The history, physical exam, and laboratory testing are required to determine the underlying cause of hyponatremia. A blood test demonstrating a serum sodium less than 135 mmol/L is diagnostic for hyponatremia. The history and physical exam are necessary to help determine if the patient is hypovolemic, euvolemic, or hypervolemic, which has important implications in determining the underlying cause. An assessment is also made to determine if the patient is experiencing symptoms from their hyponatremia. These include assessments of alertness, concentration, and orientation.

False hyponatremia, also known as spurious, pseudo, hypertonic, or artifactual hyponatremia is when the lab tests read low sodium levels but there is no hypotonicity. In hypertonic hyponatremia, resorption of water by molecules such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion) occurs. In isotonic hyponatremia a measurement error due to high blood triglyceride level (most common) or paraproteinemia occurs. It occurs when using techniques that measure the amount of sodium in a specified volume of serum/plasma, or that dilute the sample before analysis.

Excessive sodium and fluid intake:

- IV therapy containing sodium

- As a Transfusion reaction to a rapid blood transfusion.

- High intake of sodium

Sodium and water retention:

- Heart failure

- Liver cirrhosis

- Nephrotic syndrome

- Corticosteroid therapy

- Hyperaldosteronism

- Low protein intake

Fluid shift into the intravascular space:

- Fluid remobilization after burn treatment

- Administration of hypertonic fluids, e.g. mannitol or hypertonic saline solution

- Administration of plasma proteins, such as albumin

Congestive heart failure is the most common result of fluid overload. Also, it may be associated with hyponatremia (hypervolemic hyponatremia).

In those with high volume or hypervolemia:

- Intake of a hypertonic fluid (a fluid with a higher concentration of solutes than the remainder of the body) with restricted free water intake. This is relatively uncommon, though it can occur after a vigorous resuscitation where a patient receives a large volume of a concentrated sodium bicarbonate solution. Ingesting seawater also causes hypernatremia because seawater is hypertonic and free water is not available. There are several recorded cases of forced ingestion of concentrated salt solution in exorcism rituals leading to death.

- Mineralcorticoid excess due to a disease state such as Conn's syndrome usually does not lead to hypernatremia unless free water intake is restricted.

- Salt poisoning (this condition is most common in children). It has also been seen in a number of adults with mental health problems. Too much salt can also occur from drinking seawater or soy sauce.

The cornerstone of treatment is administration of free water to correct the relative water deficit. Water can be replaced orally or intravenously. Water alone cannot be administered intravenously (because of osmolarity issue), but rather can be given with addition to dextrose or saline infusion solutions. However, overly rapid correction of hypernatremia is potentially very dangerous. The body (in particular the brain) adapts to the higher sodium concentration. Rapidly lowering the sodium concentration with free water, once this adaptation has occurred, causes water to flow into brain cells and causes them to swell. This can lead to cerebral edema, potentially resulting in seizures, permanent brain damage, or death. Therefore, significant hypernatremia should be treated carefully by a physician or other medical professional with experience in treatment of electrolyte imbalance, specific treatment like ACE inhibitors in heart failure and corticosteroids in nephropathy also can be used.

Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using a microscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.

In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.

Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte count is a quantitative measure of the bone marrow's production of new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response.

If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis can help assess whether the bone marrow will be able to compensate for the loss, and at what rate.

When the cause is not obvious, clinicians use other tests, such as: ESR, ferritin, serum iron, transferrin, RBC folate level, serum vitamin B, hemoglobin electrophoresis, renal function tests (e.g. serum creatinine) although the tests will depend on the clinical hypothesis that is being investigated.

When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded.

In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.

Limitations of MCV include cases where the underlying cause is due to a combination of factors – such as iron deficiency (a cause of microcytosis) and vitamin B12 deficiency (a cause of macrocytosis) where the net result can be normocytic cells.

Lumbar puncture, in which cerebrospinal fluid (CSF) is removed from the subarachnoid space of the spinal canal using a hypodermic needle, shows evidence of hemorrhage in 3 percent of people in whom CT was found normal; lumbar puncture is therefore regarded as mandatory in people with suspected SAH if imaging is negative. At least three tubes of CSF are collected. If an elevated number of red blood cells is present equally in all bottles, this indicates a subarachnoid hemorrhage. If the number of cells decreases per bottle, it is more likely that it is due to damage to a small blood vessel during the procedure (known as a "traumatic tap"). While there is no official cutoff for red blood cells in the CSF no documented cases have occurred at less than "a few hundred cells" per high-powered field.

The CSF sample is also examined for xanthochromia—the yellow appearance of centrifugated fluid. This can be determined by spectrophotometry (measuring the absorption of particular wavelengths of light) or visual examination. It is unclear which method is superior. Xanthochromia remains a reliable ways to detect SAH several days after the onset of headache. An interval of at least 12 hours between the onset of the headache and lumbar puncture is required, as it takes several hours for the hemoglobin from the red blood cells to be metabolized into bilirubin.

After a subarachnoid hemorrhage is confirmed, its origin needs to be determined. If the bleeding is likely to have originated from an aneurysm (as determined by the CT scan appearance), the choice is between cerebral angiography (injecting radiocontrast through a catheter to the brain arteries) and CT angiography (visualizing blood vessels with radiocontrast on a CT scan) to identify aneurysms. Catheter angiography also offers the possibility of coiling an aneurysm (see below).

Pulmonary ultrasound, performed at the bedside or on the accident scene, is being explored as a diagnosis for pulmonary contusion. Its use is still not widespread, being limited to facilities which are comfortable with its use for other applications, like pneumothorax, airway management, and hemothorax. Accuracy has been found to be comparable to CT scanning.

Chest X-ray is the most common method used for diagnosis, and may be used to confirm a diagnosis already made using clinical signs. Consolidated areas appear white on an X-ray film. Contusion is not typically restricted by the anatomical boundaries of the lobes or segments of the lung. The X-ray appearance of pulmonary contusion is similar to that of aspiration, and the presence of hemothorax or pneumothorax may obscure the contusion on a radiograph. Signs of contusion that progress after 48 hours post-injury are likely to be actually due to aspiration, pneumonia, or ARDS.

Although chest radiography is an important part of the diagnosis, it is often not sensitive enough to detect the condition early after the injury. In a third of cases, pulmonary contusion is not visible on the first chest radiograph performed. It takes an average of six hours for the characteristic white regions to show up on a chest X-ray, and the contusion may not become apparent for 48 hours. When a pulmonary contusion is apparent in an X-ray, it suggests that the trauma to the chest was severe and that a CT scan might reveal other injuries that were missed with X-ray.

History and examination by a physician with characteristic signs and symptoms are sufficient in many cases in ruling out systemic causes of venous hypertension such as hypervolemia and heart failure. An ultrasound (usually a lower limbs venous ultrasonography) can detect venous obstruction or valvular incompetence as the cause, and is used for planning venous ablation procedures, but it is not necessary in suspected venous insufficiency where surgical intervention is not indicated.

In addition to tests corresponding to the above findings (such as EMG for neuropathy, CT scan, bone marrow biopsy to detect clonal plasma cells, plasma or serum protein electrophoresis to myeloma proteins, other tests can give abnormal results supporting the diagnosis of POEMS syndrome. These included raised blood levels of VEGF, thrombocytes, and/or erythrocyte parameters.

Patients diagnosed as having Castleman disease but also exhibiting many of the symptoms and signs of POEMS syndrome but lacking evidence of a peripheral neuropathy and/or clonal plasma cells should not be diagnosed as having POEMS syndrome. They are better classified as having Castleman disease variant of POEMS syndrome. These patients may exhibit high blood levels of the interleukin-6 cytokine and have an inferior overall survival compared to POEMS syndrome patients. Treatment of patients with this POEMS syndrome variant who have evidence of bone lesions and/or myeloma proteins are the same as those for POEMS syndrome patients. In the absence of these features, treatment with rituximab, a monoclonal antibody preparation directed against B cells bearing the CD20 antigen, or siltuximab, a monoclonal antibody preparation directed against interleukin-6, may be justified.

Drowning victims who arrive at a hospital with spontaneous circulation and breathing usually recover with good outcomes. Early provision of basic and advanced life support improve probability of positive outcome.

Longer duration of submersion is associated with lower probability of survival and higher probability of permanent neurological damage.

Contaminants in the water can cause bronchospasm and impaired gas exchange, and can cause secondary infection with delayed severe respiratory compromise.

Low water temperature can cause ventricular fibrillation, but hypothermia during immersion can also slow the metabolism, allowing a longer hypoxia before severe damage occurs. Hypothermia which reduces brain temperature significantly can improve outcome. A reduction of brain temperature by 10 °C decreases ATP consumption by approximately 50%, which can double the time that the brain can survive.

The younger the victim, the better the chances of survival. In one case, a child submerged in cold () water for 66 minutes was resuscitated without apparent neurological damage. However, over the long term significant deficits were noted, including a range of cognitive difficulties, particularly general memory impairment, although recent magnetic resonance imaging (MRI) and magnetoencephalography (MEG) were within normal range.

Administration of oxygen at 15 litres per minute by face mask or bag valve mask is often sufficient, but tracheal intubation with mechanical ventilation may be necessary. Suctioning of pulmonary oedema fluid should be balanced against the need for oxygenation. The target of ventilation is to achieve 92% to 96% arterial saturation and adequate chest rise. Positive end-expiratory pressure will generally improve oxygenation. Drug administration via peripheral veins is preferred over endotracheal administration. Hypotension remaining after oxygenation may be treated by rapid crystalloid infusion. Cardiac arrest in drowning usually presents as asystole or pulseless electrical activity. Ventricular fibrillation is more likely to be associated with complications of pre-existing coronary artery disease, severe hypothermia, or the use of epinephrine or norepinephrine.

Conservative treatment of CVI in the leg involves symptomatic treatment and efforts to prevent the condition from getting worse instead of effecting a cure. This may include

- Manual compression lymphatic massage therapy

- Skin lubrication

- Sequential compression pump

- Ankle pump

- Compression stockings

- Blood pressure medicine

- Frequent periods of rest elevating the legs above the heart level

- Tilting the bed so that the feet are above the heart. This may be achieved by using a 20 cm (7-inch) bed wedge or sleeping in a 6 degree Trendelenburg position. Obese or pregnant patients might be advised by their physicians to forgo the tilted bed.