User:Liber.mark/Haemodynamic Response

Topic: Hemodynamic Response

Group Members: Nahed Lakkis, Raheem Bell, Mark Liber

General Definition
In response to performing physical activities, the body must adjust its blood flow in order to deliver nutrients to stressed tissues and allow them to function. Haemodynamic Response (HR) in the context of neurobiology consists of the rapid delivery of blood to active neuronal tissues. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain.

History
The history of the haemodynamic response is closely intertwined with the history of Magnetic Resonance Imaging. The discovery of MRI was a compilation of the works of several people. Peter Mansfield and Paul Lauterbur were awarded the Nobel prize for pioneering the technique, but my no means were they the first. This list is extensive. Overall, the discovery of MRI allowed responses such as HR to be recorded. We will explore the history of this in greater detail.

Function
The role of HR is to deliver to nerve cells nutrients such as oxygen and glucose, which they use to produce energy and to function. Actively metabolizing nerve cells consume more glucose and begin to develop energy using anaerobic glycolysis. This metabolic shift indicates to the circulatory system that more glucose is needed in these tissues.

We plan to dig further in depth regarding the role of blood flow in body tissues, as well as in tissues specific to the brain.

Complications
The haemodynamic response is rapid delivery of blood to active neuronal tissue. Complications in this response arise in acute coronary syndromes, and pulmonary arterial hypertension. These complications lead to a change in the regulation of blood flow to the brain, and in turn the amount of glucose and oxygen that is supplied to neurons, which may have serious effects not only on the functioning of the nervous system, but functioning of all bodily systems.

Acute infections, such as community-acquired pneumonia (CAP), act as a trigger for acute coronary syndromes (ACS). ACS deals with symptoms that result from the obstruction of coronary arteries. Due to this obstruction there are thrombotic complications at the sites of atherosclerotic plaques. The most common symptom that prompts diagnosis is chest pain, associated with nausea and sweating. Treatment usually include aspirin, Clopidogrel, nitroglycerin, and if chest pain persists morphine. Recent study suggests that acute respiratory tract infection can act as a trigger for ACS. This in turn has major prothrombotic and haemodynamic effects.

Coagulation is normally prevented in the vascular endothelium by expression of antithrombotic factors on its surface. Sepsis, which causes disruption and apoptosis of endothelial cells results in the endothelium switching to a procoagulant phenotype. This promotes platelet adhesion and aggregation. Moreover, only once disruption of the plaque surface has occurred are these prothrombotic effects likely to be significant in the pathogenesis of ACS. Sepsis is also largely associated with haemodynamic changes. Coronary artery perfusion pressure is reduced in peripheral vasodilation, which results in reduced blood pressure and reduced myocardial contractility. Endothelial dysfunction induces coronary vasoconstriction. This is caused by catecholamine release and by infections. Severe infections lead to increase myocardial metabolic demands and hypoxia. When neuronal tissue is deprived of adequate oxygen, the haemodynamic response has less of an effect at active neuronal tissue. All of these disturbances increase the likelihood of ACS, due to coronary plaque rupture and thrombosis. Overall, ACS results from the damage of coronaries by atherosclerosis, so primary prevention of ACS is to prevent atherosclerosis by controlling risk factors. This includes eating healthy, exercising regularly, and controlling cholesterol levels.

Pulmonary hypertension (PAH) is disease of small pulmonary arteries that is usually caused by more than one mechanism. This includes pneumonia, parasitic infections, street drugs, such as cocaine and methamphetamines that cause constriction of blood vessels, and many more. Vasoactive mediators, such as nitric oxide and prostacyclin, along with overexpression of vasoconstrictors not only affect vascular tone but also promote vascular remodeling. PAH deals with increase blood pressure in pulmonary arteries, which leads to shortness of breath, dizziness, fainting, rarely hemoptysis, and many other symptoms. PAH can be a severe disease, which may lead to decreased exercise tolerance, and ultimately heart failure. It involves vasoconstrictions of blood vessels connected to and within the lungs. As a result, the heart has a hard time pumping blood through the lungs, and the blood vessels eventually undergoes fibrosis. The increased workload on the heart causes hypertrophy of the right ventricle, which leads less blood being pump through the lungs and decreased blood to the left side of the heart. As a result of all of this, the left side of the heart has a hard time pumping a sufficient supply of oxygen to the rest of the body, which deteriorates the effect of the haemodynamic response. Impaired haemodynamic responses in turn diminish exercise capacity in patients with PAH. The severity of haemodynamic dysfunction during progressive exercise in PAH can be recorded using cardiopulmonary exercise testing (CPET), and/or impedance cardiography (ICG). Furthermore, there are no current cures for pulmonary arterial hypertension, but there are treatment options for patients with the disease to help prolong their survival and quality of life.

Overall, pulmonary arterial tension and acute coronary syndromes are few of the many diseases that lead to hypoxia of neuronal tissue, which in turns deteriorates the haemodynamic response and leads to neuronal death. Prolonged hypoxia induces neuronal death via apoptosis. With a dysfunctional haemodynamic response, active neuronal tissue due to membrane depolarization lacks the necessary energy to propagate signals, as a result of blood flow hindrance. This affects many functions in the body, and may lead to severe symptoms.

Molecular Biology
The mechanism for Haemodynamic response has not yet been fully perfected but the mechanism’s emphasis lies in the neurotransmitter glutamate. As neuron activity increases, individual cells release the neurotransmitter glutamate. This release opens ‪N-Methyl-D-aspartic acid‬ (NMDA) receptors on other neurons which allows calcium ion influx. Through a net chain of reactions, which we will get into more detail later, more oxygen and glucose reaches the neuron. Glutamate also binds to the metabotropic glutamate receptor which ultimately leads to dilation in smooth muscle around the neurons and greater blood flow.

Clinical Significance
Changes in brain activity are closely coupled with changes in blood flow in those areas, and knowing this has proved useful in mapping brain functions in humans. The measurement of HR, in a clinical setting, can be used to create images of the brain in which especially active and inactive regions are shown as distinct from one another. This can be a useful tool in diagnosing neural disease or in pre-surgical planning.

Functional Magnetic Resonance Imaging (fMRI)
Functional Magnetic Resonance Imaging, or fMRI, is the medical imaging technique used to measure the haemodynamic response of the brain in relation to the neural activities. It is one of the most commonly used devices to measure brain functions and is relatively inexpensive to perform in a clinical setting. fMRI functions through the magnetic resonance property of haemoglobin. Haemoglobin is both diamagnetic and paramagnetic and this allows for fMRI to measure haemodynamic response. This is a type of specialized brain and body scan used to map neural activity in the brain or spinal cord of humans or animals by imaging the change in blood flow related to energy use by brain cells. Basically, in haemodynamic response, the blood flow and oxygen movement in the brain are directly related. When a certain part of the brain is overly active, it will consume more glucose and become less energetic. Thus, haemodynamic response causes more blood flow to those sites of higher activity to get more glucose and oxygen to those areas. This shift in blood flow can be then measured and used to create an image of the brain, with active areas clearly visible.

Division of Workload
We plan to meet once per week throughout the semester to discuss our individual findings and share them in order for us all to have a complete understanding of our topic, Haemodynamic Response. We will all be making contributions to the page throughout the project.