Pulmonary Alveolar Proteinosis is a disease in which surfactant processed by macrophages and phospholipids are accumulated in the alveoli. It can be primary or secondary (acquired).
Primary PAP –Unknown cause
Acquired (secondary) PAP
Occupational dust exposure
Allogeneic bone marrow transplantation
Physiopathology Pulmonary alveolar Proteinosis (PAP) is a lung disease with a non-specific cause with an annual incidence of 0.36 and 3.70 cases per million. However, it is known that the disorder has been presented after lung infections, inhalation of substances (dusty) such as aluminum, silica, titanium oxide and insecticides, blood-related sickness (leukemia), immune problems (such as AIDS) and it has been related to heredity. After that, patients demonstrated problems during homeostasis regarding the behavior and maturation of alveolar macrophages (white blood cell that engulfs and digests foreign substances, microbes, and cancer cells), the mucociliary escalator (mucus-producing goblet cells and the ciliated epithelium) and the production of surfactant (compound that lower the surface tension during the gas exchange). Therefore, surfactant phospholipids and proteins fill the alveoli and provoke difficulties during the gas exchange. It has been discovered that during the disease there are neutralizing autoantibodies against Granulocyte-macrophage colony-stimulating factor (GM-CSF: monomeric glycoprotein used as growth factor and immune modulator). In conclusion, it can be classified as an autoimmune disease as the patients are producing antibodies against their own stimulation factors for macrophages and granulocytes resulting in more proteinaceous material. Impairment of surfactant clearance by alveolar macrophages is the result of inhibition of the action of GM-CSF by blocking autoantibodies and congenital disease is because of mutations in surfactant protein genes.
Symptoms of PAP are:
Dyspnea (shortness of breath)
Inspiratory crackles on auscultation
Clubbing of the fingernails
Central and peripheral cyanosis.
High levels of lactate dehydrogenase (LDH), tumor markers and surfactant proteins A and D.
Fatigue and malaise
Low-grade fever and/or night sweats
Coughing blood (rare)
Can be diagnosed after a chest x-ray, which shows bilateral mid and lower-lung field opacities with a “butterfly distribution”. Also, it is revealed if bronchoalveolar lavage is done and the fluid is milky or opaque, stains PAS-positive, and has scattered surfactant-engorged macrophages, an increase in T cells, and high levels of surfactant apoprotein-A. In cases in which the lavage fluid is no diagnostic there must be an open lung biopsy. Other tests practiced are:
CT (HRCT). It shows opacification, thickened structures, and interlobular septa in polygonal shapes.
Pulmonary function tests. Show reduction in diffusing capacity for carbon monoxide. Disproportionate to the decreases in vital capacity, residual volume, and total lung capacity.
ABGs. Show hypoxemia.
Laboratory tests. Polycythemia, increased serum LDH levels, and increased serum surfactant proteins A and D.
Treatment Depends on the stage of the illness, the infections and the impairment. The normal care is the whole-lung lavage in which sterile fluid is introduced to the lung and removed with the lipoproteinaceous material. It is performed under general anesthesia, with a double-lumen endotracheal tube that is very useful since it allows ventilation and the lavage. Before the procedure the patient is ventilated with 100% oxygen and an isotonic sodium chloride solution. One lung is fixed after the other, reason why this intervention takes several hours. The patients are also treated with steroids, mucolytic and proteinase. For secondary Pulmonary Alveolar Proteinosis it is very important to know the cause. The systemic inhalation GM-CSF has been effective and provides a therapeutic effect with the autoimmune disease. Lung transplantation is also a possibility for patients with congenital PAP and adult patients with fibrosis.
Somnambulism (ie, sleepwalking) is a disorder of arousal that falls under the parasomnia group. Parasomnias are undesirable motor, verbal, or experiential events that occur during sleep. These phenomena occur as primary sleep events or secondary to systemic disease. They are categorized as those occurring in rapid eye movement (REM) sleep; those occurring during non–rapid eye movement (NREM) sleep; and miscellaneous types that do not relate to any specific sleep state.
The parasomnias have been thought to represent not pathologic cerebral functioning but rather a response to CNS activation that results in sleep-wake or REM-NREM state confusion, instability, or overlap. Recent studies, however, demonstrate differences between sleep patterns and neuronal sleep control mechanisms in individuals with parasomnias compared with those without. Normal sleep involves cyclic hypnic patterns throughout the night between wakefulness, NREM, and REM states. The CNS remains active during all sleep-wake states, although rapid changes are required in neural networks, rhythms, and neurotransmitters with state changes. The length of each cycle averages 50 minutes for a full-term newborn, increasing to approximately 90 minutes by adolescence.
Slow wave sleep (SWS) normally occurs in the first 2 hypnic cycles; younger children have an additional SWS period toward the end of the sleep period. Children typically enter their deepest sleep within 15 minutes of sleep onset, and this first SWS period lasts from 45-75 minutes. This explains why it is easy to move children without rousing them soon after sleep onset. Parasomnias occur as children are caught in a mixed state of transition from one sleep cycle to the next (eg, NREM-wakefulness). This transition state is characterized by a high arousal threshold, mental confusion, and unclear perception.
Sleepwalkers appear to have an abnormality in slow wave sleep regulation. The dissociation that occurs between body and mind sleep appears to arise from activation of thalamocingulate pathways with persisting deactivation of other thalamocortical arousal systems. The first slow wave sleep period of the night is considered to be more disturbed in somnambulistic individuals, and the entire NREM-REM sleep cycle is more fragmented. Because these disorders occur more frequently in children, these differences have been suggested as signs of CNS immaturity.
Why do elevated triglycerides cause acute pancreatitis?
Althought the two main causes of pancreatitis are by far alcohol and gallstones, the third one is hypertriglyceridemia.
I was wondering, as a friend asked me for a physiopathological explanation, whether it could be related to a problem of cellular availability of cholesterol in the liver, because of the lipoprotein disorder caused by hypertriglyceridemia. Even the slightest change in bilary salts composition can lead to crystals, and then, an increased risk of pancreatitis.
I don’t own rights for this image.
In French, this is called “Small Diagram”.
But it looks like I was wrong.
The exact mechanism is unclear but it is thought to involve increased concentrations of chylomicrons in the blood. Chylomicrons are usually formed 1-3 hours post-prandially and cleared within 8 hours. However, when triglycerides levels exceed 1,000mg/dL, chylomicrons are almost always present. These low density particles are very large and may obstruct capillaries leading to local ischemia and acidemia. This local damage can expose triglycerides to pancreatic lipases. The degradation of triglycerides to free fatty acids can lead to cytotoxic injury resulting in further local injury that increases inflammatory mediators and free radicals, eventually manifesting as pancreatitis.
Why does the ischemia seems to mainly damage the pancreas, while other traditional ischemia-sensitive organs seem to be relatively spared ? Is it because the real issue isn’t ischemia itself, but pancreatic degradation of triglycerides ?