microorganisms of human disease unit 5: 6 days. april 28 th : skin and eyes the skin is a physical...

Microorganisms of Human Disease

Unit 5: 6 days

April 28th: Skin and Eyes

• The skin is a physical and chemical barrier against microorganisms

• Moist areas of the skin support larger populations of bacteria than dry areas

Eye and Skin Anatomy Review

Normal Microbiota

• Microbes that live on the skin are resistant to desiccation and high salt concentrations

• Gram-positive cocci are abundant on the skin

• The normal skin microbiota are not completely removed by washing

• Some metabolize oil and grow in hair follicles

Vocabulary

• Vesicles are small fluid filled legions• Bullae are vesicles larger than 1 cm• Macules are flat reddened lesions• Papules are raised lesions• Pustules are raised lesions containing pus

Bacterial Diseases of the Skin

• Staphylococcal skin infections:– Gram positive bacteria that grow in clusters– S. aureus is common– Localized infections result from bacteria

entering skin openings• Sties, pimples, and carbuncles

– Toxemia occurs when toxins enter the bloodstream


• Streptococcal skin infections:– Gram positive cocci that often grow in chains– Classified according to their cell wall antigens– S. pyrogenes is common

• Most important pathogen to humans• Impetigo are isolated pustules


• Pseudomonads:– Gram negative rods– Aerobes found in soil and water – Resistant to many disinfectants and

antibiotics– P. aeruginosa causes otitis externa,

respiratory infections, burn infections, and dermatitis

– Have blue green pus


• Acne:– Propionibacterium acnes can metabolize

sebum trapped in hair follicles– Metabolic end-products (fatty acids) cause an

inflammatory response known as acne– Many drugs are used to treat acne

Viral Diseases of the Skin

• Warts:– Papillomaviruses cause skin cells to

proliferate and produce a benign growth– Warts are spread by direct contact– Warts may regress spontaneously or be

removed physically or chemically


• Smallpox:– Variola– Cause two types of skin infections, variola

major and variola minor– Transmitted by the respiratory route– Moved to the skin via the bloodstream– Humans are the only host– Eradicated as a result of the efforts by the

WHO


• Chickenpox and Shingles:– Varicella and Herpes Zoster– Caused by the Varicella-zoster Virus– Transmitted by the respiratory tract– Localized in skin cells– After chickenpox the virus remains latent in

nerve cells and be activated as shingles– A vaccine is now available


• Herpes simplex:– Cold sores and occasional encephalitis– Remains latent inside of nerve cells– Cold sores recur when the virus is activated– Transmitted by oral and respiratory routes– Herpes encephalitis occurs when herpes

infects the brain


• Measles:– Rubeola – Transmitted by respiratory route– Vaccinations provides effective long term

immunity– Macular lesions occur on the skin and Koplik

spots occur on the oral mucosa– Complications include middle ear infections,

pneumonia, encephalitis, and secondary bacterial infections


• Rubella:– Transmitted by the respiratory route– Called German measles– Can be asymptomatic– Red rash and light fevers are common– Congenital rubella syndrome can affect a

fetus• Exposure during first trimester• Stillbirth, deafness, eye cataracts, heart defects,

mental retardation• Vaccination easily available

Fungal Diseases of the Skin

• Cutaneous mycoses:– Fungi that colonize the outer layer of the

epidermis cause dermatomyces– Ringworm and athlete’s foot are common

fungal infections– Can also grow on hair and nails


• Subcutaneous mycoses:– Sporotrichosis results from a soil fungus that

penetrates the skin through wounds– The fungi grow and produce subcutaneous

nodules along the lymphatic vessels


• Candidiasis:– Candida albicans causes infections of

mucous membranes and is a common cause of thrush and vaginitis

– C. albicans is an opportunistic pathogen that may proliferate when the normal bacterial microbiota are suppressed

– Topical antifungal chemicals may be used to treat candidiasis

Parasitic Infestations of the skin

• Scabies is caused by a mite burrowing and laying eggs in the skin

• Topical application of gamma benzene hexachloride is used to treat scabies

Microbial Diseases of the Eye

• The mucous membrane lining the eyelid and covering the eyeball is the conjunctiva


• Inflammation of the eye membrane:– Conjunctivitis– Caused by several bacteria– Transmitted by improperly disinfected contact

lenses


• Bacterial diseases of the eye:– Microbiota of the eye usually originate from

the skin and upper respiratory tract– Neonatal gonorrheal opthalmia is caused by

the transmission from an infected mother to an infant during its passage through the birth canal

– Chlamydia is also transmitted by birth and unchlorinated swimming water


• Other infectious diseases of the eye:– Inflammation of the cornea is called keratitis– Herpetic keratitis causes corneal ulcers– Acanthamoeba is transmitted in water and

can cause severe keratitis

April 30th: Nervous System

• CNS and PNS

Review

Neurons and Synaptic Cleft Review

Bacterial Meningitis

• Meningitis can be caused by bacteria, viruses, fungi, and protozoa

• The three major causes of bacterial meningitis are:– Hemophilus influenzae– Neisseria meningitidis– Streptococcus pneumoniae

• Nearly 50 species of opportunistic bacteria can cause meningitis


• Hemophilus influenzae– Part of the normal throat microbiota– There are six different types, based on

capsule differences– Most common cause of meningitis in children

under 4– A vaccine is available


• Neisseria meningitidis– Meningococcal meningitis– Found in the throats of healthy carriers– Probably gain access to the meninges

through the bloodstream– Bacteria may be found in leukocytes in CSF– Symptoms are due to endotoxins– Most common in young children– military and college students vaccinated


• Streptococcus pneumoniae– Pneumococcal meningitis– Commonly found in the nasopharynx– Hospitalized patients and young children are

the most susceptible– Rare, but has a high mortality rate– Vaccine is available

Diagnosing Bacterial Meningitis

• Diagnosis is based on isolation and identification in CSF

• Cultures are usually made on blood agar

• Incubation is in atmospheres with reduced oxygen


• Listeria monocytogenes– Listeriosis– Causes meningitis in newborns, pregnant

women, the immunosuppressed, and cancer patients

– Acquired by ingestion of contaminated foods– May be asymptomatic in healthy adults– Can cross the placental barrier and cause

spontaneous abortion and stillbirth

Tetanus

• Caused by a localized infection of a wound by Clostridium tetani

• Produces a neurotoxin• Symptoms:

– Spasms, contraction of muscles controlling the jaw, and death resulting in spasms of the respiratory muscles

• Anaerobe, will grow in deep wounds, and wounds with little bleeding

Tetanus

• Acquired immunity results from vaccination

• Following an injury a person may need a booster shot with tetanus toxoid

• An unimmunized person will receive a shot with human tetanus immune globin

• Debridement (removal of tissue) and antibiotics may be used to control the infection

Botulism

• Caused by an exotoxin produced by C. botulinum growing in food

• Different types of botulism toxin vary in virulence– Type A is the most virulent

• The toxin inhibits the transmission of nerve impulses

Botulism

• Blurred vision occurs in 1 – 2 days• Progressive flaccid paralysis follows for 1

– 10 days• Possibly death results from respiratory and

cardiac failure

Botulism

• C. botulinum will not grow in acidic foods or in an aerobic environment

• Endospores are killed by proper canning• The toxin is heat labile and is destroyed by

boiling for 5 minutes

Leprosy

• Never been cultured on artificial media• Has been cultured in armadillos• Characterized by loss of sensitivity in the

skin surrounded by nodules• Not highly contagious, but can be

transmitted by prolonged contact with exudates

• Untreated individuals often die from secondary bacterial complications

Viral Diseases of the Nervous System

• Poliomyelitis– Headache, sore throat, fever, stiffness of back

and/or neck, occasionally paralysis– Transmitted by water contaminated with feces

• Rabies– Acute, usually fatal encephalitis– Multiplies in skeletal muscle and connective

tissue– Virus moves along PNS to the CNS

Fungal Diseases of the Nervous System

• Cryptococcus neoformans meningitis– Contracted by inhalation of dried pigeon

droppings– Begins as a lung infection– Most common in immunosuppressed

individuals

Protozoan Diseases of the Nervous System

• African Trypanosomiasis– Caused by Trypanosoma brucei gambiense

and T. b. rhodesiense– Transmitted by the tsetse fly– Causes lethargy and eventually coma– Can change its surface antigens

• Naegleria Meningoencephalitis– Almost always fatal– Invades the brain from the nasal mucosa

Nervous System Disorders caused by Prions

• Diseases of the CNS that progress slowly and cause spongiform degeneration are caused by prions

• Sheep scrapie and bovine spongiform encephalopathy are examples of diseases caused by prions that are transferable from one animal to another– Creutzfeldt-Jakob and kuru are others

• Prions are self-replicating proteins with no detectable nucleic acid

May 5th: Cardiovascular and Lymphatic Systems

Bacterial Diseases of the Cardiovascular and Lymphatic Systems

• Septicemia, sepsis, and septic shock:– The growth of microbes in the blood is called

septicemia– Can lead to septic shock, which is

characterized by decreased blood pressure– Usually results from a focus of infection in the

body– Usually gram negative rods– Usually caused by endotoxins


• Puerperal sepsis:– Begins as a uterine infection following

childbirth or abortion– Streptococcus pyrogenes is the most frequent

cause– Holmes and Semmelweiss demonstrated

appropriate hand washing techniques as a prevention of this disorder

– Now relatively uncommon


• Tularemia:– Caused by Francisella tularensis – Small wild mammals are the reservoir– Signs include ulceration and the site of entry

followed by septicemia and pneumonia– Humans contract it by handling diseased

carcasses, eating undercooked meat, and being bitten by vectors (such as deer flies)

– Resistant to phagocytosis


• Rheumatic fever:– Autoimmune complication of streptococcal

infections– Expressed as arthritis or inflammation of the

heart, can result in permanent damage• Often heart valves are targeted

– Can follow strep throat


• Anthrax:– Endospores in soil can survive for up to 60

years– Grazing animals acquire an infection after

ingesting the endospores– Humans contract it after handling hides from

infected animals• Bacteria enter through cuts and by inhalation

– Pustules or pneumonia can occur depending on entry route


• Gangrene:– Soft tissue death from ischemia (loss of blood

supply)– Microorganisms grow on nutrients released

from gangrenous cells– Can occur during improperly performed

abortions when bacteria invade the uterine wall

– Debridement, hyperbaric chambers, and amputation are used to treat gangrene


• Plague:– Caused by Yersenia pestis – Vector is usually a flea– Bruises on the skin and enlarged lymph

nodes (buboes)– The bacteria can enter the lungs and cause

pneumonic plague– Antibiotics are effective but they must be

administered promptly after exposure


• Lyme disease:– Transmitted by ticks– Prevalent on the U.S. Atlantic coast– Field mice provide an animal reservoir


• Typhus:– Caused by rickettsias, obligate intracellular

parasites of eukaryotic cells– Transmitted by lice– Prevalent in crowded unsanitary locations– Rash, prolonged high fever, and stupor– Spotted fevers are a variation of typhus

• Often transmitted by ticks• Endemic to the southeastern U.S., Appalachia, and

the Rocky Mountains

Viral Diseases of the Cardiovascular and Lymphatic Systems

• Burkitt’s Lymphoma:– Caused by the Epstein-Barr virus– Causes cancer in laboratory monkeys– Common in immunosuppressed patients

• Infectious mononucleosis:– Also caused by the EB virus– Causes proliferation of atypical lymphocytes– Transmitted by ingestion of saliva from

infected individuals


• Classic viral hemorrhagic fevers:– Yellow fever and Dengue fever are passed by

the vector Aedes aegypti mosquito• Yellow fever: fever, chills, headache, nausea, and

jaundice• Dengue fever: fever, muscle and joint pain, and

rash

– Mosquito reduction is necessary to control these diseases


• Emerging viral hemorrhagic fevers:– Human diseases caused by Marburg, Ebola,

and Lassa fever viruses were first noticed in the late 1960’s

– Marburg virus is found in nonhuman primates– Lassa fever viruses are found in rodents– Rodents are the reservoirs of Argentine and

Bolivian hemorrhagic fevers– Hantavirus pulmonary syndrome is contracted

by the inhalation of dried rodent urine

Protozoan Diseases of the Cardiovascular and Lymphatic Systems

• Chagas’ disease:– Trypanosoma cruzi causes Chagas’ disease– The reservoir includes many wild animals– The vector is an arthropod called ‘the kissing

bug’


• Toxoplasmosis:– Caused by the sporozoan Toxoplasma gondii– Undergoes sexual reproduction in the

intestinal tract of domestic cats– Oocysts are eliminated in cat feces– Oocysts are then ingested by cattle and other

animals– Humans contract by eating undercooked meat– Congenital issues include brain damage and

vision problems


• Babeiosis:– Caused by the protozoan Babesia microti – Transmitted to humans by ticks

• Malaria:– Chills, fever, vomiting, and headache– Transmitted by the Anopheles mosquito– Causative agent is a species of Plasmodium– A vaccine is being developed

Helminthic Diseases of the Cardiovascular and Lymphatic Systems

• Schistosomiasis:– Species of blood fluke– Eggs eliminated in feces hatch and infect an

intermediate host (snails)– Free swimming cercariae are released and

penetrate the skin of a human– Adult flukes live in veins of the liver or bladder– Chemotherapy is used to treat the disease– Snail eradication is used to prevent it

Helminthic Diseases of the Cardiovascular and Lymphatic Systems

• Swimmer’s itch:– Cutaneous allergic reaction to cercariae that

penetrate the skin– The definitive host for the fluke is wildfowl

May 8th: Respiratory Systems

Normal Microbiota of the Respiratory System

• The throat and nasal cavity normal microbes can include pathogenic species

• The ciliary elevator

usually keeps the

lower portion sterile

Upper Tract

• Specific areas can become infected to produce pharyngitis, laryngitis, tonsillitis, sunusitis, and epiglottitis

• Often caused by bacteria and viruses in combination

• Most infections are self-limiting

Bacterial Diseases

• Streptococcal Pharyngitis:– Strep throat– Inflammation of the mucous membrane and

fever, tonsillitis, and otitis media– Strep throat is usually transmitted by droplets

but at one time was commonly associated with unpasteurized milk

Bacterial Diseases

• Scarlet Fever:– Caused by strep throat

from S. pyrogenes– Produces erythrotoxins

when lysogenized by a phage

– Symptoms include red rash, high fever, and a red enlarged tongue

Bacterial Diseases

• Diptheria:– Caused by exotoxin– A membrane containing fibrin and dead

human and bacterial cells forms in the throat• Can block the passage of air

– Inhibits protein synthesis• Can cause heart, kidney, or nerve damage

Copyright Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong

Bacterial Diseases

• Otitis Media:– Earache– Can be a complication of nose and throat

infections– Pus accumulation causes pressure on the

eardrum

Viral Diseases

• The Common Cold:– Approximately 200 different viruses can be

the cause• Rhinovirus is responsible for ~50%

– Sneezing, congestion, nasal secretions– Typically transmitted by indirect contact– Incidence increases during the winter

• Likely due to the increased interpersonal indoor contact

Lower Respiratory System

• Many of the microorganisms that infect the upper respiratory system also infect the lower tract

• Diseases include bronchitis and pneumonia

Bacterial Diseases

• Pertussis:–Whooping cough–Catarrhal stage – resembles cold–Paroxysmal stage – accumulation of

mucus and deep coughs–Convalescence stage – can last for

months– Immunization is available

Bacterial Diseases

• Tuberculosis:– Bacteria have lots of lipids in their cell wall– Ingested, and then the bacteria reproduce in

the macrophages– Lesions form in the lungs– Treatment typically requires chemotherapy for

1 – 2 years– Positive skin tests remain after exposure

Bacterial Diseases

• Bacterial Pneumonias:–More than 8 different varieties–Fever, breathing difficulty, chest pain,

rust colored sputum–Many produce ‘fried egg’ colonies–Some transmitted person to person,

some from moist air, some from fowl droppings

Viral Diseases

• Influenza:– Chills, fever, headache, muscle aches– Many varieties, antigenic shifts

• Make natural immunity and vaccination less effective

– Deaths are usually from secondary bacterial infections

Fungal Diseases

• Histoplasmosis:– Subclinical– In rare cases develops into a severe

generalized disease– Caused by inhalation of airborne conidia

Fungal Diseases

• Coccidioidomycosis:– Caused by inhalation of the airborne

arthrospores– Most cases are subclinical– Fatigue or poor nutrition can cause a disease

resembling tuberculosis to result

Fungal Diseases

• Pneumocystis Pneumonia:– Pneumocystis carinii is found in healthy

human lungs– Cause disease in immunosuppressed people

Fungal Diseases

• Blastomycosis:– Infection begins in the lungs and can spread

to cause extensive abscesses

Fungal Diseases

• Other Fungal Diseases:– Opportunistic fungi can cause respiratroy

disease in immunosuppressed hosts• Especially when large numbers of spores are

inhaled

May 12th: Digestive System

Normal Microbiota

• A wide variety of bacteria colonize the mouth

• The stomach and small intestines have only a few permanent residents

• The large intestines have a LOT– Assist in degrading food– Synthesize vitamins– Up to 40% of fecal mass is microbial cells

Bacterial Diseases of the Mouth

• Dental Caries:– Tooth decay– Begin when tooth enamel and dentin are

eroded and the pulp is exposed to bacterial infection

– Bacteria adhere to teeth and produce sticky dextran, forming dental plaque

Bacterial Diseases of the Mouth

• Periodontal Disease:– Caries of the cementum and gingivitis are

caused by streptococci, actinomyces, and anaerobic gram-negative bacteria

– Chronic gum disease can cause bone destruction and tooth loss

– Periodontitis is due to an inflammatory response to a variety of bacteria growing under the gums

Bacterial Diseases of the Lower Digestive System

• Staphylococcal Food Poisoning:– Nausea, vomiting, diarrhea for ~24hrs– Exotoxins are not destroyed by boiling food

for 30 mins– Can grow easily at room temperature


• Shigellosis:– Caused by 4 different species– Blood and mucus in stools, abdominal

cramping, and fevers– Can lead to ulceration of the intestinal

mucosa


• Salmonellosis:– Caused by many Salmonella species– Nausea, abdominal pain, diarrhea– Septicemia can occur in infants and the

elderly– Mortality is less than 1%


• Typhoid Fever:– Transmitted by contact with human feces– Fever and malaise occur after a 2 week

incubation period– Symptoms last for 2 – 3 weeks– Harbored in the gall bladder of carriers– Vaccines are available for high risk people


• Cholera:– Exotoxin alters the membrane permeability of

the intestinal mucosa– Vomiting and diarrhea result

• Cause severe fluid loss

– ~3 day incubation period– 50% mortality when untreated


• Vibrio Gastroenteritis:– Onset within 24 hours of eating contaminated

foods• Crustaceans or mollusks

– Recovery after a few days


• E. coli Gastroenteritis:– Occurs as epidemic diarrhea in nurseries,

traveler’s diarrhea, and endemic diarrhea in less developed countries

– In adults the disease is usually self limiting– Can cause inflammation and bleeding of the

colon


• Campylobacter:– 2nd most common cause of diarrhea in the

U.S. – Transmitted in cow’s milk

Viral Diseases

• Mumps:– Enters and exits the body through the

respiratory tract– 16 – 18 days after exposure the virus causes

inflammation of the parotid glands– 4 – 7 days later orchitis can occur– The virus is found in blood, saliva, and urine

Viral Diseases

• Cytomegalovirus:– Herpesvirus that causes cytomegaly– Transmitted by saliva, urine, semen, cervical

secretions, and human milk– Can be asymptomatic, or progressive and

fatal– If it crosses the placental barrier it can result

in congenital infection, impaired mental development, neurological damage, and stillbirth

Viral Diseases

• Hepatitis:– Inflammation of the liver– Loss of appetite, malaise, fever, jaundice– Lots of causes

• Hep A - Contaminated cells or water• Hep B – blood transfusions, std, breast milk• Hep C – blood• Hep D – circular strand of RNA• Hep E – fecal-oral route of transmission

Fungal Diseases

• Mycotoxins are toxins produced by some fungi

• Mycotoxins affect the blood, nervous system, kidneys, and/or liver

Fungal Diseases

• Ergot Poisoning:– Most common in cereal grains

• Aflatoxin Poisoning:– Most common in peanuts

Protozoan Diseases• Giardiasis:

– Transmitted through contaminated water– Malaise, nausea, flatulence, weakness, and

abdominal cramps that persist for weeks

Protozoan Diseases

• Amoebic Dysentery:–Entamoeba histolytica–Grows in the large intestines–Feeds on red blood cells and GI tract

tissue–Severe infections result in abscesses

Protozoan Diseases

• Cryptosporidiosis:– Causes diarrhea in immunosuppressed

patients– Prolonged for months– Transmitted in contaminated water

Protozoan Diseases

• Cyclospora Diarrheal Infection:– First identified in 1993– Transmitted in contaminated produce

Helminthic Diseases

• Tapeworm Infestations:– Contracted by the consumption of

undercooked beef, pork, or fish containing the encysted larvae

– The scolex attaches to the intestinal mucosa of humans and matures into an adult tapeworm

– Eggs are shed in the feces and must be ingested by an intermediate host

Helminthic Diseases

• Hydatid Disease:– Humans infested with certain tapeworm

species may develop hydatid cysts in their lungs or other organs

– Dogs and wolves are usually the definitive hosts, and sheep or deer are the intermediate

Helminthic Diseases

• Nematode Infestations:– Pinworms– Hookworms

• Bore through the skin and migrate to the intestines

– Ascariasis– Trichinosis

• Invade muscle tissue• Fever, swelling around the eyes, GI upset

May 13th: Urogenital System

• Male

Urogenital System

• Female

Normal Microbiota

• The urinary bladder and upper urinary tract are sterile under normal conditions

• Lactobacilli dominate the vaginal microbiota during reproductive years

• The male urethra is normally sterile

Bacterial Diseases

• Cystitis:– Inflammation of the urinary bladder– Common in females– Naturally occurring microbes, careless

hygiene, and sexual intercourse contribute to the high incidence in females

Bacterial Diseases of the Urinary System

• Pyelonephritis:– Inflammation of the kidneys– Usually a complication of lower urinary tract

infections– About 75% of cases are caused by E. coli

Bacterial Diseases of the Urinary System

• Leptospirosis:– Transmitted by urine-contaminated water– Chills, fever, headache, and muscle aches

Bacterial Diseases of the Reproductive System

• Gonorrhea:– Neisseria gonorrhoeae– Reportable disease– Attaches to mucosal cells of the oral-

pharyngeal area, genitals, eyes, and rectum by means of fimbriae

– Males: painful urination and pus discharge– Can be transmitted to infants during birth and

cause eye diseases


• Nongonococcal Urethritis:–NGU–Any inflammation of the urethra not

caused by gonorrhea–Often caused by Chlamydia –Symptoms are often mild or lacking,

although uterine tube inflammation and sterility can occur

–Can be transmitted to infant’s eyes at birth


• Pelvic Inflammatory Disease:– PID– Extensive bacterial infection of the female

pelvic organs, especially of the reproductive systems

– Caused by several bacteria that gain access to the uterine tubes

– Infection of the uterine tubes is called salpingitis

– Can block the uterine tubes and result in sterility


• Syphilis:– Transmitted by direct contact– Can invade intact mucous membranes or

penetrate through breaks in the skin– Initial infection results in a chancre– The secondary stage has a disseminating

rash– Can cause neurological damage in fetuses


• Lymphogranuloma Venereum:– LGV– Primarily a disease of tropical and subtropical

regions– The initial lesion appears on the genitals and

heals without scarring– Cause enlargement of the lymph nodes and

enlargement of the genitals– Bacteria are spread through the lymph

vessels


• Chancroid:– A swollen painful ulcer on the mucous

membranes of the genitals or mouth


• Gardinella Vaginosis:– Vaginosis is infection without inflammation– Increased vaginal pH and fishy odor

Viral Diseases of the Reproductive System

• Genital Herpes:– Painful urination, genital irritation, fluid filled

vesicles– Neonatal herpes is contracted during fetal

development or birth– It can result in neurological damage or infant

fatalities– May enter a latent stage– Associated with cervical cancer


• Genital Warts:– Papillomaviruses cause warts– Associated with cervical and penile cancer


• AIDS:– Sexually transmitted– Really affects the immune system

Protozoal Diseases of the Reproductive System

• Trichomoniasis:– Occurs when the pH of the vagina increases– Purulent discharge from infection site

Fungal Diseases of the Reproductive System

• Candidiasis:– Candida albicans– Causes NGU in males and vulvovaginitis

(yeast infections) in females– Characterized by lesions that produce itching

and irritation– Predisposing factors are pregnancy, diabetes,

tumors, and chemotherapy

microorganisms of human disease unit 5: 6 days. april 28 th : skin and eyes the skin is a physical...

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