The Relevant Properties of Blood - Essay Example

?Brain MRI Review the relevant properties of blood, and the changing MRI appearance of haemorrhage in the brain over time. Within a few seconds ofan ischemic stroke, microscopically, changes are already seen with the rupture of the blood vessel wall. Within a few minutes from the initial rupture, a haematoma forms and appears as bright red acute haemorrhage and on a microscopic level there is an extravasation of the blood (Chakrabarty and Shivane, 2008). From a few minutes to the next few hours of the initial incident, a space-occupying effect would become apparent with blood filling, distorting, and compressing of the surrounding tissue (Chakrabarty and Shivane, 2008). An increased intracranial pressure would be seen, including brain stem compression. The lysis of the erythrocytes would also occur. Within the next few hours of the stroke, a peri-haematoma oedema and ischemia would develop and increase the space-occupying effect (Chakrabarty and Shivane, 2008). Within the next 2-3 weeks, the ischemia would manifest as brown discoloration. On the microscopic level, haemosiderin would form and phagocytosis by the macrophages would also occur. Astrocytes hypertrophy and new blood vessels would be seen at the margin of the haematoma (Chakrabarty and Shivane, 2008). In the next few months, a friable brown clot would become apparent and there would be an organization of the haematoma through phagocytosis of the blood and necrosis in the macrophages. From such point until the next few years, there would be a cavity which would contain blood-stained fluid in the area where the ischemia shall have occurred. The blood would also continually be resorbed (Chakrabarty and Shivane, 2008). The MRI seeks to establish the presence of blood in brain haemorrhages. It also seeks to localize the various haemorrhages, to determine if it is extra-axial, to distinguish subarachnoid haemorrhages, subdural hematoma, and to determine the presence of epidural hematoma. In case it is intra-axial, the goal is to establish the specific neuroanatomic site and to establish the age of the haemorrhage, including its cause. As the haemorrhage would age, changes in the haemoglobin would become apparent; and the different forms of oxyhemoglobin, deooxyhemoglobin, and methemoglobin before the red blood cells are then broken down into the ferritin and the hemosiderin (Atlas and Thulburn, 2002). In the hyperacute phase or in the first 24 hours of the incident, oxyhemoglobin intracellular is apparent. In the acute phase or within the first three days, deoxyhemoglobin, still intracellular is seen (Ashtekar, 2011). In the first three days or in the early subacute phase, methemoglobin in the intracellular location becomes evident. In the next seven days or during the late subacute phase, methemoglobin extracellular manifests and finally, in the chronic phase or after 14 days, ferritin and hemosiderin, extracellular becomes apparent (Ashtekar, 2011). Where there is an infarct in the brain, bleeding often follows. Haemorrhage caused by infarction may be seen with cytotoxic oedema which matches an arterial quality in the bleeding. However, such connection may be hard to assess when early significant bleeding impacts on the underlying infarct (Ashtekar, 2011). As soon as the bleeding occurs, blood is introduced into the subarachnoid space. In cases where pressure is great, the brain parenchyma is usually dissected and filled. Vascular malformations, very much like arteriovenous malformations or AVMs, arteriovenous dural fistulae, and cavernous malformations are apparent in the MRIs for brain haemorrhages (Ashtekar, 2011). On the MRI, the AVM would often be seen as a tightly packed complex honeycomb with various flow voids which translates to high-impact signal loss. Increased signal intensity may be caused by slow or high flow thrombosis (Ashtekar, 2011). Cavernous hemangiomas usually manifest as popcorn-like shapes with well-defined cores of mixed signal intensity caused by haemorrhage in different stages (Ashtekar, 2011). Significant lesions on different areas are apparent in 50% of patients with cavernous hemangiomas. Venous anomalies are seen as star-shaped groupings of venous flows which then congregate into large veins manifesting as high-velocity signal loss (Ashtekar, 2011). For possible brain tumours, MRIs appear as atypical and complex because the different ages of the blood may be mixed with the abnormal tissues. Changes in the MRI indicate signal intensity delays. The vasogenic oedema is often higher for brain tumours and often persists beyond the chronic stages of the hematoma (Ashtekar, 2011). In understanding how MRIs would work as an imaging process for brain haemorrhages, it is important to note that diamagnetic materials are substances which do not have unpaired electrons in the atomic and molecular orbitals (Atlas and Thulborn, 2002). Such materials limit the impact of an applied magnetic field. About 90% of bodily tissues are diamagnetic. For paramagnetic substances, these have unpaired electrons in their atomic or molecular orbitals and have no magnetic fields due to their lack of an applied magnetic field (Atlas and Thulborn, 2002). They can however support an applied field when they would be exposed to it. These paramagnetic substances may include copper, iron, manganese, and gadolinium (Bradley, 1992). Under the MRI, the intensity signal of any haemorrhage is usually based on the chemical properties and status of the iron in the haemoglobin; it is also based on the status of the RBC membrane itself (Bradley, 1993). The iron can sometimes be diamagnetic or paramagnetic based on the state of the orbital electrons. Under paramagnetic conditions, the iron changes the T1 and T2 relaxation periods of water protons based on the interactions of dipole-dipole (Ashtekar, 2011). The effect is usually greater on T1 than on T2. A susceptibility impact is usually seen when iron atoms are grouped in the RBC membrane (Ashtekar, 2011). In these cases, they lead to in-homogeneity of the magnetic field causing loss of phase coherence and shortening of the T2 relaxation period. When the RBC membrane breaks down, the iron is distributed homogeneously (Bradley, 1992). The changing appearance of the haemorrhage on the MRI is based on the structure and appearance of the haemoglobin, as well as its oxidation elements, and based on whether unpaired electrons are apparent (Bradley, 1992). As the haemorrhage usually progresses, it goes through five specific and easily distinguishable stages. The knowledge of these stages is an important element in dating the hemorrhagic events and in determining if various haemorrhagic events have affected the patient at different times. Although MRI can have its limitations in detecting specific types and locations of haemorrhages, it is the more sensitive test to apply after 12-24 hours. It is also more accurate than CT scanning in establishing the age of the haemorrhage. 2. Haemorrhage can occur in both intra-axial and extra-axial locations. Discuss these various sites, and the anatomical structures that are used to define these locations. Haemorrhage can occur in the intra-axial and extra-axial locations. Intra-axial indicates lesions in the brain parenchyma with some indications on intra-ventricular lesions which then arise from the parenchyma and expand into the ventricular system (Gaillard, 2005). The bleeding is within the brain and it may manifest as intraparenchymal haemorrhage when bleeding is seen within the brain tissue, or as intraventricular haemorrhage when the bleeding is within the ventricles of the brain (Asktekar, 2011). In intra-axial haemorrhage, there is usually direct contact with the skull and shear-strain deformations become apparent. The lesion is usually seen along the inferior, lateral, and anterior frontal and temporal lobes, mostly above the bony prominences in the petrous pyramid, sphenoid wing, and orbital roof (Field, 2007). The overlying cortex is mostly always involved and there is a ‘salt-and-pepper’ appearance of the lesion caused by intermixed haemorrhage and oedema (Field, 2007). The lesions for intra-axial haemorrhage are often more apparent days after the injury as the effect of the oedema and the haemorrhage usually increases (Field, 2007). Figure 1 Cerebral haemorrhage Intracranial haemorrhage has various causes including hypertensive haemorrhage, infracted brain tissue, rupture of saccular aneurysm, vascular malformations, and brain tumours. For hypertensive haemorrhage, the lenticulostriate arteries of the middle cerebray artery are involved (Ashtekar, 2011). In some cases, the small perforating branches may rupture causing thalamic bleeding. Hematomas may also dissect into the ventricles leading to intraventricular extension (Ashtekar, 2011). The other causes may be recognized under the MRI based on their other distinct qualities. In instances of extra-axial haemorrhage, the bleeding is beyond the brain tissue and is within the skull. It is classified into epidural haemorrhage, subdural haemorrhage, and subarachnoid haemorrhage. In epidural haemorrhage, the bleeding occurs in the space between the dura mater and the skull and is commonly seen in head traumas (Crippen, 2004). Laceration of arteries is the most likely source for the bleeding in this subtype. Epidural haemorrhage has usually a high pressure and can increase intracranial pressure when bleeding is not stopped (Crippen, 2004). Subdural haemorrhage, on the other hand, manifests with tearing of the veins connecting the subdural space found between the dura and the arachnoid mater. Imaging studies usually show crescent-shaped deformity (Seidenwurm, 2007). The first stages are the same as the indications seen in parenchymal hematoma, similar T1 and T2 qualities are also apparent. The chronic stage manifests with persistent oxidative denaturation of the methemoglobin causing nonparamagnetic hemotochromates to form (Ashtekar, 2011). When different intensities in signal are apparent on the MRI, recurrent bleeding in the subdural is usually present. Figure 2 Epidural haemorrhage Figure 3 Subdural and Epidural haemorrhage Figure 4 Subdural haemorrhage For subarachnoid haemorrhage, the bleeding is apparent in the space between the arachnoid and the meningeal layers of the brain (van Gijn, et.al., 2007). Blood usually layers the brain in the sulci and the fissures, as well as the cisterns (Seidenwurm, 2007). After a sub-arachnoid haemorrhage, the T1 manifests a slight decrease. This may be detected with the higher hydration layer and elevated protein content of the bloody CSF (Chakeres, 1986). Significant levels of methemoglobin are only seen after some days have passed following the haemorrhage. After about a week following the incident, the signal intensity becomes elevated in the subarachnoid space due to the formation of methemoglobin (Chakeres, 1986). Under these conditions, the RBCs are usually resorbed as soon as significant methemoglobin formulates. There is often a short T2 observed with subarachnoid haemorrhage, especially where massive bleeding occurs. Under these conditions, a fluid-level or intraventricular thrombus may also be apparent (Chakeres, 1986). For chronic subarachnoid haemorrhage, hemosiderin may affect the leptomeninges causing the appearance of short T2. The Fluid-attenuated inversion recovery (FLAIR) is a sensitive MRI pulse set forth to detect subarachnoid haemorrhage (Ashtekar, 2011). Based on FLAIR images, the haemorrhage would manifest as white (high signal intensity) as compared to black (normal hypointense) cerebrospinal fluid spaces. This type of MRI pulse has similar qualities with CT scans, especially in relation to the findings established for subarachnoid haemorrhage (Ashtekar, 2011). One T1 weighted picture or images, acute subarachnoid haemorrhage would be seen as high signal intensity in the subarachnoid space. The FLAIR results can be used in distinguishing between acute subarachnoid and chronic subarachnoid haemorrhages (Ashtekar, 2011). Magnetic resonance angiography is used in assessing aneurysms and other lesions which lead to subarachnoid haemorrhages. Elements which limit the use of MRI in evaluating acute subarachnoid haemorrhage refer to its low sensitivity for aneurysms which are less than 5 mm in size (Ashtekar, 2011). It also has a low ability to define small aneurysm contour patterns; moreover, it has difficulty in depicting high quality images among agitated and confused patients (Ashtekar, 2011). The MRI and the angiography may be sufficient in identifying and defining lesions to secure early surgery to establish ruptured intracranial aneurysms without having to use intra-arterial digital subtraction angiography during the acute stages of the disease. The skull has various layers protecting the brain from trauma. Extra-axial bleeding or haemorrhage is often caused by some form of trauma or by tumours (van Gijn, et.al., 2007). Epidural haematoma manifests with bleeding between the dura mater and the cranium. The dura mater is the outermost layer of the meninges which protect the brain. The dura also wraps around the spinal cord, as well as the brain, keeping the cerebrospinal fluid within its confines (van Gijn, et.al., 2007). Where head trauma would cause bleeding in the epidural layer, loss of consciousness may be experienced and blood accumulating in this region may continue to build and expand, thereby pushing the brain matter to also push down into the brain stem. In imaging processes, a lenticular or lens-shaped extra-cerebral blood formation which does not enter the suture lines would be apparent (van Gijn, et.al., 2007). Underneath the epidural layer, bleeding may also occur and manifest as subdural hematoma. The vein connecting the cerebral cortex and a venous sinus would likely have a tear and cause the bleeding. In some cases, arterial cuts on the brain’s surface may also occur and cause the subdural hematoma (Kushner, 1998). A crescent-shaped haemorrhage which crosses the suture lines of the brain would be apparent from the imaging processes on the brain (van Gijn, et.al., 2007). For subarachnoid haemorrhages, the bleeding is in the space between the arachnoid membrane and the pia mater which now covers the brain (van Gijn, et.al., 2007). Trauma and brain injury can cause this bleeding, but spontaneous rupturing of a cerebral aneurysm may also cause such bleeding (van Gijn, et.al., 2007). 3. Discuss the use of Tissue Plasminogen Activator (tPA) in the treatment of ischaemic stroke Tissue plasminogen activator, also known as tPA involves the breaking down of blood clots by protein components (Bode and Renatus, 1998). This tPA is considered a serine protease, seen in endothelial cells, or the cells which layer the blood vessels. It is an enzyme, therefore it catalyzes and converts plasminogen into plasmin, which is the enzyme primarily involved in breaking down blood clots (Bode and Renatus, 1998). It is used to manage embolic and thrombic strokes and is not indicated for hemorrhagic strokes. This enzyme may be artificially manufactured by utilizing the recombinant biotechnology elements. Under these conditions, the tPA may be considered as recombinant tissue plasminogen activator (Rijken, 1988). The tPA and the plasmin are the primary elements of the fibrinolytic pathway where the generation of tPA-mediated plasmin is seen. In effect, the tPA cuts the zymogen from its peptide bond and into plasmin. With higher enzyme activation, hyperfibrinolysis becomes more apparent (Rijken, 1988). Lower activity causes hypofibrinolysis which can then lead to thrombosis or embolism. In ischemic strokes, tPA must be administered immediately. tPA is often used to manage ischemic strokes which feature blood clots through the treatment known as thrombolysis. At the earliest possible time, for better efficacy, this tPA must immediately be administered (Tsurupa and Medved, 2001). Within the first three hours of the incident, it must be administered in order to achieve maximum efficacy. If administered after, it may no longer be beneficial, but may actually be harmful to the patient. This tPA can be given system-wide, especially in instances of acute ischemia strokes (The University Hospital, n.d). Different countries have different policies for its administration. In Canada for example, tPA must be administered within 4.5 hours after symptoms occur. This policy has reduced the number of patients qualified for this treatment especially due to the fact that most patients would not be aware of their symptoms and often do not seek immediate medical care for their symptoms (Caulfield and Wijman, 2008). In the US, tPA must be given also within 4.5 hours after the initial symptoms manifest. Since this treatment also places the patient at risk for haemorrhage, it is contraindicated for haemorrhagic strokes (Caulfield and Wijman, 2008). This treatment is also recommended for patients beyond 90 years of age with acute ischemic strokes. tPA is also known as thrombolytic drug therapy. Thrombolytic therapy includes the use of a thrombolytic drug which is administered to the blood vessels in order to clear up any clots which are interfering with the blood flow (The University Hospital, n.d). Genetically engineered tPA has been developed by specialists and as a result, it can now be delivered synthetically to the patient suffering from the stroke. This treatment has a 30-50% chance of managing strokes. It can either be given intravenously or intra-arterially at the clot site (The University Hospital, n.d). The IV route has been given FDA approval, however, many stroke centres have managed to achieve much success in applying the intra-arterial method. There are different elements which have to be fulfilled before this type of therapy can be carried out on the patient (Rivera-Bou, 2008). There are various qualities which the patient must meet before the patient can receive tPA therapy. Primarily, as was mentioned previously, there is a narrow time window where the therapy can be effective and when such time has passed, the patient would no longer be eligible for tPA therapy (Rivera-Bou, 2008). Secondly, there must be a complete absence of any haemorrhage or bleeding for the patient because tPA therapy can make the bleeding or haemorrhage worse. Thirdly, patients under blood thinners are also ineligible for tPA. Lastly, patients with high blood pressure, elevated blood sugar levels, recent surgery, low platelet county, and kidney disorders are also excluded from this type of therapy (The University Hospital, n.d). When given through the IV, tPA travels through the system until it gets to the point where the blockage is. High levels of tPA must be used as the drug can become diluted in the blood during its travel through the blood vessels. The faster way for the administration of tPA is intra-arterially (The University Hospital, n.d). Many cardiologists have used this method to clear clogged vessels in the heart, as well as other parts of the body. In this method, the specialist usually inserts a thin and flexible catheter into the artery, and directs it to the clotted area where the tPA is then released (The University Hospital, n.d). Less of the tPA would be needed and its impact can be faster. This type of therapy also increases the window of time when the treatment can be administered. Specialists declare that this type of therapy can work up to six hours from when initial symptoms appear since the blood flow can be expected to clear almost as soon as possible (The University Hospital, n.d). The possibility of intracranial haemorrhage is also reduced. Since the approval of IV tPA, several studies have been carried out on the value of tPA use for patients, including the safety profile and efficacy of IV tPA for ischemic strokes. A Canadian study was able to establish that IV tPA had a 36% efficacy rate (The University Hospital, n.d). The risk for intracranial haemorrhage was apparent however in instances when this therapy is used for patients beyond the 3-4 hour time window for administration. In effect, the administration of this therapy has been only supported for as long as the symptoms of stroke are detected early. In these instances, its efficacy is often strong and the potential for patient recovery is very promising (The University Hospital, n.d). Nevertheless, beyond such time window, its efficacy is very poor, moreover, it can increase the risk for intracranial haemorrhage for the patient. Figure 5 Image showing catheter insertion during intra-arterial tPA References Ashtekar, J., 2011. Intracranial hemorrhage evaluation with MRI. Medscape [online]. Available at: http://emedicine.medscape.com/article/344973-overview#aw2aab6b4 [Accessed 26 August 2012]. Atlas, S. and Thulborn, K., 2002. Intracranial hemorrhage. In: magnetic resonance imaging of the brain and spine. Philadelphia, Pa: Lippincott Williams & Wilkins. Bode, W. and Renatus, M., 1998. Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function. Curr. Opin. Struct. Biol. 7 (6), 865–72. Bradley, W., 1992. Hemorrhage and brain iron. In: Magnetic Resonance Imaging. St Louis, Mo: Mosby. Bradley, W., 1993. MR appearance of hemorrhage in the brain. Radiology, 189(1), 15-26. Caulfield, A. and Wijman, C., 2008. Management of acute ischemic stroke. Neurol Clin, 26, 345–371 Chakeres, D., 1986. Acute subarachnoid hemorrhage: in vitro comparison of magnetic resonance and computed tomography. AJNR Am J Neuroradiol., 7(2), 223-8. Chakrabarty, A. and Shivane, A., 2008. Pathology of intracerebral haemorrhage. I ACNR, 8(1), 20-21 Crippen, D., 2007. Head Trauma. Medscape [online]. Available at: http://emedicine.medscape.com/article/433855-overview [Accessed 26 August 2012]. Field, A., 2007. Introduction to neuroimaging. University of Wisconsin–Madison [online]. Available at: https://www.radiology.wisc.edu/education/med_students/neuroradiology/Neurorad-2_Brain.pdf [Accessed 26 August 2012]. Gaillard, F., 2005. Intra axial. Radiopaedia [online]. Available at: http://radiopaedia.org/articles/intra-axial [Accessed 26 August 2012]. Rijken, D., 1988. Relationships between structure and function of tissue-type plasminogen activator. Klin. Wochenschr, 66(12), 33–9. Rivera-Bou, W., 2008. Thrombolytic therapy in emergency medicine. eMedicine [online]. Available at: http://emedicine.medscape.com/article/811234-overview [Accessed 26 August 2012]. Seidenwurm, D., 2007. Introduction to brain imaging. In Brant, W. and Helms, C., Fundamentals of diagnostic radiology. Philadelphia: Lippincott, Williams & Wilkins. The University Hospital, n.d. Treating acute ischemic stroke [online]. Available at: http://www.theuniversityhospital.com/stroke/ischemic.htm [Accessed 26 August 2012]. Tsurupa, G. and Medved, L., 2001. Identification and characterization of novel tPA- and plasminogen-binding sites within fibrin(ogen) alpha C-domains. Biochemistry, 40 (3), 801–808. van Gijn, J., Kerr, R., and Rinkel, G., 2007. Subarachnoid haemorrhage. Lancet, 369 (9558), 306–18. Read More