The most common cause is viral infection and includes adenovirus, rhinovirus, influenza, coronavirus, and respiratory syncytial virus. It can also be caused by Epstein-Barr virus, herpes simplex virus, cytomegalovirus, or HIV. The second most common cause is bacterial infection of which the predominant is Group A β-hemolytic streptococcus (GABHS), which causes strep throat. Less common bacterial causes include: "Staphylococcus aureus" (including methicillin resistant Staphylococcus aureus or MRSA ),"Streptococcus pneumoniae", "Mycoplasma pneumoniae", "Chlamydia pneumoniae", "Bordetella pertussis", "Fusobacterium" sp., "Corynebacterium diphtheriae", "Treponema pallidum", and "Neisseria gonorrhoeae".

Anaerobic bacteria have been implicated in tonsillitis and a possible role in the acute inflammatory process is supported by several clinical and scientific observations.

Under normal circumstances, as viruses and bacteria enter the body through the nose and mouth, they are filtered in the tonsils. Within the tonsils, white blood cells of the immune system destroy the viruses or bacteria by producing inflammatory cytokines like phospholipase A2, which also lead to fever. The infection may also be present in the throat and surrounding areas, causing inflammation of the pharynx.

Sometimes, tonsillitis is caused by an infection of spirochaeta and treponema, in this case called Vincent's angina or Plaut-Vincent angina.

Some cases of pharyngitis are caused by fungal infection such as Candida albicans causing oral thrush.

Since the advent of penicillin in the 1940s, a major preoccupation in the treatment of streptococcal tonsillitis has been the prevention of rheumatic fever, and its major effects on the nervous system (Sydenham's chorea) and heart. Recent evidence would suggest that the rheumatogenic strains of group A beta hemolytic strep have become markedly less prevalent and are now only present in small pockets such as in Salt Lake City, USA. This brings into question the rationale for treating tonsillitis as a means of preventing rheumatic fever.

Complications may rarely include dehydration and kidney failure due to difficulty swallowing, blocked airways due to inflammation, and pharyngitis due to the spread of infection.

An abscess may develop lateral to the tonsil during an infection, typically several days after the onset of tonsillitis. This is termed a peritonsillar abscess (or quinsy).

Rarely, the infection may spread beyond the tonsil resulting in inflammation and infection of the internal jugular vein giving rise to a spreading septicaemia infection (Lemierre's syndrome).

In chronic/recurrent cases (generally defined as seven episodes of tonsillitis in the preceding year, five episodes in each of the preceding two years or three episodes in each of the preceding three years), or in acute cases where the palatine tonsils become so swollen that swallowing is impaired, a tonsillectomy can be performed to remove the tonsils. Patients whose tonsils have been removed are still protected from infection by the rest of their immune system.

In strep throat, very rarely diseases like rheumatic fever or glomerulonephritis can occur. These complications are extremely rare in developed nations but remain a significant problem in poorer nations. Tonsillitis associated with strep throat, if untreated, is hypothesized to lead to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

Pharyngitis may also be caused by mechanical, chemical or thermal irritation, for example cold air or acid reflux. Some medications may produce pharyngitis such as pramipexole and antipsychotics.

Viruses that may cause adenoiditis include adenovirus, rhinovirus and paramyxovirus. Bacterial causes include Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and various species of Staphylococcus including Staphylococcus aureus.

It is currently believed that bacterial biofilms play an integral role in the harboring of chronic infection by tonsil and adenoid tissue so contributing to recurrent sinusitis and recurrent or persistent ear disease. Also, enlarged adenoids and tonsils may lead to the obstruction of the breathing patterns in children, causing apnea during sleep.

The most common bacteria isolated are Haemophilus influenzae, group A beta-hemolytic Streptococcus, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniea. Heamophilus influenza, Moraxella catarrhalis and Streptococcus pneumonia are the three most resistant pathogens of otitis and rhinosinisitis in children suffering from these diseases.

PTA usually arises as a complication of an untreated or partially treated episode of acute tonsillitis. The infection, in these cases, spreads to the peritonsillar area (peritonsillitis). This region comprises loose connective tissue and is hence susceptible to formation of an abscess. PTA can also occur "". Both aerobic and anaerobic bacteria can be causative. Commonly involved aerobic pathogens include "Streptococcus, Staphylococcus" and "Haemophilus". The most common anaerobic species include "Fusobacterium necrophorum", " Peptostreptococcus", "Prevotella species", and "Bacteroides".

It is a commonly encountered otorhinolaryngological (ENT) emergency.

The number of new cases per year of peritonsillar abscess in the United States has been estimated approximately at 30 cases per 100,000 people. In a study in Northern Ireland, the number of new cases was 10 cases per 100,000 people per year.

In Denmark, the new number of new cases is higher and reaches 41 cases per 100,000 people per year. Younger children who develop a peritonsillar abscess are often immunocompromised and in them, the infection can cause airway obstruction.

Serious complications are uncommon, occurring in less than 5% of cases:

- CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleiosis has been linked to the development of multiple sclerosis (MS).

- Hematologic: Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur.

- Mild jaundice

- Hepatitis with the Epstein–Barr virus is rare.

- Upper airway obstruction from tonsillar hypertrophy is rare.

- Fulminant disease course of immunocompromised patients is rare.

- Splenic rupture is rare.

- Myocarditis and pericarditis are rare.

- Postural orthostatic tachycardia syndrome

- Chronic fatigue syndrome

- Cancers associated with the Epstein-Barr virus include: Burkitt's lymphoma, Hodgkin's lymphoma and lymphomas in general as well as nasopharyngeal and gastric carcinoma.

Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly. Periodically, the virus can reactivate, during which time the patient is again infectious, but usually without any symptoms of illness. Usually, a patient has few, if any, further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors, the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase the virus can spread to others.

Herpangina, also called mouth blisters, is a painful mouth infection caused by coxsackieviruses. Usually, herpangina is produced by one particular strain of coxsackie virus A (and the term "herpangina virus" refers to coxsackievirus A) but it can also be caused by coxsackievirus B or echoviruses. Most cases of herpangina occur in the summer, affecting mostly children. However, it occasionally occurs in adolescents and adults. It was first characterized in 1920.

Typically spreads via the fecal-oral route or via respiratory droplets.

The exact length of time between infection and symptoms is unclear. A review of the literature made an estimate of 33–49 days. In adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection. Onset is often gradual, though it can be abrupt. The main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches.

There is low or very-low quality evidence that probiotics may be better than placebo in preventing acute URTIs. Vaccination against influenza viruses, adenoviruses, measles, rubella, "Streptococcus pneumoniae", "Haemophilus influenzae", diphtheria, "Bacillus anthracis", and "Bordetella pertussis" may prevent them from infecting the URT or reduce the severity of the infection.

In terms of pathophysiology, rhino virus infection resembles the immune response. The viruses do not cause damage to the cells of the upper respiratory tract but rather cause changes in the tight junctions of epithelial cells. This allows the virus to gain access to tissues under the epithelial cells and initiate the innate and adaptive immune responses.

Up to 15% of acute pharyngitis cases may be caused by bacteria, most commonly "Streptococcus pyogenes", a group A streptococcus in streptococcal pharyngitis ("strep throat"). Other bacterial causes are "Streptococcus pneumoniae", "Haemophilus influenzae", "Corynebacterium diphtheriae", "Bordetella pertussis", and "Bacillus anthracis".

Sexually transmitted infections have emerged as causes of oral and pharyngeal infections.

Otitis media is a particularly common cause of otalgia in early childhood, often occurring secondary to other infectious illnesses, such as colds, coughs, or conjunctivitis.

Tonsilloliths or tonsillar concretions occur in up to 10% of the population, frequently due to episodes of tonsillitis. While small concretions in the tonsils are common, true tonsilloliths or stones are rare. They commonly occur in young adults and are rare in children.

Catarrh , or catarrhal inflammation, is inflammation of the mucous membranes in one of the airways or cavities of the body, usually with reference to the throat and paranasal sinuses. It can result in a thick exudate of mucus and white blood cells caused by the swelling of the mucous membranes in the head in response to an infection. It is a symptom usually associated with the common cold, pharyngitis, and chesty coughs, but it can also be found in patients with adenoiditis, otitis media, sinusitis or tonsillitis. The phlegm produced by catarrh may either discharge or cause a blockage that may become chronic.

The word "catarrh" was widely used in medicine since before the era of medical science, which explains why it has various senses and in older texts may be synonymous with, or vaguely indistinguishable from, common cold, nasopharyngitis, pharyngitis, rhinitis, or sinusitis. The word is no longer as widely used in American medical practice, mostly because more precise words are available for any particular pathosis. Indeed, to the extent that it is still used, it is no longer viewed nosologically as a disease entity but instead as a symptom, a sign, or a syndrome of both. The term "catarrh" is found in medical sources from the United Kingdom. The word has also been common in the folk medicine of Appalachia, where medicinal plants have been used to treat the inflammation and drainage associated with the condition.

It is normally possible to establish the cause of ear pain based on the history. It is important to exclude cancer where appropriate, particularly with unilateral otalgia in an adult who uses tobacco or alcohol.Often migraines are caused by middle ear infections which can easily be treated with antibiotics. Often using a hot washcloth can temporarily relieve ear pain.

Untreated, the infection may lead to rapid destruction of the periodontium and can spread, as necrotizing stomatitis or noma, into neighbouring tissues in the cheeks, lips or the bones of the jaw. As stated, the condition can occur and be especially dangerous in people with weakened immune systems. This progression to noma is possible in malnourished susceptible individuals, with severe disfigurement possible.

Due to the human ear's function of regulating the pressure within the head region, catarrh blockage may cause discomfort during changes in atmospheric pressure.

The mechanism by which these calculi form is subject to debate, though they appear to result from the accumulation of material retained within the crypts, along with the growth of bacteria and fungi – sometimes in association with persistent chronic purulent tonsillitis.

Recently, an association between biofilms and tonsilloliths was shown. Central to the biofilm concept is the assumption that bacteria form a three dimensional structure, dormant bacteria being in the center to serve as a constant nidus of infection. This impermeable structure renders the biofilm immune to antibiotic treatment. By use of confocal microscopy and microelectrodes, biofilms similar to dental biofilms were shown to be present in the tonsillolith, with oxygen respiration at the outer layer of tonsillolith, denitrification toward the middle, and acidification toward the bottom.

In developed countries, this disease occurs mostly in young adults. In developing countries, NUG may occur in children of low socioeconomic status, usually occurring with malnutrition (especially inadequate protein intake) and shortly after the onset of viral infections (e.g. measles).

Predisposing factors include smoking, viral respiratory infections and immune defects, such as in HIV/AIDS. Uncommon, except in lower socioeconomic classes, this typically affects adolescents and young adults, especially in institutions, armed forces, etc., or people with HIV/AIDS. The disease has occurred in epidemic-like patterns, but it is not contagious.

Causes of decreased clearance of saliva include:

- Infections such as tonsillitis, retropharyngeal and peritonsillar abscesses, epiglottitis and mumps.

- Problems with the jaw, e.g., fracture or dislocation

- Radiation therapy

- Neurologic disorders such as myasthenia gravis, Parkinson's disease, multiple system atrophy, rabies, bulbar paralysis, bilateral facial nerve palsy, and hypoglossal nerve palsy

Conditions that can cause saliva overproduction include:

- Rabies

- Pellagra (niacin or Vitamin B3 deficiency)

- Gastroesophageal reflux disease, in such cases specifically called a water brash, and is characterized by a sour fluid or almost tasteless saliva in the mouth

- Gastroparesis (main symptoms are nausea, vomiting, and reflux)

- Pregnancy

- Excessive starch intake

- Anxiety (common sign of separation anxiety in dogs)

- Pancreatitis

- Liver disease

- Serotonin syndrome

- Mouth ulcers

- Oral infections

Medications that can cause overproduction of saliva include:

- aripiprazole

- clozapine

- pilocarpine

- ketamine

- potassium chlorate

- risperidone

- rabeprazole sodium (Aciphex)

Toxins that can cause hypersalivation include:

- mercury

- copper

- organophosphates (insecticide)

- arsenic

There are various individual risk factors associated with having a silent stroke. Many of these risk factors are the same as those associated with having a major symptomatic stroke.

- Acrolein: elevated levels of acrolein, a toxic metabolite produced from the polyamines spermine, spermidine and by amine oxidase serve as a marker for silent stroke, when elevated in conjunction with C-reactive protein and interleukin 6 the confidence levels in predicting a silent stroke risk increase.

- Adiponectin: is a type of protein secreted by adipose cells that improves insulin sensitivity and possesses antiatherogenic properties. Lower levels of s-adiponectin are associated with ischemic stroke.

- Aging: the prevalence of silent stroke rises with increasing age with a prevalence rate of over twenty percent of the elderly increasing to 30%-40% in those over the age of 70.

- Anemia: children with acute anemia caused by medical conditions other than sickle cell anemia with hemoglobin below 5.5 g/dL. are at increased risk for having a silent stroke according to a study released at American Stroke Association's International Stroke Conference 2011. The researchers suggested a thorough examination for evidence of silent stroke in all severely anemic children in order to facilitate timely intervention to ameliorate the potential brain damage.

- Sickle cell anemia: is an autosomal recessive genetic blood disorder caused in the gene (HBB gene) which codes for hemoglobin (Hg) and results in lowered levels. The blood cells in sickle cell disease are abnormally shaped (sickle-shaped) and may form clots or block blood vessels. Estimates of children with sickle cell anemia who suffer strokes (with silent strokes predominating in the younger patients) range from 15%-30%. These children are at significant risk of cognitive impairment and poor educational outcomes.

- Thalassemia major: is an autosomal recessive genetically inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. Children with this disorder are at increased risk for silent stroke.

- Atrial fibrillation (AF): atrial fibrillation (irregular heartbeat) is associated with a doubled risk for silent stroke.

- Cigarette smoking: The procoagulant and atherogenic effects of smoking increase the risk for silent stroke. Smoking also has a deleterious effect on regional cerebral blood flow (rCBF). The chances of having a stroke increase with the amount of cigarettes smoked and the length of time an individual has smoked (pack years).

- C-reactive protein (CRP) and Interleukin 6 (IL6): C-reactive protein is one of the plasma proteins known as acute phase proteins (proteins whose plasma concentrations increase (or decrease) by 25% or more during inflammatory disorders) which is produced by the liver. The level of CRP rises in response to inflammation in various parts of the body including vascular inflammation. The level of CRP can rise as high as 1000-fold in response to inflammation. Other conditions that can cause marked changes in CRP levels include infection, trauma, surgery, burns, inflammatory conditions, and advanced cancer. Moderate changes can also occur after strenuous exercise, heatstroke, and childbirth. Increased levels of CRP as measured by a CRP test or the more sensitive high serum CRP (hsCRP) test have a close correlation to increased risk of silent stroke. Interleukin-6 is an interleukin (type of protein) produced by T-cells (specialized white blood cells), macrophages and endothelial cells. IL6 is also classified as a cytokine (acts in relaying information between cells). IL6 is involved in the regulation of the acute phase response to injury and infection may act as both an anti-inflammatory agent and a pro-inflammatory.Increased levels of CRP as measured by a CRP test or the more sensitive high serum CRP (hsCRP) test and elevated levels of I6 as measured by an IL6 ELISA are markers for the increased risk of silent stroke.

- Diabetes mellitus: untreated or improperly managed diabetes mellitus is associated with an increased risk for silent stroke.

- Hypertension: which affects up to 50 million people in the United States alone is the major treatable risk factor associated with silent stokes.

- Homocysteine: elevated levels of total homocysteine (tHcy) an amino acid are an independent risk factor for silent stroke, even in healthy middle-aged adults.

- Metabolic syndrome (MetS):Metabolic syndrome is a name for a group of risk factors that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes. A higher number of these MetS risk factors the greater the chance of having a silent sroke.

- Polycystic ovary syndrome (PCOS): is associated with double the risk for arterial disease including silent stroke independent of the subjects Body mass index (BMI).

- Sleep apnea: is a term which encompasses a heterogeneous group of sleep-related breathing disorders in which there is repeated intermittent episodes of breathing cessation or hypopnea, when breathing is shallower or slower than normal. Sleep apnea is a common finding in stroke patients but recent research suggests that it is even more prevalent in silent stroke and chronic microvascular changes in the brain. In the study presented at the American Stroke Association's International Stroke Conference 2012 the higher the apnea-hypopnea index, the more likely patients had a silent stroke.