BP measurement

Working group national high blood pressure education program (1996)

The following are the recommendations by this committee on BP measurement:

1.       Position-sitting

2.       Cuff width-approximately 40% of arm circumference

3.       Diastolic pressure-K5 for both child and adult

4.       Number of measurements-average of 2 or more

Small cuff increases both systolic and diastolic BP.

Non compressible arteries (Monckeberg sclerosis) will produce pseudohypertension.

American heart association updates recommendations for blood pressure measuremens:-

·         Systolic and diastolic blood pressures, as opposed to pulse pressure, remain the best means to classify hypertension. Cardiovascular risk begins to increase steadily as blood pressure rises from 115/75 mm Hg to higher values.

·         15% to 20% of patients with stage I hypertension have elevated blood pressure only in the presence of a physician. This "white-coat" hypertension  is more common in older men and women, and antihypertensive treatment in these patients may reduce office blood pressure white not affecting ambulatory blood pressure.

·          Patients who are older or have a long history of diabetes may have noncompressible brachial arteries , producing pseudohypertension.

·         Orthostatic  hypotension is defined by a decrease  in systolic blood pressure of 20mm Hg or more or diastolic blood pressure of 10mm Hg or more after 3 minutes of quite standing after being supine. Food ingestion, time of day, age, and hydration can impact this form of hypotension, as can a history of Parkinsonism, diabetes, or multiple myeloma.

·         Korotkoff sounds should be used to measure blood pressure. Compared with intra-arterial blood pressure, these sounds generally produce reduced systolic blood pressure values and higher diastolic values.

·         Mercury sphygmomanometers are considered a gold standard for blood pressure measurement, but they are being supplanted by aneroid sphygmomanometers.

·         Oscillometric blood pressure, in which the mean intra-arterial pressure is measured by the point of maximum of oscillation of the sphygmomanometer needle, affords the advantage of more accurate readings in noisy environments. However, this method is inappropriate for patients with noncompressible arteries.

·         Posture:-Before performing a blood pressure reading, the patient should be comfortably seated with the back and arm supported, the legs uncrossed, and the upper arm at the level of the right atrium.  

·         Proper cuff size selection is critical to accurate measurements. The bladder length and width of the cuff should be 80% and 40%, respectively , of the arm circumference. Blood pressure measurement errors are generally worse in cuffs that are too small vs those that are too big.

·         Blood pressure measurement in the sitting and recumbent positions is acceptable. The diastolic blood pressure can be expected to  be about 5mm Hg higher in the sitting position.

·         A different in blood pressure between the two arms can be expected in about 20% of patients. The higher value should be expected in about 20% of patients. The higher value should be the one used in treatment decisions.

·         When measuring blood pressure, the cuff should be inflated to 30mm Hg above the point at which the radial disappears. The sphygmomanometer pressure should then be reduced at 2 to 3 mm/second. Two readings should be performed at least one minute apart.

·         Blood pressure readings in the emergency department do not accurately predict hypertension on subsequent clinic visits.

·         Blood pressure machines stationed in public places are frequently inaccurate.

·         Five of 24 self-monitoring blood pressure systems have been shown to provide consistent, accurate results. Home blood pressure should be at least lower than 137/85 mm Hg. Night time home blood pressure is usually lower than daytime pressure.  

PULMONARY ALVEOLAR PROTEINOSIS

Pulmonary Alveolar Proteinosis

 

Clinical Characteristics and Presentation

Epidemiology

The average age of patients with idiopathic PAP in four recent case series comprising 140 patients was 42.6 years (range 6-73) with the majority being between 20 and 50 years old.^[2,7-9] There was a male predominance with a male to female ratio of 2.7:1. These figures are similar to earlier reports.^[2,10] Smokers outnumber nonsmokers by 3:1 in series that reported smoking status.^[2,8] Although cases from Canada, Japan, and Israel were reported soon after the original description,^[11-13] the two most recent case series from the United States (58 total patients)^[2,7] contained only Caucasian patients. Whether this represents a true racial pattern of disease is unclear. Familial patterns have been reported primarily in congenital PAP ^[14] with one report in adult siblings with an immunoglobulin deficiency.^[15] Although the incidence and prevalence remain unknown, PAP is likely a rare disorder. A report from Israel suggests a prevalence of 3.7 per 10⁶,^[16] whereas one from Pittsburgh estimates an ther incidence of 2 per 10⁷ per year.^[17]

PAP has been associated with many conditions. Hematologic malignancies, predominantly myelogenous leukemias, are well established secondary causes.^[18-21] Similarly, several exposures, including silica, aluminum, titanium, and nitrogen dioxide have been reported to precede the development of PAP.^[22-26] Infections such as pneumocystis carinii pneumonia (PCP) (with or without acquired immunodeficiency syndrome),^[27,28] mycobacteria,^[29-32] nocardia,^[33] cytomegalovirus,^[28] and anaerobes^[34] have also been associated with PAP. These infections are occasionally felt to precede the development of PAP, but often are seen complicating the disease. This is supported by reports of decreased incidence of most infections with earlier recognition and treatment of PAP.^[35] Other reported associations include amyloidosis,^[36] and lung transplantation.^[37]

Clinical Presentation

The clinical presentation is variable and nonspecific. Up to 30% of patients may be asymptomatic.^[8] Others present with acute symptoms suggestive of pneumonia. Still others present with subacute or chronic symptoms and nonresolving infiltrates. The nonspecific presentation may lead to months or years of misdiagnosis.

Symptoms are frequently milder than expected from radiographic findings. Dyspnea and cough are the most common presenting symptoms. Chest pain, hemoptysis, fever, and weight loss are variably reported (Table 1).^[1,2,7-9]

The physical exam is likewise nonspecific. Crackles, clubbing, and cyanosis all may be detected (Table 1).^[1,2,7-9] Uncommon but reported features include pneumothorax^[38] and cor pulmonale.^[39,40]

Radiology

Many patterns of chest x-ray (CXR) abnormalities have been described. Typically a bilateral, symmetric alveolar filling pattern is seen. Infiltrates classically are perihilar, extending to the periphery (lower > upper) sparing the costophrenic angles, yielding a "butterfly" distribution (Fig. 1).^[1] The pattern is similar to that of pulmonary edema and PCP. This typical picture seems somewhat less common in the latest case series.^[2,7,41] Interstitial, mixed alveolar and interstitial, nodular, asymmetric, and focal patterns have all been described.^[2,7-9] Although the absence of pleural effusions, adenopathy, and cardiomegaly help to narrow the differential diagnosis of the CXR pattern, the appearance is generally nonspecific.

 

Computed tomography (CT) is felt to more clearly define the extent, distribution, and nature of the infiltrates. This is particularly true when thin sections are used.^[42] The infiltrates have been described as patchy or diffuse, and central or peripheral. Reticular, reticulonodular, ground glass, and patchy or confluent air space patterns can be seen, oftentimes in the same patient. The infiltrates are often clearly delineated with sharp margins surrounded by normal lung. These areas have been referred to as "geographical" in appearance. A branching pattern of white linear areas forming geo-metric shapes of around 10 mm in diameter is seen overlying consolidated areas. This pattern, described as "crazy paving" (Fig. 2) has been seen in other diseases.^[43] Air bronchograms are variably reported and the visibility of the pulmonary vessels is often preserved. Again absent are pleural effusions and adenopathy. The CT appearance has been said to be characteristic of PAP^[42] though not all agree

 

 

CXR and high-resolution CT (HRCT) appearances have been shown to correlate with the presence of a restrictive ventilatory defect, reduced diffusing capacity, and hypoxemia.^[44] Although HRCT correlated somewhat better, the difference was not significant enough to justify the use of CT for follow-up.

Cases using gallium^[45] and Xenon-133^[46] scintigraphy have been described but do not have practical applications in the routine diagnosis or management of PAP.

Physiological Testing

In general, the most common pulmonary function dis-order is restriction. The forced vital capacity (FVC) and total lung capacity (TLC) are mildly reduced in most series with a disproportionate reduction in diffusing capacity. Patients tend to be mildly hypoxemic with an elevated alveolar-arterial oxygen gradient and a compensated respiratory alkalosis (Table 2).^[2,7-9] The shunt fraction has been shown to be elevated as compared to patients with other diffuse lung diseases.^[47]

The severity of pulmonary function abnormalities has varied in different case series. This may in part be explained by differences in the proportion of patients requiring whole lung lavage and mortality in these case series, suggesting the populations differed.

Diagnostic Evaluation

Although history, physical examination, radiographic studies, and physiological testing may suggest PAP, further evaluation is usually needed to confirm the diagnosis. Blood tests, sputum, and BAL results similarly support the diagnosis, however transbronchial or open lung biopsy remain the standard. Table 3 summarizes the clinical and diagnostic features of PAP.

Serum lactate dehydrogenase (LDH) levels have been shown to be elevated relative to other diffuse lung diseases.^[48] These levels are also increased in BAL fluids and have some correlation with the A-a gradient. Krebs von den Lungen-6 (KL-6), a mucin-like protein secreted from type II pneumocytes, has been reported to be elevated in serum and BAL fluids of PAP patients.^[49] The levels were higher than for interstitial lung diseases and correlated with disease activity, radiographic appearance, and pO2.

49,50 Surfactant protein A (SP-A) is elevated in sera of PAP and idiopathic pulmonary fibrosis patients compared with control and other lung diseases.^[51] It is similarly elevated in the sputum, but not all patients can expectorate.^[52] Surfactant protein D (SP-D) is also elevated in the sera of PAP patients and has been shown to correlate with disease severity.^[53] It was similarly elevated in idiopathic pulmonary fibrosis and interstitial lung disease associated with collagen vascular diseases.

BAL findings of PAP have occasionally been used as diagnostic.^[7,8] Typically, however, tissue is obtained. Traditionally tissue was obtained by open lung biopsy. It has been suggested that transbronchial biopsy can be used to accurately make the diagnosis.^[9] Recent case series support this, with a trend toward a greater percentage of cases being diagnosed with transbronchial biopsy.^[2,8]

Histopathology

Analysis of BAL fluid has revealed increased concentrations of lipids and proteins, particularly those associated with surfactant. The classes and distribution of surfactant phospholipids do not substantially differ from normals,54,55 though there is much variability. Cholesterol concentrations are consistently elevated.^[54,55] Surfactant protein levels vary considerably from patient to patient though they are consistently elevated. SP-A has been reported to increase out of proportion to the total protein^[56] though this is variable.^[57] The SP-A: phospholipid ratio is also elevated.^[55,57] SP-B is similarly increased, with an increased SP-B:phospholipid ratio and a normal SP-B:SP-A ratio.^[55] A dimeric form of surfactant associated protein C is present in increased quantities.^[58] SP-D has also been identified to be elevated in PAP patients though to a smaller degree than other surfactant associated proteins.^[59] This accumulated PAP material has been shown to have normal surface activity after processing.^[54]

A small study of cells in the BAL fluid revealed an increase in both the CD4 and CD8 lymphocyte population.^[60] The CD4:CD8 ratio tended to be high but was variable.^[60]

Macroscopically, both biopsy and necropsy specimens reveal multiple, up to 2-3 cm, yellow-gray nodular areas of consolidation. These areas are firm and exude a fatty substance when cut.^[1,7,11] Microscopically, the alveoli are filled with a granular and floccular acidophilic material that is periodic acid Schiff (PAS) positive (Fig. 3). This substance is seen to extend to the small bronchioles at times. Staining these specimens for surfactant specific apoprotein reveals uniform uptake in primary PAP and patchy uptake in secondary PAP.^[61] Alveolar and interstitial architecture are typically preserved, though infiltration of bronchial walls with lymphocytes and thickening or fibrosis may be seen. The vasculature appears normal.^[1,7,11] Electron microscopy reveals characteristic multilamellated structures within the alveolar material as well as inclusions in the cytoplasm of macrophages.^[7,62] Papanicolaou-stained specimens from PAP contain scattered, amorphous, or granular globules that are PAS positive and contain these multilamellated structures when examined ultrastructurally

 

 

telogen effuvium

Telogen Effluvium

Telogen effluvium is a form of hair loss that can result from multiple conditions including anemia (low blood count), low iron, inadequate levels of protein in the diet, thyroid disease, childbirth, major surgery, severe illness, medications and birth control pills. Generally, once the body feels the insult, hair begins to shed over the entire scalp. This is because the insult causes the hairs to switch from the growth phase to the resting phase of the hair cycle. Some individuals will notice large amounts of hair coming out in their hairbrushes, in the shower or on their pillow. The normal shedding of hair generally increases from 100 to 150 hairs daily to almost 500 hairs. However, once the insult has been withdrawn from the body, the hair loss should resolve within 6 to 12 months. Low blood count (anemia) - Patients with anemia due to excessive bleeding, low blood iron or insufficient red blood cell production tend to develop telogen effluvium. Some people don't have enough iron in their diets or may not fully absorb iron. Women who have heavy menstrual periods may develop iron deficiency. Low iron can be detected by laboratory tests and can be corrected by taking iron supplements. The cause of low blood count should be fully investigated and treated. Once the iron deficiency or low blood count is diagnosed and treated, the hair loss should resolve. Inadequate Protein in Diet - Some people, especially those who go on crash diets that are low in protein, have severely abnormal eating habits, or protein malnutrition in the intestine can experience telogen effluvium. The body will attempt to conserve protein by shifting growing hairs into the resting phase. Massive hair shedding can occur two to three months later, when hair can be pulled out at the roots fairly easily. This condition can be reversed and prevented by eating the proper amount of protein. Thyroid Disease - Either an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism) can cause hair loss in men and women. A physician can easily assess thyroid levels through laboratory testing. Hair loss associated with thyroid disease can be reversed with proper treatment. Childbirth – When a woman is pregnant, most of her hairs are in the growth phase. However, after delivery, many hairs enter the resting phase of the hair cycle. This will result in dramatic shedding that can cause thinning hair over the entire scalp. The hair loss can last three to six months, but usually resolves completely in most cases. Severe illness and Major Surgery - Illnesses or major surgery can cause hairs to enter the resting phase. Three to four months after a high fever, severe illness, infection or major surgery, a massive shed of over 250 hairs will occur. This shedding usually corrects itself within six to 12 months. Medications - Some prescription drugs may cause temporary hair shedding. Examples include some of the medicines used for the following: pain (aspirin or ibuprofen), depression, birth control pills, irregular heart beat, high blood pressure, or blood thinning. High doses of vitamin A or Accutane may also cause hair shedding. Birth Control Pills – Certain birth control pills may result in hair loss in women whom are susceptible to female pattern hair loss. This can usually be corrected by switching birth control pills by the physician. Female hair loss may also occur once a woman stops using oral contraceptives. This may continue for six months following the discontinuation of the medication.

collapsing glomerulopathy

Renal biopsy shows glomerulus with global collapse of the glomerular tuft with surrounding tubules exhibiting atrophy. Interstitial fibrosis is also present (silver methenamine stain x200).

 

Collapsing glomerulopathy is a distinct morphologic variant of focal segmental glomerulosclerosis (FSGS) characterised by marked wrinkling and 'collapse' of the glomerular basement membrane and hypertrophy and hyperplasia of overlying podocytes . Compared with classic FSGS, the collapsing variant is distinguished by a more severe nephrotic syndrome, greater resistance to immunosuppressive therapy, rapid progression to end-stage renal failure and predominant occurrence in African American patients . Collapsing glomerulopathy was reported in patients with HIV-associated nephropathy . Additionally, an idiopathic variant of collapsing glomerulopathy has been defined . An increased incidence of parvovirus B19 DNA in renal biopsies of patients with non-HIV collapsing glomerulopathy was reported . Li et al.  found evidence of Simian virus 40 replication in human kidney and suggested that this virus may contribute to the pathogenesis of FSGS.

 

Recently, Markowitz et al. described seven patients with collapsing glomerulopathy and severe tubular degenerative changes in all those cases and related the disease to treatment with high-dose pamidronate. Another case report described a patient with multiple myeloma who was treated with high-dose pamidronate and developed nephrotic syndrome due to collapsing glomerulopathy, with subsequent fluctuations in proteinuria in parallel with discontinuation and reintroduction of the drug .

Studies in primary and recurrent FSGS implicate podocytes injury in the pathogenesis of segmental glomerular scarring . Evidence from the HIV-associated and non-HIV collapsing forms also supports the concept of primary podocytes injury, resulting in a loss of differentiation markers and a dysregulated podocytes phenotype . Shankland et al.  have demonstrated that human podocytes differentiation and proliferation depends on the levels of specific cyclin-dependent kinase inhibitors. An important consequence of podocytes dysregulation is the induction of apoptotic cell death. Apoptosis may constitute a direct pathogenic mechanism for loss of podocytes in FSGS  or, alternatively, it may represent a physiological process for the elimination of sublethally injured or excessively proliferating podocytes .

Our case of pamidronate-induced collapsing glomerulopathy showed well preserved tubules and interstitium. The biopsies of patients with HIV-related glomerulopathy and previously reported cases of pamidronate-induced collapsing glomerulopathy  displayed diffuse severe degenerative changes in tubules and tubular microcyst formation. Banerjee et al. described a patient with biopsy-proven acute tubular necrosis from pamidronate with a reversible renal failure due to solely tubular damage. The mechanism of tubular toxicity of pamidronate is probably similar to that of glomerular lesions: induction of apoptosis in tubular cells. An alternative explanation for tubular injury may be tubular epithelial cell damage by transdifferentiated podocytes having acquired macrophagic epitopes and migrating from the tuft to Bowman's space or drifting within the tubular lumens as was described in progressive glomerulonephritides and collapsing glomerulopathy .

In the previously reported and our cases of pamidronate-induced glomerulopathy, the total dose of the drug administrated ranged from 1.3 to 8.6 g. This wide range indicates that additional factors may influence the patient susceptibility to renal injury, such as the duration of intravenous infusion of the drug or underlying diseases like malignancy.

In conclusion, pamidronate-induced glomerulopathy can occur at recommended doses although long-term treatment is needed. Therefore, pamidronate-treated patients should be monitored for changes in renal function and proteinuria. The development of nephrotic syndrome and renal failure during remission of multiple myeloma should raise the possibility of collapsing glomerulopathy due to pamidronate.

Thus, pamidronate represents a new, toxic cause in the aetiology of collapsing glomerulopathy in human. Apoptosis is a possible mechanism for podocyte injury in this entity.

^{aiims nov 07}

collapsing glomerulopathy

Renal biopsy shows at the bottom, glomerulus with global collapse of glomerular tuft surrounded by atrophic tubuli and interstitial fibrosis. Two other glomeruli without significant changes (silver methenamine stain, low-power field).