A combination of extrinsic (passive) and intrinsic (active) forces move lymph against a hydrostatic pressure gradient in most regions of the body. The effectiveness of the lymph pump system impacts not only interstitial fluid balance but other aspects of overall homeostasis. This review focuses on the mechanisms that regulate the intrinsic, active contractions of collecting lymphatic vessels in relation to their ability to actively transport lymph. Lymph propulsion requires not only robust contractions of lymphatic muscle cells, but contraction waves that are synchronized over the length of a lymphangion as well as properly functioning intraluminal valves. Normal lymphatic pump function is determined by the intrinsic properties of lymphatic muscle and the regulation of pumping by lymphatic preload, afterload, spontaneous contraction rate, contractility and neural influences. Lymphatic contractile dysfunction, barrier dysfunction and valve defects are common themes among pathologies that directly involve the lymphatic system, such as inherited and acquired forms of lymphoedema, and pathologies that indirectly involve the lymphatic system, such as inflammation, obesity and metabolic syndrome, and inflammatory bowel disease.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP272088

Lymphatic pumping: mechanics, mechanisms and malfunction.

The authors review the current understanding of lymphatic anatomy and physiology, and the pathophysiology of lymphedema. The skin lymphatic system consists of the initial lymphatics, which converge into lymphatic precollectors, collectors and lymphatic ducts; these in turn convey the lymph to the regional lymph nodes. Interstitial fluid and particles enter the initial lymphatics through interendothelial openings and by vesicular transport. Lymphatic uptake is enhanced by external compression. Lymphatic transport depends greatly on contraction of lymphangions, which generate the suction force that promotes absorption of interstitial fluid and expels lymph to collecting ducts. In lymphedema, various types of congenital and acquired abnormalities of lymphatic vessels and lymph nodes have been observed. These often lead to lymphatic hypertension, valvular insufficiency and lymphostasis. Accumulation of interstitial and lymphatic fluid within the skin and subcutaneous tissue stimulates fibroblasts, keratinocytes and adipocytes eventuating in the deposition of collagen and glycosaminoglycans within the skin and subcutaneous tissue together with skin hypertrophy and destruction of elastic fibers.

https://journals.sagepub.com/doi/pdf/10.1177/1358863X9700200408

Lymphedema: Anatomy, Physiology and Pathogenesis

Asthma is a chronic inflammatory disease of airways with a multifactorial pathogenesis. Both genetic and environmental factors contribute to the development of the disease which can vary in the same patient through time. Due to its complexity, natural history of asthma is poorly well-known. Generally, in the history of asthma three periods of life are taken into consideration: early childhood, adolescence and adult life. It has been demonstrated that less than one third of children who are affected by wheezing in early childhood develop a true asthma afterwards. Usually in these subjects who are male and atopic, viruses and subsequently allergens represent the most important factors responsible for the development of asthma. During adolescence airborne allergens represent the main cause of the disease: mites in infancy and pollens in late childhood. The incidence of asthma during adolescence is growing according to recent studies, and even if the symptomatology of asthma improves through time, about two thirds of patients remain asthmatic in their adult life. As regards adults etiology, it is less known, women are more frequently affected than men and the prognosis is generally poorer. Several factors negatively influence the course of asthma such as age, smoking, the severity of the disease during infancy, the persistence of functional obstructive alterations and the increased aspecific bronchial reactivity. Adequate therapy is crucially important to cope with these factors and can change the course of the disease.

The natural history of asthma

Preeclampsia is a pregnancy-specific condition that affects up to 8% of the gravid population. The syndrome is a leading cause of maternal and perinatal morbidity and mortality worldwide. Despite its relatively high prevalence, the etiology of preeclampsia remains elusive and the only definitive treatment is delivery. For pregnancies outside of term, the management of preeclampsia is a balance between promoting fetal maturity and preserving the life and well-being of both the mother and fetus.

Diagnosis and management of preeclampsia

Mechanical forces and lymphatic transport.

Red blood cells and lysate products (erythrolysate) are observed consistently in lymph draining acute and chronic inflammatory reactions and from tissues subjected to trauma or surgical procedures. Using hemoglobin as a marker for erythrolysate, we have measured hemoglobin in lymph up to the 10(-6) M range in a number of pathophysiological states. Data demonstrate that erythrolysate alters the pumping characteristics of lymphatic vessels. To test the effects of erythrolysate on lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure that stimulated pumping activity could be applied to the vessels. With a fixed transmural pressure of 6 cm H2O applied to the ducts, sheep erythrolysate depressed pumping activity between 40% and 100%, with dilutions containing between 10(-8) and 10(-5) M hemoglobin. Although the active principle in the red blood cells has not been characterized, evidence from precipitation purification experiments suggests that hemoglobin is an important component. Once suppressed, pumping could be restored in many but not all vessels (often to control levels) by elevating the distending pressure above 6 cm H2O. The relation between transmural pressure and fluid pumping is expressed as a bell-shaped curve, with pumping increasing up to a peak pressure (usually 8 cm H2O) and declining at pressures above this level. By comparing pressure/flow curves, we were able to ascertain that hemoglobin shifted the lymphatic function curve to the right and, on average, reduced the maximum pumping capability of the vessels. We speculate that the presence of erythrolysate/hemoglobin in lymph may modulate the ability of lymphatic vessels to drain liquid and protein from the tissue spaces.

Lymphatic pumping in response to changes in transmural pressure is modulated by erythrolysate/hemoglobin.

Red blood cells (RBCs) and lysate products (erythrolysate) are consistently observed in lymph draining inflammatory reactions and from tissues subjected to trauma or surgical procedures. We determined previously that erythrolysate modulates lymphatic pumping by altering the pressures over which the lymph pump is active. The purpose of this study was to test the hypothesis that oxyhemoglobin was the active material within erythrolysate. To quantitate lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure could be applied to the vessels. This procedure stimulated pumping activity. Erythrolysate was prepared from sheep RBCs by lysis in Tris buffer and a portion of this was purified by column chromatography using DEAE-Sephadex A-50. Both the purified hemoglobin (10(-5) M) and crude erythrolysate (the latter diluted appropriately in Krebs solution to contain 10(-5) M hemoglobin) reduced lymphatic fluid pumping approximately 70% over a period of 2 h. To determine whether this activity was due to the heme or the protein portion of the molecule, we compared the activity of purified oxyhemoglobin with that of its oxidized methemoglobin derivative. This was achieved by conversion with potassium ferricyanide. Methemoglobin was inactive, suggesting that the heme portion was important for the lymphatic effect. Further confirmation of this observation was provided by experiments with myoglobin which was purified from sheep heart. Oxymyoglobin, which shares an identical heme but has a different protein component, inhibited lymphatic pumping, when tested on the bovine lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS)

Heme-containing proteins suppress lymphatic pumping.

Background: Severe pre-eclampsia is one of the major causes of high maternal mortality rate in both developed and developing countries. The goals of management are to prevent progression to eclampsia thus preventing convulsions, to control the blood pressure and to prevent untoward effects in the foetus. The first-line option for the treatment and prevention of eclamptic seizures is magnesium sulphate. Objective: To determine the serum magnesium, urea and electrolyte levels in neonates of mothers treated with magnesium sulphate and compare the findings with the levels in non-exposed neonates. Methodology: A quasi experimental design was adopted where test s ubjects were neonates of mothers suffering from preeclampsia and severe eclampsia and were being treated with magnesium sulphate just before delivery at Pumwani Maternity hospital. The control group comprised neonates of hypertensive mothers without preeclampsia being treated using other drugs. Blood samples were obtained from the mother at onset of labor and from the neonates at birth and analyzed in the clinical chemistry laboratory of the University of Nairobi. Results :  A total of 54 mothers and their neonates were enrolled with 27 in each arm of the study. The mean maternal serum magnesium in the test group was significantly higher than in the control group (p = 0.008). The mean neonatal serum magnesium in the test group was also significantly higher compared to the control group (p = 0.008). There were statistically significant differences in serum sodium (p = 0.015), urea (p = 0.043) and creatinine (p = 0.008) levels between the maternal test and control groups. There were significant differences in serum urea (p = 0.007) and chloride (p = 0.017) between the neonatal test and control groups. The calcium and potassium levels were elevated in the test group but not to significant levels. There was a positive correlation between maternal and neonatal serum magnesium levels in both groups stronger in the test group (r = 0.56, p = 0.003) as compared to the control group (r = 0.35, p = 0.087). Conclusion : Maternally administered magnesium sulphate raises urea and creatinine levels to significant levels in mothers. Calcium levels are also raised while in mothers not receiving magnesium sulphate they were slightly lower. In neonates the urea and chloride levels are elevated to significant levels while the calcium and potassium levels are not significantly elevated. We suggest monitoring of both in the immediate post-partum period. Keywords : Preeclampsia, eclampsia, magnesium sulphate, neonate, serum urea and electrolytes.

Effect of Magnesium Sulphate in Mothers suffering from Toxemia of Pregnancy and their Neonates

Background: In Kenya, asthma affects 10% of the population. One of the modifiable risk factors contributing to asthma morbidity and mortality is environmental exposure . Naivasha flower farms introduce pesticides persistently into the environment and these may drift onto residential property or other areas where children play. Proximity of households to the pesticide treated farms may also increase exposure of children to the pesticides. Pesticide exposure has been shown to exacerbate already existing asthma, a relationship that has not been studied in Kenya. Objectives: To identify risk factors that exacerbate asthma and influence adequacy of Asthma control in children residing in a flower growing area in Kenya. Methodology: The design was a cross-sectional study that involved 150 asthmatic children aged 5-12 years residing a flower growing area.  The study was conducted between May and July, 2014 in Naivasha, which is home to Kenya’s largest horticultural flower farms.  Participants were interviewed using a structured questionnaire while asthma control was measured using a validated Asthma control tool. Logistic regression was done to identify variables that affected asthma control. Results: Majority of the asthmatic children were males (56.7%) while females were 43.33%. Risk factors that were found to be significantly associated with asthma control were; duration of stay in or near a flower farm (OR = 0.723, 95%CI (0.538-0.975), presence of a smoker in the family (OR = 0.463, 95%CI (0.094-22.629) and presence of household pet (OR = 4.358, 95%CI (1.182-16.057). There was no significant relationship between the child’s asthma control and age of child, sex of child, distance of school from flower, guardian’s level of education, guardian’s income, and guardian’s occupation as a flower farm worker, child’s age of diagnosis and use of indoor pesticides. Conclusion :  The use of Integrated Pest Management (IPM) should be promoted as it keeps environmental exposure pesticides to a minimum. Key words: asthma, household pet, flower farm, pesticide, smoking

Factors that influence adequacy of asthma control in children residing in Naivasha, a flower growing area in Kenya

Background: Pesticide exposure is a risk factor for asthma exacerbations in flower farm regions in the world.  Data on levels of serum cholinesterase among asthmatic children exposed to pesticides in Kenya is scanty. Objectives: To compare and identify variables which affect the concentration of serum cholinesterases in children who are exposed and unexposed to pesticides. Methodology: The design was a comparative cross-sectional study that involved exposed and unexposed children.  The study was conducted between May and July, 2014 in Naivasha, Kenya.  Patients were interviewed and serum samples were analysed for cholinesterase levels.  Multi-linear regression was done to identify variables that affected cholinesterase activity. Results: Children who were exposed to pesticides had a lower median ChE activity of 5828 [IQR 4863, 6443] compared to the unexposed arm whose median was 7133 [IQR 6063, 8179].  Five predictor variables were found to be significantly associated with depression of serum cholinesterase levels.  The most important predictor variable for the levels of ChE in children, was not using protective clothing by the parent [adjusted β -1457.0 (95% CI - 2594, 1319.8)].  Others were not using household pesticides [adjusted β 96.3, (95% CI 22.6, 170.0)], female sex [adjusted β -695.7 (95% CI -1296.2, - 95.3)], non school attendance [adjusted β -1676.8 (95% CI -3371.6, 18.1)] and not taking a break after spraying [adjusted β 1105.5 (95% CI (315.0, 1895.2)]. Conclusion: Children who were exposed to pesticides had low cholinesterase levels. Parents should therefore be encouraged to wear protective gear as this conferred protection of children from the effects of pesticide exposure. Key words : asthma, exposure, children, pesticides, cholinesterase.

G. Wandolo

Papers

Lymphatic pumping in response to changes in transmural pressure is modulated by erythrolysate/hemoglobin.

Heme-containing proteins suppress lymphatic pumping.

Effect of Magnesium Sulphate in Mothers suffering from Toxemia of Pregnancy and their Neonates

Factors that influence adequacy of asthma control in children residing in Naivasha, a flower growing area in Kenya

Effect of Pesticide Exposure on Serum Cholinesterase Levels among Asthmatic Children in Naivasha Sub-County, Kenya