4TH GRAND CPC SCRIPT

Salient Features and Approach to Diagnosis

Considering the salient features of the case both clinically and from the patient’s history, we
present the following facts:

Fact 1: The patient had gradual onset of generalized lymphadenopathy and body weakness associated with
on and off low-grade afternoon fever, gradual onset of weight loss, anorexia, pallor and hypokalemia

Fact 2: She has decreased breath sounds, dyspnea with some cyanosis, rhonchi, an O2 sat of 30%,
bilateral chest infiltrates with nodular masses seen in x-ray

Fact 3: Patient’s current living situation states that her husband has history of cough and occasional fever
and she lives in a crowded community

With these in mind, we can deduce that with the progression of signs and symptoms, neoplastic
and a non-neoplastic origin can be considered. At first glance, the generalized lymphadenopathy paired with
generalized body weakness likely point outs to a neoplastic etiology.

Differential Diagnosis

 Pulmonary carcinoma was considered primarily because of the pulmonary symptoms and nodular
masses on chest x-ray. However, it was immediately ruled out because there was no leukocytosis
or eosinophilia, hoarseness, hemoptysis, and stridor. In addition, her negative smoking history does
not support the diagnosis.

 Gastric carcinoma was considered due to the presence of abdominal pain and distention,
constitutional symptoms, anemic symptoms, and lymphadenopathy. On the other hand, factors for
ruling out includes the absence of more specific GI symptoms such as indigestion, postprandial
fullness, gut obstruction, and palpable abdominal mass.

 Lymphoma was considered as it can occur at any age with increased incidence in older women.
Anemia, abdominal pain, constitutional symptoms and a painless progressive lymphadenopathy
are commonly seen. Increased serum LDH and uric acid indicate rapid cell turnover associated
with malignancy. However, serum uric acid levels were normal in the patient. Moreover, symptoms
of hepatosplenomegaly and jaundice are absent in the patient which are said to be present in 72 or
83% in cases., respectively. Despite these facts, there are still insufficient data in confirming or
totally excluding lymphoma because it can only be confirmed histopathologically and cytologically.
Hence, it cannot be totally ruled out.

Proceeding to the non-neoplastic etiologies, inflammatory and infectious diseases can be

considered.

 Sarcoidosis can manifest as non-caseating granulomas predominantly involving the lungs, lymph
nodes and skin. It is considered because of the presence of lymphadenopathies in the patient,
together with the dyspnea, weight loss and anemia. However, the absence of mediastinal and hilar
lymphadenopathy which is present in up to 90% of cases, absence of cutaneous and ocular
manifestation in the presence of fever and the absence of coughing makes this diagnosis highly
unlikely.

Communicable diseases is highly probable due to the patient’s living condition and her husband’s
history of cough and occasional fever.

 With the signs and symptoms presented, one can say that the patient might be in a
immunocompromised state. A typical adult patient that presents with fever, weight loss, and
generalized lymphadenopathy are common with HIV infected patients. In addition, anemia,
constitutional symptoms, low to borderline normal WBC, decreased lymphocytes and increased
segmenters are present. However, the HPI does not match with a patient with HIV because 2
 months prior to the occurrence of lymphadenopathy, indicating HIV seroconversion, the patient
already manifested with signs of deterioration. Hence, it is unlikely that the patient has acquired an
HIV infection to cause immunosuppression if deterioration occurred before lymph nodes were
affected. Furthermore, there were no evidence of multiple opportunistic infections, diarrhea, and
neurologic disease which are usually present with HIV-infected patients.

 With classic non-specific presentations of generalized weakness, intermittent low-grade fever,

weight loss, anorexia, as well as histories of dyspnea and signs of anemia, pulmonary
tuberculosis must be a primary consideration. In addition, a history of living in a small house in a
crowded area, points out a high probability of exposure and transmission. With physical findings of
decreased breath sounds, a CBC picture of anemia, and chest radiography findings of bilateral
infiltrates with nodular masses, despite the absence of cough and hemoptysis, makes it a strong
consideration..

PATHOPHYSIOLOGY AND CLINICAL MANIFESTATIONS

TB is most commonly transmitted via inhalation of aerosolized TB bacilli especially in crowded and
poorly ventilated settings. Inhaled bacilli reaching the lungs may disseminate via lymph vessels and spread
to other lung sites that may present as bilateral infiltrates on chest radiograph as seen in the case. The
bacilli reach the alveoli and get phagocytosed by inactivated macrophages and enhanced by complement
activation. Alveolar macrophages secrete cytokines to form the TB granuloma and produce systemic effects
present in the case such as fever, generalized weakness, anorexia, and weight loss. A macrophage-
activated cell-mediated response activates macrophages and forms granulomatous lesions as evidenced by
pulmonary nodules in the chest x-ray. Another mechanism, the tissue-damaging response destroys bacilli-
containing inactivated macrophages and also causes caseous necrosis of involved tissues. If the
macrophage-activated response is weak, the tissue-damaging response intensifies and causes extensive
lung tissue destruction leading to decreased lung compliance resulting to dyspnea and decreased breath
sounds in the patient. Invasion of the pulmonary vasculature makes the infection access the systemic
circulation and disseminate to extra-pulmonary sites.
Extrapulmonary TB may present as tuberculous lymphadenitis during primary TB infection or as a
result of reactivation of dormant foci or direct extension from a contiguous focus. Due to the increased risk of
exposure, a primary TB infection may have occurred in the patient. The bacilli present are drained by the
lymphatics then the bloodstream, and eventually to the different parts of the body. Cervical
lymphadenopathy is the most common extrapulmonary manifestation of tuberculosis. Multiple node
involvement including inguinal and axillary nodes occurs 16% of the time.
Musculoskeletal involvement may present as tuberculous tenosynovitis resembling ganglion cysts
manifesting in this case as right wrist nodule with slight limitation of movement due to mass effect.
The patient’s peripheral blood smear showed slight anisocytosis and poikilocytosis indicate the
presence of more than one type of anemia namely: anemia of chronic disease and iron deficiency anemia.
Anemia of chronic disease and iron deficiency anemia in tuberculosis may start out as normocytic and
normochromic but then eventually develop to microcytosis and mild to moderate anisocytosis and
poikilocytosis, respectively. Toxic changes in the polymorphonuclear leukocytes were also seen. Toxic
granules indicate severe infection or inflammation.
In chronic illnesses, increased protein catabolism leads to movement of potassium ions from the
intracellular compartment to the plasma which may be lost via the vomitus. The history of vomiting and two
episodes of vomiting at the ER greatly reduced serum potassium levels. This, along with anemia contributed
to the generalized body weakness of the patient.
TB bacilli in the blood produce mycobacterial products stimulating the release of cytokines inducing
the endothelial wall to release secondary mediators, such as nitric oxide. Peripheral vasodilation results to
hypotension manifesting as pale cool extremities and peripheral cyanosis. The patient is in a setting of
septic shock. Evidences of a systemic inflammatory response in the patient include heart rate of 120 bpm,
initiation of mechanical ventilation plus an identifiable source of infection indicate the presence of sepsis.
Unresponsiveness to fluid challenge warranting vasopressor support points to cardiovascular collapse
indicating that indeed, the patient is in septic shock.
The hypotensive state of the patient results in hypoperfusion of the splanchnic circulation. Along
with food in the GI tract, mucosal irritation occurs activating the area postrema leading to vomiting.
Hypoperfusion also produces inflammatory cytokines and inflammation manifesting as rigidity and
tenderness.
Course in the ER showed aspiration of gastric contents during intubation after vomiting. The acidic
nature of the aspirated material will cause direct injury to the airways and lung parenchyma causing an
increase in airway resistance and decrease in the diffusion of oxygen that may manifest as dyspnea and
cyanosis. The possibility of a subsequent bacterial pneumonia after aspiration injury could further contribute
to the respiratory findings during the ICU confinement. This is manifested in the patient as pulmonary
findings positive for rhonchi and decreased breath sounds on the right lung field.
The patient's presentation of severe anemia indicates reduced amount of hemoglobin delivering
oxygen to tissues. Along with this, septic shock leads to hypoperfusion to tissues. Prolonged hypoxia leads
to tissue ischemia generating high levels of lactic acid. High levels of lactic acid along with decrease in
bicarbonate caused metabolic acidosis in the patient. Prolonged ischemia causes cellular damage and
release of intracytoplasmic enzymes such as lactate dehydrogenase.
Sepsis involves release of inflammatory mediators throughout the body promoting neutrophil
accumulation in the microcirculation of the lung. Neutrophils damage the vascular endothelium and alveolar
epithelium leads to pulmonary edema, hyaline formation, decreased lung compliance, and difficult air
exchange. Along with the insult contributed by the possible aspiration pneumonia also damages the alveoli.
V/Q mismatch occurs leading to hypoxemia which promoted the manifestation of cyanosis in the patient on
the fourth hospital day. The patient is most probably in acute respiratory distress syndrome. Subsequent
hypoxia to the heart prevents the muscle fibers and conductive fibers from maintaining normal electrolyte
concentration differentials across their membranes resulting to loss of excitability and automaticity of the
pacemakers. Intubation may have caused stress further contributing to the asystole. Due to the low oxygen
levels to utilize, the heart was not able to depolarize and generate normal rhythm. Persistent low oxygen
levels in the blood caused the patient to be refractory to cardioversion. Thus, cardiac arrest ensued and the
patient expired.

Final Diagnosis

Ladies and gentlemen, we present a case of “Acute Respiratory Distress Syndrome, Secondary to
Septic Shock, Secondary to Disseminated Tuberculosis, To Rule Out Lymphoma.

Roses are red, our patient is blue. There’s nothing more… that we can do.