Intravascular hemolysis describes
hemolysis
Hemolysis or haemolysis (), also known by #Nomenclature, several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may ...
that happens mainly inside the
vasculature
In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart an ...
.
As a result, the contents of the red blood cell are released into the general circulation, leading to
hemoglobinemia and increasing the risk of ensuing
hyperbilirubinemia.
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Mechanism
Intravascular hemolysis is the state when the red blood cell ruptures as a result of the complex of complement autoantibodies attached (fixed) on the surfaces of RBCs attack and rupture RBCs' membranes, or a parasite such as
Babesia
''Babesia'', also called ''Nuttallia'', is an apicomplexan parasite that infects red blood cells and is transmitted by ticks. Originally discovered by Romanian bacteriologist Victor Babeș in 1888; over 100 species of ''Babesia'' have since ...
exits the cell that ruptures the RBC's membrane as it goes.
Upon RBC's rupture, components of which are released and circulating in the blood plasma.
These components comprise hemoglobin and others.
At this stage, the hemoglobin is called free hemoglobin.
Free hemoglobin (also called naked hemoglobin) is the un-bound hemoglobin that is not enclosed in the red blood cell. The naked hemoglobin is devoid of its anti-oxidant sentries that are normally available within the RBC.
Free hemoglobin is thus vulnerable to be oxidized.
When the serum concentration of free hemoglobin is within the physiologic range of
haptoglobin
Haptoglobin (abbreviated as Hp) is the protein that in humans is encoded by the ''HP'' gene. In blood plasma, haptoglobin binds with high affinity to ''free'' hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidativ ...
, the potential deleterious effects of free hemoglobin are prevented because haptoglobin will bind to "free hemoglobin" forming a complex of "free hemoglobin-haptoglobin" evidenced by reduced amount of haptoglobin.
However, during hyper-hemolytic conditions or with chronic hemolysis, haptoglobin is depleted so the remaining free hemoglobin readily distribute to tissues where it might be exposed to oxidative conditions,
thus some of the ferrous heme (FeII), the oxygen-binding component of hemoglobin, of the free hemoglobin are oxidized and becoming
met-hemoglobin (ferric hemoglobin).
In such conditions, heme along with globin chains can be released from further oxidization of met-hemoglobin (ferric Hb).
In which, the free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. At this time,
hemopexin, another plasma glycoprotein come to bind with heme with its privilege of high heme affinity, forming a complex of heme-hemopexin, which is non-toxic, and travel together to a receptor on hepatocytes and macrophages within the spleen, liver and bone marrow.
(Note that the "free hemoglobin-haptoglobin" complex is taken up by hepatocytes and, to the lesser extent, macrophages.
) Thereafter, these complexes will undergo the metabolic mechanisms like extravascular hemolysis.
Nevertheless, if the binding capacities of haptoglobin and hemopexin are saturated, the remaining "free hemoglobin" in the plasma will be oxidized to met-hemoglobin eventually, and then further disassociates into free heme and others.
At this stage, the "free heme" will bind to albumin, forming
met-hemalbumin.
As to the remaining unbound (met)hemoglobin is filtered into the primary urine and re-absorbed via
proximal tubule
The proximal tubule is the segment of the nephron in kidneys which begins from the renal (tubular) pole of the Bowman's capsule to the beginning of loop of Henle. At this location, the glomerular parietal epithelial cells (PECs) lining bowman’s ...
s of the kidney.
In proximal tubules, the iron is extracted and stored as
hemosiderin
Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderin
Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives ri ...
.
(Long-term hemoglobinuria is associated with substantial deposition of hemosiderin in proximal tubule (excessive accumulation of hemosiderin in proximal tubule),
Fanconi syndrome
Fanconi syndrome or Fanconi's syndrome (, ) is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from t ...
(damaged renal re-absorption capability of small molecules which give rises to hyper-
aminoaciduria,
glycosuria,
hyperphosphaturia
Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softeni ...
, and
bicarbonate
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial bioche ...
and
dehydration
In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...
), and
chronic kidney failure
Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...
.
)
In the end, if the plasma concentration of the "free met-hemoglobin" and/or "free hemoglobin" is still too high for proximal tubule to absorb back into the body, then
hemoglobinuria occurs,
indicating an extensive intravascular hemolysis.
These remaining free hemoglobin entities also begin to consume
nitric oxide
Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
, which is critical regulators of vascular homeostasis and basal and stress-mediated smooth muscle relaxation and vasomotor tone, endothelial adhesion molecule expression, and platelet activation and aggregation.
The reduction of nitric oxide deeply disturbs the body's mechanism to maintain the stability of the hemodynamics.
Additionally, free hemoglobin manifests direct cytotoxic, inflammatory, and pro-oxidant effects that in turn negatively impact endothelial function.
At the meantime, free heme exerts its multiple pro-inflammatory and pro-oxidant effects to the tissues it goes through.
It is important to note that although hemosiderins are also included in the urine in the setting of intravascular hemolytic hemoglobinuria,
it will be detected only several days after the onset of the extensive intravascular hemolysis and will remain detectable several days after termination of intravascular hemolysis.
The phenomenon tells that the detection of hemosiderin in urine is indicative of either ongoing or recent intravascular hemolysis characterized by excessive hemoglobin and/or met-hemoglobin filtered through the
renal glomerulus
The glomerulus (: glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally suppor ...
as well as the loss of
hemosiderin-laden necrotic tubular cells.
See also
*
Extravascular hemolysis
Note
References
{{reflist
Hematology
Hemoglobins