Most SCLS patients report having flu-like symptoms (like a runny nose), or else gastro-intestinal disorders (diarrhea or vomiting), or a general weakness or pain in their limbs, but others get no particular or consistent warning signs ahead of their episodes. They subsequently develop thirst and lightheadedness and the following conditions measurable in a hospital emergency-room setting:

- hemoconcentration (elevated hematocrit or hemoglobin readings, with hematocrit levels >49% in men and >43% in women, not because of an absolute increase in them but because of the leak of plasma);

- very low blood pressure (profound arterial hypotension, with systolic blood pressure levels <90 mm Hg);

- albumin deficiency (hypoalbuminemia measuring <3.0 g/dL);

- partial or generalized edema, and cold extremities;

- a paraprotein in the blood (an MGUS in approximately 80% of cases).

Diffuse tightness and tenderness over the entire belly of the tibialis anterior that does not respond to elevation or pain medication can be early warning signs and suggestive of Anterior Compartment Syndrome. Other common symptoms include excessive swelling that causes the skin to become hot, stretched and glossy. Pain, paresthesias, and tenderness in both the ischemic muscles and the region supplied by the deep common fibular nerve are exhibited by patients suffering from this condition. Sensitivity to passive stretch and active contraction are common, and tend to increase the symptoms.

Capillary leak syndrome is characterized by the escape of blood plasma through capillary walls, from the blood circulatory system to surrounding tissues, muscle compartments, organs or body cavities. It is a phenomenon most commonly witnessed in sepsis, and less frequently in autoimmune diseases, differentiation syndrome, engraftment syndrome, hemophagocytic lymphohistiocytosis, the ovarian hyperstimulation syndrome, viral hemorrhagic fevers, and snakebite and ricin poisoning. Pharmaceuticals, including the chemotherapy medication gemcitabine, as well as certain interleukins and monoclonal antibodies, can also cause capillary leaks. These conditions and factors are sources of secondary capillary leak syndrome.

Systemic capillary leak syndrome (SCLS, or Clarkson's disease), or primary capillary leak syndrome, is a rare, grave and episodic medical condition observed largely in otherwise healthy individuals mostly in middle age. It is characterized by self-reversing episodes during which the endothelial cells which line the capillaries, usually of the extremities, separate for one to three days, causing a leakage of plasma mainly into the muscle compartments of the arms and legs. The abdomen, the central nervous system, and the organs (including the lungs) are typically spared, but the extravasation in the extremities is sufficiently massive to cause circulatory shock and compartment syndromes, with a dangerous hypotension (low blood pressure), hemoconcentration(thickening of the blood) and hypoalbuminemia (drop in albumin, a major protein) in the absence of other causes for such abnormalities. SCLS is thus a limb- and life-threatening illness, because each episode has the potential to cause damage to limb muscles and nerves, as well as to vital organs due to limited perfusion. It is often misdiagnosed as polycythemia, polycythemia vera, hyperviscosity syndrome, or sepsis.

If these symptoms are observed/experienced it is important to contact a physician specializing in sports medicine (MD/DO), a doctor of podiatric medicine (DPM), or other qualified health care professional immediately so as to get the appropriate advice/treatment before serious damage occurs.

The 5 Ps of Anterior Compartment Syndrome:

1. Pain

2. Pallor

3. Paresthesia

4. Pulselessness

5. Paralysis (If not treated)

Crush syndrome (also traumatic rhabdomyolysis or Bywaters' syndrome) is a medical condition characterized by major shock and renal failure after a injury to skeletal muscle. Crush "injury" is compression of extremities or other parts of the body that causes muscle swelling and/or neurological disturbances in the affected areas of the body, while crush "syndrome" is localized crush injury with systemic manifestations. Cases occur commonly in catastrophes such as earthquakes, to victims that have been trapped under fallen or moving masonry.

Victims of crushing damage present some of the greatest challenges in field medicine, and may be among the few situations where a physician is needed in the field. The most drastic response to crushing under massive objects may be field amputation. Even if it is possible to extricate the patient without amputation, appropriate physiological preparation is mandatory: where permissive hypotension is the standard for prehospital care, fluid loading is the requirement in crush syndrome.

Purple glove syndrome (PGS) is a poorly understood skin disease in which the extremities become swollen, discoloured and painful. PGS is potentially serious, and may require amputation. PGS is most common among elderly patients and those receiving multiple large intravenous doses of the epilepsy drug phenytoin. Compartment syndrome is a complication of PGS.

The first symptom of compartment syndrome is pain. Loss of function and decreased pulses or pulselessness, however, are late signs. According to Shears, paresthesia in the distribution of the nerves transversing the affected compartment has also been described as relatively early sign of compartment syndrome, and later is followed by anesthesia (Shears, 2006).

- Pain is often reported early and almost universally. The description is usually of deep, constant, and poorly localized pain out of proportion with the findings on physical examination (often incorrectly described as pain out of proportion to the injury). The pain is aggravated by passively stretching the muscle group within the compartment or actively flexing it (though this finding is not specific to compartment syndrome alone) and is not relieved by analgesia up to and including morphine.

- Paresthesia (altered sensation e.g., "pins & needles") in the cutaneous nerves of the affected compartment is another typical sign.

- Paralysis of the limb is usually a late finding. The compartment may also feel very tense and firm (pressure). Some find that their feet and even legs fall asleep. This is because compartment syndrome prevents adequate blood flow to the rest of the leg.

- A lack of pulse rarely occurs in patients, as pressures that cause compartment syndrome are often well below arterial pressures and pulse is only affected if the relevant artery is contained within the affected compartment.

- Tense and swollen shiny skin, sometimes with obvious bruising of the skin.

- Congestion of the digits with prolonged capillary refill time.

The symptoms of chronic exertional compartment syndrome (CECS) are brought on by exercise and consist of a sensation of extreme tightness in the affected muscles followed by a painful burning sensation if exercise is continued. After exercise is ceased, the pressure in the compartment will decrease within a few minutes, relieving painful symptoms. Symptoms will occur at a certain threshold of exercise which varies from person to person but is rather consistent for a given individual and can range anywhere from 30 seconds of running to about 10–15 minutes of running. CECS most commonly occurs in the lower leg, with the anterior compartment being the most frequently affected compartment. Foot drop is a common symptom of CECS.

Seigo Minami, a Japanese physician, first reported the crush syndrome in 1923. He studied the pathology of three soldiers who died in World War I from insufficiency of the kidney. The renal changes were due to methemoglobin infarction, resulting from the destruction of muscles, which is also seen in persons who are buried alive. The progressive acute renal failure is because of acute tubular necrosis.

The syndrome was later described by British physician Eric Bywaters in patients during the 1941 London Blitz. It is a reperfusion injury that appears after the release of the crushing pressure. The mechanism is believed to be the release into the bloodstream of muscle breakdown products—notably myoglobin, potassium and phosphorus—that are the products of rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions).

The specific action on the kidneys is not understood completely, but may be due partly to nephrotoxic metabolites of myoglobin.

The most devastating systemic effects can occur when the crushing pressure is suddenly released, without proper preparation of the patient, causing reperfusion syndrome. In addition to tissue directly suffering the crush mechanism, down stream tissue is subject to Ischemia-reperfusion injuries of the appendicular musculoskeletal system. Without proper preparation, the patient, with pain control, may be cheerful before extrication, but die shortly thereafter. This sudden decompensation is called the "smiling death."

These systemic effects are caused by a traumatic rhabdomyolysis. As muscle cells die, they absorb sodium, water and calcium; the rhabdomyolysis releases potassium, myoglobin, phosphate, thromboplastin, creatine and creatine kinase.

Compartment syndrome can be secondary to crush syndrome. Monitor for the classic 5 Ps: pain, pallor, parasthesias, pain with passive movement, and pulselessness.

Doctors recommend discontinuing the use of phenytoin. The application of heat can help to relieve pain. Oral phenytoin can also result in development of purple glove syndrome.

The clinical signs of minimal change disease are proteinuria (abnormal excretion of proteins, mainly albumin, into the urine), oedema (swelling of soft tissues as a consequence of water retention), and hypoalbuminaemia (low serum albumin). These signs are referred to collectively as nephrotic syndrome. Minimal change disease is unique among the causes of nephrotic syndrome as it lacks evidence of pathology in light microscopy, hence the name.

When albumin is excreted in the urine, its serum (blood) concentration decreases. Consequently, the intravascular oncotic pressure reduces relative to the interstitial tissue. The subsequent movement of fluid from the vascular compartment to the interstitial compartment manifests as the soft tissue swelling referred to as oedema. This fluid collects most commonly in the feet and legs, in response to gravity, particularly in those with poorly functioning valves. In severe cases, fluid can shift into the peritoneal cavity (abdomen) and cause ascites. As a result of the excess fluid, individuals with minimal change disease often gain weight, as they are excreting less water in the urine, and experience fatigue. Additionally, the protein in the urine causes it to become frothy.

The symptoms of rhabdomyolysis depend on its severity and whether kidney failure develops. Milder forms may not cause any muscle symptoms, and the diagnosis is based on abnormal blood tests in the context of other problems. More severe rhabdomyolysis is characterized by muscle pain, tenderness, weakness and swelling of the affected muscles. If the swelling is very rapid, as may happen after someone is released from under a collapsed building, the movement of fluid from the bloodstream into damaged muscle may cause low blood pressure and shock. Other symptoms are nonspecific and result either from the consequences of muscle tissue breakdown or from the condition that originally led to the muscle breakdown. Release of the components of muscle tissue into the bloodstream causes electrolyte disturbances, which can lead to nausea, vomiting, confusion, coma or abnormal heart rate and rhythm. The urine may be dark, often described as "tea-colored", due to the presence of myoglobin. Damage to the kidneys may give rise to decreased or absent urine production, usually 12 to 24 hours after the initial muscle damage.

Swelling of damaged muscle occasionally leads to compartment syndrome—compression of surrounding tissues, such as nerves and blood vessels, in the same fascial compartment—leading to the loss of blood supply and damage or loss of function in the part(s) of the body supplied by these structures. Symptoms of this complication include pain or reduced sensation in the affected limb. A second recognized complication is disseminated intravascular coagulation (DIC), a severe disruption in blood clotting that may lead to uncontrollable bleeding.

Abdominal compartment syndrome occurs when the abdomen becomes subject to increased pressure. Specific cause of abdominal compartment syndrome is not known, although some causes can be sepsis and severe abdominal trauma. Increasing pressure reduces blood flow to abdominal organs and impairs pulmonary, cardiovascular, renal, and gastro-intestinal (GI) function, causing multiple organ dysfunction syndrome and death.

It involves numerous anomalies including:

- Post-axial polydactyly

- Congenital heart defects (most commonly an atrial septal defect producing a common atrium, occurring in 60% of affected individuals)

- Teeth present at birth (natal teeth)

- Fingernail dysplasia

- Short-limbed dwarfism, mesomelic pattern

- Short ribs

- Cleft palate

- Malformation of the wrist bones (fusion of the hamate and capitate bones).

Minimal change disease (also known as MCD and nil disease, among others) is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the excretion of protein, which causes the widespread oedema (soft tissue swelling) and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 3 years of age.

Acute limb ischaemia can occur in patients through all age groups. Patients that smoke and have diabetes mellitus are at a higher risk of developing acute limb ischaemia. Most cases involve people with atherosclerosis problems.

Symptoms of acute limb ischaemia include:

- Pain

- Pallor

- Paresthesias

- Perishingly cold

- Pulselessness

- Paralysis

These symptoms are called "the six P's'"; they are commonly mis-attributed to compartment syndrome. One more symptom would be the development of gangrene. Immediate medical attention should be sought with any of the symptoms.

In late stages, paresthesia is replaced by anesthesia due to death of nerve cells.

In some cases, gangrene can occur within six hours of ischaemia.

The onset of this disease is usually noticed in childhood, but often not diagnosed until the third or fourth decade of life. Symptoms include exercise intolerance with muscle pain, early fatigue, painful cramps, and myoglobin in the urine (often provoked by a bout of exercise). Myoglobinuria may result from the breakdown of skeletal muscle known as rhabdomyolysis, a condition in which muscle cells breakdown, sending their contents into the bloodstream.

Patients may exhibit a “second wind” phenomenon. This is characterized by the patient’s better tolerance for aerobic exercise such as walking and cycling after approximately 10 minutes. This is attributed to the combination of increased blood flow and the ability of the body to find alternative sources of energy, like fatty acids and proteins. In the long term, patients may exhibit renal failure due to the myoglobinuria, and with age, patients may exhibit progressively increasing weakness and substantial muscle loss.

Patients may present at emergency rooms with severe fixed contractures of the muscles and often severe pain. These require urgent assessment for rhabdomyolysis as in about 30% of cases this leads to acute renal failure. Left untreated this can be life-threatening. In a small number of cases compartment syndrome has developed, requiring prompt surgical referral.

Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of the muscle breakdown products, such as the protein, myoglobin, are harmful to the kidneys and may lead to kidney failure.

The muscle damage is most often the result of a crush injury, strenuous exercise, medications, or drug abuse. Other causes include infections, electrical injury, heat stroke, prolonged immobilization, lack of blood flow to a limb, or snake bites. Some people have inherited muscle conditions that increase the risk of rhabdomyolysis. The diagnosis is supported by a urine test strip which is positive for "blood" but the urine contains no red blood cells when examined with a microscope. Blood tests show a creatine kinase greater than 1,000 U/L, with severe disease being above 5,000 U/L.

The mainstay of treatment is large quantities of intravenous fluids. Other treatments may include dialysis or hemofiltration in more severe cases. Once urine output is established sodium bicarbonate and mannitol are commonly used but they are poorly supported by the evidence. Outcomes are generally good if treated early. Complications may include high blood potassium, low blood calcium, disseminated intravascular coagulation, and compartment syndrome.

Rhabdomyolysis occurs in about 26,000 people a year in the United States. While the condition has been commented on throughout history, the first modern description was following an earthquake in 1908. Important discoveries as to its mechanism were made during the Blitz of London in 1941. It is a significant problem for those injured in earthquakes and relief efforts for such disasters often include medical teams equipped to treat survivors with rhabdomyolysis.

Ellis–van Creveld Syndrome (also called "chondroectodermal dysplasia" or "mesoectodermal dysplasia" but see 'Nomenclature' section below) is a rare genetic disorder of the skeletal dysplasia type.

The following are symptoms characteristic with individuals having the disorder. Individuals may display some, most, or all of these symptoms throughout the course of their life, though symptoms may vary with each patient.

- Abnormal hair (coarse, thick, brittle)

- Calvarial hypomineralization (soft skull)

- Y-shaped cataracts by 1–2 years of age

- Skeletal defects

- Hypertelorism (wide-set eyes)

- Facial dysmorphisms

- Late-closing fontanels

- Abnormal accumulation of proteins in the endoplasmic reticulum

- Scoliosis

- Broad forehead, nose

- Missing, small teeth or abnormal teeth positioning

- Poor skull calcification

- Flat foot

- Motor delay

- Abnormal vertebrae

- Prominent forehead and brow

- High nose bridge

- Capillary hemangioma

- Delayed tooth eruption

- Long upper lip groove

- Large mouth

- High arched palate

- Narrow hips and rib cage

- Thin lips

- Narrow and sloping shoulders

- Hyperpigmentation

- Hyperextensible joints

Onset of the disease is in neonatal development and infancy, and symptoms tend to become evident soon after birth.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication during the treatment of cancer, where large amounts of tumor cells are killed off (lysed) at the same time by the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias. In oncology and hematology, this is a potentially fatal complication, and patients at increased risk for TLS should be closely monitored before, during, and after their course of chemotherapy.

Tumor lysis syndrome is characterized by high blood potassium (hyperkalemia), high blood phosphorus (hyperphosphatemia), low blood calcium (hypocalcemia), high blood uric acid (hyperuricemia), and higher than normal levels of blood urea nitrogen (BUN) and other nitrogen-containing compounds (azotemia). These changes in blood electrolytes and metabolites are a result of the release of cellular contents of dying cells into the bloodstream from breakdown of cells. In this respect, TLS is analogous to rhabdomyolysis, with comparable mechanism and blood chemistry effects but with different cause. In TLS, the breakdown occurs after cytotoxic therapy or from cancers with high cell turnover and tumor proliferation rates. The metabolic abnormalities seen in tumor lysis syndrome can ultimately result in nausea and vomiting, but more seriously acute uric acid nephropathy, acute kidney failure, seizures, cardiac arrhythmias, and death.

Acute uric acid nephropathy (AUAN) due to hyperuricosuria has been a dominant cause of acute kidney failure but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia. Two common conditions related to excess uric acid, gout and uric acid nephrolithiasis, are not features of tumor lysis syndrome.

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Retroperitoneal fibrosis or Ormond's disease is a disease featuring the proliferation of fibrous tissue in the retroperitoneum, the compartment of the body containing the kidneys, aorta, renal tract, and various other structures. It may present with lower back pain, kidney failure, hypertension, deep vein thrombosis, and other obstructive symptoms. It is named after John Kelso Ormond, who rediscovered the condition in 1948.

When a limb is ischemic in the non-acute (chronic) setting, the condition is alternatively called peripheral artery disease or critical limb ischemia, rather than ALI. In addition to limb ischemia, other organs can become ischemic, causing:

- Renal ischemia (nephric ischemia)

- Mesenteric ischemia

- Cerebral ischemia

- Cardiac ischemia