates important reflexes
Coordinates complex motor sequences

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5
Q

What are spinal cord enlargements and how many are there

A

Cervical
Motor and sensory upper limb supply
Lumbar
Motor and sensory lower limb supply

Enlargement due to the vast bundle of motor and sensory supply in that region.

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6
Q

What are efferents and afferents

A

General Memory Aid: Afferent pathways Arrive, Efferent pathways Eff off

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7
Q

What does dorsal and ventral roots do

A

Dorsal Root
Sensory pathway through the somatic afferent
Autonomic sensory through visceral afferent

Ventral Root
Motor pathways through somatic efferent
Autonomic motor and secretory pathways through visceral efferent

Somatic = Skin, Muscles, Bones and Joints
Visceral = Organs

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8
Q

What is the lymphatic system

A

The lymphatic system is the body’s drainage system

It removes excess fluid from the body

Cleans fluid and returns it to the blood

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9
Q

What is the 3 main functions of the lymphatic system

A

3 main functions:
Tissue drainage
Fat transport
Immune responses

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10
Q

What are the primary and secondary lymphoid organs

A

Primary lymphoid organs = where lymphocytes are made
Thymus: T cells
Red Bone marrow: B cells

Secondary lymphoid organs:
Spleen
Lymph nodes

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11
Q

What is Lymph

A

Lymph = clear fluid that is transported through lymph vessels. In the capillary beds, 20L of fluid per day leak out of the capillaries, 17L are reabsorbed, leaving 3L lost in the interstitium

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12
Q

How does tissue drainage occur in the lymph

A

When there is high pressure in the interstitium in the lymphatic capillary endothelial 1 way mini-valves open absorbing the fluid. When the pressure in the interstitium is less than the pressure in the capillary the endothelial valves are pushed shut.

Lymphatic capillaries merge to form lymphatic vessels, which drain lymph through lymph nodes until lymphatic trunks are formed, and as the lymph vessels get bigger their walls get thicker.

Finally lymphatic trunks converge to form lymphatic ducts: specifically; right lymphatic duct and the thoracic duct

There are no pumps in the lymph system instead SM in walls of lymph vessels squeeze, and skeletal muscle exerts external pressure to keep lymph flowing. Lymph vessels have valves like veins.

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13
Q

What are the 2 main lymph drainage system

A

Right lymphatic duct drains:
R side of head and neck
R side of chest
R upper limb
Drains into the right venous angle: meeting point of the right IJV and R subclavian vein

Thoracic duct drains:
L side of head and neck
L side of chest
L upper limb
Abdomen
Both lower limbs

The thoracic duct begins as the cisterna chyli: dilated sac where lymphatic trunks from lower limbs, abdominal viscera and pelvis converge

The thoracic duct travels through the thoracic cavity and drains into the left venous angle: meeting point of left IJV and subclavian.

Once drained into the right and left venus angles, the lymph from the thoracic duct and the right lymphatic duct mixed with the blood drain into the SVC > right atrium of the heart

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14
Q

How is fat absorbed

A

The lymphatics absorb fats and fat soluble vitamins from the digestive system

The mucosa that lines the small intestine is covered in villi

In each villi there are blood vessels and lymph vessels - lacteals.

The blood capillaries absorb most nutrients but fatty acids (which are packaged into balls of fat: chylomicrons by the small intestine) are too big to move across into capillaries so they go into the lacteals.

The chylomicrons make their way into the thoracic duct and subsequently travel into the venous blood

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15
Q

How does the lymph aid in immune response

A

1) Lymph enters the lymph nodes via the afferent lymphatic vessels
2) Valves stop lymph from flowing in the wrong direction
3) Medullary sinus = densely packed with B-cells, T-cells, macrophages and plasma cells, which will sample and present any antigens and decide what to do
4) Lymph then drain out by the efferent vessel

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16
Q

What is the functions of an antibody

A

Functions:
Opsonize pathogens
Neutralize toxins
Activate complement

Key concept- each B cell produces antibodies with specificity for a single antigen

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17
Q

What does antibody affinity and avidity mean

A

Affinity - the strength of binding at one single sight

Avidity: the total binding strength of an antibody

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18
Q

What is the structure of an antibody

A

Each antibody has 2 identical light chains & two identical heavy chains

Antigen binding Region: Fab
Heavy chains : V, D and J segments
Light chains: V & J

Heavy chains are connected by a double disulphide bond.
Heavy and light chains are connected by a single disulphide bond

Constant region: Fc
Interacts with cell surface receptors
Determined by the heavy and light chain constant genes
C =Constant and Cell surface

19
Q

What is lymphopoiesis

A

Refers to the production of new lymphocytes, including B lymphocytes, T lymphocytes, and natural killer (NK) cells.

20
Q

How does the B-cell develop

A

Developing B cells interact with the stromal cells of the bone marrow: mesenchymal stem cells (which are multipotent differentiating into endothelial cells and macrophages.
Mesenchymal cells supply B cells with adhesion molecules and growth factors: IL-7, which they need to grow and proliferate.

21
Q

How does the B-cell develop step by step

A

Step 1: Starts with a common lymphoid progenitor cell: RAG-1 and RAG-2 are expressed signifying its now an early Pro-B cell

Step 2: D and J segments are spliced together, when D and J segments are successfully spliced then creates a late Pro-B cell

Step 3: The late Pro-B cell has to attach its DJ segment to a V segment which requires VDJ recombinase, once these heavy chains combine the VDJ antigen binding portion of the heavy chain is complete. It then needs to attach to the mu gene. The Mu gene codes for the IgM constant region of the antibody = now a large Pre-B cell.

Step 4: It now tests out if the heavy chain is functional and binds to a surrogate light chain (made of VpreB and lambda 5). The surrogate light chain and complete heavy chain are transported to the cell membrane in a vesicle if they dock correctly to make a functional heavy chain a signal is sent to the nucleus - triggering rapid proliferation = small Pre-B cell

Step 5: The Small Pre-B cells start rearranging its light chains, they all have the same heavy chain, but their own distinct light chain.

There are two types of light chain Kappa and Lambda, Kappa starts first.
If the light chain doesn’t work, the small Pre-B cell either iterates or is killed off = Prevents self-reactive B cells

22
Q

How is B-cell development regulated

A

To prevent self-reactive B cells, there is the AIRE (AutoImmune REgulator) gene
AIRE is expressed in primary lymphoid organs and enables them to express antigens that are normally found all around the body.
It allows primary lymphoid organs to serve as a microcosm of the rest of the body, the primary lymphoid organs test the newly formed B cell in a controlled environment. If it attaches strongly to a self-antigen it is apoptosed. Whereas if it only attaches with intermediate force it rearranges its light chain to reduce affinity to the self antigen. The Pre-B cell creates new VJ rearrangements on their light chain: kappa chromosome 1, then 2, lambda chromosome 1, then 2.

Step 6: Only small Pre-B cells who don’t reactive to self-antigens at all become immature B cells.

Step 7: To get into the blood, the B cell undergoes alternative splicing: some use the mu gene - IgM constant region, whereas some use the delta gene - IgD constant region, but both IgM and IgD have the same antigen binding specificity. When an immature B cell displays both IgM and IgD it can then leave the bone marrow.

23
Q

What are the key checkpoints of B-Cell Development

A

Production:
Pro-B cells undergo heavy chain rearrangement = checkpoint 1 (bone marrow)

Pre-B cells: kappa or lambda light chain rearrangement = checkpoint 2 (bone marrow)

Small pre-B cells are tested for self-reactivity if IgM binds to self ‘antigens’ = apoptosis checkpoint 3

Immature B cells have to express both IgM and IgD before they are deemed mature and can move to secondary lymphoid tissue where they can respond to foreign antigens they encounter (proliferation and development

Antibodies are secreted B-cell receptors, once a B cell has bound to its specific antigen - the B cell will differentiate into a plasma cell - which secretes antibody specific antigens.

24
Q

How does plasma and Memory B-cell production happen

A

B-cells express IgM on surface (BCR)
BCR recognises antigen = engulfs
Presents antigen on MHCII
CD40 expression on cell surface

Meanwhile, macrophage presents the same antigen to naïve CD4+ T-cell
Activates CD4+ into Th2 cells
Th2 cells recognise the antigen

Interaction between B-cell and Th2 via antigen presenting MHCII and TCR
CD40L expression on Th2 interacts with CD40
Cytokine production – IL-4 and IL-21, causing proliferation and differentiation of B-cells into antibody producing plasma cells & memory B-cells

25
What are the 5 main types of Immunoglobins
IgG, IgA, IgM, IgD, IgE
26
What is an amyloid and why is it dangerous for the body
Amyloid = any protein which has assembled abnormally into beta-pleated sheets This renders the protein insoluble The body cannot break down these proteins and there is no inflammatory response to it Slowly it builds up in extracellular spaces leading to cell strangulation and death Gradual organ failure Often undiagnosed until patients are gravely ill due to organ failure Most common affected organs = kidneys, heart, GI tract
27
What is amyloidosis
A group of conditions in which there is an excess deposition of amyloid in tissues Amyloid proteins are designated A followed by an abbreviation to designate the protein of origin AA and AL = most common
28
What are the risk factors of Multiple Myeloma
**Strong** Age >65 years Male 2x higher risk Afro-Caribbean 2x higher risk Obesity **Weak** Family Hx Radiation exposure Epstein-Barr Virus (EBV)
29
What the differential diagnosis of Multiple Myeloma
Skeletal metastases Amyloidosis Osteoporosis Connective tissue disorders Chronic infection Other rarer plasma cell disorders Any other condition that causes lower back pain
30
What is the epidemiology of Multiple Myeloma
1% of all cancers 19th most common cancer Incidence = 10/100,000 Prevalence = 18,000 Mortality = 3100 deaths per year
31
What is the aetiology for Multiple Myeloma
**MGUS - Monoclonal Gammopathy of Unknown Significance** Non-cancerous production of paraprotein (M protein - light chain fragment) Higher risk of developing myeloma **Smouldering Myeloma** Classic M protein and bone marrow myeloma findings but with NO symptoms 50% go on to develop myeloma **Multiple Myeloma** A form of active, malignant leukaemia Extensive and diffuse plasma cell involvement (<60%) Symptomatic - CRAB symptoms
32
What are the clinical features of Multiple myeloma
There are a specific set of symptoms and clinical features that present with Multiple Myeloma, termed CRAB symptoms * hyperCalcaemia Cellular signalling from Il3 + 6 causes increased breakdown and decreased building of bone * Renal dysfunction Buildup of paraproteins in fine capillaries in the nephron Leads to renal dysfunction * Anaemia Bone marrow colonisation of hyperproliferative B cells Less production of erythrocytes * Bone pain Generalised thinning of the bone and local bone damage Collapsing of bones leading to compression fracture **General cancer red flags:** Fatigue Weight loss Loss of appetite Night sweats **Specific myeloma red flag:** Pain that wakes the patient up Pain does not improve with pain relief
33
What are the clinical features of Hypercalcaemia
4 key features * Bones Bony pain * Stones Renal stones * Abdominal groans Nausea Vomiting Constipation Indigestion * Psychological moans Lethargy Depression Memory loss Psychosis
34
What is CRAB, regarding the clinical features of Multiple Myeloma
35
What is the pathophysiology of Multiple Myeloma
**M Cells crowd out the production of blood cells, causing pancytopenia** Causes anaemia Immunsuppression Thrombocytopenia **MM cells overproduce abnormal Igs** Accumulates in kidney Precipitate in tissues Precipitate in blood **MM cells release cytokines →IL-6,IL-3 and DKK1 (there are others too)** Increase osteoclast activity, decrease osteoblast activity Osteolytic lesions Bony pain Hypercalcaemia
36
Why does Multiple Myeloma cause Hypercalcemia
Bones are comprised of: Calcium - Ca2+ Phosphate - PO43- 2 key cells Osteoblasts - build bone (B for Build) Osteoclasts - break down bone (C for Crumble)
37
Why do you get renal impairment with Multiple Myeloma and how.
**3 causes of renal impairment in MM:** Light chain paraprotein deposition Forms casts in the convoluted tubules Forms amyloid which deposits in the glomeruli Hypercalcaemia Renal calculi → insoluble deposits NSAIDs Used to treat bony pain Cause kidney damage Prostaglandin inhibition → revise mechanism
38
What are the investigations for multiple myeloma
**Bloods** FBC Anaemia or leukopenia Calcium Raised in myeloma ESR Increased in myeloma Plasma Viscosity Increased in myeloma U&E For renal impairment **Gene Profiling** Some genes will give a better or worse prognosis **Bone Marrow Biopsy - this is DIAGNOSTIC ** Confirms diagnosis and perform cytogenetic testing **Imaging** Whole-body MRI Whole-body low dose CT Skeletal survey - X-Ray images of the entire skeleton Typically will show well-defined lytic lesions, diffuse osteopenia and abnormal (pathological) fractures Raindrop/pepper pot skull refers to the lytic lesions seen in the skull upon x-ray
39
What are the specialsit investigations for Multiple Myeloma
**Specialist Analysis** * Serum protein electrophoresis (SPEP) Detection of paraproteinaemia Intact paraproteins give a spike in the gamma region of the graph * Serum-free light-chain assay Detection of abnormally abundant light chains Used when SPEP does not detect paraprotein Kappa or lambda - normal is 2:1, abnormal can be >100:1 * Urine protein electrophoresis Detection of Bence Jones Protein - precipitation of light chains Presentation in 75% of cases (heavy and light chain myeloma)
40
What is the management for Multiple Myeloma
**Initial** Oncology and Haematology MDT Coordinate treatment to control the disease **Chemotherapy - VTD Therapy is 1st line in otherwise healthy patients ** Bortezomib (Velcade) Thalidomide Dexamethasone **Stem Cell Transplant** Autologous Using the person’s own stem cells Allogenic Using stem cells from a healthy donor
41
What are the management fro symptoms
**Symptom Management** * Bisphosphonates Osteoclast apoptosis Adverse effect = osteonecrosis of the jaw * Denosumab Decreased osteoclast activity through RANKL inhibition * EPO injections + transfusions Anaemia treatment * Renal Dialysis Avoidance of nephrotoxic drugs (like NSAIDs) * Radiotherapy Bone lesions can improve bone pain * Orthopaedic Surgery Stabilise bones - inserting prophylactic intramedullary rod Treat fractures * Cement augmentation Injecting cement into vertebral fractures or lesions to improve spine stability and pain
42
MICRA VTD (Bortezomib (Velcade), Thalidomide, Dexamethasone)
43
What is the prognonsis of Multiple myeloma
**Prognosis** Survival rate in 15-49 year olds → 74% Survival rate in 80-99 year olds → 25% **Complications** Infection Bone pain Fractures Renal failure Anaemia Hypercalcaemia Peripheral neuropathy Spinal cord compression Hyperviscosity syndrome VTE