CLIN PATH: EXAM #2 (PULM/DERM MIXED)

acini

conducting airways and terminal respiratory units

what area of the lungs does emphysema effect

-the alveoli! remember capillaries usually surround the alveoli to allow more surface area for gas exchange

**asthma effects the bronchioles (smallest conducting non-respiratory unit)

main functions of the skin

-maintain body temp

-provide protective barrier from invading organisms and UV radiation and trauma

-receives external sensory stimuli

-controls insensible water loss

layers of the epidermis

-stratum corneum (anuclueated flattened keratinocytes)

-stratum lucidum (only in thick skin-palms/soles)

-stratum granulosum (cells w/ cytoplasmic granularity from accumulation of keratin complexes and other structural proteins)

-stratum spinosum (cells with ample cytoplasm and prominent desmosomes)

-stratum basal (cuboidal germinative keratinocytes that serve as foundation)

"Come Lets Get Some Beer"

oldest cells of the skin are found in what layer

stratum corneum

-these old skin cells flake off and new cells move upwards from the basal layer

cells in the basal layer that serve to provide a dispersed screen against UV rays of the sun

melanocytes

(produce reddish-brown biochrome melanin)

cells in the midspinous layer that are bone-marrow derived antigen presenting cells (part of immunity)

langerhans cell

-both langerhans and melanocytes are dendritic cells that are intercalated among keratinocytes of the epidermis

what causes us to get wrinkles as we age?

collagen types I and III and elastic microfibrils that are woven throughout the dermis go away with age

3 types of skin diseases

-inflammatory

-infectious

-neoplastic

non-palpable area of increased or decreased pigmentation <1 cm

macule

-in superficial layers only

macular type lesion that is circumscribed, >1 cm in diameter, and non-palpable

patch

superficial solid lesion <0.5 cm in diameter that often occurs in clusters and with rashes (palpable)

papule

occurs due to:

-inflammation (infected/abraded skin)

-accumulated secretions (blocked oil glands)

-infection (disseminated histoplasmosis)

-hypertrophy of skin cells

-acne

plateau-like elevation with surface area > its height and >1 cm in size

plaque

-often has lichenification or rough and thickened surface

does a lichenified plaque have cracks in it?

no! just accentuates normal skin lines

pruritic skin disorders associated with "tree bark" like skin

chronic eczema and atopic dermatitis often have lichenified plaque which look like tree bark

vesicle vs bulla vs pustule

-vesicles are small fluid filled lesions <1cm on or below the skin

-bulla are circumscribed collection of free fluid >1cm

-pustules are vesicles or bulla containing purulent fluid; superficial skin cavity contain purulent exudate (yellow, white, green-white, hemorrhagic)

how do vesicles and bulla form and why?

-these are blisters and form as a defense mechanism of the body

-epidermis separates from the dermis and a pool of lymph and other body fluids collect between the 2 layers while the skin re-grows underneath

blisters occur due to

chemical/allergic rxn

physical injury (heat, frostbite, friction)

solid circular lesion >1 cm that invades the epidermis and lower dermis

nodules

a patient that is having an allergic reaction to a bee that just bit them may present with edematous plaques called

wheals

-urticarial exanthem/urticaria

-rounded or flat topped

-no scaling

-can be round, oval, gyrate, annular or serpiginous

darier's sign and dermatographism reproduce

wheals

-darier's sign is gentle rubbing or stroking of the lesions that follows with local itching, erythema, and wheal formation within 2-5 minutes

-dermatographism is "writing on the skin" and is a very common hive rxn

cyst vs abscess

-cyst=encapsulated lesion filled with fluid or semi-solid material; elevated circumscribed and palpable; enclosed sac w/ distinct membrane lining

-abscess=collection of pus

dried serum or exudates on the skin surface that present after blisters rupture

crusts

-blood=brown

-serum=honey colored (impetigo)

-pus=yellow/green

what causes desquamation of the skin (scales)

-these abnormal areas of the stratum corneum are due to increased rate of epidermal cell proliferation

erosion vs ulcer

-erosion heals without a scar since it only involves the epidermis

-ulcers heals with a scar since it involves a loss of the epidermis and upper layer of the dermis

Petechiae vs. Purpura vs. Ecchymosis

-petechiae are <3 mm and occur due to minor hemorrhage, thrombocytopenia and decreased platelet function

-purpura are 3mm-10mm and indicate bleeding under the skin

-ecchymosis are >1cm and occurs due to capillary damage that allows blood to extravasate into surrounding tissues; usually from blunt trauma

*will NOT* blanch with pressure

solid lesion with elevation and depth usually involving epidermis, dermis and possible SC tissue

tumor

-may be pigmented

->2 cm diameter

9 patterns of inflammatory disease

-perivascular dermatitis (no epidermal involvement; hives)

-spongiotic derm (intercelluar epidermal edema; ACD)

-psoriasiform derm (epidermal thickening from elongated rete ridges; psoriasis)

-interface derm (cytotoxic rxn affecting dermis and epidermis; vacuoles and lymphocyte infiltrates; lichen planus)

-vesiculobullous derm (intradermal or subepidermal cleavage; bullous pemphigoid)

-vasculitis (damage to cutaneous vessel walls; leukocytoclastic vasculitis)

-folliculitis (rxn against colliculo-sebacous units; acne folliculitis)

-nodular derm (diffuse dermal infiltrate w/o epidermal changes; cutaneous sarcoidosis)

-panniculititis (involves subcutaneous fat; erythema nodosum)

sharply marginated and erythematous and surmounted by silvery scales think

psoriasis

etiology of psoriasis

-not well know; likely multifactorial: infection, injury, inherited condition (+Fhx is common); genetic factors

epidermal hyperplasia, elongation of rete ridges, thickening/clubbing/fusing of rete ridges, "squirting dermal papillae", inflammatory cells in the epidermis, and parakeratotic hyperkeratosis (extra skin formation) all describe

psoriasis

-squirting dermal papillae=migration of neutrophils from the dermal papillae into the overlyinf epidermis

what areas are spared from psoriasis?

-mucosal surfaces are spared

-scalp, extensor/flexural surfaces of extremities and nail beds are commonly affected

what is the only extracutaneous manifestation of psoriasis?

psoriatic arthritis

-distal interphalangeal joints of fingers and toes often involved

-this is a seronegative spondyloarthropathy meaning it's not autoimmune

inflammatory skin conditions in which the junction between the papillary dermis and epidermis is obscured; meshed together

-lichen planus (chronic interface derm) and erythema multiforme (acute interface derm)

-lymphocytes attack the basal layer of the epidermis causing vacuolar change or necrosis of basal keratinocytes

pathophysiology of interface dermatitis

-T cell mediated damage to keratinocytes and remodeling of the basement membrane zone

-damage to the basal keratinocytes produces vacuoles along dermoepidermal junction

-liquefaction degeneration=vacuolization

adult woman with skin condition after taking an antimalarial agent (quinine or chloroquine) think

lichen planus (interface derm)

other drugs that can cause lichen planus:

-therapeutic gold

-penicillamine

-thiazides

-tetracycline, isoniazid, streptomycin

-anticonvulsants (carbamazepine, phenytoin)

lichen planus pathogenesis (know)

-infiltrate of T lymphocytes in the papillary and superficial dermis--> keratinocytes and melanocytes damaged

-T cells destroy keratinocytes producing vacuoles; these vacuoles are seen in lower epidermis

-colloid bodies also present (esosinophilic hyaline ovoid bodies)

-mature lesions are composed of CD8 (cytotoxic T cells)

pruritic polygonal (angular) purple papules think

lichen planus

-flexor surfaces of extremities

-genital skin

-mucous membranes (remember psoriasis spares mucous membranes)

minute whitish streaks on the surface of lesions with lichen planus is called

wickham's striae

-keratinocytes and melanocytes damaged by T cells

cell mediated immune rxn that results in necrosis of epidermal keratinocytes

erythema multiforme (interface derm)

triggered by:

-HSV infection

-Rxn to meds

-idiopathic

target-like or bullseye lesions in crops on acral surfaces (distal portion of limbs) think

erythema multiforme

-monomorphous pattern=target like (red macule or thin papule that expands from center outward)

-center of the lesion can become necrotic

EM minor vs major

-minor: scattered lesions or with limited mucosal involvement

-major: prominent involvement in at least 2 of 3 mucosal sites (oral, anogenital, conjunctival)

EM major can be life threatening due to formation of

-stevens johnson syndrome (profound mucosal involvement)

-toxic epidermal necrolysis (large areas of skin and mucosa become necrotic w/ secondary vesiculation)

usually result of medications

-similar pathology of a severe burn in that integrity of a patient's skin fails-->risk of infectious/metabolic sequelae

blistering disease in which fluid-filled spaces develop within erythematous inflamed skin due to detachment of the epidermis from the dermis

bullous pemphigoid (vesiculobullous derm)

-immunoglobulins and complement are deposited along the epidermal-dermal junction (form of autoimmune disease)

in bullous pemphigoid the separation occurs

within the lamina lucida of the basement membrane

-subepidermal vesiculation occurs and subepidermal cleft contains numerous eosinophils and lymphocytes

large tense blisters on an erythematous base (also sometimes pruritic)

bullous pemphigoid

-pruritis may occur due to eosinophils in the dermal infiltrate within the subepidermal cleft

-may seen mucous membrane lesions in 1/3 of patients

-pre-eruptive/uritcarial bullous pemphigoid-->when someone presents with itchy erythematous plaques without blisters for period of time

palpable purpura or eruption of reddish/violaceous papules in crops/groups on lower extremities that persist less than 1 month

leukocytoclastic vasculitis -->inflam rxn involving blood vessels w/ accumulation of necrotic nuclear debris

-often occurs post streptococcal and post staphylococcal infections like strep pharyngitis, strep pneumo ect

-can also occur from drugs like PCNs, thiazides, NSAIDs

the erythematous or purpuric quality of leukocytoclastic vasculitis is due to

-numerous erythrocytes that accumulate in the dermis of the lesions

-these lesions are also raised/papular because of an intense vasocentric infiltrate containing numerous neutrophils

edema of the epidermis causing keratinocytes to separate from one another is called

spongiosis

-infiltrate is typically lymphocytes but eosinophils are often concurrent

induction phase of allergic contact dermatitis (spongiotic dermatitis)

delayed type IV hypersensitivity rxn

-allergen binds to endogenous protein creating a foreign protein

-langerhan's cells engulf the complex and partially degrade it

-langerhan's then present the antigenic fragments to MHC II molecules--> forms allergen complex

-T cell receptors bind with the allergen complex and T cells clone themselves

-this first exposure may not yield a rxn but patient is now sensitized

elicitation phase of ACD (spongiotic dermatitis)

-antigen appears again

-langerhan's cells process the antigen and migrate to lymph nodes

-T cell presentation occurs at the site of contact since the antigen is recognized

-inflammatory cytokines create an amplification loop-->clinically recognized dermatitis

-24-48 hrs to develop usually

common causes of ACD

-rhus dermatitis-appears linear (poison ivy/poison oak)

-nickel allergy

-soaps/detergents

lesions with difficult demarcation that usually appear on the anterior lower extremities (shins)

erythema nodosum (panniculitis)

-demarcation is difficult because of the depth of origin; this involves inflammation of the subcutaneous layer

Erythema nodosum often occurs as an end result of inflammation from (know)

-infection (strep pharyngitis)

-sulfonamides

-hormones (pregnancy, OCPS containing estrogen)

-inflammatory bowel disease

septal and lobular panniculitis (erythema nodosum) know

-inflammation occurs in the septal divisions between fat compartments

-septa thicken and become fibrotic

-infiltrate consists of lymphocytes, histiocytes, granulocytes (neutrophils and eosinophils) and can spread to lobules

-fat necrosis often spreads to the subcutaneous lobules-->appears as foamy (lipid-laden) macrophages or small stellate clefts within macrophages

E. nodosum (panniculitis) is what type of hypersensitivity rxn?

type IV delayed rxn in the septal fat

erythema nodosum (panniculitis dermatitis) presents as tender, deep red-brown nodules that appear as bruises with age on the anterior shins and often is the presenting sign of

sarcoidosis

-this skin condition will persist as long as the triggering stimulus is present so find underlying causes

hugely varied clinical spectrum of cutaneous sarcoidosis (nodular dermatitis)

can be a mild asymptomatic disease or a life threatening lung disease

-often present on the face

-nodular granulomas can also occur in the pulmonary tree and other viscera

what inflammatory skin condition occurs mostly in young adults, african americans, and is due to M. tuberculosis, histoplasma, viruses, or genetics

cutaneous sarcoidosis (nodular derm)

pathogenesis of cutaneous sarcoidosis (know bolded stuff)

-granulomas (collection of tissue macrophages) are present in the dermis

-non-caseating w/o central coagulation necrosis

-antigenic stimuli elicit T cell rxn

-antigens induce T cells-->cytokines-->macrophages recruited

-CD4 helper cells direct immune response and CD8 suppressor cells limit extent of the response

CXR showing bilateral pulmonary hilar LAD, acute E. nodosum, fever, arthralgia, uveitis think _____ syndrome

Lofgren's syndrome

-one of the prototypical presentations of sarcoidosis

beadlike papules at rims of nares think

lupus pernio presentation of sarcoidosis (nasal rim sarcoidosis)

-this indicates significant tracheobronchial tree or lung parenchyma involvement

a male patient comes in with disfiguring nodulocystic acne but he has not hit puberty yet. Should he be worried about scarring?

no! severe scarring can usually only occur after puberty

comedonal acne is manifested by

widened follicle with a dense keratin plug within its infundibulum (pore)

open vs closed comedone

-open comedone="black heads"; follicular orifice is open

-closed comedone= "white heads"; orifice is normal and follicle is plugged below the skin surface

*if neutrophils are also mixed with the keratinous plug this will create a pustular lesion*

what causes inflammatory acne lesions?

consequence of follicles that have been ruptured resulting in spillage of keratinous debris into the perifollicular dermis-->evokes an inflammatory rxn w/ mixture of neutrophils, lymphocytes, histiocytes

4 components to develop acne lesions

1. folliculosebaceous unit is plugged by keratin

2. sebum production

3. overgrowth of cutibacterium aka propionibacterium acnes

4. secondary inflammatory process

**being dirty does not cause acne and vigorous cleansing will not cure the condition

pathogenesis of acne

1. keratinocytes become sticky and fail to slough off-->follicular plugging

2. increased sebum within the follicle acts as good source of C. acnes-->bacterial overgrowth

3. C. acnes recruits neutrophils-->pustule forms

4. popping the pustule or neutrophilic enzymes weaken follicular wall-->ruptures-->inflam reactants released into dermis

5. lymphocytes, macrophages, neutrophils respond to inflam rxns

comedone now transformed into inflamed papule, pustule, or nodule of acne

what causes acne scarring?

follicular wall rupture and intense secondary reaction from sending inflammatory markers throughout dermis (why you should never pop pimples)

causes of acne in neonates and puberty

neonates: maternal androgens stimulate enlargement of sebaceous glands and increased sebum production

-acne continues until maternal androgens are cleared and sebaceous glands atrophy to normal size

puberty: androgens stimulate enlargement of sebaceous glands--> sebum production on face, chest, back,neck

what diseases can acne present in

stein-leventhal syndrome (polycystic ovary disease)

SAPHO syndrome (synovitis, acne, palmoplantar pustulosis, hyperostosis, osteitis)

acne classification

-mild: few to several papules/pustules (<10 usually)

-moderate: 10-40 papules/pustules along with comedones and few to several nodules

-severe: numerous or extensive papules/pustules and many nodules

at rest the tendency of the lungs to get smaller is balanced by

the tendency of the chest wall to expand

-remember inspiration is active and exhalation is passive

what two things maintain the anatomic integrity of the lungs

surfactant and connective tissue

-connective tissue allows lung to support itself and retain airway patency

-surfactant reduces surface tension allowing expansion of alveoli (alveoli would collapse w/o surfactant)

efferent pulmonary nervous system

- parasympathetic fibers (muscarinic/ cholinergic) mediate bronchoconstriction, pulmonary vasodilation, and mucous gland secretion

-sympathetic fibers mediate bronchial smooth muscle relaxation, pulmonary vasoconstriction, and inhibition of secretory gland activity

-NANC (non-adrenergic non-cholindergic) system=ATP,NO, peptide neurotransmitters-->inhibitory events including bronchodilation

a patient with an FEV1/FVC ratio that is less than 80% most likely has what kind of lung disease?

obstructive! like COPD (emphysema, asthma, chronic bronchitis)

-this ratio is diminished in obstructive diseases since the patients can get the air in just fine but they struggle getting the air out!

-TLC may be increased (air trapping)

afferent (vagal) pulmonary nervous system

-bronchopulmonary stretch receptors sense lung inflation and results in bronchodilation and increased HR (helpful w/ exercise and breathing in deeper)

-irritant receptors in the proximal airways produce cough, mucus secretion and bronchoconstriction (keeping irritants from getting in)

-C fibers or fibers from juxtacapillary (J) receptors respond to mechanical and chemical stimuli--> rapid shallow breathing pattern, mucus secretion, cough and heart rate slowing with inspiration

two categories of defense in the lungs

1. nonspecific physical: clearance, secretions, cell defenses, biochemical defenses (mucous trapping foreign material and coughing it out)

2. chemical: antibody mediated, antigen presentation to lymphocytes, cell mediated, non-lymphocyte cellular immune responses

compliance of the lungs

ability to relate to changes in volume to changes in pressure

-just like compliance of the heart

-chest wall favors being expanded; natural tendency to recoil after inspiration

O2 and CO2 transfer in the lungs

-more O2 in the alveoli so O2 transfers readily from the alveoli into the blood

-more CO2 in the venous blood entering the lungs and less CO2 in the atmospheric air so CO2 diffuses into the lungs and we breathe it off

1. air that is inhaled and exhaled with each breath (normal breathing)

2. max amt of air inhlaed above normal tidal volume

3. max amt of air exhaled below normal tidal volume

4. amt of air left in the lungs after a max exhalation

1. tidal volume (TV)

2. inspiratory reserve volume (IRV)

3. expiratory reserve volume (ERV)

4. residual volume (RV)

1. oxygen content in the blood depends on _____ and ____

2. tissue oxygen delivery depends on _____ and ______

1. arterial PO2, hemoglobin level

2. O2 content in arterial blood, cardiac output

1. Vital capacity (VC) is a summation of

2. Total lung capacity (TLC) is a summation of

1. VC= IRV + ERV + TV

2. TLC= IRV + ERV + TV + RV

CO2 is carried in the blood as

HCO3-

-CO2 dissolves in plasma

-exists as carbaminohemoglobin

**CO2 is 20x more soluble in plasma than O2 is so the greater the oxygenation of Hgb in the capillaries, the less ability to bind CO2

forced vital capacity (FVC) maneuver

-begins with an inhalation from FRC (functional residual capacity aka the amt of air left in the lung after normal exhalation) to TLC (about 1 second)

-this is followed by a forceful exhalation from TLC to RV (about 5 seconds)

-essentially breathing all the air in then blowing it out as fast as you can

2 main components of breathing effected by lung disease

-elastic forces (natural recoil of lungs to exhale)

-resistance to airflow (obstructive diseases)

forced expiratory volume in 1 second (FEV1) KNOW

amt of has exhaled during first second of the maneuver

-should be getting 80% of air out in this first second!!

based off of gravity, which lung zone has the greatest perfusion? ventilation?

-zone 3 or the base has the greatest perfusion

-zone 1 or the apex has the greatest ventilation and less perfusion

-V/Q ratio changes with position

normally the V/Q ratio is highest at the __a.___ and lowest at the __b.___

a. apex (more ventilation than perfusion here)

b. base (more perfusion than ventilation here)

-ideally we want ventilation and perfusion to be matched; V/Q mismatch is the reason for most abnormalities in O2 and CO2 exchange

a patient with an increased FEV1/FVC ratio most likely has what kind of lung disease

restrictive! (pulmonary fibrosis, sarcoidosis, obesity etc)

-this ratio is increased in restrictive diseases since the patients have a hard time getting air in to fill the lungs because their ability to expand their lungs is restricted; they have no problem with exhaling the air

-TLC or lung volume is reduced

how does V/Q mismatch occur

-extremes of shunts (no blood going to lung tissue so being ventilated not perfused)

-wasted ventilation (not being ventilated or perfused)

normal V/Q ratio

0.8 (4L of ventilation per minute and 5L of blood per minute; 4/5=0.8)

-V/Q > 0.8 means ventilation exceeds perfusion

-V/Q< 0.8 means perfusion exceeds ventilation

if a patient has a V/Q ratio of 1.0 what may you suspect?

-a V/Q ratio >0.8 makes you think that area of the lungs is getting ventilated but not perfused so this may indicate a clot or Pulmonary embolism is present

-could also indicated cardiac arrest

if a patient has a V/Q ratio of 0.5 what may you suspect?

-a lower V/Q ratio makes you think that area of the lung is getting perfused but not ventilated; usually caused by ET tube displacement

driving force of breathing

co2 levels

-breathing originates in the medulla within the brainstem; pneumotaxic centers are here

what allows for spontaneous breathing w/o conscious thought?

respiratory neurons

-they signal the phrenic nerve to control the diaphragm and spinal nerves to control intercostal and abdominal muscles

sensory input for breathing occur via

carotid bodies and aortic bodies

-carotid bodies function as sensors for arterial oxygenation (these are what cause an increase in ventilation in response to hypoxia)

which disease of COPD is reverisble?

asthma

-emphysema and chronic bronchitis are irreversible

GOLD classification of COPD

mild: FEV1 > or = to 80%

moderate: FEV1 between 50-80%

severe FEV1 between 30-50%

very severe FEV1 is <30% predicted

in obstructive lung diseases the increase in resistance to airflow occurs due to

-obstructive secretions in the lumen (asthma and chronic bronchitis)

-airway wall thickening and narrowing (seen w/ asthma and chronic bronchitis

-structures that support the airway disrupted (emphysema-lung elastic tissue is destroyed)