on 17-Nov-2021 (Wed)

But mammals like pigs can't selectively provision their offspring the way birds do

And yet the strongest piglets still seem to have an edge.

But it turns out that vigorous stimulation of one mammary gland can increase blood flow in neighboring glands.

so that the smaller ones could take advantage of their larger counterparts.

Thalassemias are the most common genetic disorders in the world, affecting nearly 200 million people worldwide.

Sickle cell disease is the most common structural hemoglobinopathy,

Hemoglobinopathies are autosomal codominant traits—thus, com- pound heterozygotes who inherit a different abnormal mutant allele from each parent exhibit composite features of each. For example, patients inheriting sickle β thalassemia exhibit features of β thalas- semia and sickle cell anemia. The α chain is present in HbA, HbA 2 , and HbF; α-chain mutations thus cause abnormalities in all three. The α-globin hemoglobinopathies are symptomatic in utero and after birth because normal function of the α-globin gene is required throughout gestation and adult life. In contrast, infants with β-globin hemoglo- binopathies tend to be asymptomatic until 3–9 months of age, when HbA has largely replaced

Laboratory evaluation remains an adjunct, rather than the sole diagnostic aid. Diagnosis is best established by recognition of a charac- teristic history, physical findings, peripheral blood smear morphology, and abnormalities of the complete blood cell count (e.g., profound microcytosis with minimal anemia in thalassemia trait).

The sickle cell syndromes are caused by a mutation in the β-globin gene that changes the sixth amino acid from glutamic acid to valine. HbS (α 2 β 2 6 Glu→Val ) polymerizes reversibly when deoxygenated to form a gelatinous network of fibrous polymers that stiffen the RBC membrane, increase viscosity, and cause dehydration due to potassium leakage and calcium influx (Fig. 94-3). These changes also produce the sickle shape (Fig. 94-4). Sickled cells lose the pliability needed to traverse small capillaries. They possess altered “sticky” membranes that are abnormally adherent to the endothelium of small venules. These abnormalities provoke unpredictable episodes of microvascular vasoocclusion and premature RBC destruction (hemolytic anemia) in the liver and spleen. The rigid adherent cells also clog small capillaries and venules, causing tissue ischemia, acute pain, and gradual end- organ damage. This venoocclusive component usually dominates the clinical course. Prominent manifestations include episodes of ischemic pain (i.e., painful crises) and ischemic malfunction or frank infarction in the spleen, central nervous system, bones, joints, liver, kidneys, and lungs (Fig. 94-3). Several sickle syndromes occur as the result of inheritance of HbS from one parent and another hemoglobinopathy, such as β thalassemia or HbC (α 2 β 2 6 Glu→Lys ), from the other parent. The prototype disease, sickle cell anemia, is the homozygous state for HbS

Most patients with sickling syndromes suffer from hemolytic anemia, with hematocrits from 15 to 30%, and significant reticulocytosis

Granulocytosis is common. The white count can fluctuate substan- tially and unpredictably during and between painful crises, infectious episodes, and other intercurrent illnesses. Granulocytes, platelets, and mononuclear inflammatory cells, and the inflammatory mediators that they release at the sites of vasoocclusion, are being increasingly appreciated as key contributors to the initiation and aggravation of the morbidity associated with vasoocclusive crises.