Case 1 Independent Learning Flashcards
What are the layers of a vessel wall from inside to outside
Tunica intima, subendothelium, internal elastic lamina, tunica media and tunica adventitia
Describe tunica intima
Also known as endothelum. Composed of endothelium cells and is a continuous membrane
Describe subendothelium
Composed of fibrous collagen which means the blood vessel retains its shape during contraction and expansion
Describe internal elastic lamina
Composed of elastin fibres which means the blood vessel retains its shape during contraction and expansion
Describe tunic media
Composed of smooth muscle fibres, elastin and collagen is fed by the autonomic nervous system which stimulates vasoconstriction or vasodilation
Describe tunica adventitia
Composed of collagen, fibroblasts and elastin which provide support and shape the vessel around the surrounding tissue
What is formed in primary haemostasis
A soft clot involving platelets and von willebrand factor. The soft clot heals the sight of damage however is not strong or stable enough on its own
What happens during secondary haemostasis
The clot is stabilised by fibrin which goes over and through the clot
During primary haemostasis what sticks platelets to the wall of the vessel
von Willebrand factor
What happens when the vessel wall is damaged
Collagen of the subendothelium is exposed resulting in von Willebrand factor changing shape which causes platelets to bind
What happens when platelets bind to the damaged vessel wall
They activate other platelets via platelet aggregation resulting in the formation of a soft clot
What is factor II called when inactive and then when active
II= prothrombin IIa= thrombin
What is factor III called and where does is come from
Tissue factor which comes from outside the blood
What is factor I called when inactive and then when active
I= fibringogen, Ia= fibrin
Where does the the common pathway start
At X being converted to Xa.Va
What is Xa.Va called
Prothrombinase complex
What are the three stages of the current model
Initiation, amplification and propagation
What happens in initiation
Coagulation occurs as surrounding tissue is activated and combines with tissue factor
What happens in amplification
Vessel damage results in primary haemostasis and thrombin activated incoming coagulation factors
What happens in propagation
The negative platelet surface attracts coagulation factors which bind to platelets which results in large amounts of thrombin being produces which is a called a ‘trombin burst’ and results in fibrization
What are the 3 aspects of the classic model
Intrinsic pathway (starts factor XII), extrinsic pathway (starts and factor III) and common pathway (starts at factor X)
What do people with haemophilia A lack
Factor VIIIa
What do people with haemophilia B lack
Factor IXa
Which model explains why haemophiliacs bleed
Only the current model (not the classic)
What do people with Haemophilia C lack
Factor XI
Describe Von Willibrand Type 1 disease
Some levels of VWF deficiency
Describe Von Willibrand Type 2 disease
Normal levels of VWF but it doesn’t function properly
Describe Von Willibrand Type 3 disease
No VWF present at all
Describe thrombocytopathia
Vitamin C deficiency- weakened blood vessels (vitamin C is involved in the formation of collagen present in the vessel wall)
Describe Vitamin K deficiency
Vitamin K is required for the synthesis of certain clotting factors (e.g. prothrombin); disorder of the liver
What type of joint is the knee
A bicondylar synovial joint- 3 articulations
What is the joint between the foot and the lower leg
Synovial joint
What is the function of fibrocartilage
Increases stability of the joint by deepening the articular surfaces, provides shock absorption
What is made of fibrocartilage
Menisci
Where is hyaline cartilage and what is its function
Surrounds ends of the bones and provides a smooth surface
Describe the structure and function of bursae
Filled with synovial fluid for smooth movement
Describe the structure and function of ligaments
A ligament is a bone to bone attachment which limits allowable movements and inhibits unwanted movements, proprioception, can hold tendons in place, made of dense regular tissue
Describe the structure and function of a tendon
Muscle to bone attachments, make muscle contraction more economical, allows the muscle belly to be distant from the site of action, consists of type I collagen and dense regular connective tissue (layers of collagen and fibroblasts)
What is foot drop caused by
Damage to the common fibular nerve
Describe a tibial or fibular fracture (tibia shaft)
Open fracture, the nutrient canal containing the nutrient artery could be damaged causing excessive bleeding
Describe compartment syndrome
Results in swelling (oedma) and subsequent loss of function, increases intra-compartmental pressure
Describe ACL damage
hyperextension (not landing properly when jumping), tend to be complete ruptures
Describe PCL damage
Dashboard injury, tend to be more partial tears
Describe medial ligament damage
Pain on medial rotation and medial meniscus
Describe lateral ligament damage
Pain on lateral rotation
What is the function of the patella
To increase the angle at which the joint can act (patellar ligament)
Describe the peroneal nerve
Also known ad the deep fibular nerve. branch of the sciatic nerve (L4-F3), trauma or injury to the knee are common causes of damage
Describe A delta fibres
Sharp pain, myelinated
Describe C fibres
Dull, achy pain, polymodal
What is secondary hyperalgesia
Increase in pain sensitivity due to build-up of substance P in dorsal horn
What is the role of nociceptors in the joint capsule
Release neuropeptides such as substance P
What is the release of substance P required for
Stimuli to be perceived as moderate to intense pain
What do all primary sensory neurones use as their main excitatory transmitter
Glutamate
What other neurotransmitters do nociceptive afferents use
Substance P or CGRP
What does substance P stimulate
Release of histamine from mast cells and causes vasodilation which contributes to teh inflammatory response
What does CGRP do
Promote vasodilation
What do histamine, prostaglandins and bradykinin do
Increase the sensitivity of nociceptive sensory endings
What is primary hyperalgesia
Histamine, prostaglandins and bradykinin increasing the sensitivity of nociceptive sensory endings
What can NMDA receptor antagonists be used as
Analgesics
What happens when there is prolonged stimulation of nociceptors
Build up of substance P in dorsal horn accompanied by progressive increase in activity of nociceptove pathways which is associated with changes in the responsiveness of NMDA type gulamate receptor which may lead to long term potentiation of synapses in pain= secondary hyperalgesia
What is allodynia
Touch sensory neurones may start to generate the sensation of pain
What do spinothalamic neurones receive input from
Both nociceptive and touch sensitive sensory neurones
Describe the action of nociceptors on spinothalamic neurones
Stimulate spinothalamic neurones leading to perceieved sensation of pain
Describe the action of mechanoreceptors on spinothalamic neurones
Low threshold mechanoreceptors stimulate spinothalamic neurones only weakly which is not perceived as pain
What closes the gate to pain pathway
Stimulation of low threshold mechanoreceptors
Where are cutaneous receptors located
In the skin
Where are somatic receptors located
In the body e.g. joint teceptors and golgi tendon organs (detect tensile force in the tendons)
What triggers the inflammatory response
Cytokines released by sentinel macrophages
What are the macrophages activated by in inflammation
Macrohphages are activated by PAMP’s (pathogen associated molecular patterns) expressed on the pathogen tnan can bind and activate PRRs including the toll-like receptor
What are the main cytokines produced by macrophages
IL-1, IL-6, IL-8, IL-12, TNFα
How does TNFα work
It is able to act on the local endothelium to make it leaky, thereby allowing the entry of blood plasma containing complement proteins.
What does TNFα release result in
Up-regulation of adhension receptors on teh endothelial cell to permit the binding and extravastion of blood neutrophils.
What is oedema
The medical term for fluid retention in the body, the build-up of fluid causes affected tissue to become swollen. Swelling outside the joint
What contribute activation product also contributes to inflammation
C5a
What are prostaglandins derived from
Membrane phospholipids
What are prostaglandins produced in response to
IL-1β and TNFα mediated activation of phospholipid A2
What do prostaglandins play a role in
Inflammation, induce vasodilation and contribute to pain (reduce the threshold for sensing pain)
What do NSAIDs such as aspirin and ibubrofen inhibit
Prostaglandin synthesis and thereby reduce the inflammation and pain
Describe C3 convertase
Cleaves C3 into C3a and C3b, also cleaves C5 into C5a and C5b
Describe the role of C3b
Involved in opsonisation, circulated in the blood, generated C3 convertase, C3b binds to C5 which allows it to be cleaved by the convertase
What is C3a needed for
Mast cells to degranulate
What is C5a needed for
Mast cells to degranulate
What is haemarthrosis
Bleeding in the joint, normally causes by an injury resulting in rapid swelling
If a swollen knee develops a few hours-days after an injury what is it most likely due to
An increase in synovial fluid in the joint
What is knee effusion
An increase of synovial fluid in the joint (swelling in the joint
What does (P)RICE stand for
Protection, rest, ice, compress, elevate
Which antibody crosses the placenta
IgG
Which antibody is found in breast milk
IgA
