Methemoglobinemia may be acquired. Classical drug causes of methemoglobinaemia include antibiotics (trimethoprim, sulfonamides, and dapsone), local anesthetics (especially articaine, benzocaine, and prilocaine), and aniline dyes, metoclopramide, rasburicase, chlorates, and bromates. Ingestion of compounds containing nitrates (such as the patina chemical bismuth nitrate) can also cause methemoglobinemia.

In otherwise healthy individuals, the protective enzyme systems normally present in red blood cells rapidly reduce the methemoglobin back to hemoglobin and hence maintain methemoglobin levels at less than one percent of the total hemoglobin concentration. Exposure to exogenous oxidizing drugs and their metabolites (such as benzocaine, dapsone, and nitrates) may lead to an increase of up to a thousandfold of the methemoglobin formation rate, overwhelming the protective enzyme systems and acutely increasing methemoglobin levels.

Infants under 6 months of age have lower levels of a key methemoglobin reduction enzyme (NADH-cytochrome b5 reductase) in their red blood cells. This results in a major risk of methemoglobinemia caused by nitrates ingested in drinking water, dehydration (usually caused by gastroenteritis with diarrhea), sepsis, or topical anesthetics containing benzocaine or prilocaine. Nitrates used in agricultural fertilizers may leak into the ground and may contaminate well water. The current EPA standard of 10 ppm nitrate-nitrogen for drinking water is specifically set to protect infants. Benzocaine applied to the gums or throat (as commonly used in baby teething gels, or sore throat lozenges) can cause methemoglobinemia.

Arterial blood with elevated methemoglobin levels has a characteristic chocolate-brown color as compared to normal bright red oxygen-containing arterial blood. If methemoglobinemia is suspected, an arterial blood gas and co-oximetry panel should be obtained.

The following guideline values (ppm values rounded) and periods of time-weighted average exposures have been determined in such a way that the carboxyhaemoglobin (COHb) level of 2.5% is not exceeded, even when a normal subject engages in light or moderate exercise:

- 100 mg/m3 (87 ppm) for 15 min

- 60 mg/m3 (52 ppm) for 30 min

- 30 mg/m3 (26 ppm) for 1 h

- 10 mg/m3 (9 ppm) for 8 h

For indoor air quality 7 mg/m3 (6 ppm) for 24 h (so as not to exceed 2% COHb for chronic exposure)

Carbon monoxide is a product of combustion of organic matter under conditions of restricted oxygen supply, which prevents complete oxidation to carbon dioxide (CO). Sources of carbon monoxide include cigarette smoke, house fires, faulty furnaces, heaters, wood-burning stoves, internal combustion vehicle exhaust, electrical generators, propane-fueled equipment such as portable stoves, and gasoline-powered tools such as leaf blowers, lawn mowers, high-pressure washers, concrete cutting saws, power trowels, and welders. Exposure typically occurs when equipment is used in buildings or semi-enclosed spaces.

Riding in the back of pickup trucks has led to poisoning in children. Idling automobiles with the exhaust pipe blocked by snow has led to the poisoning of car occupants. Any perforation between the exhaust manifold and shroud can result in exhaust gases reaching the cabin. Generators and propulsion engines on boats, especially houseboats, has resulted in fatal carbon monoxide exposures.

Poisoning may also occur following the use of a self-contained underwater breathing apparatus (SCUBA) due to faulty diving air compressors.

In caves carbon monoxide can build up in enclosed chambers due to the presence of decomposing organic matter. In coal mines incomplete combustion may occur during explosions resulting in the production of afterdamp. The gas is up to 3% CO and may be fatal after just a single breath. Following an explosion in a colliery, adjacent interconnected mines may become dangerous due to the afterdamp leaking from mine to mine. Such an incident followed the Trimdon Grange explosion which killed men in the Kelloe mine.

Another source of poisoning is exposure to the organic solvent dichloromethane, found in some paint strippers, as the metabolism of dichloromethane produces carbon monoxide.

Hemoglobinopathy is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Hemoglobinopathies are inherited single-gene disorders; in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease. It is estimated that 7% of world's population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in populations from Africa, the Mediterranean basin and Southeast Asia.

Hemoglobinopathies imply structural abnormalities in the globin proteins themselves. Thalassemias, in contrast, usually result in underproduction of normal globin proteins, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some hemoglobinopathies are also thalassemias, but most are not.

Either hemoglobinopathy or thalassemia, or both, may cause anemia. Some well-known hemoglobin variants such as sickle-cell anemia and congenital dyserythropoietic anemia are responsible for diseases, and are considered hemoglobinopathies. However, many hemoglobin variants do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies, because they are not considered pathologies. Hemoglobin variants are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Other variants cause no detectable pathology, and are thus considered non-pathological variants.

Some hemoglobinopathies (and also related diseases like glucose-6-phosphate dehydrogenase deficiency) seem to have given an evolutionary benefit, especially to heterozygotes, in areas where malaria is endemic. Malaria parasites live inside red blood cells, but subtly disturb normal cellular function. In patients predisposed for rapid clearance of red blood cells, this may lead to early destruction of cells infected with the parasite and increased chance of survival for the carrier of the trait.

Hemoglobin functions:

- Transport of oxygen from the lungs to the tissues: This is due to the peculiar cooperation of the globin chains that allows the molecule to take in more oxygen where there is increased oxygen and to release oxygen in low concentration of oxygen.

- Transport of carbon dioxide from the tissues to the lungs: The end product of tissue metabolism is acidic which increases hydrogen ions in solution. The hydrogen ions combine with bicarbonates to produce water and carbon dioxide. The carbon dioxide is mop up by hemoglobin to favor this reversible reaction.

- Transport of nitric oxide: Nitric oxide is a vasodilatator. This assists in the regulation of vascular reaction in times of stress as experienced during inflammation.

Pathology and organic structural abnormalities may lead to any of the following disease processes:

- Anemia due to reduced life span of the red cells of reduced production of the cells e. g. hemoglobin S, C and E.

- Increased oxygen affinity: The red blood cells do not release their oxygen content readily in hypoxic conditions. The bone marow therefore needs to produce more red blood cells and there is polycythemia.

- Unstable hemoglobins: Red blood cells are easily destroyed under stress and hemolysis occurs with possible jaundice.

- Methemoglobinemia: The iron in the heme portion of hemoglobin is easily oxidised and this reduces the ability of hemoglobin to bind oxygen. More deoxygenated hemoglobin are formed and the blood becomes cyanotic.

Central cyanosis is often due to a circulatory or ventilatory problem that leads to poor blood oxygenation in the lungs. It develops when arterial oxygen saturation drops to ≤85% or ≤75%.

Acute cyanosis can be as a result of asphyxiation or choking, and is one of the definite signs that respiration is being blocked.

Central cyanosis may be due to the following causes:

1. Central nervous system (impairing normal ventilation):

- Intracranial hemorrhage

- Drug overdose (e.g. heroin)

- Tonic–clonic seizure (e.g. grand mal seizure)

2. Respiratory system:

- Pneumonia

- Bronchiolitis

- Bronchospasm (e.g. asthma)

- Pulmonary hypertension

- Pulmonary embolism

- Hypoventilation

- Chronic obstructive pulmonary disease, or COPD (emphysema)

3. Cardiovascular diseases:

- Congenital heart disease (e.g. Tetralogy of Fallot, right to left shunts in heart or great vessels)

- Heart failure

- Valvular heart disease

- Myocardial infarction

4. Blood:

- Methemoglobinemia * Note this causes "spurious" cyanosis, in that, since methemoglobin appears blue, the patient can appear cyanosed even in the presence of a normal arterial oxygen level.

- Polycythaemia

- Congenital cyanosis (HbM Boston) arises from a mutation in the α-codon which results in a change of primary sequence, H → Y. Tyrosine stabilises the Fe(III) form (oxyhaemoglobin) creating a permanent T-state of Hb.

5. Others:

- High altitude, cyanosis may develop in ascents to altitudes >2400 m.

- Hypothermia

- Obstructive sleep apnea

Peripheral cyanosis is the blue tint in fingers or extremities, due to an inadequate or obstructed circulation. The blood reaching the extremities is not oxygen-rich and when viewed through the skin a combination of factors can lead to the appearance of a blue color. All factors contributing to central cyanosis can also cause peripheral symptoms to appear but peripheral cyanosis can be observed in the absence of heart or lung failures. Small blood vessels may be restricted and can be treated by increasing the normal oxygenation level of the blood.

Peripheral cyanosis may be due to the following causes:

- All common causes of central cyanosis

- Reduced cardiac output (e.g. heart failure or hypovolaemia)

- Cold exposure

- Chronic obstructive pulmonary disease (COPD)

- Arterial obstruction (e.g. peripheral vascular disease, Raynaud phenomenon)

- Venous obstruction (e.g. deep vein thrombosis)

Following diagnosis, mean survival of patients with PPH is 15 months. The survival of those with cirrhosis is sharply curtailed by PPH but can be significantly extended by both medical therapy and liver transplantation, provided the patient remains eligible.

Eligibility for transplantation is generally related to mean pulmonary artery pressure (PAP). Given the fear that those PPH patients with high PAP will suffer right heart failure following the stress of post-transplant reperfusion or in the immediate perioperative period, patients are typically risk-stratified based on mean PAP. Indeed, the operation-related mortality rate is greater than 50% when pre-operative mean PAP values lie between 35 and 50 mm Hg; if mean PAP exceeds 40-45, transplantation is associated with a perioperative mortality of 70-80% (in those cases without preoperative medical therapy). Patients, then, are considered to have a high risk of perioperative death once their mean PAP exceeds 35 mm_Hg.

Survival is best inferred from published institutional experiences. At one institution, without treatment, 1-year survival was 46% and 5-year survival was 14%. With medical therapy, 1-year survival was 88% and 5-year survival was 55%. Survival at 5 years with medical therapy followed by liver transplantation was 67%. At another institution, of the 67 patients with PPH from 1652 total cirrhotics evaluated for transplant, half (34) were placed on the waiting list. Of these, 16 (48%) were transplanted at a time when 25% of all patients who underwent full evaluation received new livers, meaning the diagnosis of PPH made a patient twice as likely to be transplanted, once on the waiting list. Of those listed for transplant with PPH, 11 (33%) were eventually removed because of PPH, and 5 (15%) died on the waitlist. Of the 16 transplanted patients with PPH, 11 (69%) survived for more than a year after transplant, at a time when overall one-year survival in that center was 86.4%. The three year post-transplant survival for patients with PPH was 62.5% when it was 81.02% overall at this institution.

Portopulmonary hypertension (PPH) is defined by the coexistence of portal and pulmonary hypertension. PPH is a serious complication of liver disease, present in 0.25 to 4% of all patients suffering from cirrhosis. Once an absolute contraindication to liver transplantation, it is no longer, thanks to rapid advances in the treatment of this condition. Today, PPH is comorbid in 4-6% of those referred for a liver transplant.

Fetal hydantoin syndrome, also called fetal dilantin syndrome is a group of defects caused to the developing fetus by exposure to teratogenic effects of phenytoin or carbamazepine. Dilantin is the brand name of the drug phenytoin sodium in the United States, commonly used in the treatment of epilepsy.

It may also be called congenital hydantoin syndrome, Fetal Hydantoin Syndrome, Dilantin Embryopathy, or Phenytoin Embryopathy.

Association with EPHX1 has been suggested.

About one third of children whose mothers are taking this drug during pregnancy typically have intrauterine growth restriction with a small head and develop minor dysmorphic craniofacial features and limb defects including hypoplastic nails and distal phalanges (birth defects). A smaller population will have growth problems and developmental delay, or intellectual disability. Methemoglobinemia is a rarely seen side effect.

Heart defects and cleft lip may also be featured.

Urinary catheterization increases the risk for urinary tract infections. The risk of bacteriuria (bacteria in the urine) is between three and six percent per day and prophylactic antibiotics are not effective in decreasing symptomatic infections. The risk of an associated infection can be decreased by catheterizing only when necessary, using aseptic technique for insertion, and maintaining unobstructed closed drainage of the catheter.

Male scuba divers utilizing condom catheters and female divers utilizing external catching devices for their dry suits are also susceptible to urinary tract infections.

In young sexually active women, sexual activity is the cause of 75–90% of bladder infections, with the risk of infection related to the frequency of sex. The term "honeymoon cystitis" has been applied to this phenomenon of frequent UTIs during early marriage. In post-menopausal women, sexual activity does not affect the risk of developing a UTI. Spermicide use, independent of sexual frequency, increases the risk of UTIs. Diaphragm use is also associated. Condom use without spermicide or use of birth control pills does not increase the risk of uncomplicated urinary tract infection.

Women are more prone to UTIs than men because, in females, the urethra is much shorter and closer to the anus. As a woman's estrogen levels decrease with menopause, her risk of urinary tract infections increases due to the loss of protective vaginal flora. Additionally, vaginal atrophy that can sometimes occur after menopause is associated with recurrent urinary tract infections.

Chronic prostatitis in the forms of chronic prostatitis/chronic pelvic pain syndrome and chronic bacterial prostatitis (not acute bacterial prostatitis or asymptomatic inflammatory prostatitis) may cause recurrent urinary tract infections in males. Risk of infections increases as males age. While bacteria is commonly present in the urine of older males this does not appear to affect the risk of urinary tract infections.