Histology

Adiposis dolorosa (Dercum’s disease)

Adiposis dolorosa (Dercum's disease), coined by Dercum in 1892, is a rare disease of subcutaneous fat characterized by localized overgrowth of fat with painful subcuta­neous plaques. 

It is commonly seen in menopausal obese females and is often associ­ated with fatigue, weakness and severe emotional disturbances. The fat deposits give 'bag of worms' feel on palpation. The lesions may be localized or generalized, can occur anywhere but most common sites are the juxta articular areas. Pain occurs spontaneously or on pressure in cyclical pattern. Patient may lose weight and become asthenic as the disease progresses. The most common locations for painful fat and for lipomas are the extremities, the trunk, the pelvic area, and the buttocks. Dercum’s disease most commonly appears between the ages of 35 and 50 years. It is five to thirty times more common in women than in men and, originally, Dercum proposed that the condition mainly affects postmenopausal women. Furthermore, Dercum attributed the disease to an endocrine dysfunction such as thyroid gland or hypophyseal dysfunction. The disease does not respond to routine analgesics but only to IV lidocaine.

Histology

                                       

                                                        Aplastic Anemia

                    Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. Although the anemia is often normocytic, mild macrocytosis can also be observed in association with stress erythropoiesis and elevated fetal hemoglobin levels.

                    The FDA has approved a supplemental new drug application for eltrombopag (Promacta), an oral thrombopoietin receptor agonist, for the treatment of severe aplastic anemia in patients who fail to respond adequately to immunosuppressive therapy. Eltrombopag is already approved for the treatment of thrombocytopenia in patients with refractory chronic immune thrombocytopenia and for use in patients with chronic hepatitis C.

                                                   Purkinje fibers

                  Purkinje fibers are located in the inner ventricular walls of the heart, beneath the endocardium in a space called the sub endocardium. The Purkinje fibers are specialized conducting fibers larger than cardiomyocytes with fewer myofibrils, no T-tubules and a large number of mitochondria that are able to conduct cardiac action potential more quickly and efficiently than any other cells in the heart. These cells are connected together by desmosomes and gap junctions, but not by intercalated discs. Purkinje fibers allow the heart's conduction system to create synchronized contraction of its ventricles, and are, therefore, essential for maintaining a consistent heart rhythm.  

                                          Brown adipose tissue (BAT)

                               Brown adipose tissue (BAT) or brown fat is one of two types of fat or adipose tissue (the other being white adipose tissue, or white fat) found in mammals. It is especially abundant in newborns and in hibernating mammals. Its primary function is to generate body heat in animals or newborns that do not shiver.

Histology

                                                                     Scleroderma 

             Scleroderma is an autoimmune disease which means that it is a condition in which the body’s immune attacks its own tissue and causes inflammation and damage. Scleroderma (the name means ‘hard skin”) is a group of diseases that affect connective tissue in the body which results from an overproduction and accumulation of collagen in body tissues. Then, for unknown reasons, the immune system turns against the body, producing inflammation and the overproduction of collagen. Scleroderma involves tissue that gets hard or thick. It can also cause swelling or pain in the muscles and joints.

               Scleroderma’s main types are localized and systemic. Localized means the disease affects only certain parts of the body. Systemic means it can affect the whole body.

•       The localized type often affects only skin tissues. It does not harm major organs. It may get better or go away without help. But it can be severe in some people and can leave skin damage.

•       The systemic type affects the skin, tissues under it, blood vessels, and major organs.

          Scleroderma is more common in women than men. Choctaw Native Americans and African-Americans are more likely than Americans of European descent to develop the type of scleroderma that affects internal organs.

http://www.niams.nih.gov/health_info/scleroderma/scleroderma_ff.pdf

http://sclerodermacoping.com/map-scleroderma/

Histology

                                                  Marfan Syndrome

       Marfan syndrome is a genetic disorder that affects the connective tissue in many parts of the body.

      Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression.

        Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making fibrillin-1 protein. Fibrillin-1 binds to other fibrillin-1 proteins and other molecules to form microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Also, microfibrils store growth factor beta, or TGF-β , and release them at various times to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 and microfibrils, which leads to decreased microfibril formation. As a result, excess growth factors TGF-β are released and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues.

       There is no cure for Marfan syndrome, treatment focuses on preventing the various complications of the disease.

                         

http://disorders.eyes.arizona.edu/disorders/marfan-syndrome

http://www.glogster.com/faithbreen18/marfan-syndrome/g-6lkpl0ukh0id80elm3hu1a0

http://www.glogster.com/kathrynd/marfan-syndrome/g-6lo6plekddcpqv7fksfvpa0

Histology

                                                   Epithelial Metaplasia

                                                   Barrett’s esophagus

Metaplasia means the conversion, in postnatal life, of one cell type to another. 

Metaplasia is important for two reasons.

1)  We understand the normal developmental biology of the tissues that interconvert.

2)  Metaplasia predisposes to certain forms of neoplasia.

One of the examples of metaplasia is Barrett's metaplasia or the appearance of intestinal-like columnar tissue in the oesophagus. 

Barrett's metaplasia develops as a result of gastro–oesophageal reflux and is considered the precursor lesion for oesophageal adenocarcinoma. Barrett’s esophagus is a condition marked by an abnormality in the lining of the lower esophagus. It is believed to be due to severe, longstanding, gastroesophageal reflux disease (GERD).

Normally, the esophageal lining (the epithelium) consists of flat, layered cells similar to those in the skin. This squamous epitheliumtops abruptly at the junction of the esophagus with the stomach near the lower end of the lower esophageal sphincter. The epithelium of the rest of the gut, down to the anus, consists of a single layer of side-by-side rectangular cells, which is called columnar epithelium. In some people, the transition from squamous to columnar epithelium occurs higher within the esophagus than normal. There may also be islands of columnar epithelium above the normal junction of the stomach and esophagus. The process of cell change from flat, layered squamous to tall columnar epithelium is an example of metaplasia.

Columnar cells are more resistant to acid and pepsin and the metaplasia may be a defense against refluxed acid. 

http://www.sciencedirect.com/science/article/pii/S0304419X07000078

Microbiology

                                         

                                         Overview of Hypersensitivity Reactions

·                         Altered reaction to an Ag that results in pathologic reactions upon the exposure of a sensitized host to that Ag

·                         Not necessarily an “over-reactive” immune response, but an inappropriate one (“abnormally active”)

·                         Both endogenous and exogenous Ag may elicit hypersensitivity reactions

·                         The development of hypersensitivity diseases is often associated with the inheritance of particular susceptibility genes. 

·                         All reaction types have a sensitization phase and effector phase

·                         Hypersensitivity reflects an imbalance between the effector mechanisms of immune responses and the control mechanisms that serve to normally limit such responses.

·                         Four types based on the mechanism by which immune reactions initiate tissue injury

·                         Increasingly recognized that multiple mechanisms may be operative in any one hypersensitivity disease and some disease represent a continuum of reaction types.

Type	Prototype Disorder	Immune Mechanisms	Pathologic Lesions
Type I hypersensitivity (immediate)	Anaphylaxis; allergies; bronchial asthma (atopic forms)	Production of IgE antibody → immediate release of vasoactive amines and other mediators from mast cells; recruitment of inflammatory cells (late-phase reaction)	Vascular dilation, edema, smooth muscle contraction, mucus production, inflammation
Type II hypersensitivity	IMHA; Good pasture syndrome	Production of IgG, IgM → binds to antigen on target cell or tissue → phagocytosis or lysis of target cell by activated complement or Fc receptors; recruitment of leukocytes	Cell lysis; inflammation
Type III hypersensitivity (immune complex- mediated)	SLE; some forms of glomerulonephritis; serum sickness; Arthus reaction	Deposition of antigen-antibody complexes → complement activation → recruitment of leukocytes by complement products and Fc receptors → release of enzymes and other toxic molecules	Necrotizing vasculitis (fibrinoid necrosis); inflammation
Cell-mediated (type IV) hypersensitivity	Contact dermatitis; multiple sclerosis; type I, diabetes; transplant rejection; tuberculosis	Activated T lymphocytes → i) release of cytokines and macrophage activation; ii) T cell-mediated cytotoxicity	Perivascular cellular infiltrates; edema; cell destruction; granuloma formation

Cell biology

                                                         Cell cycle check point

            The cell cycle checkpoints determine if a cell is ready to progress to the next stage.

            Late in the G1 phase, the G1 checkpoint determines if the cell will enter the following S phase.

            In animals, the G1 checkpoint or restriction point, is largely controlled by growth factors.

The G2 checkpoint determines if the cell will enter the M phase and requires the proper completion of DNA synthesis.

         The third cell cycle checkpoint is the spindle assembly checkpoint which occurs between metaphase and anaphase and requires the proper attachment of all the chromosomes to the spindle apparatus.

          The fusion of cells in different stages of the cell cycle (to form a heterokaryon) demonstrated that lat    ter stages possess factor trigger progression. 

G1 + S _____ G1 nucleus enters S phase immediately. 
S + G2 _____  G2 nucleus does not enter S phase before mitosis. 
M+ G1, S or G2  ____non-M phase nuclei enters mitosis, whether or not the DNA is duplicated.