Keratin & collagen Flashcards
What is keratin?
Diverse structural proteins for intermediate filament network
How many keratin families? Divided in?
30 different keratin families
➤ acidic or basic
Functions of keratin?
o Influence architecture and mitotic activity of epithelial cells
o Scaffold aids to sustain mechanical stress, maintain structural integrity, mechanical resilience, protects against hydrostatic pressure
o Involved in cell signalling, cell transport, cell differentiation, apoptosis
o Influence metabolic processes
o Transport of vesicles
Keratin - Disease result as a mutation of …
Occur as a result of mutation in the genes encoding the keratin protein
Examples of keratin related disorders?
o Epidermolysis bullosa (EB): large heterogeneous diseases- 1,000 mutations- increased fluid filled blister formation
o Epidermolysis bullosa simplex (EBS): numerous mutations some very rare forms are lethal- blistering with secondary infections often issue
o Mutations in hair and nails
Give an example of disorder of keratin associated proteins
Pemphigus
What is pemphigus? What does it affect? What is the treatment?
- Pemphigus affects skin and mucus membrane often affects pressure points
- Autoimmune disease ➤ intraepithelial blistering disease.
- Lesions later become dry and hyperkeratotic and fissured.
- Can be life threatening affect desmosomes.
- Tx: corticosteroids (local and systemic) and other immunosuppressive agents and supportive therapies
What can cause pemphigus? How does it resolve?
o Can get drug induced pemphigus- days, weeks or months after prescription
o Rare – 200 cases in literature
o Drugs include- Thiol drugs includes enalapril; Antibiotics- penicillin, vancomycin, cephalosporins; Antihypertensive drugs; piroxicam
o 50% resolve when medication withdrawn, otherwise treatment corticosteroids
How many people are affected by psoriasis? Which gender?
Psoriasis –affects 20% of the population occurs both genders
Is psoriasis infectious?
No
What is psoriasis link to?
T cells malfunction
When is psoriasis onset?
Onset anytime but more common in second and third decades- can have periods of remissions- worse in winter
What is the distribution of psoriasis?
Symmetric distribution lesions elbows scalp knees- plaques slivery in appearances
Those with moderate to severe psoriasis can also present with what?
30% inflammatory arthritis - swelling and stiffness in the joints. Can affect any joint.
People suffering from psoriasis are at increased risk of what?
anxiety
depression
heart d/s
stroke
What can trigger psoriasis?
- Certain medications can cause psoriasis to flare- beta blockers, lithium
- Other triggers: infections, stress and/or alcohol, smoking, vit D deficiency, injury to skin
Risk factors for psoriasis
o Family Hx o Viral and bacterial infections- HIV recurrent strep infections o Stress o Obesity o Smoking
Signs & symptoms of psoriasis
o Worsening of long term erythematous scaly area
o Sudden area of small areas of scaly redness
o Recent strep infection, trauma, immunization, viral infection,
o Pain (psoriatic arthritis)
o Pruritus
o Can affect eye lids- corneal involvement rare
Psoriasis - Tx
o Topical: corticosteroids, vitamin D and vitamin D analogues, tar preparations etc
o Second line: phototherapies and systemic non-biological agents e.g. methotrexate
o Third line: systemic biological therapies TNF antagonists
Psoriasis - Cx
o Secondary infections o Psoriatic arthritis o Mitral valve prolapse o Increased risk of lymphoma o Increased risk CVD and IHD
Types of psoriasis
- Scalp
- Inverse (under the breast, groin, armpits) ➤ smooth ,dry & well-defined salmon-coloured patches
- Erythrodermic (entire body surface) ➤ scales + itch
- Nails (finger + toes) ➤ become pitted, discoloured, thickened and loose
- Guttate (trunk, torso, face) ➤ not as red or scaly as plaque psoriasis and looks like ‘droplets’ on the skin
- Pustular (thumb, palm of fingers and soles of the feet) ➤ large fluid-filled blister-like areas
- Plaque (knees, elbows, lower back, ears, scalp) ➤ red plaques surrounded by white silvery scales, itchy and sore
Itchthyosis - What is it?
Continuous scaling affects the whole body
Itchthyosis - caused by what?
- Mostly congenital but rare forms due to malignancy, nutritional deficiency, infection, autoimmune
- Abnormal epidermal differentiation
- Barrier function is compromised ➤ decreased ability to protect
- Mutations in over 50 genes ➤ alter host of cellular activities
Itchthyosis - types
- Non syndromic includes Ichthyosis vulgaris (IV) 1 in 250 births typically mild- autosomal dominant in filaggrin gene - epidermal differentiation and barrier
- Syndromic - eg affect least 1 other organ eg Sjögren Larsson syndrome
Itchthyosis - Tx
o No cure ➤ manage
o Twice daily intensive use of moisturisers can contain antiseptics/antibiotics
o Sometimes use of retinoids
Disorders of collagen - example?
Elhers-Danlos syndromes
What is the most abundant protein?
90% collagen type I
Disorders of collagen - how many types described?
28
EDS - what is it? S&S? Management?
o Group rare inherited conditions that affect connective tissue
o Increased ROM
o Stretchy skin which bruises easily
o Fragile skin but other issues in some mutations include rupture of arteries, organs blood vessels depending on mutation
o Can be mild or severe causing disabilities and death
o Advised to help maintain their health – avoid contact sport, care with heavy lifting, wear protective clothing
