[HELLP syndrome]. / HELLP-syndromet.

BACKGROUND: The HELLP syndrome (H = hemolysis, EL = elevated liver enzymes, LP = low platelets) is a pregnancy complication which affects 10-20% of cases of severe preeclampsia. MATERIAL AND METHODS: The article is a review of the literature. RESULTS: Approximately 70% of HELLP syndrome cases occur before delivery, 15% as early as in the second trimester, the remainder after delivery. The classical HELLP syndrome is characterised by abdominal pain, pathological liver tests and low platelets. However, some cases are atypical; hypertension and abdominal pain may both be absent. Genetic as well as immunologic factors are involved in the pathogenesis. There is an imbalance in the coagulation process in the placenta. Activated leukocytes and macrophages induce production of cytokines that may reach the general circulation and cause endothelial dysfunction. In the HELLP syndrome fibrin deposits are also found in the vessels and in the liver sinusoides. INTERPRETATION: A mother with a classic HELLP syndrome should be delivered after stabilisation of the clinical condition. A partial HELLP syndrome can be observed. Treatment with corticosteroids is beneficial.

[Pathophysiology and clinical manifestations in pre-eclampsia]. / Patofysiologi og kliniske manifestasjoner ved preeklampsi.

BACKGROUND: Preeclampsia is a progressive, multisystem disorder characterised by hypertension and proteinuria. A body of evidence suggest a genetic basis; it is generally accepted that the underlying pathological processes are in the placenta. MATERIAL AND METHODS: This article is a review of the pathophysiology of preeclampsia based on literature mainly obtained through PubMed and Medline searches. RESULTS: A poorly perfused placenta, secondary to defective placental invasion of the spiral arteries, may lead to hypoxia and insufficient perfusion and cause release of cytokines which damage endothelial cells and cause dysfunction. Women with preeclampsia have markedly elevated concentrations of triglyceride-rich lipoproteins. Lipid peroxidation also causes endothelial dysfunction and thus contributes to preeclampsia. Placenta is one source of the lipid peroxides. Antioxidant deficiency is also a predisposing factor. Hyperhomocysteinaemia, protein S and protein C deficiency, and activated protein C resistance appear to be involved in the pathophysiology of severe preeclampsia and early onset preeclampsia. INTERPRETATION: The new information about mechanisms for development of preeclampsia gives a basis for new treatment modalities.

[Pre-eclampsia--a review]. / Preeklampsi--en oversikt.

BACKGROUND: Preeclampsia is characterized by hypertension and proteinuria with or without oedema. MATERIAL AND METHODS: The authors highlight some aspects of preeclampsia: epidemiology, classification, clinical evaluation and treatment. RESULTS: The condition may be classified as light or severe. Preeclampsia can induce damage to the placenta, liver, kidneys and brain, in addition to complications like the HELLP syndrome, placental abruption and eclampsia. Thrombocyte activation may cause activation of the coagulation system and thrombocytopenia. Early onset preeclampsia (< 34 weeks) is often associated with placental infarcts and reduced fetal growth. INTERPRETATION: We focus on early signs and close clinical surveillance. The diastolic blood pressure should be estimated with Korotkoffs' phase V. Patients with early onset preeclampsia should be hospitalized, as should women with hypertension and newly developed proteinuria. Antihypertensive treatment is discussed. Cases with reduced fetal growth and those with severe preeclampsia should in most cases be delivered preterm. Vaginal delivery is preferable. Labour may be induced by oxtocin, following cervical prostaglandin stimulation as indicated. In such cases cardiotocography surveillance during labour should be performed. Caesarean section may be performed in selected cases. Patients with mild preeclampsia can await spontaneous vaginal delivery at term, but delivery should be induced if they proceed past term.

Role of histamine and calcitonin gene-related peptide in the hyperemic response to hypertonic saline and H+ back-diffusion in the gastric mucosa of cats.

BACKGROUND: The present study was undertaken to measure the output of histamine and calcitonin gene-related peptide (CGRP) from injured and restituting gastric mucosa into venous blood and to study the effect of acid back-diffusion on the release of these mediators and their role in the hyperemic response to injury. METHODS: Stomachs of cats were perfused with saline at pH 1.0 or 7.4. Gastric mucosal blood flow (GMBF) was determined with radioactive microspheres, and blood flow in the portal vein and celiac artery was determined by transit-time flowmetry. H+ back-diffusion/secretion was measured by pH-stat titration and by measuring the arteriovenous base excess difference. Mucosal injury was produced by exposure to 2 M NaCl. Histamine and CGRP in portal venous blood were measured by radioimmunoassay. RESULTS: During mucosal exposure to 2 M NaCl GMBF increased, and histamine (0.23 nmol/min) and CGRP (1.2 pmol/min) were released from the mucosa into blood. The hyperemic response was reduced by pretreatment with H1 and H2 blockers and still further by addition of the blocker CGRP8-37. After mucosal damage and luminal perfusion at pH 7.4, GMBF and output of CGRP and histamine decreased towards base-line levels within 30 min. During luminal perfusion at pH 1.0 associated with acid back-diffusion, GMBF and histamine output remained high, whereas the output of CGRP decreased to base-line level. Pretreatment with H1 and H2 blockers reduced the hyperemic response as measured 30 min after damage. CONCLUSIONS: The hyperemic response caused by 2 M NaCl is most likely mediated by histamine and CGRP and maintained by histamine released by back-diffusion of H+ through the superficially damaged gastric mucosa.

Gastric mucosal repair and release of HCO3- after damage by 2 M NaCl in cat: role of systemic acid base status.

To study the influence of acid base balance on gastric mucosal repair, NH4Cl or NaHCO3 was given intravenously to anesthetized cats after mucosal damage induced by intraluminal 2 M NaCl. Saline at pH 5 or 1 was perfused via an oral tube through the stomach lumen and evacuated via a pyloric tube to a chamber with pH and PCO2 electrodes. Luminal bicarbonate (HCO3-) was markedly increased early after damage in both acidotic and alkalotic animals. In alkalotic animals mucosal blood flow increased about twofold in response to mucosal damage, whereas the early hyperemic response was either completely attenuated or blunted in acidotic animals. HCO3- release was correlated to availability of HCO3- by blood in alkalotic animals with luminal pH 5. Alkalotic animals showed improved repair compared with acidotic animals, and mucosal restitution was correlated to availability of HCO3- by blood. We conclude that luminal leakage of HCO3- or plasma after mucosal damage depends on availability by blood and consumption of HCO3- within the mucosa and that blood borne HCO3- has a major influence on gastric mucosal repair.

Role of bicarbonate in blood flow-mediated protection and repair of damaged gastric mucosa in the cat.

BACKGROUND/AIMS: The hyperemic response after superficial gastric mucosal damage is essential for repair of the mucosa. Only indirect evidence suggests that this is caused by supply of bicarbonate. Therefore, this study tested the effect of maintaining the availability of bicarbonate after prevention of the hyperemic response after damage by 2 mol/L NaCl. METHODS: Celiac artery flow was reduced, as monitored by Doppler ultrasonography, by gradual constriction of the vessel after mucosal damage. Saline (pH 1.0) was perfused through the stomach lumen and thereafter through a closed chamber with pH and PCO2 electrodes. RESULTS: Exposure to 2 mol/L NaCl produced a marked increase of mucosal blood flow as measured by microspheres (P < 0.025) and a high degree of mucosal restitution 90 minutes after damage as judged by microscopy, whereas prevention of the hyperemic response caused extensive erosions and much less restitution (P < 0.001). The latter effect was completely counteracted by intravenous bicarbonate. High blood concentration of bicarbonate increased luminal release of bicarbonate, whereas high mucosal blood flow did not. CONCLUSIONS: These data show that bicarbonate is an important factor in blood flow-mediated protection and repair of damaged gastric mucosa and suggest that concentration gradients are the major determinants for transport of bicarbonate across the damaged and restituted mucosa.

Release of bicarbonate from damaged and restituted gastric mucosa in the cat.

BACKGROUND: Gastric mucosal damage leads to luminal alkalinization, but its dependence on mucosal blood flow and acid secretory state of the mucosa is not known. This study examined release of bicarbonate to the gastric lumen and mucosal blood flow in cats after mucosal damage caused by 2 mol/L NaCl and during 90 minutes of epithelial restitution. METHODS: Bicarbonate was calculated from measurements of pH and PCO2 in the luminal perfusate. Mucosal blood flow was measured with microspheres. RESULTS: Luminal bicarbonate increased more than twofold after damage in pharmacologically nontreated, pentagastrin-treated, and omeprazole-treated animals (P < 0.001). Luminal bicarbonate thereafter decreased completely to pre-damage level in pentagastrin-treated, partly in nontreated, but remained elevated in omeprazole-treated animals. Mucosal blood flow increased about 100% 15 minutes after damage (P < 0.001), irrespective of secretory state. Bicarbonate availability (arterial [HCO(3-)] x mucosal blood flow) was significantly related to luminal release of bicarbonate from the newly damaged (P < 0.01) but not from the restituted mucosa. CONCLUSIONS: (1) From the newly damaged mucosa, the luminal release of bicarbonate is related to availability of blood-borne bicarbonate. (2) From acid-stimulated restituted mucosa, the bicarbonate produced by the parietal cells is not released to the lumen, but either consumed within the mucosa by back-diffusing H+ or distributed to the systemic circulation.

Gastric mucosal injury and associated changes in mucosal blood flow and gastric fluid secretion caused by dimethyl sulfoxide (DMSO) in rats.

Dimethyl sulfoxide applied intragastrically for 10 min in rats caused extensive mucosal damage. In concentrations of 5%, 10%, or 100%, dimethyl sulfoxide caused superficial damage to 33%, 36%, and 97%, respectively, of the corpus mucosa, and 28%, 44%, and 96%, respectively, of the antral mucosa. Concentrated dimethyl sulfoxide also caused damage to the pits and glands in some areas of the mucosa. The amount of fluid in the stomach increased by 0.24 ml, 0.48 ml, and 2.07 ml during application of 5%, 10%, and 100% dimethyl sulfoxide. The 10% dimethyl sulfoxide increased mucosal blood flow by 0.57 ml/min/g in the antrum, and 100% dimethyl sulfoxide increased mucosal blood flow by 2.21 ml/min/g in the antrum and by 1.17 ml/min/g in the corpus. We conclude that dimethyl sulfoxide is a gastric irritant, which should be considered when it is used as an oxygen radical scavenger, as a drug or carcinogen vehicle, or as oral medication in patients. The protective effect of intragastric dimethyl sulfoxide against stress and various drug-induced gastric injury may be due to "adaptive cytoprotection" rather than an oxyradical scavenger effect.

Adaptive protection related to clearance of ethanol in gastric mucosa of cats.

This study was designed to test the hypothesis that hyperemia after exposure to 2 M NaCl protects the gastric mucosa against damage caused by absolute ethanol by removing ethanol diffusing from the gastric lumen into the mucosa. The stomach of anesthetized cats was perfused with saline at pH 1.0. Gastric mucosal blood flow was determined by radioactive microspheres, and portal vein blood flow was measured by Doppler ultrasound flowmetry. The concentration of ethanol in the corpus mucosa and the amount of ethanol transported away from the stomach in portal blood were measured by using absolute ethanol containing trace amounts of 14C-labeled ethanol. Pretreatment with 2 M NaCl for 10 min increased mucosal blood flow and prevented the development of deep mucosal lesions after subsequent application of absolute ethanol. An inverse correlation was found between mucosal blood flow and the degree of ethanol-induced damage. The mucosal content of ethanol was low in animals pretreated with hyperosmolar NaCl, and the degree of mucosal damage was related to the tissue concentration of ethanol. The amount of ethanol transported by blood from the stomach increased with increasing mucosal blood flow. We conclude that the mild irritant, 2 M NaCl, increases mucosal blood flow, which protects the mucosa by removing ethanol diffusing from the lumen. Thus, the mucosal ethanol concentration remains below a level that causes damage.

Role of blood flow in adaptive protection of the cat gastric mucosa.

This study was designed to test the hypothesis that adaptive cytoprotection is related to increased blood flow caused by mild irritants. The stomach of cats was perfused with saline at pH 1.0. Mucosal blood flow was determined by radioactive microspheres, and celiac artery blood flow was measured by Doppler ultrasound. Gastric blood flow was left undisturbed or reduced by tightening a vessel loop around the celiac artery. Mucosal exposure to absolute ethanol for 2 minutes caused extensive damage to the surface epithelium, the pits, and the upper half of the glands. Pretreatment of the mucosa with 2 mol/L NaCl for 10 minutes prevented the development of mucosal lesions after subsequent application of absolute ethanol. The mucosal blood flow increased markedly after treatment with 2 mol/L NaCl. When this hyperemic response was inhibited by reducing celiac artery blood flow, ethanol caused lesions of similar degree as in animals not pretreated with 2 mol/L NaCl. A highly significant correlation was obtained between mucosal blood flow, as determined just before the application of ethanol, and the degree of ethanol-induced damage. At a chosen level of blood flow, ethanol caused the same degree of damage with or without pretreatment with 2 mol/L NaCl. In conclusion, high mucosal blood flow caused by a mild irritant is an important factor in adaptive gastric protection. With the present experimental setup, the protection could be fully explained as a result of the hyperemic response caused by 2 mol/L NaCl.

Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.