clinico-pathological case 1 [trinity college dublin] prof t rogers prof o sheils dr c d’adhemar

Clinico-pathological case 1

[Trinity College Dublin]

Prof T Rogers

Prof O Sheils

Dr C D’Adhemar

Clinical Summary A 66-year-old, emaciated man was admitted on the

19/06 from a nursing home facility with a 2 day history of increasing confusion.

He had been under continuous medical care in the nursing home for three months when he was admitted for a complaint of "feeling bad".

There was a history of intravenous drug use (heroin), smoking crack cocaine, and hepatitis C, but he was HIV negative.

He was afebrile. The white blood cell count was 8.3x109/L.

End-stage renal disease (membranoproliferative glomerulonephritis thought to be secondary to hepatitis C) requiring hemodialysis,

R knee and L wrist septic arthritis (Staph aureus and Strep pneumoniae), and

anaemia (Hct 28%) were diagnosed.

Blood cultures were also positive for Staph aureus, and he was treated with flucloxacillin and gentamicin.

The course was complicated by recurrent line infections and fasciitis.

A trans-oesophageal echocardiogram showed no vegetations in the heart. In mid May, he was transferred to a nursing home for continued care.

On admission from the nursing home, his observations were as follows:

T 98.9°, HR 80/min, RR 26/min, BP 144/83, and O2 saturation of 96% on room air.

Lungs were clear. No cardiac murmurs were heard. The R knee and L wrist were again swollen.

Laboratory values were: WBC 18x109/L, Hct 30%, and platelets 187x109/L.

A blood culture yielded gram positive cocci. Vancomycin was begun.

Q1. What is the differential diagnosis in this case?

Q2. What clinical investigations would you perform?

Q3. What organism was most likely identified in the blood culture?

Q4. Discuss the antibiotic policy in this patient.

A trans-oesophageal echocardiogram was performed, and a chest radiograph was taken.

On the 22/06, a cross-sectional, two-dimensional echocardiographic view of the aortic and pulmonic (PV) valves showed thickening of the leaflets of the PV and one of two pedunculated vegetations that prolapsed 3 cm into the pulmonary artery during systole. There was no valvar insufficiency. The tic marks at the edge of the photograph are 1 cm apart. Landmarks are indicated on the same photo below.

RV = right ventricular chamber. PV = thickened pulmonic valve. V and 2 arrows = vegetation on stalk during systole. AO = aorta. The small arrow below AO indicates a normal, thin aortic valve leaflet. The arrowheads indicate the wall of the pulmonary artery trunk.

The patient was not considered to be a candidate for a surgical procedure.

Questions

Q5. What is the cause of the vegetations in the heart?

Q6. Comment on the location of the vegetations.

Q7. Can you list the causes of heart valve vegetations?

Radiographic Findings

On the 26/06, a frontal CXR film showing the right lung demonstrated multiple areas of mass-like consolidation, at least two of which showed central cavitation.

There was a small right effusion. The left lung appeared normal.

The largest area of consolidation is at the right lung base (lower arrow).

Superior to it is another mass-like consolidation containing a central cavity. A smaller mass-like consolidation is present in the right upper lobe (upper arrow). To its right is a well-formed cavity of approximately the same size.

QUESTIONS

Q8. What are the causes of the lung consolidation?

Q9. What are the causes of the lung cavitations?

Q10. How would you further investigate these lesions?

Bacteremia persisted, thrombocytopenia developed, and he remained confused.

He was found dead on the 30/06. An autopsy was performed.

Autopsy Findings A serosanguineous pleural effusion (300 ml)

was present on the right side. The heart was enlarged (380 g, normal 300 g). Look at each of the following photos and explain what has happened.

A. Valves were normal except for the pulmonic, which is shown here. Compare it with an example of a normal pulmonic valve below (B).

One commissure is indicated at the arrow.

B. Normal pulmonic valve. Note the thin, translucent cusps and normal commissures.

QUESTION Q11. What is the lesion on the pulmonic

valve?

Answer:

The pulmonic valve had large vegetations, about 2 cm in diameter, on each of 2 cusps.

They were very friable, and one (on the leaflet to the right of the arrow) was dislodged before the photo was taken, revealing a hole, 5 x 3 mm in diameter (not shown), in the cusp.

The vegetation that is present (anterior leaflet) obscures the commissure and has spread to the wall of the pulmonary artery.

No pedunculated portion was present at autopsy. The valve leaflets are thickened: a congenital anomaly.

C. The right lung weighed 1000 g and the left, 900 g (normal about 300-400g each).

The right lung had a fibrinous pleuritis.

After distension with formalin and fixation, one slice from the left lung showed two yellowish lesions.

QUESTION Q12. What is the lesion cut surface of the

lung?

Answer: The slice of lung shows two

segmental pulmonary arteries that are occluded by thrombus.

Note the airway next to the vessel near the centre. No infarct or haemorrhage is present in the distal parenchyma.

These two thrombi probably came from the pedunculated portions of the vegetations that were identified in the echocardiogram.

D. A slice of the right lower lobe showed two lesions.

QUESTION

Q13. What are the lung lesions in image D?

Answer: The slice of lung in D shows

two cavities with thin walls. The larger abuts the pleura

and may have been responsible for the para-pneumonic effusion.

Both cavities show small amounts of residual necrotic lung, which is dark in the smaller cavity and pale in the larger one.

The cavitation is the result of pneumonia and ischemia caused by septic thromboemboli as in C.

Note the pleuritis at the base (lower left).

QUESTION

Q14. How did the patient get the lesions in the lung?

The photos show typical consequences of right-sided infective endocarditis: cavitated, pneumonic infarcts and pulmonary emboli without infarction.

The liver (2200 g, normal 1500-1800 g) and spleen (320 g, normal 100 g) were enlarged. The kidneys were shrunken (R 75 g, L 92 g, normal 150 g each) from the chronic membranoproliferative glomerulonephritis. The brain was normal.

Histological changes at autopsy

The pulmonic vegetation is composed of a proteinaceous coagulum that contains neutrophils and bacteria (dark blue). There was no evidence of organization to indicate healing.

The following sequence of photos shows the histological features.

Section of the thrombus in one of the segmental arteries shown on the previous page shows the same pattern as the vegetation, with PMNs and bacteria. Note that the inflammation has

spread into the vessel wall (blue staining at arrows).

The lack of parenchymal hemorrhage or infarction related to this lesion, which is several days old, signifies that heart failure was absent.

Heart failure is a major factor that predisposes to infarction after pulmonary embolism of a segmental artery.

Higher magnification of the same artery shown in B. The infected thrombus (T) has caused transmural inflammation of the arterial wall (between 2 arrows).

A portion of normal arterial wall (N) is also shown. Rupture of the vessel can occur as a result of such an infective arteritis. When an infected vessel dilates, it is called a mycotic aneurysm

This vessel has an acute thrombus with some faint lines of Zahn (platelet-fibrin columns (arrow)), transmural arterial inflammation, and adjacent pneumonia with a necrotizing component (N) at the bottom left--the beginning of a septic infarct.

. A section from a cavitating lesion shows numerous, dark blue bacteria in vessels and surrounding pneumonic consolidation of parenchyma that shows coagulative necrosis with preservation of tissue outlines

Other changes seen at autopsy [1]: A slice of lung from the left upper lobe (A) and a histological

section from the same area (B) are shown.

Q15. Look at the slices carefully and describe the lesions.

A. Hint: The abnormality is related to colour.

Answer:

Black pigment is present in a large area in addition to being present around respiratory bronchioles as small spots.

While the latter are common in cigarette smokers, large areas of black pigment are not.

Also, the air spaces in the blackened areas are slightly enlarged with thin walls: emphysema.

B. Two abnormalities are present here.

Hint: The colour of the macrophages is important. What about alveolar size?

The histological section shows large numbers of alveolar macrophages with black pigment.

A stain for hemosiderin pigment was negative.

Air spaces are enlarged compared to normal.

Diagnoses are:

1. excess black pigment caused by smoking crack cocaine

2. focal emphysema.

The photo shows a tube of dusky lavage fluid from another crack smoker.

Pulmonary Complications of Smoking Crack Cocaine

Black sputum or lavage fluid Barotrauma: pneumomediastinum,

pneumothorax Vascular injury: noncardiogenic pulmonary

edema, pulmonary hemorrhage, infarction Parenchymal injury: acute eosinophilic

pneumonia, organising pneumonia sometimes with granulomas

Other changes seen at autopsy [2]: A. This photo taken with

polarized light shows birefringent crystals (bright spots) in the lung of the patient.

Numerous, scattered crystals up to 40 µm long were located mainly in the interstitium.

A few foreign-body giant cells were present, but granulomas and scar were absent

B. Similar crystals were found

in macrophages in the portal triads of the liver shown here.

Most were less than 10 µm long, as these crystals had traversed the pulmonary capillary bed.

A granulomatous response was absent.

Crystals were also found in the spleen.

Crystals in intravenous drug users (IVDUs):

Examination of the lung sections of this patient with polarized light showed deposits of foreign crystals.

The crystals are deposited in arterioles and capillaries but may erode through the vessel wall into the interstitium.

In some cases granulomas and fibrosis develop.

Effects of injection of oral medications:

IVDUs sometimes inject intravenously drugs that are intended for oral use.

The tablets are ground to a powder and dissolved in water before injection.

Tablets, including methadone, methamphetamine (speed), and methylphenidate (Ritalin), contain fillers of talc, microcrystalline cellulose, or starch.

These particles are trapped primarily in the pulmonary vasculature, but some particles less than about 5 µm in diameter traverse the capillary bed.

As a result of systemic spread, the crystals may be viewed in the microcirculation of the retina ophthalmoscopically.

The crystals do not interfere with visual acuity or other organ function.

Pulmonary effects may include fibrosis, emphysema, or hypertension.

Diagnoses:

Infective endocarditis [IE] (methicillin resistant S. aureus), pulmonic valve [congenitally malformed].

Infected emboli, lung. Infective pulmonary arteritis. Infected, cavitated infarcts in the lung. Disseminated birefringent crystals in lungs,

liver, spleen (intravenous drug use). Crack black lung.

Clinical Comment: Review of the trans-oesophageal echocardiogram

from 05/05 (about 2 months before death) showed a small (0.7 cm) vegetation on an abnormally thickened pulmonic valve (PV).

The diagnosis was probably dismissed because the PV is almost never involved in infective endocarditis (IE).

The onset of IE probably coincided with the development of the septic arthritis.

Death was ascribed to respiratory failure from septic emboli, infarcts, and pneumonia.