Trigger 2 Flashcards
What is Ischemia
restriction in blood supply
What is an atheroma
degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis.
What are the 4 stages of plaque formation
Endotheial Dysfunction
Stable Plaque Formation
T- Cell activation
Plaque repture & blood coagulation
What happens in the endothelial dysfunction stage
Risk factors = ROS, hyperglyceamia, hypercholesterolaemia, hypertension
Monocytes adhere to endothelium via VCAM-1 (vascular cell adhesion molecule-1) & infiltrate
Monocytes become macrophages in intima
Macrophages uptake modified (oxidised & glycated) LDL
Macrophages become foam cells
= Fatty Streak
What happens in the Stable Plaque Formation stage
Many Foam Cells in intima
Vascular Smooth muscle cells migrate from tunica media, proliferate & act like myofibroblasts to produce collagen
Fibrous cap containing collagen fibres forms
What happens in the T- Cell activation stage
Th1 & Th2 recruited & activated
Matrix metalloproteinases (MMPs - produced by foam cells
Proinflammatory cytokines released
MMPs start to break down fibrous cap
What happens in the Plaque repture & blood coagulation stage
MMPs & Proinflammatory cytokines break fibrous cap
Tissue factor released from endothelium
Start of Extrinsic Coagulation Cascade
TF Binds to Factor VIIa (serine protease) & activates (coagulation factors are inactive zymogens)
Catalyses conversion of Factor X → Factor Xa
Initiates common pathway of blood clotting Prothrombin→ thrombin & fibrinogen → fibrin
Blood vessel stenosis, occlusion or thrombi released
What is reperfusion?
Return of blood supply and oxygen
What is the process of reperfusion
O2 returns --> ATP serca pumps restart ROS generated --> damage membranes ER breakdown, Ca2+ released Ca2+ uptake into the mitochondria Mitochondira permability tranistion pores open and Na2+/Ca2+ exchanger reversed --> Ca2+ released Endothelial dysfunction Haemostasis and prothrombosis Pro-inflammatory cytokines released
What is an ishemic stroke
When an artery to the brain is blocked
What is an thrombotic stroke
when a cerebral artery becomes blocked with a clot that formed in the brain blood vessels
responsible for 50% of all strokes
What is an embolic stroke
when an artery becomes blocked with a clot that formed somewhere other than the brain
what is the ischemic cascade
a series of biomechanical reactions that are iniated in the brain and other aerobic tissues after seconds to minute of ischemia
Stages of Ischemic Cascade
decrease in O2 - ATP shortage
anaerobic metabolism –> Lactatic acid production
Na2+ build up in neuron –> water moves in causes cytotoxic odema
Na2+/Ca2+ pumps stop working –> excitotoxicity
Cell membrane broken down by phopholipodase
Mitochondarial breakdown
Casacde dependant cascade –> Apoptosis
Inflammatory response
What are stents used for
placed in an artery as part of percutaneous conorary intervention procedure
small mesh tube
supports narrow or weak arteries
What are Cardiac Markers
molecules that show up in your blood after you heart has been under servere stress due to low oxygen
used in combination with ECG to diagnose heart attacks
What happens to creatine kinase
normally doubles if youve had a heart attack CK-MB expressed by the myocardium appears 4-6 hours after peaks at 24 hours
What happens to troponin levels
cardiac specific troponin I expressed by the myocardium increases 3-12 hours peak 24-48 hours highly sensitive and specific
What does the cerebellum control
coordination of movement, planning and execution of movement, maintenance of posture, and coordination of head and eye movements.
What symptoms would show if an indivdual had a stroke in the cerebellum
A stroke involving the cerebellum may result in a lack of coordination, clumsiness, shaking, or other muscular difficulties. These are important to diagnose early, since swelling may cause brainstem compression or hydrocephalus.
What does the pons control?
participates in balance maintenance of posture and in regulation of breathing. In addition, the pons relays information from the cerebral hemispheres to the cerebellum.
What does the medulla control?
It contains autonomic centers that regulate breathing and blood pressure, as well as the centers that coordinate swallowing, coughing, and vomiting reflexes
Role of the frontal lobe
planning
personality
intelligenece
Brocas area
Role of the parietal lobe
interprets language
interprest signals from vision, hearing, motor, sensory and memory
sensory strip - touch and heat
Role of the occipital lobe
processes and interprets colour, light and movement to vision
Role of the temporal lobe
memory
hearing
wernicks areas
Role of the ryhmicity centre
controls the rate of breathing
contains the Dorsal and ventral respiratory group
Appneustic area
prolongs and slow the rate of breathing
stimulates inspiratory neurons of VRG and DRG
overridden by the pneumotaxic
Pneumotaxic area
inhibirtory impluse, limits breath duration
speeds up breathing
peripheral Chemoreceptors
respond to pH - decrease fall in O2 below 60mmHg increase in H+ inside the cell blocks K+ channels causes a build up of positive charge Ca2+ rushes in causes the release of dopamine vesicles dopamine binds to nerve cells, signal via the vagus nerve to brain, increase breathing
Central chemoreceptors
Increase in CO2
H+ can’t pass through the blood brain barrier, CO2 moves into the CSF
Binds with water via carbonic anhandrayse to form carbonic acid
H2CO3 dissociates into HCO3- and H+
Decrease in pH is detected by chemoreceptors
What does Arterial Blood Analysis measure
The acidity and PO2 and PCO2 in the arteries
how well your lungs are able to move O2 into the blood and remove CO2
What are the normal values for AGB
pH 7.34-7.45 pO2 10-14kPa pCO2 4.5-6 kPa base excess -2 - 2 mmol/L HCO3 22-26 mmol/L
What is the acid base balance
the concentration to hydrogen ions in the body fluids
How is the acid base balance achieved
utiliastion of buffers in extracellular fluid
respiratory mechainsms
renal mechanisms
What is respiratory acidosis
Increased pCO2
decresed pH
hypoventilation (abnormally slow)
What is respiratoty alkalosis
decrease pCO2
increased pH
hyperventilation (fast)
Outline Bicarb reabsorption in the kidenys
Na+/H+ exchanger in luminal membrane, Na+ in, H+ out
H+ combines with HCO3- to form H2CO3
H2CO3 decomposes into CO2 and H2O, catalysed by brush border carbonic anhydrase
CO2 and H2O enter the cell
reaction reversed, H2CO3 formed
Convereted to H+ and HCO3-
HCO3- transported across basolateral membrane via Na+/HCO3- and Cl-/HCO3- transporters
H+ restarts in the cycle
Describe the HIF pathway in Normoxia conditions
PHD1,2,3 are oxygen sensors
hydroxlate HIFa
HIFa is ubiquinated
sends it to the proteasome where is it degraded
Describe the HIF pathway in hypoxic conditions
Low O2, HIFa cant be hydroxlated
HIFa translocates to the nucleus where it combines with HIFb and HRE
Transcribes gene
The genes are involved in - metastasis, cell surival, metabolism, immune response, angiogensis
e.g EPO, VEGF, iNOS
What is the circle of willis
a circle of communincating arteries made up from the cartoid and vertebrobilsilar arteries
Where does the anterior cerebral artery supply and what would be affected in a stroke
Supplies the frontal lobe
stroke results in opposite leg weakness
profound mental symptoms
Where does the middle cerebral artery supply and what would be affected in a stroke
Largest branch on the carotid supplying the frontal, temporal and partieal
most often occluded in stroke
symptoms could be severe, even fatal depending where along the artery it occurs
affects speech, motor and senosry fucntion of the face, hands and arms
Where does the posterior cerebral artery supply and what would be affected in a stroke
stems from the basilar artery, supplying the temporal and occipital lobes
stroke damage is usually secondray to embolsim from lower segments of vertebral basilar system or heart
what are lenticulstriates?
small deep penetrating arteries branching from the middle cerebral artery
How is the intrinsic coagulation pathway activated?
activated when blood comes into contact with sub-endothelial connective tissues or negatively charged surfaces
Outline the steps of the intrinsic pathway
Hageman factor --> factor XII, binds to subendothlial surafce prekallikrein and HMWk also interact Factor XII actiavated --> factor XIIa prekallikrein --> Kallikrein Factor XIIa and Ca2+ activate Factor XI Factor IX activated Factor X activated by IXa and VIIIa Factor Xa is the first molecule of the common pathway
Outline the steps of the extrinsic pathway
Tissue Factor activated
Binds to Factor VII
Factor VIIa, TF, Ca2+ and a phosophlipid activate factor X
outline the steps of the common pathway
Factor Xa combines with Va, Ca2+ and a phospholipid to activate Thrombin from Prothrombin
Fibrogen activated by Thrombin to form Fibrin and XIIIa
Cross linked fibrin clot formed
What is Fibrinolysis
removal of clot of thrombus
outline the steps of fibrinolysis
Plasminogen –> Plasmin via plasminogen activators e.g tPa
Plamsin digest fibriogen, fibrin and Factors II, V and VIII
plasmin attacks fibrinin at least 50 different sites, reducing its size so it no longer has Hameostatic activity
what is excitotoixcity
pathological process by which neurons are damaged and killed by the overactivations of receptors for the excitatory neurotransmitter glutamate
why does excitotoixity occur
Low O2 –> reduced ATP and H+ gradient not maintained = ROS and Ca2+ generation
High Ca2+ activates nNOS, increased ROS
ROS damage dna and membrane proteins leading to activation of caspases (apoptosis)
what happens when Glutamine is present
Glu binds to AMPA in pre synaptic membrane
NA2+ floods in
depolarises membrane
NMPA Mg2+ block is relased allowing Ca2+ to flood in.
low O2, so mitochondria relase Ca2+
VOCC L-type channels opwn so Ca2+ increases
no ATP generated so SERCA and PMCA pumps stop
IP3 binds to IP3R so Ca2+ released from Smooth ER
where is brocas area located and what does it allow
located in the frontal lobe
allows the movements required to speak
where is wernicks area located and what does it allow
in the pareital and temporal lobe
understanding of written and spoken language
Which artery is most frequently occluded in patients with stroke?
Middle Cerebral artery
