Neurophysiology: Neuron Division and Brain Metabolism

Neuron Structure and Function

• Mature neurons do not divide, which is important to consider when neurons are injured, as new neurons are not generated to replace those that have lost function through damage or death.
• Neurons have three components: the soma (cell body), dendrites, and axons.
• Dendrites are multiple branch extensions of the cell body that carry nerve impulses towards the cell body and receive stimulation from other nerves.
• The soma is the cell body that synthesizes the components necessary to maintain the function of the axon and its terminals.
• Axons are long, conductive projections from the cell body that carry impulses away from the cell body.

Brain Metabolic Requirements

• The brain comprises 2% of body weight but receives 15% of cardiac output and consumes 20% of oxygen.
• The brain cannot store oxygen and cannot participate in anaerobic metabolism.
• If there is an interruption in blood or oxygen, brain cells can function for around 10 seconds without oxygen, and unconsciousness occurs with cardiac arrest.
• Death of brain cells occurs within 4-6 minutes without oxygen, and glucose is the major fuel source with no provision for storing glucose.

Brain Structure and Divisions

• The brain has three major divisions based on embryologic origin: forebrain, midbrain, and hindbrain.
• The forebrain is formed by the two cerebral hemispheres, the midbrain is formed by the cerebral peduncles, and the hindbrain is formed by the cerebellum, pons, and medulla.
• The midbrain, medulla, and pons make up the brain stem.
• Supporting cells, also known as neuroglial cells, provide structure, support, and nutrition for neurons.

Multiple Sclerosis and Guillain-Barré Syndrome

• Multiple sclerosis is a demyelination disease, and the cause is unknown, although there appears to be a genetic tendency towards developing the disease.
• Lesions are hard, demyelinated or sclerotic patches throughout the white matter of the CNS, and they can be seen in the optic nerve, periventricular white matter, brain stem, cerebellum, and spinal cord white matter.
• Axons die with demyelination.
• Guillain-Barré Syndrome is a peripheral nervous system disease that causes demyelination of the ventral spinal roots, and the cause is unknown.
• The disease is characterized by progressive ascending muscle weakness of the limbs, producing a symmetric flaccid paralysis.

Blood-Brain Barrier

• The blood-brain barrier is a protective CNS mechanism that permits the passage of essential substances, such as water, proteins, and electrolytes.
• The barrier is more permeable at birth than in adulthood and can be altered by acute cerebral lesions, such as trauma and infection.
• The barrier prevents many drugs from entering the brain, including highly water-soluble compounds, but lipid-soluble molecules, such as alcohol, nicotine, and heroin, can cross with ease.

Blood Supply and Regulation

• The blood supply to the brain is provided by the two internal carotid arteries anteriorly and the vertebral arteries posteriorly.
• The Circle of Willis is a communication network between the distal branches of the internal carotid and vertebral arteries.
• Anastomosis of arteries provides continued circulation if blood flow through one of the main vessels is disrupted.
• Regulation of cerebral blood flow is largely controlled by autoregulation, which maintains constant cerebral blood flow despite changes in systemic arterial pressure.

Cerebral Blood Flow and Regulation

• Cerebral blood flow is approximately 750ml/minute, which is about 1/6 of cardiac output.
• Autoregulation is efficient within a range of MAP 60-140 mmHg.
• Increases in carbon dioxide concentration and/or hydrogen ion concentration will increase cerebral blood flow, as will decreased oxygen concentration.
• Acidosis will depress neuronal activity, and the increased blood flow is the body's attempt to "wash out" toxins.

Cerebral Vascular Accident (Stroke)

• A stroke is an acute focal deficit from a vascular disorder that injures brain tissue.
• Known risk factors include age, heart disease, polycythemia, sickle cell, alcohol, and cocaine.
• There are two main types of strokes: ischemic and hemorrhagic.
• Ischemic strokes occur when there is a blockage in the blood vessels, while hemorrhagic strokes occur when there is a rupture of the blood vessels.

Hepatic Encephalopathy

• Ammonia is a by-product of protein metabolism and intestinal bacterial action that can accumulate and cause symptoms of hepatic encephalopathy.
• In liver failure, ammonia is not converted to urea, leading to altered cerebral metabolism and interference with neurotransmitters.
• Neurologic signs of hepatic encephalopathy include rigidity, hyperreflexia, and, rarely, seizures, and can lead to fatal coma.

Hepatorenal Syndrome

• Hepatorenal syndrome is a complication of advanced liver disease that refers to the occurrence of renal failure in association with advanced liver disease.
• It can be caused by a sudden decrease in blood volume, which leads to decreased GFR and tubular necrosis.
• The liver's inability to remove vasoconstrictive substances can also contribute to renal vasoconstriction.

Hepatitis

• Hepatitis refers to inflammation of the liver and can have various causes, including viral infections, reactions to drugs and toxins, and infectious disorders.
• Hepatitis A is caused by a small RNA-containing virus and is transmitted through the fecal-oral route.

Hepatitis A

• The incubation period for Hepatitis A is 2-4 weeks, and individuals can be contagious for up to 2 weeks before the onset of symptoms.
• The disease usually runs its course within approximately 4 months after exposure and does not cause a carrier state or chronic hepatitis.

Hepatitis C

• Hepatitis C is a single-strand RNA virus that is the most common blood-borne infection in the US.
• It is a major concern, as even small amounts of blood during tattooing, acupuncture, and body piercing can facilitate transmission.
• Chronic hepatitis occurs in 50-80% of cases, and it is the most common cause of chronic liver disease, cirrhosis, and liver cancer worldwide.

Hepatitis D (Delta)

• Hepatitis D is a defective RNA virus that cannot infect hepatocytes on its own and requires hepatitis B virus for replication.
• It can convert mild HBV infection into severe, fulminant disease.

Hepatitis E

• Hepatitis E is common in developing countries and clinically resembles Hepatitis A.
• It does not cause chronic or carrier states, but has a high mortality rate (20%) among pregnant women, leading to fulminant hepatitis.

Pathophysiology of Hepatitis

• Two mechanisms of liver injury with hepatitis virus are direct cellular injury and induction of immune responses against the viral antigen.
• Hepatic cell necrosis, scarring, and Kupffer cell hyperplasia can occur, leading to fibrosis, cholestasis, and obstructive jaundice.

Clinical Course of Hepatitis

• The clinical course of hepatitis consists of four phases: incubation, prodromal, icteric, and post-necrotic.
• The prodromal phase begins about 2 weeks after exposure and ends with the appearance of jaundice, accompanied by symptoms such as fatigue, nausea, and RUQ pain.
• The post-necrotic phase can result in portal hypertension, ascites, bleeding varices, and encephalopathy.