Pathophysiology: increased pulmonary vascular resistance, due to: 1.

Vascular remodeling with vascular inflammation & endothelial cell proliferation 2. Platelet dysfunction and thrombosis 3. Vasoconstriction due to a. Endothelial dysfunction resulting in overproduction of vasoconstrictors such endothelin-1 and underproduction of vasodilators such as nitric oxide, prostacyclin, vasoactive intestinal peptide b. Abnormal voltage-gated potassium channels The clinical classification was revised in 2003 and is organized using a pathophysiologic framework 1. Pulmonary arterial hypertension (PAH) a. Idiopathic PAH b. Familial PAH c. PAH associated with 1. Collagen vascular disease (scleroderma, SLE, mixed connective tissue disease) 2. Congenital systemic-pulmonary shunts 3. Portal hypertension (1-6% of patients) 4. HIV infection (0.5%) 5. Drugs or toxins (defexfluramine or fenfluramine containing appetite suppressants, amphetamine, methamphetamine, cocaine) d. PAH associated with significant venous or capillary involvement (pulmonary veno-occlusive disease or capillary hemangiomatosis) 2. Pulmonary hypertension with left heart disease (ventricular, atrial, valvular) 3. Pulmonary hypertension associated with lung disease or hypoxemia a. COPD, interstitial lung disease, sleep disordered breathing, alveolar hypoventiliation, chronic exposure to high altitude 4. Pulmonary hypertension due to chronic thromboembolic disease (proximal or distal pulmonary arteries) 5. Miscellaneous (sarcoidosis; compression of pulmonary vessels due to adenopathy, tumor, fibrosing mediastinitis) TREATMENT A. Depends on underlying etiology, correct underlying cause when possible 1. For obstructive sleep apnea, administer continuous positive airway pressure. 2. For chronic thromboembolism, begin anticoagulation and consider thromboendarterectomy. 3. For valvular disease, replace the valve. 4. For congenital heart disease, repair surgically. 5. For left ventricular dysfunction, optimize medical regimen. B. Oxygen therapy for patients with hypoxemia (PO2 < 55 mm Hg at rest, O2 saturation < 85% with exercise) C. Most patients require loop diuretics. D. Most medication trials showing improvement in hemodynamics and/or exercise capacity have included patients with idiopathic, fenfluramine-associated, and CT diseaseassociated pulmonary hypertension 1. Currently available drugs include oral endothelin antagonists (bosentan), oral phosphodiesterase-5 inhibitors (sildenafil), prostacyclins (epoprostenol (parenteral) or iloprost (inhaled)) 2. Calcium blockers are effective in a few patients.

scites Textbook Presentation: patient complains of an inability to fasten her pants due to increasing abdominal girth, sometimes accompanied by dyspnea and edema. A. Ascites develops over 5 years in 30% of patients with compensated cirrhosis, defined as the absence of manifestations of portal hypertension. 1-year survival rates drop significantly once ascites develops. B. Complications of ascites 1. Respiratory compromise due to compression of lung volumes 2. Hepatorenal syndrome (HRS) a. Diagnostic criteria

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(1) Cirrhosis with ascites (2) Serum creatinine > 1.5 mg/dL (3) Serum Cr stays >1.5 mg/dL after at least 2 days of diuretic withdrawal and volume expansion with albumin (4) Absence of shock (5) No current or recent treatment with nephrotoxic drugs (6) Absence of parenchymal kidney disease (< 500 mg/day of proteinuria, < 50 RBC/hpf, abnormalities on renal ultrasound) g. Clinical syndromes (1) Acute renal failure (type 1 HRS): serum Cr doubles or increases to > 2.5 mg/dL in less than 2 weeks (2) Refractory ascites (type 2 HRS): serum Cr 1.252.5 mg/dL with a steady or slowly progressive course i. Incidence in patients with cirrhosis and ascites is 18% at 1 year and 39% at 5 years j. The prognosis is poor (Figure 153) k. Precipitants of type 1 HRS include bacterial infections (especially spontaneous bacterial peritonitis), GI bleeding, alcoholic hepatitis, overdiuresis, and large volume paracentesis. l. HRS is due to peripheral vasodilation which causes systemic vascular resistance, resulting in renal arteriolar vasoconstriction, renal blood flow, and a GFR m. Treatment of HRS (1) Liver transplantation is the definitive treatment for both types of HRS. (2) limited data regarding use of transvenous intrahepatic portosystemic shunts (TIPS) and vasopressin derivatives to treat type 1 HRS. Spontaneous bacterial peritonitis (SBP) a. 1030% in hospitalized cirrhotic patients, with 1-year recurrence rate of 70% and mortality rate of ~ 20%; b. Overgrowth of intestinal bacterial and intestinal permeability lead to movement of bacteria into mesenteric lymph nodes; bacteria can then enter systemic circulation & colonize the ascitic fluid (3 most common are E coli, Klebsiella pneumo, pneumococci. c. Symptoms: fever (5075% of patients), abdominal pain (2772%), chills (1629%), nausea/vomiting (821%), mental status changes (up to 50%), renal function (33%); 13% of patients are asymptomatic. d. Risk factors for SBP include ascitic fluid total protein level 1 g/dL, upper GI bleeding, prior episode of SBP e. Diagnosis of SBP (1) Criteria for performing a dx paracentesis in patients with cirrhosis and ascites: (a) Admission to the hospital (b) Change in clinical status (fever, abdominal pain, mental status changes, ileus, septic shock) (c) Development of leukocytosis, acidosis, or renal failure (d) Active GI bleeding (2) Always inoculate blood culture tubes at the bedside to maximize yield of ascitic fluid cultures. (3) Interpretation of ascitic fluid cell counts and cultures (Table 152)