Why does sepsis cause hypotension

This calcium-induced calcium release is mediated by the cardiac ryanodine receptor RyR2. The calcium binds to troponin-C which then leads to conformational change and allows the binding of actin to myosin causing shortening of the myocyte and the onset of systole. A decrease in intracellular calcium concentration then occurs and prepares the myocardium for the next systolic event. The clinical picture of early sepsis is a patient with a low systemic vascular resistance SVR and a normal or increased cardiac output, although the heart is compromised by poor contractility.

Although the stroke volume may be maintained, there is an increase in left ventricular end-systolic volume LVESV and left ventricular end-diastolic volume LVEDV and very often a decrease in the ejection fraction EF , with cardiac output maintained by an increase in heart rate.

There is also diastolic dysfunction with decreased left ventricular compliance and a subsequent increase in left ventricular end-diastolic pressure LVEDP Figs 1—3. Pressure—volume curve for the normal LV. Phase A represents diastolic filling.

B represents isovolumetric contraction. C represents ventricular ejection. D represents isovolumetric relaxation. Point 1 represents opening of the mitral valve. Point 2 represents closure of the mitral valve. Point 3 represents opening of the aortic valve. Stroke volume SV is demonstrated. The slope of this line represents the contractility of the heart. Pressure—volume curve for the LV during sepsis.

Stroke volume SV is maintained. The end-systolic pressure—volume relationship demonstrates decreased contractility. Pressure—volume curve for the LV during severe sepsis. There is hypotension. In these circumstances, cardiac force is compromised by the resulting abnormalities of fibre length. Finally, NO decreases the sensitivity of the myocardium to endogenous adrenergic ligands by altering the response of second messenger systems. The protein kinase and cyclic GMP messenger systems are affected in this manner.

Vasodilatation is the principal physiological abnormality in the cardiovascular response to sepsis. This leads to a low SVR and hypotension. One of the physiological functions of NO is to provide an intrinsic response to alterations in peripheral blood flow myogenic control.

When NO is formed in the endothelium, it diffuses into the vascular smooth muscle cells where it activates the enzyme guanylyl cyclase. This increases concentrations of cyclic GMP levels which lead to a reduction in intracellular calcium levels and activation of potassium channels. This leads to vascular smooth muscle relaxation. Peripheral vascular dysfunction during sepsis is mediated by excessive production of NO by the enzyme iNOS.

Increased NO concentration leads to hyperpolarization of potassium channels and persistent relaxation of smooth muscle. In addition to vasodilatation, there is a failure of the cardiovascular reflexes, which normally control arterial pressure.

The sympathetic and neuroendocrine responses to shock cause vasoconstriction, which is mediated by G-proteins and second messenger systems, in turn activating intracellular pathways. These responses to sympathetic activity and angiotensin II are decreased due to the increased production of NO, which decreases the cellular activity of signal transduction mechanisms.

The right ventricle RV differs embryologically, structurally, and functionally from the LV. The principle function of the RV is to facilitate efficient gas exchange.

It has a thin wall with a low muscle mass, ejecting into the pulmonary circulation, which has a low resistance and a high compliance. The pressures generated on the right side are low; mean pulmonary artery pressure is 15 mm Hg.

The RV depolarizes and then contracts in a longitudinal manner from the inflow tract to the outflow tract and produces a wave which is peristaltic in manner. This contrasts with the circumferential pressure generating contraction of the left side of the heart. Like the LV, the cardiac output of the RV is determined by changes in preload, afterload, and contractility. The changes in ventricular function in sepsis are similar to those on the left side.

The function is compromised by changes in contractility and afterload. The free wall of the RV has a low muscle mass and can respond to increases in preload by dilating, but it responds poorly to afterload because of its relative inefficiency as a muscle pump.

The onset of sepsis leads to a change in contractility due to effects of circulating inflammatory mediators which are the same as those outlined above. There is a decrease in RVEF similar to that in the systemic circulation. The stresses imposed by sepsis on the RV muscle mass and the changes in afterload can ultimately lead to right ventricular failure. The pulmonary circulation is a low-pressure system, which can respond to an increased cardiac output during exercise or after a physiological stress.

The ability of the pulmonary circulation to respond to a large cardiac output without a major change in pressure ensures that effective gas exchange can take place. It is important to consider the concept of blood flow in addition to generated pressure when considering the physiology of the pulmonary circulation.

The right-sided circulation responds to changes in cardiac output by recruitment of pulmonary vessels which have low perfusion during stable conditions. In addition to recruitment, distension of these vessels allows an increase in blood flow which will support the need for improved gas exchange. These processes occur without vasomotor control. The major stress imposed on the RV during sepsis is an increase in the afterload due to pulmonary hypertension. Hypoxic pulmonary vasoconstriction HPV is a response of the small arterioles of the pulmonary circulation to a decrease in alveolar or mixed venous oxygen content.

The greater influence is from alveolar hypoxia. The function of this response is to divert blood from the hypoxic areas of the lungs to those which are ventilated, thus attempting to maintain optimum ventilation and perfusion ratios and ensure efficient gas exchange. It is a rapid response and occurs within seconds of induced hypoxia.

The reflex occurs in the isolated lung and is independent of neural connections. The precise mechanism has not been proven, but NO is implicated. During sepsis, unregulated NO production in the systemic circulation leads to vasodilatation. In the presence of hypoxia, NO production decreases in the pulmonary circulation and local vasoconstriction occurs.

It is also thought that local release of the potent vasoconstrictor endothelin occurs due to hypoxia. There is evidence that the active control of the pulmonary circulation is influenced by ligands of systemic origin which lead to receptor activation. There are both cholinergic and adrenergic receptors in the pulmonary vascular tree, which allow changes in pulmonary vascular tone and resistance. The predominant response is vasoconstriction. Cholinergic parasympathetic nerves cause vasodilatation by stimulation of muscarinic M3 receptors, with NO acting as a mediator for cholinergic transmission.

Other circulating humoral factors can induce a local vasoconstrictor response, including endothelin, angiotensin, and histamine. Pulmonary hypertension is thus a multifactorial consequence of sepsis and is probably due to inhibition of NO production due to hypoxia and also an enhanced vasoconstriction due to acidosis, increased adrenergic stimulation, and local mediators such as endothelin Table 2.

The mediators involved in the active control of the pulmonary circulation 6. Ventricular interdependence is defined as the forces that are transmitted from one ventricle to the other ventricle through the myocardium and pericardium, independent of neural, humoral, or circulatory effects.

Ventricular interdependence is a result of the close anatomical correlation of the ventricular cavities within the pericardium. The ventricles can be considered in series. Stroke volume of systolic contraction of one cavity creates the preload of the next Fig.

This is an oblique transverse section of the heart taken through the mid-cavity. It demonstrates the thick walled LV and the thinner wall of the RV. It demonstrates the crescentic shape of the RV in comparison with the round ventricular cavity on the left. The septum is noted. The failing RV can impede left-sided performance by decreasing LV preload. This severe RV diastolic dysfunction can be seen in sepsis Fig.

This is a four-chamber view of the heart observed with transoesophageal echocardiography. It is taken during end-diastole. The atrioventricular TV and MV valves are open. There is volume overload of the RV which has moved the septum towards the left side of the heart. Septic shock can be fatal because of complications like these.

It's likely you'll be admitted to an intensive care unit ICU for urgent treatment and to carefully monitor your progress. In some cases treatment may begin in the emergency department. To help you breathe more easily, you'll be given oxygen through a face mask, a tube inserted into your nose, or an endotracheal tube inserted into your mouth. If you have severe shortness of breath , a mechanical ventilator may be used.

You'll probably be given fluids directly into a vein. This will help raise your blood pressure by increasing the amount of fluid in your blood. To increase the blood flow to your vital organs, such as your brain, liver, kidneys and heart, you may be prescribed inotropic medicines or vasopressors.

Inotropic medicines inotropes , such as dobutamine, stimulate your heart. They increase the strength of your heartbeat, which helps get oxygen-rich blood to your tissues and organs, where it's needed. These medicines will cause your blood vessels to narrow, increasing your blood pressure and the flow of blood around your body. This will allow your vital organs to start functioning properly. Antibiotics are often used to treat the associated bacterial infection. The type of antibiotic used depends on the type of bacterial infection and where in the body the infection started.

You may be started on antibiotics immediately to increase your chances of survival. Initially, two or three types of antibiotics may be used. The most effective type of antibiotic can be used once the bacterium responsible for the infection is identified.

In severe cases of sepsis or septic shock, the large decrease in blood pressure and blood flow can kill organ tissue. If this happens, surgery may be required to remove the dead tissue. Then, excessive bleeding disseminated intravascular coagulation Disseminated Intravascular Coagulation DIC Disseminated intravascular coagulation is a condition in which small blood clots develop throughout the bloodstream, blocking small blood vessels.

The increased clotting depletes the platelets The risk of sepsis is increased in people with conditions that reduce their ability to fight serious infections.

These conditions include the following:. Being a newborn see Sepsis in Newborns Sepsis in Newborns Sepsis is a serious bodywide reaction to infection spread through the blood. Newborns with sepsis appear generally ill—they are listless, do not feed well, often have a gray color, and may have Having certain chronic disorders such as diabetes Diabetes Mellitus DM Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar glucose levels to be abnormally high.

Urination and thirst are The scar Having a weakened immune system due to use of drugs that suppress the immune system such as chemotherapy drugs Chemotherapy Chemotherapy involves the use of drugs to destroy cancer cells.

Although an ideal drug would destroy cancer cells without harming normal cells, most drugs are not that selective. Instead, drugs The cells have lost normal control mechanisms and thus are able to multiply continuously, invade nearby HIV is transmitted The risk is also increased in people who are more likely to have bacteria enter their bloodstream. Such people include those who have a medical device inserted into the body such as a catheter inserted into a vein or the urinary tract, drainage tubes, or breathing tubes.

When medical devices are inserted, they can move bacteria into the body. Bacteria may also collect on the surface of such devices, making infection and sepsis more likely. The longer the device is left in place, the greater the risk. Injecting recreational drugs Recreational Drugs and Intoxicants read more : The drugs and needles used are rarely sterile. Each injection may cause bacteremia to varying degrees. People who use these drugs are also at risk of disorders that can weaken the immune system such as AIDS.

Having an artificial prosthetic joint Surgery Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints Each ventricle has The bacteria may then continuously or periodically be released into the bloodstream.

Having an infection that persists despite treatment with antibiotics: Some bacteria that cause infections and sepsis are resistant to antibiotics. Antibiotics do not eradicate the resistant bacteria. Thus, if an infection persists in people who are taking antibiotics, it is more likely to be caused by bacteria that are resistant to antibiotics and that can cause sepsis.

Most people have a fever, but some have a low body temperature. People may have shaking chills and feel weak. Other symptoms may also be present depending on the type and location of the initial infection for example, people with pneumonia may have cough, chest discomfort and trouble breathing. Breathing, heart rate, or both may be rapid. As sepsis worsens, people become confused and less alert. The skin becomes warm and flushed. The pulse is rapid and pounding, and people breathe rapidly.

People urinate less often and in smaller amounts, and blood pressure decreases. Later, body temperature often falls below normal, and breathing becomes very difficult.

The skin may become cool and pale and mottled or blue because blood flow is reduced. Reduced blood flow may cause tissue, including tissue in vital organs such as the intestine , to die, resulting in gangrene Gas Gangrene Gas gangrene is a life-threatening infection of muscle tissue caused mainly by the anaerobic bacteria Clostridium perfringens and several other species of clostridia. Gas gangrene can develop Tests to find the source of infection tests usually include chest x-rays and other imaging tests and cultures of fluid or tissue samples.

Doctors usually suspect sepsis when a person who has an infection suddenly develops a very high or low temperature, a rapid heart rate or breathing rate, or low blood pressure. To confirm the diagnosis, doctors look for bacteria in the bloodstream bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. Samples of blood are taken to try to grow culture Culture of Microorganisms Infectious diseases are caused by microorganisms, such as bacteria, viruses, fungi, and parasites.

Doctors suspect an infection based on the person's symptoms, physical examination results, However, if people have been taking antibiotics for their initial infection, bacteria may be present but may not grow in the culture.

Sometimes catheters are removed from the body, and the tips are cut off and sent for culture. Finding bacteria in a catheter that had contact with the blood indicates that bacteria are probably in the bloodstream. To check for other infections that may cause sepsis, doctors take samples of fluids or tissue, such as urine, cerebrospinal fluid, tissue from wounds, or sputum coughed up from the lungs.

These samples are cultured and checked for bacteria. Chest x-rays and other imaging tests, such as ultrasonography Ultrasonography Ultrasonography uses high-frequency sound ultrasound waves to produce images of internal organs and other tissues.