Synaptic Science

Systemic Sclerosis

noreply@blogger.com (Unknown) — Sun, 19 Jun 2011 05:42:00 +0000

Systemic sclerosis is a chronic disease characterized by: (1) chronic inflammation thought to be the result of autoimmunity, (2) widespread damage to small blood vessels, and (3) progressive interstitial and perivascular fibrosis in the skin and multiple organs.^[90] Although the term scleroderma is ingrained in clinical medicine, this disease is better named systemic sclerosis because it is characterized by excessive fibrosis throughout the body. The skin is most commonly affected, but the gastrointestinal tract, kidneys, heart, muscles, and lungs also are frequently involved. In some patients the disease seems to remain confined to the skin for many years, but in the majority it progresses to visceral involvement with death from renal failure, cardiac failure, pulmonary insufficiency, or intestinal malabsorption. The clinical heterogeneity of systemic sclerosis has been recognized by classifying the disease into two major categories: diffuse scleroderma, characterized by widespread skin involvement at onset, with rapid progression and early visceral involvement; and limited scleroderma, in which the skin involvement is often confined to fingers, forearms, and face. Visceral involvement occurs late; hence, the clinical course is relatively benign. Some patents with the limited disease also develop a combination of calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia, called the CREST syndrome. Several other variants and related conditions, such as eosinophilic fasciitis, occur far less frequently.

- The cause of systemic sclerosis is not known. Autoimmune responses, vascular damage, and collagen deposition all contribute to the ultimate tissue injur.

-
It is proposed that CD4+ T cells responding to an as yet unidentified antigen accumulate in the skin and release cytokines that activate inflammatory cells and fibroblasts.^[92] Although inflammatory infiltrates are typically sparse in the skin of patients with systemic sclerosis, activated CD4+ T cells can be found in many patients, and T_H2 cells have been isolated from the skin. Several cytokines produced by these T cells, including TGF-β and IL-13, can stimulate transcription of genes that encode collagen and other extracellular matrix proteins (e.g., fibronectin) in fibroblasts. Other cytokines recruit leukocytes and propagate the chronic inflammation.
There is also evidence for inappropriate activation of humoral immunity, and the presence of various autoantibodies provides diagnostic and prognostic information.^[93] Virtually all patients have ANAs that react with a variety of nuclear antigens. Two ANAs strongly associated with systemic sclerosis have been described. One of these, directed against DNA topoisomerase I (anti-Scl 70), is highly specific. Depending on the ethnic group and the assay, it is present in 10% to 20% of patients with diffuse systemic sclerosis. Patients who have this antibody are more likely to have pulmonary fibrosis and peripheral vascular disease. The other, an anticentromere antibody, is found in 20% to 30% of patients, who tend to have the CREST syndrome or limited cutaneous systemic sclerosis. Only rarely does the same patient have both antibodies. The role of these ANAs in the pathogenesis of the disease is unclear; it has been postulated that some of these antibodies may stimulate fibrosis, but the evidence in support of this idea is not convincing.

- Microvascular disease is consistently present early in the course of systemic sclerosis and may be the initial lesion. Intimal proliferation is evident in 100% of digital arteries of patients with systemic sclerosis. Capillary dilation with leaking, as well as destruction, is also common. Nailfold capillary loops are distorted early in the course of disease, and later they disappear. Thus, there is unmistakable morphologic evidence of microvascular injury. Telltale signs of endothelial activation and injury (e.g., increased levels of von Willebrand factor) and increased platelet activation (increased percentage of circulating platelet aggregates) have also been noted. However, what causes the vascular injury is not known; it could be the initiating event or the result of chronic inflammation, with mediators released by inflammatory cells inflicting damage on microvascular endothelium. Repeated cycles of endothelial injury followed by platelet aggregation lead to release of platelet and endothelial factors (e.g., PDGF, TGF-β) that trigger perivascular fibrosis. Activated or injured endothelial cells themselves may release PDGF and factors chemotactic for fibroblasts. Vascular smooth muscle cells also show abnormalities, such as increased expression of adrenergic receptors. Eventually, widespread narrowing of the microvasculature leads to ischemic injury and scarring. Whether endothelial injury can also be initiated by toxic effects of environmental triggers remains uncertain but cannot be definitively excluded.

- The progressive fibrosis characteristic of the disease may be the culmination of multiple abnormalities, including the actions of fibrogenic cytokines produced by infiltrating leukocytes, hyperresponsiveness of fibroblasts to these cytokines, and scarring following upon ischemic damage caused by the vascular lesions. There is also evidence for a primary abnormality in collagen production. Consistent with this notion is the finding that a polymorphism in the gene encoding connective tissue growth factor is associated with systemic sclerosis.^[94] In mouse models of Marfan syndrome caused by mutations in the fibrillin-1 gene, some features of systemic sclerosis are also seen,^[95] suggesting again that connective tissue abnormalities may contribute to this disease.
- Virtually all organs can be involved in systemic sclerosis. Prominent changes occur in the skin, alimentary tract, musculoskeletal system, and kidney, but lesions also are often present in the blood vessels, heart, lungs, and peripheral nerves.

- A great majority of patients have diffuse, sclerotic atrophy of the skin, which usually begins in the fingers and distal regions of the upper extremities and extends proximally to involve the upper arms, shoulders, neck, and face. Histologically, there are edema and perivascular infiltrates containing CD4+ T cells, together with swelling and degeneration of collagen fibers, which become eosinophilic. Capillaries and small arteries (150 to 500 μm in diameter) may show thickening of the basal lamina, endothelial cell damage, and partial occlusion. With progression of the disease, there is increasing fibrosis of the dermis, which becomes tightly bound to the subcutaneous structures. There is marked increase of compact collagen in the dermis, usually with thinning of the epidermis, loss of rete pegs, atrophy of the dermal appendages, and hyaline thickening of the walls of dermal arterioles and capillaries. Focal and sometimes diffuse subcutaneous calcifications may develop, especially in patients with the CREST syndrome. In advanced stages the fingers take on a tapered, clawlike appearance with limitation of motion in the joints, and the face becomes a drawn mask. Loss of blood supply may lead to cutaneous ulcerations and to atrophic changes in the terminal phalanges. Sometimes the tips of the fingers undergo autoamputation.

- The alimentary tract is affected in approximately 90% of patients. Progressive atrophy and collagenous fibrous replacement of the muscularis may develop at any level of the gut but are most severe in the esophagus. The lower two thirds of the esophagus often develops a rubber-hose inflexibility. The associated dysfunction of the lower esophageal sphincter gives rise to gastroesophageal reflux and its complications, including Barrett metaplasia ( Chapter 17 ) and strictures. The mucosa is thinned and may be ulcerated, and there is excessive collagenization of the lamina propria and submucosa. Loss of villi and microvilli in the small bowel is the anatomic basis for the malabsorption syndrome sometimes encountered.

- Inflammation of the synovium, associated with hypertrophy and hyperplasia of the synovial soft tissues, is common in the early stages; fibrosis later ensues. These changes are reminiscent of rheumatoid arthritis, but joint destruction is not common in systemic sclerosis. In a small subset of patients (approximately 10%), inflammatory myositis indistinguishable from polymyositis may develop.

- Renal abnormalities occur in two thirds of patients with systemic sclerosis. The most prominent are the vascular lesions. Interlobular arteries show intimal thickening as a result of deposition of mucinous or finely collagenous material, which stains histochemically for glycoprotein and acid mucopolysaccharides. There is also concentric proliferation of intimal cells. These changes may resemble those seen in malignant hypertension, but in scleroderma the alterations are restricted to vessels 150 to 500 μm in diameter and are not always associated with hypertension. Hypertension, however, does occur in 30% of patients with scleroderma, and in 20% it takes an ominously rapid, downhill course (malignant hypertension). In hypertensive patients, vascular alterations are more pronounced and are often associated with fibrinoid necrosis involving the arterioles together with thrombosis and infarction. Such patients often die of renal failure, which accounts for about 50% of deaths in persons with this disease. There are no specific glomerular changes.

- The lungs are involved in more than 50% of individuals with systemic sclerosis. This involvement may manifest as pulmonary hypertension and interstitial fibrosis. Pulmonary vasospasm, secondary to pulmonary vascular endothelial dysfunction, is considered important in the pathogenesis of pulmonary hypertension. Pulmonary fibrosis, when present, is indistinguishable from that seen in idiopathic pulmonary fibrosis

- Pericarditis with effusion and myocardial fibrosis, along with thickening of intramyocardial arterioles, occurs in one third of the patients. Clinical myocardial involvement, however, is less common.

- Systemic sclerosis has a female-to-male ratio of 3 : 1, with a peak incidence in the 50- to 60-year age group. Although systemic sclerosis shares many features with SLE, rheumatoid arthritis ( Chapter 26 ), and polymyositis ( Chapter 27 ), its distinctive features are the striking cutaneous changes, notably skin thickening. Raynaud's phenomenon, manifested as episodic vasoconstriction of the arteries and arterioles of the extremities, is seen in virtually all patients and precedes other symptoms in 70% of cases. Dysphagia attributable to esophageal fibrosis and its resultant hypomotility are present in more than 50% of patients. Eventually, destruction of the esophageal wall leads to atony and dilation, especially at its lower end. Abdominal pain, intestinal obstruction, or malabsorption syndrome with weight loss and anemia reflect involvement of the small intestine. Respiratory difficulties caused by the pulmonary fibrosis may result in right-sided cardiac dysfunction, and myocardial fibrosis may cause either arrhythmias or cardiac failure. Mild proteinuria occurs in as many as 30% of patients, but rarely is the proteinuria severe enough to cause a nephrotic syndrome. The most ominous manifestation is malignant hypertension, with the subsequent development of fatal renal failure, but in its absence progression of the disease may be slow. The disease tends to be more severe in blacks, especially black women. As treatment of the renal crises has improved, pulmonary disease has become the major cause of death in systemic sclerosis.

- As mentioned earlier, the CREST syndrome is seen in some patients with limited systemic sclerosis. It is characterized by calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia, and the presence of anticentromere antibodies. Patients with the CREST syndrome have relatively limited involvement of skin, often confined to fingers, forearms, and face, and calcification of the subcutaneous tissues. Involvement of the viscera, including esophageal lesions, pulmonary hypertension, and biliary cirrhosis, may not occur at all or occur late. In general the patients live longer than those with systemic sclerosis with diffuse visceral involvement at the outset.

References:
1. Kumar, Raminder et al. Robbins and Cotran Pathologic Basis of Disease 8th Ed. Sander Elsevier. 2010.

Hyper-IgM Syndrome

noreply@blogger.com (Unknown) — Sun, 19 Jun 2011 01:42:00 +0000

- In hyper-IgM syndrome the affected patients make IgM antibodies but are deficient in their ability to produce IgG, IgA, and IgE antibodies.
- It is now known that the defect in this disease affects the ability of helper T cells to deliver activating signals to B cells and macrophages.
- Many of the functions of of CD4+ helper T cells require the engagement of CD40 on B cells, macrophages and dendritic cells by CD40L (also called CD154) expressed on antigen-activated T cells.
- This interaction triggers Ig class switching and affinity maturation in B cells, and stimulates the microbicidal functions of macrophages.
- Approximately 70% of individuals with hyper-IgM syndrome have the X-linked form of the disease, caused by mutations in the gene encoding CD40L located on Xq26.
- In the remaining persons the disease is inherited in an autosomal recessive pattern.
- Most of these patients have mutations in the gene encoding CD40 or the enzyme called activation-induced deaminase, a DNA-editing cytosine deaminase that is required for class switching and affinity maturation.

- The serum of persons with this syndrome contains normal or elevated levels of IgM but no IgA or IgE and extremely low levels of IgG.
- The number of B cells and T cells is normal.
- Many of the IgM antibodies react with elements of blood, giving rise to autoimmune hemolytic anemia, thrombocytopenia, and neutropenia.
- In older patients there may be uncontrolled proliferation of IgM-producing plasma cells with infiltrations of the gastrointestinal tract.
- Although the proliferating B cells are polyclonal, extensive infiltration may lead to death.

- Clinically, individuals with hyper-IgM syndrome present with recurrent pyogenic infections, b/c the level of opsonizing IgG antibodies is low.
- In addition, those with CD40L mutations are also susceptible to pneumonia caused by the intracellular organism Pneumocysticis jiroveci, b/c of the defect in cell-mediated immunity.

References:
1. Kumar, Raminder et al. Robbins and Cotran Pathologic Basis of Disease 8th Ed. Sander Elsevier. 2010.

X-Linked Agammaglobulinemia

noreply@blogger.com (Unknown) — Sun, 19 Jun 2011 01:17:00 +0000

- X-linked agammaglobulinemia is one of the more common forms of primary immunodeficiency.
- It is characterized by the failure of B-cell precursors (pro-B cells and pre-B cells) to develop into mature B cells.
- During normal B-cell maturation in the bone marrow, the Ig heavy-chain genes are rearranged first, in pre-B cells, and these are expressed on the cell surface in association with a "surrogate" light chain, where they deliver signals that induce rearrangement of the Ig light-chain genes and further maturation.
- This need for Ig-initiated signals is a quality control mechanism that ensures that maturation will proceed only if functional Ig proteins are expressed.
- X-linked agammaglobulinemia is caused by mutations in a cytoplasmic tyrosine kinase, called Bruton tyrosine kinase (Btk); the gene that encodes it is located on the long arm of the X chromosome at Xq21.22.
- Btk is a protein tyrosine kinase that is associated with the Ig receptor complex of pre-B and mature B cells and is needed to transduce signals from the receptor.
- When it is mutated, the pre-B cell receptor cannot deliver signals, and maturation stops at this stage.
- B/c light chains are not produced, the complete antigen receptor molecule (which contains Ig heavy and light chains) cannot be assembled and transported to the cell membrane.

- As an X-linked disease, this disorder is seen almost entirely in males, but sporadic cases have been described in females, possibly caused by mutations in some other gene that functions in the same pathway.
- The disease usually does not become apparent until about 6 months of age, as maternal immunoglobulins are depleted.
- In most cases, recurrent bacterial infections of the respiratory tract, such as acute and chronic pharyngitis, sinusitis, otitis media, bronchitis, and pneumonia, call attention to the underlying immune defect.
- Almost always the causative organisms are Haemophilus influenzae, Streptococcus pneumoniae, or Staphylococcus aureus.
- These organisms are normally opsonized by antibodies and cleared by phagocytosis.
- B/c antibodies are important for neutralizing infectious viruses that are present in the bloodstream or mucosal secretions or being passed from cell to cell, individuals with this disease are also susceptible to certain viral infections, especially those caused by enteroviruses, such as echovirus, poliovirus, and coxsackievirus.
- These viruses infect the gastrointestinal tract, and from here they can disseminate to the nervous system via the blood.
- Thus, immunization with live poliovirus carries the risk of paralytic poliomyelitis, and echovirus can cause fatal encephalitis.
- For similar reasons, Giardia lamblia, an intestinal protozoan that is normally resisted by secreted IgA, causes persistent infections in persons with this disorder.
- In general, however, most intracellular viral, fungal, and protozoal infections are handled quite well by the intact T cell-mediated immunity.

- The classic form of this disease has the following characteristics:
   - B cells are absent or markedly decreased in the circulation, and the serum levels of all classes of immunoglobulins are depressed. Pre-B cells, which express the B-lineage marker CD19 but not membrane Ig, are found in normal numbers in the bone marrow.
   - Germinal centers of lymph nodes, Peyer's pathces, the appendix, and tonsils are underdeveloped
   - Plasma cells are absent throughout the body
   - T cell-mediated reactions are normal

- Autoimmune diseases, such as arthritis and dermatocyositis, occur with increased frequency, in as many as 35% of individuals with this disease, which is paradoxical in the presence of an immune deficiency.
- It is likely that these autoimmune disorders are caused by a breakdown of self-tolerance resulting in autoimmunity, but chronic infections associated with the immune deficiency may play a role in inducing inflammatory reactions.
- The treatment of X-linked agammaglobulinemia is replacement therapy with immunoglobulins.
- In the past, most patients succombed to infection in infancy or early childhood.
- Prophylactic intravenous Ig therapy allows most individuals to reach childhood.

References:
1. Kumar, Raminder et al. Robbins and Cotran Pathologic Basis of Disease 8th Ed. Sander Elsevier. 2010.

Turner's Syndrome

noreply@blogger.com (Unknown) — Wed, 08 Jun 2011 13:09:00 +0000

- Turner's Syndrome (45, XO) is associated with an increased incidence of coarctation of the aorta.

References:
1. Blackwell's Underground Clinical Vignettes: Anatomy, 3rd Ed. Bhushan, Vikas, M.D., et al. Blackwell Science Publishing. 2002.

Atrial Septal Defect

noreply@blogger.com (Unknown) — Wed, 25 May 2011 23:02:00 +0000

- Symptoms of an Atrial Septal Defect include shortness of breath on exertion and palpitations.

- Physical examination of patients may present systolic ejection flow murmur in the left second intercostal space; a widely split, fixed S2 (i.e., it doesn't change with breathing).

- Lab results for patients with this condition show atrial fibrillation on the ECG

- imaging shows increased pulmonary vascularity and paradoxical septal movement.

- the most common form is in the midseptum, in the area of the foramen ovale (ostium secondum); those in the lower septum (ostium primum) are associated with AV valve anomalies (most common in Down's Syndrome); those in teh upper septum (sinus venosus) are associated with anomalous pulmonary venous return.
- surgical or interventional angiographic closure of defect with prosthetic patch. Operative repair is recommended in all symptomatic patients with ostium secundum defects regardless of size of defect.
- Oxygenated blood from the left atrium passes into the right atrium, increasing right ventricular output and pulmonary flow.
- Acyanotic (left-to-right shunt); the most common congenital heart disease in adults.
- Sequelae of untreated atrial septal defects include paradoxic emboli, infective endocarditis, and congestive heart failure.

Reference:

1. Blackwell's Underground Clinical Vignettes: Anatomy, 3rd Ed. Bhushan, Vikas, M.D., et al. Blackwell Science Publishing. 2002.

Congenital Myeloperoxidase Deficiency

noreply@blogger.com (Unknown) — Sun, 15 May 2011 00:33:00 +0000

- In congenital myeloperoxidase deficiency, microbial killing power is reduced b/c hypochlorous acid is not formed.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Glucose-6-Phosphate Dehyhdrogenase Deficiency

noreply@blogger.com (Unknown) — Sun, 15 May 2011 00:32:00 +0000

- In severe congenital glucose-6-phosphate dehydrogenase deficiency, there are multiple infections b/c of failure to generate the NADPH necessary for O2- production.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Chronic Granulomatous Disease

noreply@blogger.com (Unknown) — Sun, 15 May 2011 00:29:00 +0000

- In chronic granulomatous disease, there is a failure to generate O2- in both neutrophils and monocytes and consequent inability to kill many phagocytosed bacteria.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Neutrophil Hypomotility

noreply@blogger.com (Unknown) — Sun, 15 May 2011 00:21:00 +0000

- In neutrophil hypomotility, actin in the neutrophils does not polymerize normally, and the neutrophils move slowly.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Testotoxicosis

noreply@blogger.com (Unknown) — Sun, 15 May 2011 00:19:00 +0000

- Testotoxicosis is an interesting disease that combines gain and loss of function. In this condition, an activating mutation of Gs(alpha) causes excess testosterone secretion and prepubertal sexual maturation. However, this mutation is temperature-sensitive and is active only at the relatively low temperature of the testes (33*C). At 37*C, the normal temperature of the rest of the body, it is replaced by loss of function, with the production of hypoparathyroidism and decreased responsiveness to TSH.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Pseudohypoparathyroidism

noreply@blogger.com (Unknown) — Sun, 15 May 2011 00:00:00 +0000

- G proteins can undergo loss-of-function or gain-of-function mutations that cause disease. In one form of pseudyhypoparathyroidism, a mutated Gs(alpha) fails to respond to parathyroid hormone, producing the symptoms of hypoparathyroidism without any decline in circulating parathyroid hormone.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Carnitine Deficiency

noreply@blogger.com (Unknown) — Sat, 14 May 2011 22:31:00 +0000

- Deficient beta-oxidation of fatty acids can be produced by carnitine deficiency or genetic defects in the translocase or other enzymes involved in the transfer of long-chain fatty acids into the mitochondria. This causes cardiomyopathy. In addition, it causes hypoketonemic hypoglycemia with coma, a serious and often fatal condition triggered by fasting, in which glucose stores are used up because of the lack of fatty acid oxidation to provide energy. Ketone bodies are not formed in normal amounts because of the lack of adequate CoA in the liver.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Ketoacidosis

noreply@blogger.com (Unknown) — Sat, 14 May 2011 22:27:00 +0000

- The normal blood ketone level in humans is low (about 1 mg/dL) and less than 1mg is excreted per 24h, b/c the ketones are normally metabolized as rapidly as they are formed. However, if the entry of acetyl-CoA into the citric acid cycle is depressed because of normally decreased supply of the products of glucose metabolism, or if the entry does not increase when the supply of acetyl-CoA increases, acetyl-CoA accumulates, the rate of condensation to acetoacetyl-CoA increases, and more acetoacetate is formed in the liver. The ability of the tissues to oxidize the ketones is soon exceeded, and they accumulate in the bloodstream (ketosis). Two of the three ketone bodies, acetoacetate and beta-hydroxybutyrate, are anions of the moderately strong acids acetoacetic acid and beta-hydroxybutyric acid. Many of their protons are buffered, reducing the decline in pH that would otherwise occur. However, the buffering capacity can be exceeded, and the metabolic acidosis that develops in conditions such as diabetic ketosis can be severe and even fatal. Three conditions lead to deficient intracellular glucose supplies, and hence to ketoacidosis: starvation; diabetes mellitus; and a high-fat, low-carbohydrate diet. The acetone odor on the breath of children who have been vomiting is due to the ketosis of starvation. Parenteral administration of relatively small amounts of glucose abolishes the ketosis, and it is for this reason that carbohydrate is said to be antiketogenic.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Gout

noreply@blogger.com (Unknown) — Sat, 14 May 2011 22:15:00 +0000

- Gout is a disease characterized by recurrent attacks of arthritis; urate deposits in the joints, kidneys, and other tissues; and elevated blood and urine uric acid levels. The joint most commonly affected initially is the metatarsophalangeal joint of the great toe. There are two forms of "primary" gout. In one, uric acid production is increased because of various enzyme abnormalities. In the other, there is a selective deficit in renal tubular transport of uric acid. In "secondary" gout, the uric acid levels in the body fluids are elevated as a result of decreased excretion or increased production secondary to some other disease process. For example, excretion is decreased in patients treated with thiazide diuretics and those with renal disease. Production is increased in leukemia and pneumonia because of increased breakdown of uric acid-rich white blood cells.
- The treatment of gout is aimed at relieving the acute arthritis with drugs such as colchicine or nonsteroidal anti-inflammatory agents and decreasing the uric acid level in the blood. Colchicine does not affect uric acid metabolism, and it apparently relieves gouty attacks by inhibiting the phagocytosis of uric acid crystals by leukocytes, a process that in some way produces the joint symptoms. Phenylbutazone and probenecid inhibit uric acid reabsorption in the renal tubules. Allopurinol, which directly inhibits xanthine oxidase in the purine degradation pathway, is one of the drugs used to decrease uric acid production.

Reference:
1. Ganong's Review of Medical Physiology: 23rd Edition. Kim E. Barrett et al. McGraw-Hill Publishing. 2010.

Arteriovenous Fistula

noreply@blogger.com (Unknown) — Thu, 12 May 2011 18:38:00 +0000

- Symptoms of arteriovenous fistula includes palpitations, weakness, fatigue, and coldness of the right foot.
- Patients may experience marked tachycardia, continuous murmur, and a diminished pulse.
- Pathology of this condition is an abnormal communication between artery and vein.
- Treatment for arteriovenous fistula is surgical repair if symptomatic and large; angiographic embolization if smaller. Ultrasound-guided direct compression is sometimes an option.
- Arteriovenous fistula may clinically present as high-output cardiac failure. Iatrogenic arteriovenous fistulas may be seen after arteriography.

Reference:
1. Blackwell's Underground Clinical Vignettes: Anatomy, 3rd Ed. Bhushan, Vikas, M.D., et al. Blackwell Science Publishing. 2002.

Friedrich B. Reinke

noreply@blogger.com (Unknown) — Thu, 12 May 2011 17:23:00 +0000

- Beginning at puberty, many Leydig cells display rod-shaped or wedge-shaped rectangular or diamond-shaped protein crystals in different numbers and sizes. These protein crystals are named Reinke crystals; named after anatomist, Friedrich B. Reinke (1862-1919).

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Franz von Leydig

noreply@blogger.com (Unknown) — Thu, 12 May 2011 17:22:00 +0000

- The Leydig cells synthesize mostly male hormones; the most important one is testosterone, and are named after the anatomist Franz von Leydig (1821-1910)

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Enrico Sertoli

noreply@blogger.com (Unknown) — Thu, 12 May 2011 17:20:00 +0000

- Sertoli cells are named after the histologist Enrico Sertoli (1842-1910). They are support cells and line the seminiferous tubules. With the exception of spermatogonia, Sertoli cells surround practically all germ cells.

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Karl Wilhelm von Kupffer

noreply@blogger.com (Unknown) — Thu, 12 May 2011 15:59:00 +0000

- The inner surfaces of the liver sinusoids are lined with fenestrated epithelium. Kupffer cells are other fixed cells in this lining. Because of their often star-like shape, they used to be called "stellate cells of Kupffer" (named after Karl Wilhelm von Kupffer, 1829-1902).

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Joseph Paneth

noreply@blogger.com (Unknown) — Thu, 12 May 2011 15:45:00 +0000

- Clusters of cells with apical granulation are found in the intestinal epithelium at the fundus of the crypts. These cells were named Paneth cells (Paneth cell glands) after Joseph Paneth (1857-1890) who first described them.

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Johannes Evangelista Purkinje

noreply@blogger.com (Unknown) — Mon, 09 May 2011 12:45:00 +0000

-J.E. Purkinje is the physiologist for whom Purkinje cells are named after.

Paul Ehrlich

noreply@blogger.com (Unknown) — Sat, 30 Apr 2011 06:06:00 +0000

- Mast cells contain a rounded nucleus. Their cytoplasm is loaded with basophilic, methachromic granules. Paul Ehrlich (1877) interpreted these as alimentary storage granules (Ehrlich's mast cells).

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Johann Jakob Harder

noreply@blogger.com (Unknown) — Sat, 30 Apr 2011 05:32:00 +0000

- In 1694, Johann Jakob Harder described a large gland in the medial upper quadrant of the orbit in a deer. Today, we know that it exists in many mammals and reptiles. Subsequently, this gland became known as the Harderian gland, although its function is still not completely elucidated.

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Adrenoleukodystrophy

noreply@blogger.com (Unknown) — Sat, 30 Apr 2011 05:27:00 +0000

- Genetic disease based on peroxisomal defect.

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.

Refsum Syndrome

noreply@blogger.com (Unknown) — Sat, 30 Apr 2011 05:26:00 +0000

- Genetic disease that is based on peroxisomal defect.

Reference:
1. Color Atlas of Cytology, Histology, and Microscopic Anatomy 4th Edition. Wolfgang Kuehnel, M.D. Thieme Publications. 2003.