Waterhouse-Friderichsen syndrome

Definitions & Key takeaways

Waterhouse-Friderichsen syndrome is a rare and potentially life-threatening condition that occurs when the adrenal glands fail and produce insufficient amounts of cortisol and other hormones. This condition is usually caused by an overwhelming bacterial infection, most commonly meningococcal septicemia, but it can also be caused by other bacterial infections.

The characteristic symptom of the syndrome is a petechial rash throughout the body, which can turn into large purpura over time. Another potential complication of this syndrome is an Addisonian crisis, which can cause sudden lower back, abdominal or leg pain, vomiting, diarrhea, and low blood pressure leading to loss of consciousness. Other symptoms include fever and chills, which can be a sign of sepsis.

Waterhouse-Friderichsen syndrome is a medical emergency and requires immediate treatment with antibiotics to treat the underlying bacterial infection, as well as glucocorticoids to help support the person's blood pressure and metabolic needs. Other supportive care measures may also be necessary, such as IV fluids, oxygen therapy, and monitoring of vital signs.

Chapters:

Watch video only

Introduction0:00–0:31

Waterhouse-Friderichsen syndrome occurs when the blood vessels in the adrenal gland rupture during a severe bacterial infection, turning the adrenal glands into sacks of blood.
This results in adrenal crisis, or acute adrenal insufficiency, which is when the adrenal gland suddenly stops producing hormones.
The syndrome is named after two physicians - Waterhouse and Friderichsen who separately described the syndrome back in the early 1900’s.

Physiology0:31–2:13

Now, there are two adrenal glands, one above each kidney, and each one has an inner layer called the medulla and an outer layer called the cortex.
The adrenal cortex is subdivided into three more layers, the zona glomerulosa, zona fasciculata, and the zona reticularis.
The adrenal cortex secretes hormones under the control of adrenocorticotropic hormone, released by the pituitary gland. The outermost layer is the zona glomerulosa, which makes the hormone aldosterone.
Aldosterone acts on the nephrons of the kidney, and decrease potassium levels, increase sodium levels, and increase blood volume and blood pressure.
The middle layer is the zona fasciculata, which makes the hormone cortisol, as well as other glucocorticoids. The main job of glucocorticoid is to increase blood glucose levels, especially when there’s emotional and physical stress.
Finally, the innermost layer is the zona reticularis, which makes a group of sex hormones called androgens. In men, androgen stimulates development of male reproductive tissues and secondary sex characteristics like facial hair and a large Adam’s apple.
In women, androgen causes a growth spurt, and growth of underarm and pubic hair during puberty. The adrenal gland gets blood through three main arteries- the superior, middle, and inferior suprarenal arteries.
All three divide into branches that supply the adrenal cortex and the adrenal medulla. After delivering oxygen to those tissues, the blood starts to collect again in the medullary vein and eventually into the suprarenal vein.

Pathology2:13–4:23

The root cause of Waterhouse-Friderichsen syndrome is severe bacterial infection, or sepsis. This sepsis is typically due to Neisseria meningitidis, which is a gram-negative bacteria that is best known for causing meningitis.
Other bacteria that can cause Waterhouse-Friderichsen syndrome include Pseudomonas aeruginosa and Haemophilus influenzae.
The outer membrane of these bacteria contains endotoxins, which are large clunky lipopolysaccharide molecules, or LPS. These LPS molecules directly damage endothelial cells of the blood vessels, and cause them to release procoagulant-like tissue factor, which promotes blood clot formation within blood vessels.
When that happens during an infection, bacteria can start growing in these clots, forming septic emboli, which can drift away and get lodged within other blood vessels.
The procoagulants also trigger disseminated intravascular coagulation, or DIC, which is when there’s extensive clotting in blood vessels throughout the body and it quickly consumes platelets and clotting factors.
Without enough platelets circulating in the blood, other parts of the body begin to bleed with even the slightest damage to the blood vessel walls.
In Waterhouse-Friderichsen, this chain of events can happen and a septic emboli can get lodged in a small blood vessel in the adrenal gland.
That can cause pressure in the vessel to increase, stretching the blood vessel walls, and potentially making the blood vessel rupture.
When a vessel breaks, the DIC makes it hard to form clots, and a lot of blood starts to pool within the adrenal gland. That big pool of blood sitting within the confined space of the adrenal gland increases the local pressure, and that pressure pinches shut the nearby blood vessels.
That results in ischemia and eventually necrosis of the various hormone producing cells in the adrenal gland. Waterhouse-Friderichsen syndrome results in addisonian crisis, which is when both the adrenal glands suddenly stop producing hormones, especially aldosterone and cortisol.
Left untreated, an addisonian crisis can be fatal. A characteristic symptom seen in Waterhouse-Friderichsen syndrome caused by Neisseria meningitidis is a petechial rash throughout the body which fuse together to form large purpura over time.

Signs and symptoms4:23–4:53

Addisonian crisis can cause sudden pain in the lower back, abdomen, or legs, severe vomiting and diarrhea, low blood pressure; and eventually a loss of consciousness.
Other symptoms include fever and chills, due to sepsis. Diagnosis of Waterhouse-Friderichsen syndrome begins with measuring the amount of cortisol and aldosterone produced after giving adrenocorticotropic hormone, which normally increases adrenal hormone production.

Diagnosis4:53–5:15

A blood culture is done to look for the bacteria, and imaging with ultrasound or CT scans usually show collections of blood within the adrenal glands.

Treatment5:15–5:32

Waterhouse-Friderichsen syndrome needs emergency treatment with antibiotics to fight the infection, and glucocorticoids to help support a person’s metabolic needs and blood pressure.
Supplementary hormones typically have to be taken for the rest of an individual’s life. All right, as a quick recap, in Waterhouse-Friderichsen syndrome there is often a combination of a serious bacterial infection, often Neisseria meningitidis, which leads to DIC.

Review5:32–6:05

Tiny blood vessels in the adrenal glands can break turning the adrenal glands into sacks of blood. Adrenal tissue dies due to tissue necrosis and is unable to produce hormones.
That leads to an addisonian crisis, which can be severe if not diagnosed early and treated with antibiotics and glucocorticoids.