IS a weak gram + bacteria, aerobic, facultative intracelular, no movility, no capsule and no spore former. Is alchol acid resistant bacilli and has a very width cellular wall. The wall consist in N-acetyl glucosamine, arabinose polymers, mycolic acids, glicolipids and lipoarabinomanam.
Virulence
Cordon factor which is a mycolic acid is very immunogenic and interrupts fagolisosome fusion and electron transporter chain. Lipoarabinomanam is an immune-modulator that elicits inflammatory response due TOLL like receptors. Bacterian urease adjust cytoplasmic ambient becoming alkaline allowing his survival.
The infection occurs when a patient elicits bacilli in aerosol shaped secretions, the bacilli arrives to the alveoli and is phagocitated by dust macrophages, this cell is not able to destroy it so travel to the hiliar nodes in the lymphatic system creating ghon complex, which is a calcificated and fibrous node. This action constitute the first stage, the second is spread via bloodstream to other organs. The thirs stage is very slow, and is very usual with pleurisy. The latest stage constitutes the resolution in which the patient stops the bacilli colonization.
The macrophage with the bacilli is surrounded by other inflammatory cells and dies becoming caseose forming granulome, with lymphocytes CD4 and Cd8, fibroblasts and giant cells. This stoping situation is the normal, but when is immune depletion the bacilli can become wild again and multiply. HIV can elicit bacilli reinfection, so is very normal this co-infection.
Clinical manifestations
There is a wide spectrum of disease’s ways.
1º pulmonary TB: is more frecuent in children and affects the middle and lower lobes of the lungs, is usually accompanied by pleural effusion . It occurs when the infection with bacilli is new. There are lymphatic nodes in the hilious region.
Pulmonary Tb pos-first: Is usual in adults and affects more frequent the apex because of the major oxygen ability, it can cause cavitations with abces and necrosys regions. There are lymphatic nodes that can compress the bronchium and elicit collapse of a lung segment. Is very usual due to reactivation of the bacilli. Clasical symptoms include: fever, malaise, night sweat, weight loss, comsumption and anorexy. Hemoptisys and anforic bruit are very frequent. Tha X-ray shows bilateral infiltrate and nodes in the hilio.
This Image shows a bilateral and nodular infiltrates on the superior left lung. There is an air-level in the low right lung. (Cortesy of NEJM) Extrapulmonar TB: Can affect the nervous system, digestive system, cutaneous lesions, millliar disease, bone and articulation lesions (pott’s disease) and only lymphatic nodes affection (Scrafula).
Vaccination
Is a replicative vaccine and consists of BCG attenuated that bring immune contact and allow the immune system his recognition and resolution of the infection.
Dx
The diagnosis is with the culture of sputum and PPD test, X-ray, clinical manifestations.
HIV is virus that belongs to retroviruses and more specifically to lentiviruses, is enveloped and contains two RNA strains with positive polarity. His genome is composed by 9 genes clasificated in 3 groups: structural genes: gag, pol, env; regulatory genes: tat, rev; accessory genes: vpr, vpu, vif and nef. Gag genes code for core proteins which consists of p24, p17 and p7. Env codes for envelope proteins which consists of gp120 (surface protein) and gp41 (transmembrane protein). Pol codes for protease, integrase and reverse transciptase.
Tat gene codes for a genome binding protein that ensures the full-transcription of the viral genome, and rev is a protein that allos virus pass through early to late phase, this protein links immature ARN without splicing and take it outside nucleus.
Nef genes encode a protein that inhibits CD4+ and MHC-1, vpr is a transporter protein that inserts itself in every cell membrane, allowing virus infect non-dividing cells, translocate the preintegration complex through the nucleus and eliciting apoptosis by his insertion in the mitochondrial membrane. Vif are essencial for viral transcription and VPU destroy the CD4+ like Nef.
Infection
The infection occurs in every cell with CD4+ and co receptor: CCR5 or CXCR4 in macrophages or lymphocytes respectively. But the first contact is with the DC via DC-sign this cell carry the virus to a lymphatic node where meets the susceptible cells. The gp 120 links the CD4+ and the co receptor and change the conformation allowing the gp41 bring the hydrophobic domain for membrane fusion. When the virus enter the cells is decapsidated and laves the RNA and constitutional proteins in the cytoplasm, the reverse transcriptase converse the RNA to DNA, then the integrase cuts the genome limits allowing the insertion in the host genome, where the protease cut the new RNAm in small peptides that constitutes the viral proteins. The viral genome replicates and destroys the host cell bringing new virions.
There are two types of HIV phenotypes: R5 and X4, R5 occurs when the virus infects first macrophages and X4 when infects lymphocytes. X4 is more aggressive and develop very quickly toward AIDS.
The pathogenesis is explained by cell lysis and the mechanisms are three: apoptosis, depletion by immune system and delayed lymphocytes regeneration.
Obliterant tromboangitis is an occlusive vascular disease that comprises middle and small arteries, and distal extremities veins. His prevalence is bigger in Asian population and masculine population with less than 40 years. There is no evidence about the cause but there is an association with cigarettes.
In the lesion place are polymorphic nuclear cells. Later, arrives monocytes, fibroblasts and giant cells. In advance disease is very frequent perivascular fibrosis. There is no intime layer compromise but it can be thrombus formation.
Clinical
The patient with tromboangitis presents a triad: extremity claudication, Reynaud phenomena and migrans thrombo-phlebitis. The patient conserves the humeral and popliteal pulse, but radial, ulnae and pedis pulse are absent. It can present nail atrophy, vessels ulcers and gangrene lesions. Therefore, extremities claudication is localized in calf and feet, and superior extremity claudicate on the hand and forearm.
The first image shows a patient with a hanged-foot and the second after elevation.
Dx
The diagnostic is via excicional biopsy and pathological study. Arteriography is very useful.
Treatment
There is no treatment; the only recommendation is to cease smoking, while this neither warranty nothing cause probably won’t improve. Can proceeds with angioplasty derived from big arteries. Anticoagulation and corticoids doesn’t work.
References: Harrison - Intern Medicine - 16º Edition.
Chronic venous disease of the lower limbs is manifested by a range of signs, the most obvious of which are varicose veins and venous ulcers. However, the signs also include edema, venous eczema, hyperpigmentation of skin of the ankle, atrophie blanche (white scar tissue), and lipodermatosclerosis
(induration caused by fibrosis of the subcutaneous fat).
Chronic venous disease can be graded according to the descriptive clinical, etiologic, anatomical, and pathophysiological (CEAP) classification, which provides an orderly framework for communication and decision making.1,2 The clinical signs in the affected legs are categorized into seven classes designated C0 to C6.
Prevalence
Chronic venous disease is extremely common, although the prevalence estimates vary. A cross-sectional study of a random sample of 1566 subjects 18 to 64 years of age from the general population in Edinburgh, Scotland,3 found that telangiectases and reticular veins were each present in approximately 80 percent of men and 85 percent of women. Varicose veins were present in 40 percent of men and 16 percent of women, whereas ankle edema was present in 7 percent of men and 16 percent of women.3 Active or healed venous leg ulcers occur in approximately 1 percent of the general population.3,4Although not restricted to the elderly, the prevalence of chronic venous disease, especially leg ulcers, increases with age.3-5 Most studies have shown that chronic venous disease is more prevalent among women, although in a recent study, the difference between sexes was small.6 In the Framingham Study, the annual incidence of varicose veins was 2.6 percent among women and 1.9 percent among men,7 and in contrast to the Edinburgh Vein Study, the prevalence of varicose veins was higher in men.3,8 In the San Diego Population Study, chronic venous disease was more prevalent in populations of European origin than in blacks or Asians.9 Risk factors for chronic venous disease include heredity, age, female sex, obesity especially in women), pregnancy, prolonged standing, and greater height.
Economic impact
In a population study in the United Kingdom, the median duration of ulceration was nine months, 20 percent of ulcers had not healed within two years, and 66 percent of patients had episodes of ulceration lasting longer than five years.
Symptoms
Symptoms traditionally ascribed to chronic venous disease include aching, heaviness, a feeling of swelling, cramps, itching, tingling, and restless legs. Chronic venous disease is associated with a reduced quality of life, particularly in relation to pain, physical function, and mobility. It is also associated with depression and social isolation.19 Venous leg ulcers, the most severe manifestationof chronic venous disease, are usually painful20 and affect the quality of life.
VENOUS HYPERTENSION
Despite the diversity of signs and symptoms associated with chronic venous disease, it seems likely that all are related to venous hypertension. In most cases, venous hypertension is caused by reflux through incompetent valves,6,24 but other causes include venous outflow obstruction and failure of the calf-muscle pump owing to obesity or leg immobility. Reflux may occur in the superficial or deep venous system or in both. A review of 1153 cases of ulcerated legs with reflux found superficial reflux alone in 45 percent, deep reflux alone in 12 percent, and both forms in 43 percent. 25 An analysis of cases of chronic venous disease indicated that primary valvular incompetence was present in 70 to 80 percent and a congenital anomaly in 1 to 3 percent; valvular incompetence was due to trauma or deep-vein thrombosis in 18 to 25 percent.
Pressure in the veins of the leg is determined by two components: a hydrostatic component related to the weight of the column of blood from the right atrium to the foot and a hydrodynamic component related to pressures generated by contractions of the skeletal muscles of the leg and the pressure in the capillary network. During standing without skeletal-muscle activity, venous pressures in the legs are determined by the hydrostatic component and capillary flow, Skeletal-muscle contractions, as during ambulation, transiently increase pressure within the deep leg veins.
Changes in Venous Valves
Venous valve incompetence is central to the venous hypertension that appears to underlie most or all signs of chronic venous disease. Alterations in and damage to valves have been noted on examination with an angioscope, a fiberoptic catheter that allows clinicians to view the interior of a blood vessel. These changes include stretching, splitting, tearing, thinning, and adhesion of valve leaflets.27 A reduction in the number of valves per unit length has been observed in segments of saphenous veins from patients with chronic venous insufficiency.28 An important step forward came when Ono et al.29 found infiltration of valve leaflets and the venous wall by monocytes and macrophages in all vein specimens from patients with chronic venous disease and in no specimens from controls. Infiltration was associated with areas of endothelium that expressed intercellular adhesion molecule 1 (ICAM-1).
Structural changes
Histologic and ultrastructural studies of varicose saphenous veins have found hypertrophy of the vein wall with increased collagen content,31 together with disruption of the orderly arrangements of smooth-muscle cells and elastin fibers.32,33 Cultures of smooth-muscle cells from varicose saphenous veins have disturbed collagen synthesis, resulting in overproduction of collagen type I and reduced synthesis of collagen type III.
Degradation of extracellular matrix proteins is caused by an array of proteolytic enzymes, including matrix metalloproteinases (MMPs) and serine proteinases, which are produced by vascular cells and inflammatory cells such as macrophages.35 MMPs are released as inactive proenzymes that are activated by other proteinases, including those produced by mast cells,36,37 whereas tissue inhibitors of MMPs (TIMPs) reduce MMP activity. In varicose veins, ratios of TIMP-1 to MMP-2 and TIMP-2 to MMP-2 have been found to be 3.6 times and 2.1 times, respectively, those in veins of control subjects.
In rats, production of an arteriovenous fistula between the femoral artery and vein abruptly increased the pressure in the femoral vein to approximately 90 mm Hg.43-45 Although the valves were stretched immediately by the increased pressure, reflux did not occur until at least two days later and then increased with time. After three weeks, the numbers of granulocytes, monocytes, macrophages, and lymphocytes were increased in the pressurized valves, and MMP-2 and MMP-9 levels were raised. Morphologic changes in the valves also occurred; there were reductions in leaflet height and width, and some valves disappeared. These studies suggest that valves can tolerate high pressures for limited periods, but when there is prolonged pressure-induced inflammation, valve remodeling and loss and reflux occur.
Venous valves are operated by pressure rather than by flow-driven devices, so that little or no reflux is needed to bring about complete closure of the valve.
Physiology
Venous flow is normally pulsatile; venous valves open and close approximately 20 times per minute while a person is standing. When the valve leaflets are fully open, they do not touch the sinus wall (Fig. 3). Flow through the valve separates into a proximally directed jet and a vortical flow into the sinus pocket behind the valve cusp; the vortical flow prevents stasis in the pocket and ensures that all surfaces of the valve are exposed to shear stress. Valve closure occurs when the pressure caused by the vertical flow exceeds the pressure on the luminal side of the valve leaflet because of the proximally directed jet. Interestingly, foot movements, which increase the velocity of the jet, reduce the pressure on the luminal side of the valve leaflets and cause closure of the valve. Thus, minimal reflux occurs and endothelial surfaces are not generally exposed to reverse blood flow.
Venous stasis, even in the absence of reflux, produces regions of low or zero shear stress, whereas subsequent structural changes and irregularities in vessel walls may induce regions of disturbed and even turbulent flow. All of these events can initiate and maintain inflammatory
reactions.
Skin changes
An increase in the occurrence of leg ulceration with increasing postexercise venous pressure was also observed in patients with chronic venous disease; the changes ranged from 0 percent venous ulceration in patients with postexercise venous pressures of less than 30 mm Hg up to 100 percent in patients with postexercise venous pressures of more than 90 mm Hg.
Basal plasma levels of the adhesion molecules ICAM-1, endothelial leukocyte-adhesion
molecule 1, and vascular-cell adhesion molecule 1 were higher in patients with chronic venous disease than in control subjects, and increased significantly in response to venous hypertension provoked by standing.
Unrestrained MMP activity may contribute to the breakdown of the extracellular matrix,
which promotes the formation of ulcers and impairs healing.
In lipodermatosclerosis, the skin capillaries are elongated and tortuous,81 and they may take
on a glomerular appearance, with proliferation of the capillary endothelium in more advanced
cases. Furthermore, plasma VEGF levels were higher in patients with chronic venous disease
with skin changes than in such patients with normal skin.
Another feature of the skin changes associated with chronic venous disease is dermal tissue fibrosis. TGF-β1 is a fibrogenic cytokine.
The hyperpigmentation of skin in lipodermatosclerosis may not be just an innocent by-product
of capillary hyperpermeability. The extravasation of red cells leads to elevated levels of ferritin and ferric iron in affected skin.88,89 These increases may cause oxidative stress, MMP activation, and the development of a microenvironment that exacerbates tissue damage and delays healing.
