Beatrica Kurbel

The role of gastric mast cells, enterochrornaffin-like cells and parietal cells in the regulation of acid secretion

The idea presented here is that, in gastric mucosa, two independent regulatory systems use the same transmitter: histamine molecules. The IgE/mast cell system is dispersed throughout the body, while the other regulates the gastric acid secretion. IgE molecules in gastric mucosa are attached to the mast cells. Mast cells release histamine molecules after the antigen has been recognized by IgE. These molecules normally act on vascular H1 receptors to promote extravasation and chemotaxy. Gastrin molecules are released from antral G cells to stimulate gastric acid secretion. Their influence on parietal cells is indirectly augmented by gastrin governed release of histamine molecules from enterochromaffin-like cells. These histamine molecules normally act on H2 receptors of parietal cells to promote gastric acid secretion. Chronic infection of gastric mucosa (i.e. with Helicobacter pylori), autoimmune disorders or repetitive mucosal exposure to the same antigen, can develop chronic inflammation of gastric mucosa. Gastric acid secretion is diminished with secondary hypergastrinemia and increased release of histamine from enterochromaffin-like cells in an attempt to stimulate the few remaining parietal cells. Hypothetically, increased concentrations of released histamine in gastric mucosa might activate the vascular H1 receptors with extravasation and aggravated inflammation. This can further decrease the number of active parietal cells, reduce gastric acid secretion and potentiate hypergastrinemia. In this hypothetical setting, H1 blockers might reduce the damage by abolishing the vascular reactions. The prolonged antigen load on gastric mucosa can promote production of specific IgE antibodies. Further exposures to the same antigen degranulate sensitized mucosal mast cells. Liberated histamine can produce extravasation through the vascular H1 receptor and, hypothetically, local hyperacidity through the parietal cell H2 receptors. The result would be hyperacidity and hypogastrinemia with possible ulcer disease. Some individuals are more predisposed to IgE production or have increased numbers of mast cells that might explain why only some people develop ulcer disease after H. pylori infection.

Inertia of endocrine systems due to hormone binding to circulatory proteins

It is often presumed that the main role of hormone binding to albumins and binding proteins (BPs) is to reduce oscillating levels of free hormone molecules and to transport steroid hormones. This paper is an attempt to define possible consequences of hormone molecules binding to carrier proteins in circulation. Binding to albumins and BPs prevents exact and quick control of hormone actions. Hormones without significant protein binding govern vital and fast acting regulatory mechanisms (blood glucose or calcium) in which any added inertia might be dangerous. In the presented model, the added inertia for a partially bound hormone (H) is defined as: H(bound)/H(free). Values, calculated from the reported data, range from 0.4 for GH to more than 2000 for T(4). In comparison to albumins, high-affinity BPs make more stable reserve that would cover periods of low or no hormone secretion. At the same time, hormone molecules are taken away from the blood level control and thus might be considered sequestrated. For hormones without protein binding, the well-perfused areas of the body, or the areas with increased capillary permeability, would be more exposed, making an uneven distribution among target tissues. For the hormone that binds blood proteins, places of secretion and tissue perfusion become unimportant, since the hormone is being liberated anywhere in the circulation (i.e., for strongly bound IGFs, IGF binding proteins do not just stabilize proinsulin actions of IGF-1, but also make all parts of body to be under the same exposure to liberated IGFs, an important feature to promote a symmetrical bone growth). Estrogens are known to stimulate liver secretion of different BPs. A possible explanation is that in the follicular phase there is a small initial mass of granulosa cells, and it takes time to saturate free estrogen carriers, before the normal free hormone level can be reached and FSH secretion inhibited. Less inert peptide inhibin might suppress FSH before free estrogens reach the required level. Without inhibin suppression, an increased FSH level with an increased number of growing follicles can be expected. Estrogens increased production of BPs augments inertia of the estrogen loop and possibly modulates the FSH/estrogen negative feedback.

Model of pulmonary fluid traffic homeostasis based on respiratory cycle pressure, bidirectional bronchiolo-pulmonar shunting and water evaporation

The main puzzle of the pulmonary circulation is how the alveolar spaces remain dry over a wide range of pulmonary vascular pressures and blood flows. Although normal hydrostatic pressure in pulmonary capillaries is probably always below 10 mmHg, well bellow plasma colloid pressure of 25 mmHg, most textbooks state that some fluid filtration through capillary walls does occur, while the increased lymph drainage prevents alveolar fluid accumulation. The lack of a measurable pressure drop along pulmonary capillaries makes the classic description of Starling forces unsuitable to the low pressure, low resistance pulmonary circulation. Here presented model of pulmonary fluid traffic describes lungs as a matrix of small vascular units, each consisting of alveoli whose capillaries are anastomotically linked to the bronchiolar capillaries perfused by a single bronchiolar arteriole. It proposes that filtration and absorption in pulmonary and in bronchiolar capillaries happen as alternating periods of low and of increased perfusion pressures. The model is based on three levels of filtration control: short filtration phases due to respiratory cycle of the whole lung are modulated by bidirectional bronchiolo-pulmonar shunting independently in each small vascular unit, while fluid evaporation from alveolar groups further tunes local filtration. These mechanisms are used to describe a self-sustaining regulator that allows optimal fluid traffic in different settings. The proposed concept is used to describe development of pulmonary edema in several clinical entities (exercise in wet or dry climate, left heart failure, people who rapidly move to high altitudes, acute cyanide and carbon monoxide poisoning, large pulmonary embolisms).