Anaemias of oral significance

Anaemia is not a disease in itself. It is a sign of a single or multiple diseases. Anaemia is said to exist when the haemoglobin concentration is below normal for the age and sex of an individual. The synthesis and normal circulatory level of haemoglobin in any given individual depend on factors such as an adequate supply of haemopoietic nutrients, normal functioning of bone marrow, and proper utilization of haemoglobin. Based on these factors anemia can be broadly grouped into three categories: 1. Anaemia due to lack of haemopoietic nutrients (nutritional anemia) 2. Anaemia due to bone marrow dysfunction (aplastic anaemia) 3. Anaemia due to excessive breakdown of red blood cells (haemolytic anaemia) (AU)

The effect of splenectomy on whole body protein turnover in homozygous sickle cell disease

In individuals with homozygous sickle cell (SS) disease, haemolysis creates a demand for increased red cell production. In children with hypersplenism haemolysis may be further increased and in such cases the excessive red cell production may be reduced by splenectomy (1). Whole body protein turnover is increased in SS disease and a large part of this increase is the consequence of increased turnover of red blood cells (2). Whole body protein turnover has therefore been measured in children with SS disease before and after splenectomy to find out if the reduction of the haemolytic rate following splenectomy was associated with a decrease in protein turnover. (AU)

Increased urea metabolism in sickle cell disease - abstract

In normal man, a portion of the urea produced in the body (20-30 percent) is potentially made available for metabolism by hydrolysis in the bowel. In sickle cell disease (HbSS), continuing haemolysis modifies the metabolism of protein, with the probability that urea production, and possibly hydrolysis, is increased. We have therefore compared urea metabolism in 5 adults with HbSS (age 38ñ15yrs, weight 56ñ10Kg) with 6 normal adults (age 31ñ4 years, weight 72ñ8Kg). Urea metabolism was measured with an oral primed intermittent infusion of 30N urea over 24 hours, on a daily intake, of 36-44 Kcal/Kg and 1.2 gm protein/Kg. The enrichment in urinary urea and daily urea excretion was used to calculate urea production rate, rate of urea hydrolysis in the bowel, and rate of recycling of hydrolysed urea-nitrogen to urea synthesis. All aspects of urea metabolism were significantly increased in HbSS compared to normal. Whereas production ö intake was 70 percent for normals, it was 120 percent in HbSS, in large part due to the recycling of urea-N to urea synthesis. A greater proportion of urea was excreted in normals (70 percent) than in HbSS (50 percent). Consequently, the rate of urea hydrolysis in HbSS was significantly increased. The results would suggest that the increased nitrogen demands in HbSS associated with augmented red cell synthesis enhance urea recycling. The pattern of urea metabolism seen in HbSS is similar to that seen in normals taking a low-protein diet. These findings serve to support the suggestion that protein requirements in HbSS are greater than in normal (AU)

Splenific opacification in homozygous sickle cell disease

A prospective radiological and haemotological study of 182 patients with homozygous sickle cell anaemia has been undertaken to assess the prevalence and pattern of splenic opacification and relate this to the blood indices. Opacification was observed in 31 percent of patients. In 55 percent of these, the pattern was punctuate, whereas in 32 percent it was amorphous. A curvilinear appearance was seen in the remainder. In the amorphous group, a high percentage (72 percent), the spleen was severely contracted. The pattern of opacification and degree of contraction was related to age. The haemotological indices indicate a lower haemolytic rate in patients with splenic opacifications indicating a milder disease process with a greater persistence of the splenic capillary bed (AU)

Plasma haemoglobin and complement activation in sickle cell disease

The role of haemolysis in producing deficient complement function in homozygous sickle cell disease was studied by measuring indices of complement activation and of haemolysis in 30 asymptomatic patients. Plasma concentration of C3d (an index of increased C3 turnover) was elevated in 40 percent of patients and modest decreases in serum concentration of C3 and functionally (haemolytically) active factor B were found. There was a positive correlation between C3d and plasma haemoglobin concentration (r = 0.56, p less than 0.005). Reticulocyte count and foetal haemoglobin concentration also contributed to variation in C3d, though to a lesser extent than plasma haemoglobin. Intravascular haemolysis in sickle cell disease may produce activation of complement and thus cause partial depletion of functional factor B and C3. This may reduce the immune function of the alternative pathway. (AU)

Activation of the alternative pathway of human complement by haemoglobin

Haemoglobin solutions (concentration >1.5mg/ml), prepared from lysates of erythrocytes from a normal subject and from a patient with sickle cell anaemia, caused factor B and C3 cleavage and loss of haemolytic activity of factor B when incubated with fresh autologous serum. Under the same experimental conditions, preparations of erythrocyte stroma or of buffy coat lysates did not produce factor B and C3 cleavage. This reaction required Mg++ but not Clq or C4, indicating that the alternative complement pathway was activated (Summary)

The internal auditory canal and sensori-neural hearing loss in homozygous sickle cell disease

The dimensions of the internal auditory canal were compared in patients with SS disease and with or without abnormal audiograms to investigate the role of auditory nerve compression by expansion of the petrous, temporal bone in hearing loss. There was no correlation between abnormal audiograms and narrowing of the internal auditory canals and it was concluded that this mechanism was not responsible for the hearing loss in SS disease (AU)

The irreversibly sickled cell: a determinant of haemolysis in sickle cell anaemia

Red cell survival was estimated in a group of adult sickle cell anaemia patients using the 51Cr technique. Counts of irreversibly sickled cells were performed on thin coverslip preparations of capillary blood. These counts are relatively constant within the same individual but show marked variations between individuals. A significant correlation has been demonstrated between the irreversibly sickled cell count and the red cell survival. This correlation does not apply to sickle cell anaemia patients with splenomegaly in whom the irreversibly sickled cell count is always low (AU)

An unusual type of hemoglobinopathy resembling sickle cell-thalassemia disease in a Jamaican family

Three generations of a Jamaican family of African extraction are desribed, in several members of which an abnormal gene is carried. This gene produces high levels of fetal hemoglobin unassociated with the usual stigmata of thalassemia. It is found in all three generations of the family associated with hemoglobin A only and is also found in at least two members of the family interacting with hemoglobin S. In the latter combination little or no disability results. The mode of inheritance of this abnormal gene is discussed, and reasons are put forward for a possible protective effect of high fetal hemogobin levels due to inhibition of sickling. The findings in the cord blood of the youngest child, including an unusually high percentage of sickling, are discussed, together with follow-up studies to the age of 25 weeks.(AU)

The hereditary haemolytic syndromes

A review is made of recent developments in the study of the hereditary haemolytic syndromes. Current concepts in the pathogenesis of haemolysis are briefly discussed and the various intrinsic haemolytic disorders classified, with particular reference to anaemias due to red cell defects. The hereditary haemolytic syndromes are discussed in detail, as regards to both their genetic interrelationship and the recent demonstration of abnormal haemoglobin moieties in sickle cell trait and anaemia, and in haemoglobin C. disease. Reference is made to the recent application of paper electrophoretic analysis to the identification of these abnormal haemoglobins. Whilst hereditary sphercytosis and the thalassaemia syndromes are but rarely seen in the Caribbean area, the incidence of sickle cell trait is noted to vary between 5-12 percent of the mixed populations. Haemoglobin C. trait has been found to occur in 2 per cent of North American Negroes, so that these two anomalies alone or together may be present in a significant proportion of persons. Emphasis is placed on the potentiating effect which results from the linking of the dissimilar genes responsible for the hereditary haemolytic syndromes. The simultaneous occurrence of any one of these together with that determining the sickle cell trait is the probable cause of the so-called "mild" anaemia found to occur in those heterozygous children of whom one parent fails to show the sickling trait. It is stressed that while the hereditary haemolytic syndromes have many feature in common, the actual cause of red cell destruction varies with the shape to which the erythrocyte is ultimately changed (AU)