Cholesterol embolism
Encyclopedia
Cholesterol embolism occurs when cholesterol
is released, usually from an atherosclerotic plaque
, and travels along with the bloodsteam (embolism
) to other places in the body, where it obstructs blood vessel
s. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene
of the extremities and sometimes renal failure
; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. When the kidney
s are involved, the disease is referred to as atheroembolic renal disease (AERD). The diagnosis usually involves biopsy
(removing a tissue sample) from an affected organ. Cholesterol embolism is treated by removing the cause and with supportive therapy; statin
drugs have been found to improve the prognosis.
, muscle ache
and weight loss. Embolism to the legs causes a mottled appearance and purple discoloration of the toe
s, small infarcts and areas of gangrene
due to tissue death
that usually appear black, and areas of the skin that assume a marbled pattern known as livedo reticularis
. The pain is usually severe and requires opiates. If the ulcerated plaque is below the renal arteries the manifestations appear in both lower extremities. Very rarely the ulcerated plaque is below the aortic bifurcation and those cases the changes occur only in one lower extremity.
Kidney involvement leads to the symptoms of renal failure, which are non-specific but usually cause nausea
, reduced appetite
(anorexia
), raised blood pressure
(hypertension), and occasionally the various symptoms of electrolyte disturbance
such as an irregular heartbeat. Some patients report hematuria
(bloody urine) but this may only be detectable on microscopic examination of the urine. Increased amounts of protein
in the urine may cause edema
(swelling) of the skin (a combination of symptoms known as nephrotic syndrome
).
If emboli have spread to the digestive tract, reduced appetite, nausea and vomiting may occur, as well as nonspecific abdominal pain
, gastrointestinal hemorrhage (vomiting blood, or admixture of blood in the stool
), and occasionally acute pancreatitis
(inflammation of the pancreas
).
Both the central nervous system
(brain and spinal cord
) and the peripheral nervous system
may be involved. Emboli to the brain may cause stroke
-like episodes, headache
and episodes of loss of vision in one eye (known as amaurosis fugax
). Emboli to the eye can be seen by ophthalmoscopy
and are known as plaques of Hollenhorst
. Emboli to the spinal cord may cause paraparesis (decreased power in the legs) or cauda equina syndrome
, a group of symptoms due to loss of function of the distal part of the spinal cord - loss of control over the bladder
, rectum
and skin sensation around the anus. If the blood supply to a single nerve is interrupted by an embolus, the result is loss of function in the muscles supplied by that nerve; this phenomenon is called a mononeuropathy.
of the large arteries such as the aorta
. In the other 75% it is a complication of medical procedures involving the blood vessels, such as vascular surgery
or angiography. In coronary catheterization
, for instance, the incidence is 1.4%. Furthermore, cholesterol embolism may develop after the commencement of anticoagulant
s or thrombolytic
medication that decrease blood clotting or dissolve blood clots, respectively. They probably lead to cholesterol emboli by removing blood clots that cover up a damaged atherosclerotic plaque; cholesterol-rich debris can then enter the bloodsteam.
s) are not specific for cholesterol embolism, which makes diagnosis difficult. The main problem is the distinction between cholesterol embolism and vasculitis
(inflammation of the small blood vessels), which may cause very similar symptoms - especially the skin findings and the kidney dysfunction. Worsening kidney function after an angiogram may also be attributed to kidney damage by substances used during the procedure (contrast nephropathy). Other causes that may lead to similar symptoms include ischemic renal failure
(kidney dysfunction due to an interrupted blood supply), a group of diseases known as thrombotic microangiopathies
and endocarditis
(infection of the heart valve
s with small clumps of infected tissue embolizing through the body).
(C-reactive protein
and the erythrocyte sedimentation rate
) are typically elevated, and abnormal liver enzymes may be seen. If the kidneys are involved, tests of renal function
(such as urea
and creatinine
) are elevated. The complete blood count
may show particularly high numbers of a type of white blood cell
known as eosinophils (more than 0.5 billion per liter); this occurs in only 60-80% of cases, so normal eosinophil counts do not rule out the diagnosis. Examination of the urine may show red blood cell
s (occasionally in casts
as seen under the microscope) and increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. If vasculitis is suspected, complement
levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system
. Complement levels are frequently reduced in cholesterol embolism, limiting the use of this test in the distinction between vasculitis and cholesterol embolism.
s (medication that reduces cholesterol levels) have been shown to halve the risk of requiring hemodialysis
.
physiologist
Dr Peter Ludvig Panum
and published in 1862. Further pathological evidence that eroded atheroma was the source of emboli came from American pathologist
Dr Curtis M. Flory, who in 1945 reported the phenomenon in 3.4% of a large series of patients with severe atherosclerosis of the aorta
.
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
is released, usually from an atherosclerotic plaque
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
, and travels along with the bloodsteam (embolism
Embolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
) to other places in the body, where it obstructs blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s. Most commonly this causes skin symptoms (usually livedo reticularis), gangrene
Gangrene
Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood...
of the extremities and sometimes renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
; problems with other organs may arise, depending on the site at which the cholesterol crystals enter the bloodstream. When the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s are involved, the disease is referred to as atheroembolic renal disease (AERD). The diagnosis usually involves biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(removing a tissue sample) from an affected organ. Cholesterol embolism is treated by removing the cause and with supportive therapy; statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
drugs have been found to improve the prognosis.
Signs and symptoms
The symptoms experienced in cholesterol embolism depend largely on the organ involved. Non-specific symptoms often described are feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, muscle ache
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
and weight loss. Embolism to the legs causes a mottled appearance and purple discoloration of the toe
Toe
Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being digitigrade. Humans, and other animals that walk on the soles of their feet, are described as being plantigrade; unguligrade animals are those that walk on hooves at the tips of...
s, small infarcts and areas of gangrene
Gangrene
Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood...
due to tissue death
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
that usually appear black, and areas of the skin that assume a marbled pattern known as livedo reticularis
Livedoid vasculitis
Livedo reticularis is a common cutaneous finding consisting of a mottled reticulated vascular pattern that appears like a lace-like purplish discoloration of the lower extremities. The discoloration is caused by swelling of the medium veins in the skin, which makes them more visible...
. The pain is usually severe and requires opiates. If the ulcerated plaque is below the renal arteries the manifestations appear in both lower extremities. Very rarely the ulcerated plaque is below the aortic bifurcation and those cases the changes occur only in one lower extremity.
Kidney involvement leads to the symptoms of renal failure, which are non-specific but usually cause nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, reduced appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...
(anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
), raised blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
(hypertension), and occasionally the various symptoms of electrolyte disturbance
Electrolyte disturbance
Electrolytes play a vital role in maintaining homeostasis within the body. They help to regulate myocardial and neurological function, fluid balance, oxygen delivery, acid-base balance and much more. Electrolyte imbalances can develop by the following mechanisms: excessive ingestion; diminished...
such as an irregular heartbeat. Some patients report hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
(bloody urine) but this may only be detectable on microscopic examination of the urine. Increased amounts of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
in the urine may cause edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
(swelling) of the skin (a combination of symptoms known as nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
).
If emboli have spread to the digestive tract, reduced appetite, nausea and vomiting may occur, as well as nonspecific abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, gastrointestinal hemorrhage (vomiting blood, or admixture of blood in the stool
Hematochezia
Hematochezia is the passage of fresh blood per anus, usually in or with stools . Hematochezia is commonly associated with lower gastrointestinal bleeding, but may also occur from a brisk upper GI bleed...
), and occasionally acute pancreatitis
Acute pancreatitis
Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
(inflammation of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
).
Both the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(brain and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
) and the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
may be involved. Emboli to the brain may cause stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
-like episodes, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and episodes of loss of vision in one eye (known as amaurosis fugax
Amaurosis fugax
Amaurosis fugax is a transient monocular visual loss.-Pathophysiology and etiology:...
). Emboli to the eye can be seen by ophthalmoscopy
Ophthalmoscopy
Ophthalmoscopy is a test that allows a health professional to see inside the fundus of the eye and other structures using an ophthalmoscope . It is done as part of an eye examination and may be done as part of a routine physical examination...
and are known as plaques of Hollenhorst
Hollenhorst plaque
A Hollenhorst plaque AKA "Eickenhorst plaque" is a cholesterol embolus that is seen in a blood vessel of the retina.-Clinical significance:It is usually seen when a physician performs ophthalmoscopy, during which a plaque will appear bright, refractile, and yellow...
. Emboli to the spinal cord may cause paraparesis (decreased power in the legs) or cauda equina syndrome
Cauda equina syndrome
Cauda equina syndrome ' is a serious neurologic condition in which there is acute loss of function of the lumbar plexus, neurologic elements of the spinal canal below the termination of the spinal cord.-Causes:...
, a group of symptoms due to loss of function of the distal part of the spinal cord - loss of control over the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
, rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
and skin sensation around the anus. If the blood supply to a single nerve is interrupted by an embolus, the result is loss of function in the muscles supplied by that nerve; this phenomenon is called a mononeuropathy.
Causes
It is relatively unusual (25% of the total number of cases) for cholesterol emboli to occur spontaneously; this usually happens in people with severe atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
of the large arteries such as the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
. In the other 75% it is a complication of medical procedures involving the blood vessels, such as vascular surgery
Vascular surgery
Vascular surgery is a specialty of surgery in which diseases of the vascular system, or arteries and veins, are managed by medical therapy, minimally-invasive catheter procedures, and surgical reconstruction. The specialty evolved from general and cardiac surgery...
or angiography. In coronary catheterization
Coronary catheterization
A coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional purposes....
, for instance, the incidence is 1.4%. Furthermore, cholesterol embolism may develop after the commencement of anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s or thrombolytic
Thrombolysis
Thrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
medication that decrease blood clotting or dissolve blood clots, respectively. They probably lead to cholesterol emboli by removing blood clots that cover up a damaged atherosclerotic plaque; cholesterol-rich debris can then enter the bloodsteam.
Differential diagnosis
Findings on general investigations (such as blood testBlood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s) are not specific for cholesterol embolism, which makes diagnosis difficult. The main problem is the distinction between cholesterol embolism and vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
(inflammation of the small blood vessels), which may cause very similar symptoms - especially the skin findings and the kidney dysfunction. Worsening kidney function after an angiogram may also be attributed to kidney damage by substances used during the procedure (contrast nephropathy). Other causes that may lead to similar symptoms include ischemic renal failure
Acute tubular necrosis
Acute tubular necrosis or is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water . Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely...
(kidney dysfunction due to an interrupted blood supply), a group of diseases known as thrombotic microangiopathies
Microangiopathic hemolytic anemia
In medicine microangiopathic hemolytic anemia is a microangiopathic subgroup of hemolytic anemia caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.-Presentation:It is referred as Runner's anemia...
and endocarditis
Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...
(infection of the heart valve
Heart valve
A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...
s with small clumps of infected tissue embolizing through the body).
Blood and urine
Tests for inflammationInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
(C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
and the erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
) are typically elevated, and abnormal liver enzymes may be seen. If the kidneys are involved, tests of renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
(such as urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
and creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
) are elevated. The complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
may show particularly high numbers of a type of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
known as eosinophils (more than 0.5 billion per liter); this occurs in only 60-80% of cases, so normal eosinophil counts do not rule out the diagnosis. Examination of the urine may show red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s (occasionally in casts
Urinary casts
Urinary casts are cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy.They form via precipitation...
as seen under the microscope) and increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. If vasculitis is suspected, complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Complement levels are frequently reduced in cholesterol embolism, limiting the use of this test in the distinction between vasculitis and cholesterol embolism.
Biopsy
Biopsy of affected organs shows characteristic changes in about half to 75% the clinically diagnosed cases.Treatment
Treatment of an episode of cholesterol emboli is generally symptomatic, i.e. it deals with the symptoms and complications but cannot reverse the phenomenon itself. In kidney failure resulting from cholesterol crystal emboli, statinStatin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s (medication that reduces cholesterol levels) have been shown to halve the risk of requiring hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
.
History
The phenomenon of embolisation of cholesterol was first recognized by the DanishDenmark
Denmark is a Scandinavian country in Northern Europe. The countries of Denmark and Greenland, as well as the Faroe Islands, constitute the Kingdom of Denmark . It is the southernmost of the Nordic countries, southwest of Sweden and south of Norway, and bordered to the south by Germany. Denmark...
physiologist
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
Dr Peter Ludvig Panum
Peter Ludvig Panum
Peter Ludvig Panum was a Danish physiologist and pathologist born in Rønne. The Panum Institute in Copenhagen is named in his honor....
and published in 1862. Further pathological evidence that eroded atheroma was the source of emboli came from American pathologist
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
Dr Curtis M. Flory, who in 1945 reported the phenomenon in 3.4% of a large series of patients with severe atherosclerosis of the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
.
External links
- Patient.co.uk - summary
- MedlinePlus - atheroembolic renal disease