Cause of Death: Saddle Pulmonary Embolism; The Bread and Butter of Pathology

This is one of my favorite natural causes of death! It is so rewarding for an eviserator just like myself when you perform an autopsy and can determine the exact cause of death from the gross appearance of the organs. I remove the chest plate, open the pericardial sac and cut the heart out. It is at this time I put a tiny incision in the artery and open it slowly to check for a saddle pulmonary embolism . It is called “saddle” embolus because sometimes the blood clot takes the shape of the curved conjunction of the right and left pulmonary arteries.  If I identify a large thrombus (blood clot) in the pulmonary arteries, I know exactly why my patient died.

A pulmonary embolism or PE is a large thrombus or blood clot that travels to the lungs. This thrombus is usually from the deep veins of the legs but it can also come from other sources such as the pelvic vasculature. There are many reasons blood decides to form a large clot in the deep veins of the legs. A hyper-coagulable (an increase of clotting in the blood) patient is at high risk for a PE. Blood clots can form when a patient is immobile for long period of time. For example patients that are sick in bed for weeks and people taking airplane flights for long periods of time without movement of the legs. Cancer, clotting disorders and some medications also increase the risk of PE’s. Once this large clot forms in the deep veins of the legs it just sits there. Sometimes swelling of one leg can occur. Then the blood begins to back up creating pressure. At some time the clot begins to get dislodged. If the clot is large enough it will travel up the femoral veins, then the iliacs and next will enter the inferior vena cava (IVC). The clot then enters the right atrium of the heart from the IVC and goes into the right ventricle. The clot leaves the right ventricle and enters the pulmonary artery and if it is big enough it will get stuck. The blood suddenly can not enter the lungs for oxygenation or enter the left heart and get pumped out to the rest of the organs. Boom- the patient drops dead suddenly. There are only a few things that make you drop dead with no warning. That is why this finding is super cool. I always ask if the patient dropped dead, or died slowly over a period of time (days/weeks) before I start the autopsy. This is why.

This illustration shows the anatomy of the heart and lungs. The pulmonary artery is the blue vessel exiting the right ventricle of the heart and entering the lungs. If a large clot got stuck here it would stop the blood flow. The blood would never reach the lungs. Because the blood is not exiting the lungs and returning to the heart oxygenated, the heart never receives the blood to feed the rest of the bodies organs oxygen.

In this photo you can see a nicely dissected pulmonary artery. A blood clot of this size is lethal. This clot is taking on the “saddle” form.

This picture is super cool. Here you can see the lung cut off and a 2 huge dark-red clots sticking out. Another cool thing about PE’s is that the clots actually take the width of of the deep veins they came from and sometimes you can even see the valves of the veins in the clot.

Blood in this location alone during autopsy does not necessarily mean this is a “real” thrombus or PE. A “real” thrombus needs do be distinguished from a post mortem clot. Real thrombi formed in a rapidly flowing bloodstream are usually dry, friable gray masses composed of almost regularly arranged layers of platelets and fibrin, irregularly mixed with small amounts of darker red coagulated blood. The resulting laminations are the ”lines of Zhan”. Clots like this are also adherent to the vessel walls, post mortem clots are not. Post mortem clots are also referred to as current jelly or chicken fat. Post mortem clots occur when the components of blood are evenly distributed throughout the clot.

In this photo you can see a “real” thrombus exibiting the lines of Zhan.

Here you can see the eviscerator gently tugs on the clot but it is adherent to the vessel wall. This is another indication that this is clot is real.

Sections of the thrombi should be taken for microscopic analysis. The lines of Zahn should also be seen microscopically.

Ghon is My Boy…

Dr. Anton Ghon is a pathologist from back in the day (early 1900′s). There are a few autopsy techniques that have been implemented over time and perfected by these old school pathologists. One of the reasons I love autopsy so much is that little has changed in 100 years and gross pathology and anatomy knowledge are key for diagnosis of death. Dr. R L Virchow’s autopsy technique is removing the organs one by one. This is the most widely used autopsy technique. It allows the eviscerator to examine each organ as they are taken out. Dr. Anton Ghon’s autopsy technique is removing the organs en bloc by organ systems. This is a good technique if one organ system has suspected pathology and needs to be examined- e.g. heart/lungs, urinary or GI system. Other autopsy techniques include a Rokitansky which is an insitu examination of the organs with subsequent en bloc removal of organ systems if necessary and Letulle which is removing all of the organs from larynx to anus all in one block or en masse. The term “Rokitansky Technique” is commonly misused by pathologists to describe the techniques described by Letulle and Ghon. I use a modified Virchow/Ghon technique that was taught to me by my mentor Joey at Penn (DiReinzi technique). For every autopsy I have a procedure which I change up according to the suspected pathology or distorted anatomy I find when I open the body.

Getting back to my boy Ghon. He was also a specialist in the field of bacteriology, particularly tuberculosis (TB). His work lead to describing the Ghon focus and the Ghon complex in reference to an infection with TB.

So, the patient inhales TB for the first time. It starts to grow in the lung and forms a lesion that can be solid/ friable/ calcified. This lesion is called the Ghon focus. The bacteria leave the lung and go to a hilar lymph node. This involvement in the hilar lymph node is known as a Ghon complex. In most people, this complex kinda burns out- meaning the TB has become inactive and did not cause clinical disease.

Sometimes we will receive a lung lobe specimen to the surgical lab labeled “lung tumor”. However, if we cut it and it has this gross appearance we are immediately alarmed this is a TB lesion. This tan-white cheesy appearance is known as caseous necrosis and is classic for a TB infection. This lesion in the lung is called the Ghon focus.

Dr. Ghon then described the Ghon complex. The Ghon complex is a Ghon focus lesion in the lung with a lymph node in the hilum that also can grossly appear yellow or have a white-tan cheesy appearance. He described this as a classic finding in a primary TB infection.

The presence of the Ghon complex is indicative of a primary TB infection. The primary infection can progress and cause clinical illness, this is called progressive primary TB. The primary infection can inactivate and just sit there for the rest of the patients life with no complications. In a small number of patients the bacteria can then become active and cause reactivation secondary TB. This reactivated secondary infection can not be differentiated from a secondary “re”infection of TB. The secondary reactivation or reinfection is when clinical signs are present such as cough and fever.

The early Ghon focus together with the lymph node lesion constitute the Ghon complex. At any time the TB organisms can reactive and cause clinical symptoms or burn out and inactivate. When a once active lesion begins to heal over time the lesion becomes scarred and the lymph nodes and sometimes the lesion begin to calcify. The combination of late fibrocalcific lesions of the lung and lymph node which evolved from the Ghon complex is referred to as the Ranke complex (radiologically).

This is what fibrocalcified hilar lymph nodes look like. The are crunchy and hard to cut with a scalpel blade. The black color is from anthrocotic pigment which is a common pigment found in smokers and people who live in a city and inhale smog. This finding alone. in more than one hilar or peri bronchial LN could be indicitive of a progessive primary TB lesion that burned out, or a reactivated or reinfected secondary TB infection that burned out.

This is the anterior view of the lungs. Here if you look closely you can see bilateral apical scarring on the upper lobes of both lungs. This finding suggest 2 possible lesions which may indicate a secondary reinfection. It is suggested the bacteria like the apex of the lung because the  they require more oxygen to grow.

Oncocytoma of the Kidney

This is a pretty cool, more rare gross finding. An oncocytoma of the kidney is actually a benign tumor (non cancerous) but does cause enough issues that it needs to be surgically removed. These tumors rarely become malignant and metastasize. Sometimes this tumor can be seen on imaging because it has a very specific appearance with a central scar. The true diagnosis of an oncocytoma can not be made until it is received in the pathology laboratory and grossly and microscopically examined. The presence of a scar alone does not mean this is an oncocytoma, scars can be seen in cancerous kidney tumors as well, but it is less likely. Scars are more common in benign tumors because they are slow growing. The center of the tumor can “die off” because of lack of blood supply. In slow growing tumors, the center tissue has time to repair itself causing a scar. Because malignant tumors are usually faster growing the center dies and does not have time to heal itself before it is surgically removed. Malignant tumors can have a central area of necrosis or dead tissue.

This is what an oncocytoma would like like on CT imaging. The red arrows are pointing to the oncocytoma tumor in the kidney.

Grossly it is smooth, homogenous and said to have a mahogany color with a central scar. I have seen a few and the color can range from a tan-orange to a red- brown mahogany color. The location of this particular oncocytoma is in the upper/mid pole and is rather large. It is very close to the hilium (which is where the ureter and renal vein and artery enter the kidney). This tumor could not be removed (partial nephrectomy) because of the location to these delicate structures so the surgeon had to do a radical nephrectomy (removal of entire kidney and a portion of the ureter).

Closer examination of the tumor shows the scar.

Most cases of renal oncocytomas are asymptomatic, discovered incidentally on CT or ultrasound imaging of the abdomen. Some of the possible symptoms are: hematuria (bloody urine), flank pain and abdominal mass.

Gangrene…

Gangrene specimens are nasty. It can be seen anywhere on the body, but is most common on the digits, feet and hands. The term gangrene in the medical field refers to an area of the body that has lost blood supply and the tissue in that area is dead. Tissue can lose its blood supply for many reasons including PVD (peripheral vascular disease), diabetes, vasculitis, trauma or infections.

There are two major types of gangrene referred to as dry and wet. Many cases of dry gangrene are not infected. All cases of wet gangrene are considered to be infected, almost always by bacteria (e.g. Clostridium perfringens). Clostridium perfringens is an anaerobic bacteria and grows best in areas with a lack of oxgen. Because there is no arterial blood flow carrying oxygenated blood to this site of infection, it is the perfect condition for these bacteria to grow. Many other organisms such as Streptococcus, Staphylococcus, Bacteroides, and Escherichia can also be seen in wet gangrene.

Wet gangrene is the most dangerous type of gangrene because if it is left untreated, the patient usually develops sepsis and dies within a few hours or days. Sepsis is when bacteria leaves the localized area of infection and goes into the blood stream. When bacteria is in the blood it gives the bacteria access to all of the bodies organs. The bacteria then “attacks” all the organs and the patient will die from multi-system organ failure. Sepsis can sometimes be treated by IV antibiotics. If a patient is not healthy there is a high risk of death associated with sepsis. Certain bacteria can cause massive destruction to even a healthy patient resulting in death (such as Neisseria meningitidis, a bacteria that can cause bacterial meningitis) .

Wet gangrene results from an untreated (or inadequately treated) infection in the body where the local blood supply has been reduced or stopped by tissue swelling, gas production in tissue, bacterial toxins, or all of these factors in combination. Conditions that compromise the blood flow such as burns or vascular trauma can occur first. Then the locally compromised area becomes infected, which can result in wet gangrene. Wet gangrene is the type that is most commonly thought of when the term gangrene is used. This photo is a good example of wet gangrene. The right foot of this patient is slightly bloated with dusky, purple-gray skin that is sloughed or slipping. The dermis beneath this slipped skin is usually red-purple or can even be gray-green, “wet” appearing and very malodorous.

Internal gangrene is a variant of wet gangrene, has less obvious initial symptoms because the wet gangrene occurs in the internal organs. The patient may be septic with gangrene but show few if any visual symptoms that are characteristic for wet gangrene. When the surgeon exposes the infected organ, the signs of wet gangrene are apparent. This photo shows a segment of gangrenous bowel. Gangrenous bowel is also referred to as ischemic, infarcted or dead bowel. This particular segment of bowel is dead because it got stuck in a hernia and the blood supply was cut off. To read more about hernias check out this post: http://iheartautopsy.com/?p=1302

Dry gangrene, if it does not become infected and progress to wet gangrene, usually does not cause sepsis or cause the patient to die. Usually, the progression of dry gangrene is slower (days to months) than wet gangrene because the vascular compromise slowly develops due to the progression of diseases that can result in local arterial blockage over time. There are many things that may lead to dry gangrene; the most common are diabetes, atherosclerosis and smoking. Dry gangrene often produces cool, “dry” and discolored digits (sometimes termed “mummified”). To think that mummification can occur to a person who is alive is beyond disturbing. Here is a low power view of bilateral transmetatarsal amputations for dry gangrene.

On a higher power view you can appreciate how “mummified” these toes are. They are usually black  and rock hard in appearance and have to be sampled with a bone saw rather than a scalpel blade. Eventually without treatment, the tissue could slough off itself. Than means essentially that a digit can just fall off. This is called an autoamputation.

An example of autoamputation

The diagnosis is usually based on the clinical symptoms of either wet or dry gangrene.  CT or MRI studies are done to see how far gas or necrosis has progressed from the local site in wet gangrene. These studies are often done to help determine the extent of gangrene in both limb and internal types of gangrene. Blood cultures as well as cultures of the infected tissue and exudates are usually done to determine the infective agent and to determine appropriate antibiotic therapy. For dry gangrene, vascular surgeons often do angiography (a radiologic study with dye that shows arterial blood flow in tissues) to see the extent of ongoing or potential arterial blood loss to tissue.

Gangrene needs attention. The surgeon may start off by removing the dead tissue or digit. This is called debridement. All attempts will be made to save the limb. If debridement doesn’t work, the next step is an amputation. We can see anywhere from 5-10 specimens a day for gangrene.