GEP (Life Protection) Week 2 Flashcards
How many vertebrates does the human body have, seperrate them into their sections and what is the strucutre inbetween the discs.
- 33 vertebrae
-7 cervical
-12 thoracic
-5 lumbar
-5 sacral
-4 coccygeal
-Intervertebral discs between vertebrae
What are the 4 natural curvature of the spine
Cervical lordosis
Thoracic kyphosis
Lumbar lordosis
Sacral kyphosis
-Kyphosis = concave anteriorly and convex posteriorly
-Lordosis = opposite
Name these anatomical areas on the vertebral
How many segments is the spinal cord broken down into and what is its function
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
What are spinal cord enlargements and how many are there
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.
What are efferents and afferents
General Memory Aid: Afferent pathways Arrive, Efferent pathways Eff off
What does dorsal and ventral roots do
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
What is the lymphatic system
The lymphatic system is the body’s drainage system
It removes excess fluid from the body
Cleans fluid and returns it to the blood
What is the 3 main functions of the lymphatic system
3 main functions:
Tissue drainage
Fat transport
Immune responses
What are the primary and secondary lymphoid organs
Primary lymphoid organs = where lymphocytes are made
Thymus: T cells
Red Bone marrow: B cells
Secondary lymphoid organs:
Spleen
Lymph nodes
What is Lymph
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
How does tissue drainage occur in the lymph
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.
What are the 2 main lymph drainage system
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
How is fat absorbed
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
How does the lymph aid in immune response
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
What is the functions of an antibody
Functions:
Opsonize pathogens
Neutralize toxins
Activate complement
Key concept- each B cell produces antibodies with specificity for a single antigen
What does antibody affinity and avidity mean
Affinity - the strength of binding at one single sight
Avidity: the total binding strength of an antibody
What is the structure of an antibody
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
What is lymphopoiesis
Refers to the production of new lymphocytes, including B lymphocytes, T lymphocytes, and natural killer (NK) cells.
How does the B-cell develop
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.
What are the key checkpoints of B-Cell Development
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.
How does plasma and Memory B-cell production happen
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
What are the 5 main types of Immunoglobins
IgG, IgA, IgM, IgD, IgE
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
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
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
What is CRAB, regarding the clinical features of Multiple Myeloma
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
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)
MICRA VTD (Bortezomib (Velcade),
Thalidomide,
Dexamethasone)
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
