Meningitis is inflammation of the meninges and the meninges are the layers that surround and protect our brain. In this video we're going to mainly focus on bacterial meningitis. The main causative organisms of meningitis include group B streptococcus, streptococcus pneumoniae, Neisseria meningitidis, gram-negative bacilli, and Haemophilus influenzae. Introduction of the Haemophilus influenzae and pneumococcal vaccination have decreased infant-associated mortality due to meningitis.
The causative agents have to be in contact with the meninges in order to cause meningitis, but the meninges is essentially surrounded by the skull because the meninges itself coats the brain. Therefore, the infective organisms usually cause a primary infection first, or they can enter the area because of some abnormality or deformity. of the skull.
So for example there can be a cribriform plate defect, the primary infection can be otitis media, sinusitis, there could be a basal skull fracture, it could be secondary to pneumonia, and all these primary problems can subsequently lead to meningitis. So now let's look at the pathophysiology as to how the bacteria get from the primary problem here into the meninges and cause a problem. Bacteria themselves pose as virulent factors that help in four aspects in the pathophysiology. Colonization, invasion, immune evasion, and meningeal invasion.
In order to learn about these four aspects of bacteria, virulence, let us create a scenario. In this scenario, we are going to look at the hematogenous spread of the bacteria from the primary source or from the primary infection. Here is the lumen of the nose or gut or the lungs.
And here is the mucus. This is the epithelium. And under the epithelium is the interstitial layer.
And then you have your capillaries basically, your blood vessels, which then circulates all around your body. The lumen is obviously an access point for the bacteria. It can be in the ear, the gut, the nose, wherever.
Colonization refers to the bacteria's ability to colonize the area. So for example, the bacteria Strep pneumoniae and Necessaria meningitidis have the ability to break down host's antibodies using IgA proteases, which break down the mucosal antibody IgA, and these allow bacteria to colonize the area. Some bacteria also have pili or fimbriae, allowing them to latch onto the host's epithelium and invade through. We can say now that the bacteria has caused an infection, and we could say that this is the primary infection, be it pneumonia or simositis.
Some bacteria have virulent factors or mechanisms which allow them to evade the immune system. For example, the bacteria group B streptococcus and streptococcus pneumonia have a capsule which allows it to evade macrophages as well as complement factors around the area. The bacteria can enter the bloodstream, causing infection.
bacteremia, and then it can travel towards the brain. And this is of course the hematogenous spread. It's important to know that the bacteria can invade the meninges through hematogenous spread, so through the blood, directly, so for example from sinusitis, from a bone infection, or it can go through the cerebrospinal fluid somehow.
And this is the scenario that we will look at. Before continuing on with the pathophysiology, it's important to revise and recap the anatomy and physiology of the brain, specifically the cerebrospinal fluid. The cerebrospinal fluid is the fluid produced by the brain and it helps nourish the brain tissues.
Cerebrospinal fluid or CSF is produced by the ventricles of the brain. For simplicity, the fluid is produced by the lateral ventricles which then flows to the third ventricles, then the fourth ventricles, And from the fourth ventricles, it will enter the subarachnoid space. And from the subarachnoid space, it will go through the arachnoid granulation and enter the venous sinus.
And the venous sinus is essentially the big veins that will bring the blood back down to the heart. The meninges that we've been talking about all this time are the layers above and below. below the subarachnoid space.
Now, the arachnoid space itself also contains blood vessels, and there are even blood vessels which reach the ventricles of the brain. And this is important because blood carries important things with it, and the brain needs these important things to function. So let us compare blood vessels traveling to the ventricles as opposed to blood vessels traveling around the brain.
The brain is actually ingeniously physically protected by the blood-brain barrier. The blood-brain barrier is a semi-permeable membrane barrier which really separates circulation and the brain tissue, and it essentially prevents substances from getting inside the brain, because as we know, the brain is such a delicate organ. Blood vessels or the capillaries are of course made up of endothelial cells. Surrounding the endothelial cells is the basement membrane.
And surrounding the basement membrane are astrocytes, which are glial cells, which are the brain's supporting cells. And this formation allows only certain things to pass through inside the brain. So the blood-brain barrier allows glucose and oxygen to get inside the brain, because the brain obviously needs glucose for energy and oxygen as well.
If we compare the blood-brain barrier to the blood-cerebrospinal fluid barrier, where the ventricles are, the capillaries are made up of endothelium as well, and are surrounded by the basal membrane. But here there are no astrocytes. Rather, there are these other supporting cells called epidymal cells, which are the cells responsible for the production of cerebrospinal fluid inside the ventricle cavity.
So cerebrospinal fluid is produced by the choroid plexus, which is essentially epidermal cells, and circulate around the brain as we have learned. Because the choroid plexus is the site of cerebrospinal fluid production, more blood products are able to move here. So for example, glucose can enter, oxygen, ions, and even vitamins can get into this area.
Sadly though, bacteria can also get here. Bacteria can invade the meninges through this mechanism. What is very interesting here is that cerebrospinal fluid is so sterile, there is inadequate humoral immunity. There is low immunoglobulins here and there's low complement proteins. And so you can imagine the hematogenous spread, the bacteria can enter the ventricles and then enter the cerebrospinal fluid.
Now it is important to again recap. the cerebrospinal fluid flow around the brain and look at it in a bit more detail. So let's say the bacteria are in the lateral ventricles. They can move to the third ventricles via the interventricular foramen, then into the fourth ventricles via the cerebral aqueduct, then again gain access to the subarachnoid space through the medial and lateral apertures.
And this is where the bacteria really want to be I guess because they are now surrounded by the meninges and so can trigger meningitis through an inflammatory reaction. To make the story complete however, the cerebrospinal fluid can continue and be reabsorbed into the venous sinus via the arachnoid granulation and from the venous sinus back into circulation back to the heart. On a side note, the fourth ventricle also continues on down down the spinal cord because the cerebrospinal fluid also needs to supply the spinal cord with its goods.
But the focus of our story is the subarachnoid space. So let's just orientate ourselves as to where the subarachnoid space is. So here is the skull, your skull bone, the outside I guess.
Below your skull is the dura mater, below that is the arachnoid membrane, and then the arachnoid space which is like a lot of spider webby like projections. Remember we said that the arachnoid space also contains blood vessels. The blood vessels travel also deep between the brain sulci to supply it with oxygen and glucose. Below the arachnoid space is the pia mater and finally below the pia mater is the brain parenchyma, the brain tissue, the clean slate, the tabula rasa. The pia mater arachnoid membrane and the dura mater make up the three layers of the meninges.
The meninges are pain sensitive, particularly the dura mater. Let us now zoom and focus on this area again. the subarachnoid space. In this diagram on the left side you have the vasculature, the circulation in the arachnoid space. And then on the right you have where the cerebrospinal fluid is traveling and where bacteria are right now.
Bacteria in the cerebrospinal fluid can use up the glucose in the area and use glucose as a source of energy. So in the cerebrospinal fluid now we have the bacteria. Now, the vasculature will respond to the presence of bacteria and will increase the vessel wall permeability.
You have also a decrease in perfusion pressure and possibly subsequent ischemia. There will be increase in adhesion proteins for leukocytes to allow it to invade the area, and also you will actually have endothelial damage, so vessel damage. in response to cytokine-mediated inflammation.
So let's talk about each of those points. So for example, you have neutrophils entering the area thanks to an increase in vascular permeability and adhesion proteins. They essentially cause inflammation. They trigger inflammation.
They release so many cytokines. Macrophages also enter the area and cause inflammation. It's important to note that macrophages also use glucose as a source of energy.
Because there is an increase in vascular permeability, water and proteins can leak inside the subarachnoid space, causing cerebral edema and subsequently increasing intracranial pressure. Therefore, if you were to perform a lumbar puncture on someone you suspect to have bacterial meningitis, in the cerebrospinal fluid from the lumbar puncture, you would find bacteria, increase in proteins, increase in neutrophils, and decrease in glucose. Due to the irritation and inflammation of the meninges, the classical signs and symptoms of meningitis include fever, headache, photophobia, nausea, vomiting, neck stiffness. We of course looked at the hematogenous spread of bacteria into the cerebrospinal fluid causing meningitis.
However, the bacteria can also locally invade the meningitis, for example, through the sinuses. As well, it can invade into brain tissue through normal circulation straight into the subarachnoid space via the vessels within the subarachnoid space.