Senin, 31 Oktober 2011

Behçet’s disease-Short note


Behçet’s disease
  • Idiopathic multisystem disease 
  • More common in men
  • Occurs in 3rd - 4th decade
  • Highest incidence in Mediterranean region and Japan
  • Associated with HLA-B5


Aetiology
: Unknown
Various bacteria and viruses suggested
No good evidence to suggest any of them
Perpetuated by autoimmune response and CD4 + T-cells
Tumour necrosis factor (TNF) thought to be important

Oral aphthous ulceration – 100%


Genital ulceration – 90%


Skin lesions – 80%
Erythema Nodosum
  • Acneiform
  • Uveitis 70% (inflam. of iris, ciliary body or choroid)
 

CNS involvement – strokes, fits

Major vessels eg superior Vena cava obstruction
Increased skin response to trauma eg blood taking

Ocular Features

Acute iritis
  • Pain, redness & ¯VA
  • Flare (PTN exudation)
  • Inflammatory cells in anterior chamber
  • KPs (Inflammatory cells at posterior surface of cornea)
 
Recurrent hypopyon
  • (Fluid level of WBC)
  • The red or white eye

Marked inflammation of the eye
Retinal vasculitis and haemorrhage (inflam. of retinal vessels)
Occlusive periphlebitis (venous sheathing &  occlusion)
Retinal microinfarcts
Very damaging to vision: retinal damage and optic nerve atrophy
Cataract or glaucoma


Treatment

  • Systemic Steroids
  • Systemic immunosuppressive agents
  • Interferon-alpha may have immunodulating effects
  • Anti-TNF monoclonal antibodies may be of help



Mucocele, Ranula and Dermoid cyst-Short note


Mucocele
Mucocele of lower lip

Mucocele of Tongue


Definition Mucoceles, or mucous cysts, are a common phenomenon or lesion of the oral mucosa, originating from minor salivary glands and their ducts.

Etiology Local minor trauma and duct rupture or ductal obstruction, probably due to a mucous plug.

Clinical features Two main types of mucocele are recognized, according to their pathogenesis: extravasation mucocele (common), which results from duct rupture due to trauma and spillage of mucin into the surrounding soft tissues; and mucous retention cyst (uncommon), which usually results fromductal dilation due to ductal obstruction. 

Clinically, mucocele presents as a painless, dome-shaped, solitary, bluish or translucent, fluctuant swelling that ranges in size from a few millimeters to several centimeters in diameter. A common finding is that the cyst partially empties and then re-forms due to the accumulation of new fluid. The lower lip is the most common site of involvement, usually laterally, at the level of the bicuspids. Less common sites are the buccal mucosa, tongue, floor of the mouth, and soft palate. Extravasation mucoceles display a peak incidence during the second and third decades, while the mucous retention types are more common in older age groups.

Laboratory tests Histopathological examination.

Differential diagnosis Lymphangioma, hemangioma, lipoma, mucoepidermoid carcinoma, Sjögren syndrome, lymphoepithelial cyst.

Treatment Surgical excision or cryosurgery.

Ranula
Ranula
 

Definition Ranula is a formof mucocele that occurs exclusively on the floor of the mouth.

Etiology Trauma or ductal obstruction.

Clinical features It presents as a smooth, fluctuant, painless swelling on the floor of the mouth, lateral to the midline. The color ranges fromnorm al to a translucent bluish, and the size is usually in the range of 1–3 cm, or larger. The diagnosis is usually based on clinical  criteria.

Laboratory tests Histopathological examination.

Differential diagnosis Dermoid cyst, abscess, hemangioma, lymphangioma, lymphoepithelial cyst.

Treatment Surgical removal or marsupialization.

Dermoid Cyst
Dermoid cyst


Definition and etiology Dermoid cyst is an uncommon developmental cystic lesion arising from embryonic epithelial remnants.

Clinical features It presents as a slow-growing, painless swelling with a normal or yellowish-red color and a characteristic soft dough like consistency on palpation. The size varies from a few millimeters to 10 cm in diameter, and the lesion usually occurs in the midline of the floor of the mouth. If the cyst is located above the geniohyoid muscle, it can displace the tongue upward and create difficulty in mastication, speech, and swallowing. When the cyst occurs below the geniohyoid muscle, it may protrude submentally. Rarely, dermoid or epidermoid cysts may develop in the lips. The cyst frequently appears in early adulthood.

Laboratory tests Histopathological examination.

Differential diagnosis Ranula, abscess, lymphoepithelial cyst, cystic hygroma.

Treatment Surgical removal.

Jumat, 28 Oktober 2011

Examination of Eye-Video

Systematic way of Examining the Eye-Video
  • Brief introductionBrief introduction
  • USE the alcohol cleansing gel BEFORE you touch the patient
  • Ask ––‘‘May I examine you?’’
  • Ask ––‘‘Is your ear/nose/neck tender?’

Neck Examination Video

Systematic way of Examining the of Neck-Video

  • Brief introductionBrief introduction
  • USE the alcohol cleansing gel BEFORE you touch the patientyou patient
  • Ask ––‘‘May I examine you?you?’’
  • Ask ––‘‘Is your ear/nose/neck tender?tender?’



Regeneration healing (repair)-General Pathology Lecture note



Objectives of this Post
  • Review the normal physiology and concepts of cell proliferation, cell growth, cell “cycle”, and cell differentiation
  • Understand the basic factors of tissue regeneration
  • Understand the relationships between cells and their extracellular matrix (eECM)
  • Understand the roles of the major players of healing---angiogenesis, growth factors (GFS), and fibrosis
  • Differentiate 1st & 2nd intention healing
Definitions:
Regeneration: growth of cells to replace lost tissues
Healing: a reparative tissue response to a wound, inflammation or necrosis, often leads to fibrosis 
Granulation tissue 
“Organizing” inflamation

Regeneration
  • Replacement of lost structures
  • Is dependent on the type of normal turnover the original tissue has
  • Can be differentiated from “compensatory” growth

Healing (repair)
  • Needs a wound, inflammatory process, or necrosis
  • Many disease appearances anatomically are the result of “healing” such as atherosclerosis
  • Often ends with a scar
  • Fibrosis, as one of the 3 possible outcomes of inflammation, follows “healing”
  • Requires a connective tissue “scaffold”
  • Fibrosis occurs in proportion to the damage of the ECM
 
Cell population fates
Proliferation
  • Hormonal, especially steroid hormones
  • Eg., EPO, CSF
Differentiation*
  • Unidirectional, gain and loss

Apoptosis
*One of the most key concepts in neoplasia
  • Ectoderm
  • Mesoderm
  • Entoderm

Cell cycle

G0
Quiescent (not a very long or dominent phase)

G1
Pre-synthetic, but cell growth taking place

S
  • Cells which have continuous “turnover” have longer, or larger s-phases, i.e., dna synthesis
  • S-phase of tumor cells can be prognostic
G2
Pre-mitotic

M (mitotic:, P,M,A,T cytokinesis)

Cell types
Labile: eg. marrow, GI
Quiescent: liver, kidney
Non-mitotic: neuron, striated muscle

Stem cells (totipotential*)
  1. Embryonic
  2. Adult
Embryonic stem cells
  • Differentiation
  • Knockout mice (mice raised with specific gene defects)
  • Repopulation of damaged tissues, in research
Adult Stem cells

Marrow (hemocytoblast)
(hematopoetic stem cells)

Non-marrow (reserve)

Marrow stromal cell

Adult tissue differentiation and regeneration parallels embryonic development

Growth factors (GFS)
Polypeptides
Cytokines
  • Locomotion
  • Contractility
  • Differentiation
  • Angiogenesis
Growth factors (GFS)
Epidermal
Transforming (alpha, beta)
Hepatocyte
Vascular endothelial
Platelet derived
Fibroblast
Keratinocyte
Cytokines (TNF, IL-1, interferons)


Cell players (source and targets)
  • Lymphocytes, especially t-cells
  • Macrophages
  • Platelets
  • Endothelial cells
  • Fibroblasts
  • Keratinocytes
  • “mesenchymal” cells
  • Smooth muscle cells
E(epidermal) GF
  • Made in platelets, macrophages
  • Present in saliva, milk, urine, plasma
  • Acts on keratinocytes to migrate, divide
  • Acts on fibroblasts to produce “granulation” tissue
T(transforming) GF-alpha
  • Made in macrophages, t-cells, keratinocytes
  • Similar to egf, also effect on hepatocytes
H(hepatocyte) GF
  • Made in “mesenchymal” cells
  • Proliferation of epithelium, endothelium, hepatocytes
  • Effect on cell “motility”
Ve(vascular endothelial) GF
  • Made in mesenchymal cells
  • Triggered by hypoxia
  • Increases vascular permeability
  • Mitogenic for endothelial cells
  • Key substance in promoting “granulation” tissue
Pd(platelet derived) GF
  • Made in platelets, but also many other cell types
  • Chemotactic for many cells
  • Mitogen for fibroblasts
  • Angiogenesis
  • Another key player in granulation tissue
F(fibroblast) GF
  • Made in many cells
  • Chemotactic and mitogenic, for fibroblasts and keratinocytes
  • Re-epithelialization
  • Angiogenesis, wound contraction
  • Hematopoesis
  • Cardiac/skeletal (striated) muscle
T(transforming) GF-beta
  • Made in many cells
  • Chemotactic for PMNS and many other types of cells
  • Inhibits epithelial cells
  • Fibrogenic
  • Anti-inflammatory
K(keratinocyte) GF

  • Made in fibroblasts
  • Stimulates keratinocytes:
    • Migration
    • Proliferation
    • Differentiation
I (insulin-like) GF-1
  • Made in macrophages, fibroblasts
  • Stimulates:
    • Sulfated proteoglycans
    • Collagen
    • Keratinocyte migration
    • Fibroblast proliferation
  • Action similar to gh (pituitary growth hormone)
TNF (tumor necrosis factor)
  • Made in macrophages, mast cells, t-cells
  • Activates macrophages
  • Key influence on other cytokines
Interleukins
  • Made in macrophages, mast cells, t-cells, but also many other cells
  • Many functions:
  • Chemotaxis
  • Angiogenesis
  • Regulation of other cytokines

Interferons
  • Made by lymphocytes, fibroblasts
  • Activates macrophages
  • Inhibits fibroblasts
  • Regulates other cytokines
Signaling
  • Autocrine (same cell)
  • Paracrine (next door neighbor) (many gfs)
  • Endocrine (far away, delivered by blood, steroid hormones)

Transcription factors
Hepatic
Regeneration
  • TNF
  • IL-6
  • HGF

Extracellular matrix (ECM)
  • Collagen(s) I-xviii
  • Elastin
  • Fibrillin
  • Cams (cell adhesion molecules)
    • Immunoglobulins, cadherins, integrins, selectins
  • Proteoglycans
  • Hyaluronic acid
ECM
  • Maintain cell differentiation
  • “scaffolding”
  • Establish microenvironment
  • Storage of GF’s
  1. Collagen one - bone (main component of bone)
  2. Collagen two - cartwolage (main component of cartilage)
  3. Collagen three - rethreeculate (main component of reticular fibers)
  4. Collagen four - floor - forms the basement membrane
Genetic collagen disorders
  • I                               osteogenesis imperfecta, e-d
  • Ii                              achondrogenesis type ii               
  • Iii                             vascular ehlers-danlos
  • V                             classical  e-d
  • Ix                            stickler syndrome
  • Iv                            alport syndrome
  • Vi                            bethlem myopathy
  • Vii                           dystrophic epidermolysis bullos.
  • Ix                            epiphyseal dysplasias
  • Xvii         gen. Epidermolysys bullosa
  • Xv, xviii knobloch syndrome

Definitions:
Regeneration: growth of cells to replace lost tissues
Healing: a reparative tissue response to a wound, inflammation or necrosis

Healing
  • Follows inflammation
  • Proliferation and migration of connective tissue cells
  • Angiogenesis (neovascularization)
  • Collagen, other ecm protein synthesis
  • Tissue remodeling
  • Wound contraction
  • Increase in wound strength (scar = fibrosis)
Angiogenesis (neovascularization)
  • From endothelial precursor cells
  • From pre-existing vessels
  • Stimulated/regulated by gf’s, especially VEGF
  • Also regulated by ECM proteins
  • AKA, “granulation”, “granulation tissue”, “organization”, “organizing inflammation”



Wound healing
1 intention
Edges lined up
 
2 intention
Edges not lined up
Ergo….
More granulation
More epithelialization
More fibrosis



“Healthy” granulation tissue

Fibrosis/scarring
  • Deposition of collagen by fibroblasts
  • With time (weeks, months, years?) The collagen becomes more dense, ergo, the tissue becomes “stronger”
Wound retarding factors (local)
  • Decreased blood supply
  • Denervation
  • Local infection
  • FB
  • Hematoma
  • Mechanical stress
  • Necrotic tissue
Wound retarding factors (systemic)
  • Decreased blood supply
  • Age
  • Anemia
  • Malignancy
  • Malnutrition
  • Obesity
  • Infection
  • Organ failure