31 October 2010

Neuroanatomical Techniques

Neuroanatomical Techniques

Presentation by
Armin Blesch, Ph.D.
Harvey Karten, M.D.


Neuroanatomical techniques
History of modern neuroanatomy
Rudolf  Albert von Kölliker  (1817-1905)
nucleus  of Kölliker (Rexed  lamina X), continuity of axon and neuron
Heinrich  Wilhelm Gottfried Waldeyer (1837-1921)
Introduced  the term “neuron”  and “chromosome”

Camilio  Golgi   (1843-1926)
Golgi  method; Golgi cells;  Golgi apparatus; Golgi  tendon organ; Golgi-Mazzoni  corpuscle
Santiago  Ramon y Cajal (1852-1934)
Cajal's gold-sublimate method for astrocytes
horizontal  cell of Cajal (Retzius-Cajal cell in cortex
interstitial  nucleus of Cajal

Golgi Stain

Common immunohistochemical stains
Golgi: selective random neuron and fibers
Hematoxylin/Eosin: cell stain
Nissl (thionin): cell body stain
Kluver Barrera: mixed cell fiber stain
Weil: myelinated fiber stain
Anterograde and Retrograde Tracing
Brief History of Tracing
(Grafstein, 1967)
(Kristensson & Olsson, 1971)
Fink-Heimer stain
(Heimer 1999)


Anterograde tracing with radioactive amino acids
Edwards and Hendrickson
in: Neuroanatomical tract tracing
Retrograde labeling of spinal motor neurons with HRP
Van der Want  et al.1997
Types of tracers
Application of tracers
Uptake Mechanisms
Active uptake:
Passive incorporation: lipophilic substances
Intracellular injection
Enzyme reaction: HRP (WGA-HRP, CTB-HRP)
Antibodies e.g. CTB
Streptavidin-HRP conjugate for biotinylated tracers e.g. BDA, biocytin
Lectins and Toxins
Cholera Toxin beta subunit (CTB)
Retrograde, anterograde and transganglionic
Detection: antibody, HRP conjugate, conjugated to fluorophor
Application: 1 % aqueous solution, iontophoresis or pressure injection
Different efficiency in labeling among different neuronal populatioins and species
Transganglionic tracing of sensory axons with CTB
Anterograde tracing with PHA-L
Gerfen et al. in:
Neuroanatomical tract tracing
Fluoresceine isothiocyanate (FITC): green Rhodamine isothiocyanate (RITC): emission >590 nm (red)
Anterograde and retrograde transport
Pressure injection of 1-3% aqueous solution
Lipophilic Carbocyanine Dyes
Lipophilic Carbocyanine Dyes
Labeling of radial glia
Thanos et al. 2000
Dextran amines
Biotinylated dextran amine (BDA)
Reiner et al. 2000
Anterograde tracing of corticospinal axons
Application: 5% solution, pressure injection or iontophoresis
Fast degradation-short survival time 2-3 days
Mostly anterograde transport
Requires glutaraldehyde fixation
Retrograde tracers
All anterograde tracers are partially transported retrogradely
Purely retrograde tracers:
Fast Blue (FB)
Diamidino Yellow (DiY)
Edmund Hollis, UCSD
Scale bar 100 µm
Naumann et al. 2000
Ling Wang, UCSD
Cell filling
Choosing the Right Tracer
Transgenic “Golgi” stains

 Objective: generate BAC-transgenic mice expressing GFP or CRE under the control of a gene specific promoter
 In situ Hybridization
 Emulsion Autoradiograpy
 Double labeling

Blurton-Jones et al
Blurton-Jones et al

Multiplex mRNA detection
Dave Kosman (Ethan Bier and Bill McGinnis labs, UC San Diego)
 Detection Methods

Neuroanatomical Techniques.PPT


The Athlete’s Knee

The Athlete’s Knee
Presentation by:
John R. (Trey) Green, III, MD
University of Washington
Sports Medicine Clinic

Anterior Knee Anatomy
* Superficial fascia
* Quadriceps muscle group
* Patella
* Synovium / plicae
* Bursae

Anterior Knee Anatomy
* Quadriceps muscle group
o Rectus femoris
o Vastus medialis
o Vastus lateralis
o Vastus intermedius

Quadriceps Muscle Group
* Vastus medialis
o Larger, and more distal insertion than vastus lateralis
o Oblique distal fibers (VMO)

Patella Articular Surface

* Thickest articular cartilage in the body (5mm)
* 25% non articular (inferior pole)

Anterior Knee Anatomy

* Bursae
o Occur to assist tissue gliding
o Variable location

Patellofemoral Biomechanics

* Patella function
o Act as a fulcrum to increase the lever arm of the quadriceps muscle

Resultant Force on the Patella

* Compression
* 2-3 x body weight
* Maximum force at 70-80 degrees of flexion

Q Angle

* Angle between the quadriceps tendon and patella tendon in full extension

Anterior Knee Pain History
* Pain
* Instability
* Catching
* Crepitation
* Weakness
* Swelling

Physical Examination

* Gait

Physical Examination

* Limb length

Physical Examination
* Compartment assessment (crepitation)
* Observation
Prepatellar Bursal Fluid
* Range of Motion (ROM)
* Anterior knee
* Patellar position
* Patellar tracking
* Muscle tone/bulk
* Thigh circumference
* Sitting
* Lying
* Hip abductor strength
* Prone quadriceps tightness

Radiologic Examination
Rosenberg View
Merchant View
Measuring Merchant’sView
Anterior Knee Pain Treatment
* Rehab with therapist
Anterior Knee Pain Treatment
* Refer to Orthopaedist

Assessment of Meniscus, Ligament and Articular Cartilage Injuries
* Most require orthopaedic consultation
Pain Location
Meniscus Tears
* Meniscus tears are common
* Rapid flexion with rotation is most common mechanism
* A history of mechanical symptoms and joint line pain and tenderness suggests meniscal tear
Meniscus Tear Types
Meniscus Tears
* Arthroscopy is the gold standard for diagnosis and treatment
* Basic principles of meniscus surgery are:
o Conserve meniscal tissue
o Remove abnormal tissue
o Prevent further tear propagation
o Repair when possible
Articular Cartilage Injury
* Limited intrinsic repair capability
* Likely to eventually progress to arthrosis
* History of pain with recurrent effusions may indicate cartilage lesion
Articular CartilageTreatment Options
Medial Collateral Ligament
Beware Co-existing ACL or PCL Injury
Lateral Sided Ligament Injury
ACL Tear
PCL Tears
Knee Physical Exam
Physical Examination
Collateral Ligament Testing

The Athlete’s Knee.ppt


Blood Brain Barrier: Structure, Function and Bypass by Microorganisms

What is the Blood Brain Barrier?
Structure of Blood Brain Barrier
Integrity of BBB
Astrocyte end feet
Tight Junctions between BMEC
Barrier Function of Occludin and Claudin
Junction Adhesion Molecules:
BMEC intercellular space
Barrier function of JAM
Cytoplasmic accessory proteins
Membrane associated guanylate kinase-like proteins (MAGUKS)
Adherens Junction
Astrocyte end feet
Circumventricular organs
Circumventricular organ functions:
Normal BBB transport
Factors produced by astrocytes
Tumor necrosis factor alpha TNF-α
Interleukin beta IL-β
Substance P
Qionolonic acid
Platelet activating factor
Free radicals
E. Coli model
Physical damage of BBB
Ligand receptor interactions followed by host cell actin cytoskeletal rearrangements
Transcellular transport while maintaining integrity of BMEC
Physcial damage of BBB

Blood Brain Barrier: Structure, Function and Bypass by Microorganisms Download


21 October 2010

Cool NUCLEUS 3D Medical Animation


HIV Replication 3D Medical Animation

HIV Replication 3D Medical Animation 


11 July 2010

Hematology Presentations

Monoclonal Gammopathies

Hypomethylation:Turning on silenced genes and silencing the critics?

Aurora Kinases As  Anti-Cancer Targets

Bleeding Disorders

Renal Disorders in Multiple Myeloma Hematology Grand Rounds

Management of AMI in old patient

Adjuvant Therapy for NSCLC

Hairy Cell Leukemia

Follicular Lymphomas  A Post ASH Update Grand Rounds 10 Dec 2004

Gastrointestinal Stromal Tumors

Esophageal Cancer and Combined modality Treatment

Sickle Cell Hepatopathy: The role of transplantation


05 July 2010

Procedures Consult of MDConsult

Procedures Consult of MDConsult

What's Procedures Consult?
A medical procedures reference that helps physicians reduce potential medical errors and complications by providing information and resources to high-risk/high-volume procedures as well as medical procedures performed infrequently, but are critical to a patient's safety.

Centered as a medical resource, Procedures Consult is tailored to address the needs of medical personnel. Its contents are:

1. High quality videos with accurate procedures
2. Developed in conjunction with the US’s top medical institutions
3. Edited by medical professionals from esteemed medical facilities

Who Requires Procedures Consult?
Medical procedures videos from Procedures Consult address the needs of:
1. Physician/Resident/Student
2. The Educator
3. The Purchaser

Launch Features
Procedures Consult launches with content targeted at 3 major medical fields, with more than 160 in depth medical procedure videos that are developed in conjunction with the US’s top medical institutions and leveraging on Elsevier’s leading reference texts.
1. Anesthesia Module (34 procedures)
2. Emergency Medicine Module (50 procedures)
3. Orthopaedic Module (39 procedures)
4. Internal Medicine Module (42 procedures)

And more.


Now free trial for 30 days.


21 May 2010

Cutaneous Fungal Infections

Cutaneous Fungal Infections
* Dermatophytosis - "ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes.
* Dermatomycosis - more general name for any skin disease caused by a fungus.

* Etiological agents are called dermatophytes - "skin plants". Three important anamorphic genera, (i.e., Microsporum, Trichophyton, and Epidermophyton), are involved in ringworm.
* Dermatophytes are keratinophilic - "keratin loving". Keratin is a major protein found in horns, hooves, nails, hair, and skin.
* Ringworm - disease called ‘herpes' by the Greeks, and by the Romans ‘tinea' (which means small insect larvae).

Infections by Dermatophytes
* Severity of ringworm disease depends on (1) strains or species of fungus involved and (2) sensitivity of the host to a particular pathogenic fungus.
* More severe reactions occur when a dermatophyte crosses non-host lines (e.g., from an animal species to man). Among dermatophytes there appears to be a evolutionary transition from a saprophytic to a parasitic lifestyle.
o Geophilic species - keratin-utilizing soil saprophytes (e.g., M. gypseum, T. ajelloi).
o Zoophilic species - keratin-utilizing on hosts - living animals (e.g., M. canis, T. verrucosum).
o Anthropophilic species - keratin-utilizing on hosts - humans (e.g., M. audounii, T. tonsurans)

Clinical manifestations of ringworm infections are called different names on basis of location of infection sites
* tinea capitis - ringworm infection of the head, scalp, eyebrows, eyelashes
* tinea favosa - ringworm infection of the scalp (crusty hair)
* tinea corporis - ringworm infection of the body (smooth skin)
* tinea cruris - ringworm infection of the groin (jock itch)
* tinea unguium - ringworm infection of the nails
* tinea barbae - ringworm infection of the beard
* tinea manuum - ringworm infection of the hand
* tinea pedis - ringworm infection of the foot (athlete's foot)

Species found in different anamorphic genera are the cause of different clinical manifestations of ring worm
* Microsporum - infections on skin and hair (not the cause of TINEA UNGUIUM)
* Epidermophyton - infections on skin and nails (not the cause of TINEA CAPITIS)
* Trichophyton - infections on skin, hair, and nails.

Major sources of ringworm infection
* Schools, military camps, prisons.
* Warm damp areas (e.g., tropics, moisture accumulation in clothing and shoes). Historical note: More people were shipped out of the Pacific Theater in WWII back to U.S. because of ringworm infection then through injury.
* Animals (e.g., dogs, cats, cattle, poultry, etc.).

* Note the symptoms.
* Microscopic examination of slides of skin scrapings, nail scrapings, and hair. Often tissue suspended in 10 % KOH solution to help clear tissue. Slides prepared this way are not permanent. These degrade rapidly due to presence of base.
* Isolation of the fungus from infected tissue.
* Proper treatment is dependent on diagnosis and prognosis.

* tinea pedis - Athletes' foot infection
* between toes or toe webs (releasing of clear fluid) - 4th and 5th toes are most common.
* Soreness and itching of any part of the foot.
* In one study - 85 % of college students carried a ringworm fungus.
* Common disease but fairly recent was not recognized until late 19th century.
* Spread of disease correlated with introduction and generalized distribution of T. rubrum into Europe and America probably due to massive movement of peoples due to colonial occupation, slave trade, and World War II.
* Origin of T. rubrum may have been SE Asia or Africa.
* Fungi probably transmitted host to host through infected squames; flat, keratinised, dead cells shed from the outermost layer of a stratified squamous epithelium.
* Three causal agents, T. rubrum (source of inoculum comes from people with chronic infections, because fungus not long-lived in squames), T. mentagrophytes, and Epidermophyton floccosum (source of inoculum comes from long-lived arthrospores that reside in squames deposited in rugs and carpets (fomites).
* Three Grades of Infection
* Grade I - Subclinical
o An itching between toes, skin may be soft and macerated, blistering my occur.
o Treatment - keeping feet dry and clean, drying between the toes lightly each time you bathe to remove some skin. Application of fungicidal powders or ointments containing (1) salicylic acids to promote peeling of the skin and/or (2) tonaftate or other topical fungicides.
* Grade II
o Host is conscious of a burning sensation while walking and standing.
o Soaks are recommended (paints or liquids) such as 1:4000 KMnO4 (stains the skin purple) or topical fungicides.
o Remove clear liquid from blisters by having a doctor puncture near the base or unroofing the blister.
o Dusting powder in morning to help keep feet dry.

Tinea Pedis – Athlete’s Foot Infection
* Grade III
* Allergic reactions are sometimes associated with tinea pedis and other ringworm infections.
* dermatophytid - an "id" allergic reaction.
* toxins get into blood stream and reaches a site other than the site of infection.
* blistering occurs on fingers and hands.
* in diagnosis, rule out allergic reaction to poison ivy, detergents or other substances.
* during diagnosis, look for tinea (pedis, often) on the body.
* treat the primary site of infection where the antigen is being produced.
* treat secondary site - blisters.

Dermatophytid Reaction
* tinea corporis - body ringworm
* Generally restricted to stratum corneum of the smooth skin.
* Symptoms result form fungi metabolites such as toxin/allergens.
* Disease found throughout the world.
* Produces concentric or ring-like lesions on skin, and in severe cases these are raised and may become inflamed.
* All forms of tinea corporis caused by T. rubrum, T. mentagrophytes, T. tonsurans, M. canis, and M. audouinii are treatable with topical agent containing tolnaftate, ketoconazole, miconazole, etc...
* Disease transmitted through infected scales hyphae or arthroconidia on the skin.
* Also transmitted through direct contact between infected humans or animals, by fomites (any agent such a bedding or clothing capable of retaining a pathogen and transmitting to a new host).
* Transfer form on area to the body to another (from tinea pedis to tinea corporis).
* Tinea Corporis normally resolves itself in several months.
* T. verrucosum and T. violaceum infections require more vigorous treatment including cleaning of area to remove of scales and older fungicidal topical applications of ammoniated mercury ointment, 3 % salicylic and sulfuric acid, or tincture of iodine for several weeks.
* Widespread tinea corporis and more severe types (lesions) require systemic griseofulvin treatment (about 6 weeks for effective treatment).

Tinea corporis – body ringworm
* tinea cruris - ringworm of the groin and surrounding region
* More common in men than women.
* Infection seen on scrotum and inner thigh, the penis is usually not infected.
* Epidemics associated with grouping of people into tight quarters - athletic teams, troops, ship crews, inmates of institutions.
* Several causes of tinea cruris include T. rubrum (does not normally survive long periods outside of host), E. flocossum (usually associate with epidemics because resistant arthroconidia in skin scales can survive for years on rugs, shower stalls, locker room floors), T. mentagrophytes (usually of animal origin, such as rodents), and Microsporum gallinae (rarely seen - usually found on gallinaceous birds like turkeys and chickens).
* Predisposing factors include persistent perspiration, high humidity, irritation of skin from clothes, such as tight fitting underwear or athletic supporters, pre-existing disease, such as diabetes and obesity.
* Diagnosis
o If lesion "weep", it is likely caused by a yeast, such as, Candida albicans, and not by a dermatophyte, especially if infections are seen in a woman.
o KOH examination of skin scrapings.
o Culture of dermatophyte from skin scrapings.
* Treatment
o Tolnaftate (Tinactin trademark) treatment protocol for tinea corporis.
o Relief of symptoms occur within 3 days and treatment continued until all signs of disease are gone.
o Area is sensitive so the other care needs to be taken into to add to irritation of region.

Tinea Cruris – Jock Itch
* tinea unguium - ringworm of the nails
* Tinea unguium or onchomycosis can take two forms:
o Leukonychia mycotica - superficial white onychomycosis, invasion of fungus restricted to patches or pits on surface of the toenail.
o Invasive subungual dermatophytosis - lateral or distal edges first involved, followed by establishment of the infection beneath the nail plate. Invasion of nail plates by dermatophytes.
* Onychomycosis (infection of nails caused by non-dermatophytic fungi and yeasts)
* Most commonly caused by T. rubrum, then E. floccosum or other Trichophyton species.
* Resistant to treatment, rarely resolves spontaneously.
* Topical treatments - poor record of cure.
* Ablation - surgical or chemical removal of nail.
* Systemic griseofulvin therapy can lead to remission (usually a year or more of treatment required - results vary about 29 % cure rate).
* Use of other systemic antifungal (i.e., Lamisiltrademark or terbinafine HCl).
* Filing down the nail to paper thin consistency and soaking or painting with KMnO4 (1:4000), phenol, 10 % salicylic acid, or 1% iodine is useful adjunct to systemic griseofulvin treatment.

Tinea Unguium – Nail Infection
* tinea capitis - ringworm of the scalp, eyebrows and eyelashes
* Caused by species of Microsporum and Trichophyton.
* Fungus grows into hair follicle.
* Using a Wood's lamp, on hair Microsporum species tend to fluoresce green while Trichophyton species generally do not fluoresce.
* Lack of fluorescence does not mean it isn't Microsporum.
* Subculture any strands of hair that fluoresce to help identify the causal agent.
* Ectothrix infection - fragmentation of mycelium into conidia (called arthroconidia) around the hair shaft or just beneath the cuticle with destruction of the cuticle. This type of infection caused by M. audounii, M. canis, M. ferrugineum, T. mentagrophytes, T. verrucosum and T. megninii.
* Endothrix infection - arthroconidia formation occurs by fragmentation of hyphae with the hair shaft with destruction of the cuticle. This type of infection caused T. tonsurans (most common cause), T. violaceum, T. rubrum, and T. gourvillii. All these pathogen species are anthropophilic.
* "Gray patch ringworm" ectothrix common disease in children usually not associated with inflammation.
* Zoophilic and geophilic dermatophytes infections on man associate with inflammation. Microsporum canis, T. verrucosum, and T. mentagrophytes (zoophilic); M. gypseum and M. fulvum (geophilic species).
* "Id" reaction may occur.

Treatment of Tinea Capitis
* Ectothrix infections often resolve on their own.
* Endothrix infections my become chronic and may continue into adulthood.
* Topical treatments are ineffective (don't bother using tonaftate or topical griseofulvin)
* Fungistatic agents are somewhat effective (miconazole, clotrimazole) in combination to systemic administration of griseofulvin.
* Vigorous daily scrubs of scalp help removal of infectious debris. Do not use this treatment on patients with porphyria (an accumulation of blood pigment called porphyrins in blood stream and urine) or is hypersensitive to griseofulvin.

Tinea Capitis Gray Patch
Ectothrix and Endothrix
Fluorescing hair (under Wood's lamp) is seen in dogs and cats infected with some dermatophytes
Arthroconidia on hair
Microsporum canis
Teleomorph: Arthroderma otae
Microsporum gypseum
Epidermophyton floccosum
* Trichophyton rubrum
* Infects nails and smooth skin (rarely found on hair).
* Most common and widely distributed dermatophyte on man and rarely isolated from animals, never from soils.
* No teleomorph (possibly lost in transition from saprophytic lifestyle to man).
* Resistant and persistent (some people become carriers for life).
* Slow-growing in culture.
* When intensely pigmented in culture the color is reminiscent of port burgundy wine or venous blood.
* Production of pigment increased, if fungus grown on corn meal agar.
* Microconidium are clavate or "teardrop" shape with a broad attachment point of the hyphae.
* Microconidia may develop on sides of macroconidium.
* In vitro - lack of hair penetrating organs, unlike T. mentagrophytes.
* T. violaceum grows poorly without thiamine. T. megninii grows poorly without L-histidine. T. rubrum requires neither thiamine or L- histidine.
* Trichophyton violaceum
* Attacks hair, scalp, skin and nails.
* Nail infections are persistent.
* Endothrix (black dot infection of scalp).
* Found in humans, rarely in animals.
* Disease has been reported in horses, cats, dogs, mice and pigeons.
* Very slow growing in culture with a waxy appearance.
* Colony deep violent in color, purplish pigment diffuses into media.
* Rarely produces microconidia and macroconidia.
* In culture this species requires thiamine for proper growth.
* Hyphae coarser in appearance than seen in other dermatophytes.
* Chlamydoconidia are seen in culture.
* Trichophyton verrucosum
* Associated with cattle ("barn itch").
* Large-spored ectothrix.
* Causes severer infections in humans on the scalp and beard.
* Very slow growing, no pigment on reverse to yellow.
* Grows best at 37 C.
* On unenriched media - chains of chlamydoconidia and antler-like hyphae.
* On thiamine-enriched media, produces many small microconidia and occasionally macroconidia are produced.

Trichophyton verrucosum
* Trichophyton schoenleinii
* Endothrix infection of hair.
* Causes tinea favosa (cup-shaped crusts on scalp called favus).
* tinea favosa may lead to alopecia or permanent baldness.
* Colonies waxy to suede-like; off white in color.
* Colony may become convoluted from folds that develop
* No conidia (micro- or macro-) even on enriched media .
* Grows will at 37 C.
Trichophyton schoenleinii
* Trichophyton ajelloi
* Teleomorph - Arthroderma uncinatum.
* Common soil dermatophilic fungus.
* Rarely causes infection in man or animals (cattle, dogs, horses, squirrels).
* Readily isolated from soil by hair baiting.
* Cigar-shaped macroconidia with smooth ends.

Cutaneous Fungal Infections.ppt


Hyponatremia and Hypernatremia

Hyponatremia and Hypernatremia
By:Conor Gough, HO – III

* Defined as sodium concentration < 135 mEq/L * Generally considered a disorder of water as opposed to disorder of salt * Results from increased water retention * Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia * Thus, in most cases, some impairment of renal excretion of water is present Causes * Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level * Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels * Causes of Hyponatremia can be classified based on either volume status or ADH level o Hypovolemic, Euvolemic or Hypervolemic o ADH inappropriately elevated or appropriately suppressed ADH suppresion ADH elevation
First step in Assessment: Are symptoms present?
* Hyponatremia can be asymptomatic and found by routine lab testing
* It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy
* Or it may present with more severe symptoms such as seizures, coma or respiratory arrest

Presentation determines if immediate action is needed
* If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline
* If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia
* Oral fluid restriction is good first step as it will prevent further drop in sodium
* NOTE: This does not mean that you can’t give isotonic fluids to someone who is truly volume depleted

* With no severe symptoms and fluid restriction started, next step is to assess volume status to help determine cause
* Hypovolemic – urine output, dry mucous membranes, sunken eyes
* Euvolemic – normal appearing
* Hypervolemic – Edema, past medical history, Jaundice (cirrhosis), S3 (CHF)

Volume status helps predict cause
* Hypovolemia
o True Volume Depletion
o Adrenal insufficiency
o Thiazide overdose
o Exercised induced hyponatremia
* Euvolemia
o Primary Polydipsia
* Hypervolemia
o Cirrhosis and CHF

Workup for Hyponatremia
How to interpret the tests?
* Serum Osmolality
o Can differentiate between true hyponatremia, pseudohyponatremia and hypertonic hyponatremia
* Urine Osmolality
o Can differentiate between primary polydipsia and impaired free water excretion
* Urine Sodium concentration
o Can differentiate between hypovolemia hyponatremia and SIADH

Additional Tests
* TSH – high in hypothyroidism
* Cortisol – low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm
* Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia
* Iatrogenic infusion of hypotonic fluids (“Surgeon sign”)
* Ecstasy use – increased water intake with inappropriate ADH secretion
* Underlying infections
* NSIAD – Nephrogenic syndrome of inappropriate antidiuresis – Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels
* Reset Osmostat – Occurs in elderly and pregnancy where regulated sodium set point is lowered

SIADH: Important concept to understand
Main diagnostic criteria for SIADH
Treatment is based on symptoms
Severe symptoms present
What if little to no symptoms are present?
Formulas that may help: How much sodium does the patient need?
* Sodium deficit = Total body water x (desired Na – actual Na)
* Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men

How about an example:
What if the sodium increases too fast?
Risk Factors for demyelination
Treatment Options
Summary of Hyponatremia
Moving on to Hypernatremia
Causes of Hypernatremia
Symptoms of Hypernatremia
Diagnosis of Hypernatremia
Treatment of Hypernatremia
Summary of Hypernatremia

Hyponatremia and Hypernatremia.ppt


Monocyte / Macrophage Disorders

Monocyte / Macrophage Disorders
Northeast Regional Medical Center/KCOM

Granuloma Annulare
* Localized
* Generalized
* Macular
* Deep
* Perforating
* In HIV
* In Lymphoma
* Common, Idiopathic, all races
* 50% patients IgM and C3 in vessels
* LCV changes sometimes seen
* Suggests Ab mediated vasculitis
* Common in HIV patients
* EBV sometimes found
* Occurs in resolved lesions Zoster

GA - Histology
Interstitial GA
* Upper dermis
* “Skip areas”
* Mucin
* Deep dermis, subQ
* No “skip” areas
* No mucin

Localized GA
* Young adults
* Acral
* Annular, scalloped
* White or pink flat topped papules spread peripherally
* 75% clear in 2 yrs
* 25% last 8 yrs
Diffuse GA
Subcutaneous GA
Perforating GA
GA in HIV disease
GA and Lymphoma
GA- Treatment
Annular Elastolytic Giant Cell Granuloma of Meischer/Actinic Granuloma of O’Brien
Photoexacerbated GA
Granuloma Mulitforme of Leiker
* Multisystem Disease
* Lungs, lymph nodes, skin and eyes MC.
* 10x more frequent in blacks in US
* Women under age 40
* Irish, African, Afro-Caribbean.
* Presence inversely proportional to the incidence of TB and/or Leprosy.
* Etiology unknown
* HLA-A1 – Lofgren’s syndrome
* HLA-B13 – Chronic & Persistent form
* HLA-B8
* Final common pathway is granuloma formation
“NAKED” meanse a sparse rather than a dense infiltrate. Lymphocytes, macrophages & fibroblasts may occur
Sarcoid Skin Involvement
Sarcoid – like syphillis, mimics many other dz’s
Papular Sarcoid
Annular Sarcoidosis
Hypopigmented Sarcoid
Punched-Out Lytic lesions, Bone Cysts
Ulcerative Sarcoidosis
Lupus Pernio
Darier-Roussy Sarcoid
Scar Sarcoid
Erythrodermic Sarcoid
Ichthyosiform Sarcoid
Morpheaform Sarcoid
Mucosal Sarcoid
Erythema Nodosum in Sarcoid
Systemic Sarcoidosis
Heerfort’s Syndrome
Mikulicz’s Syndrome
CXR- Hilar Adenopathy
Sarcoidosis in Fingers
Candle-wax drippings – granulomatous uveitis
Sarcoid - Treatment
Non-X Histocytoses
* Juvenile Xanthogranuloma
* Benign Cephalic Histiocytosis
* Solitary/Multicentric Reticulohistiocytosis
* Generalized Eruptive Histiocytoma
* Necrobiotic Xanthogranuloma
* Xanthoma Disseminatum
* Papular Xanthoma
* Indeterminate Cell Histiocytosis
* Progressive Nodular Histiocytoma
* Hereditary Progressive Mucinous Histiocytosis
* Rosai-Dorfman Disease
* Sea-Blue Histiocytosis
Juvenile Xanthogranuloma (JXG)
JXG Histopathology
Reticulohistiocytic Granuloma
Multicentric Reticulohistiocytosis
“Coral Bead” Paronychia
Tx: Multicentric Reticulohisticytosis
Generalized Eruptive Histiocytoma
Necrobiotic Xanthogranuloma (NXG)
NXG and Malignancy
Xanthoma Disseminatum
XD - Pathology
Papular Xanthoma
Indeterminate Cell Histiocytosis
Progressive Nodular Histiocytosis
Hereditary Progressive Mucinous Histiocytosis in Women
Rosai-Dorfman Disease
Rosai-Dorfman Disease – LN Biopsy
RDD - Emperipolesis – Histiocytes engulf plasma cells and lymphocytes
RDD - Treatment
Sea-Blue Histiocytosis
Sea-Blue Histiocytosis – Bone Marrow
X-type Histiocytoses
Hashimoto-Pritzker Before and After
Histiocytosis X
Histiocytosis X - TX

Monocyte / Macrophage Disorders.ppt


30 April 2010

The BioArtificial Liver

The BioArtificial Liver
By:Susana Candia
Jahi Gist
Hashim Mehter
Priya Sateesha
Roxanne Wadia

Biology of the Liver
Left lobe
Right lobe
Falciform Ligament
Inferior Vena Cava
Abdominal Aorta

What does the Liver do?
Among the most important liver functions are:
* Removing and excreting body wastes and hormones as well as drugs and other foreign substances
* Synthesizing plasma proteins, including those necessary for blood clotting
* Producing immune factors and removing bacteria, helping the body fight infection

Other important but less immediate functions include:
* Producing bile to aid in digestion
* Excretion of bilirubin
* Storing certain vitamins, minerals, and sugars
* Processing nutrients absorbed from digestive tract

Why would someone need a BioArtificial Liver?
Liver Transplantation Now
* Patients are in waiting list ranked according to severity of disease and life expectancy among other variables.
* Can be from a cadaveric donor or from a live donor.
* Involves heavy use of immunosuppressants during and after surgery.
* The risk of rejecion is always present.

What does a BioArtificial Liver need to do?
* Cellular components must be purified and every component in it must be clearly identified.
* The cellular preparation must be clearly shown to not transmit any infectious diseases of any kind.
* The cellular component must stay viable and active
* The synthetic component must be fully biocompatible, integrity of the material and parts must also be demonstrated
* The device must be able to introduce the therapeutic and regulatory molecules that a healthy liver provides, and it must also filter substances from the blood the way that the normal liver does.
* Must be immunocompatible.
* Blood must perfuse properly through system

Enabling Technologies
* Hemodialysis/hemofiltration hollow fibers- controlled interaction of cells and circulating fluids
* Maintenance and creation of a cell line
* Immortalizing cells
* Encapsulation-envelopment of hepatocytes in a polymeric matrix.
* Microcarriers- polymeric particles containing cells

Works in Progress: Points to Consider
Bioreactor designs/Membrane configurations
Cellular vs. Acellular system
Porcine vs. Human hepatocytes
Point in Development
Liver Dialysis Unit
* FDA approved in 1994
* Plate dialyzer with blood on one side, dialysate is a mixture of sorbents, activated charcoal being the essential component.
* For a substance to be removed, must be dialyzable and able to bind to charcoal.
* “Bridge to recovery” for treat acute hepatic encephalopathy and overdoses of drugs
* Post-market trials have shown the LDU to be effective in improving physiological and neurological status.

* Limited to investigational use in US.
* Hollow fiber membrane hemodialyzer.
* Blood on one side, human albumin on other.
* Albumin recycled through circuit containing another dialyzer and carbon and anion exchanger adsorption columns.
* Removes both water-soluble and protein bound substances
* Keep valuable proteins
* Trial have found it safe and associated with clinical improvement

* Uses cultured human hepatocytes express normal liver-specific metabolic pathways. hollow fiber dialyzer.
* Dialyzer cartridge connected to continuous hemodialysis machines, like those used for renal therapy.
* Blood separated into a cellular component and a plasma component.
* Plasma through dialyzer, hepatocytes on outside of hollow fibers.
* Currently involved in a phase 2 clinical trial to evaluate the safety and efficiency.
* Extracorporeal hemofiltration hollow fiber membrane bioreactor with 100 grams of primary porcine hepatocytes
* Whole blood is filtered
* Contains blood pump, heat exchanger, oxygenator to control oxygenation and pH, and hollow fiber bioreactor
* Currently undergoing phase I/II clinical trials
* Patients show some improvement

HepAssist 2000 System
* Four components: a hollow fiber bioreactor containing porcine hepatocytes, two charcoal filters, a membrane oxygenator, and a pump.
* Must be used in conjunction with a commercially available plasma separation machine
* Blood separated; plasma processed through charcoal filters to remove particulates, bacteria, then enters bioreactor
* Hepatocytes must be heated and oxygenated
* FDA mandated full Phase III trials
* Hollow fiber cartridge
* Primary porcine hepatocytes suspended in a cold collagen solution and injected inside fibers
* Blood circulates outside the hollow fibers
* Designed to treat both acute and chronic liver failure
* Phase I/II clinical trials are underway to test the safety of efficacy of this device
* Anyone treated with the LIVERx2000 will be monitored for PERV
* Parallel plate design
* Human hepatocytes attached to semipermeable membranes on parallel plate
* Plasma separator, then plasma passes into the bioreactor
* In the bioreactor, the plasma flows over the semipermeable membrane where the hepatocytes are adhered.
* Current trials in Europe show promise

Demographics and Cost
* Market for liver support is estimated to be substantial: $700 million in the United States and $1.4 billion worldwide.
* Liver transplants have more than doubled in the past ten years, with the transplant waitlist growing in a similar fashion

Current and Future Challenges
* GOAL: To produce a fully implantable bioartificial liver.

Cell viability
Fibrosis around implanted capsules
Proteins greater than pore size cannot be released

To achieve density of cells needed to replace liver, an estimated 1000m of hollow fibers would be needed

The BioArtificial Liver.ppt


Renal Replacement Therapy

Renal Replacement Therapy

* What is it?
* How does it work?
Where did it come from?
History of Pediatric Hemofiltration
Mechanisms of Action: Convection
* Hydrostatic pressure pushes solvent across a semi-permeable membrane
* Solute is carried along with solvent by a process known as “solvent drag”
* Membrane pore size limits molecular transfer
* Efficient at removal of larger molecules compared with diffusion
* Solvent moves up a concentration gradient
* Solute diffuses down an concentration gradient

Mechanisms of Action: Diffusion
Semi-permeable Membranes
o Urea
o Creatinine
o Uric acid
o Sodium
o Potassium
o Ionized calcium
o Phosphate
o Almost all drugs not bound to plasma proteins
* Allow easy transfer of solutes less than 100 Daltons
o Bicarbonate
o Interleukin-1
o Interleukin-6
o Endotoxin
o Vancomycin
o Heparin
o Pesticides
o Ammonia
* Sieving Coefficient
* Sieving Coefficient is “1” for molecules that easily pass through the membrane and “0” for those that do not
* Continuous hemofiltration membranes consist of relatively straight channels of ever-increasing diameter that offer little resistance to fluid flow
* Intermittent hemodialysis membranes contain long, tortuous inter-connecting channels that result in high resistance to fluid flow

How is it done?
* Peritoneal Dialysis
* Hemodialysis
* Hemofiltration
* The choice of which modality to use depends on
o Patient’s clinical status
o Resources available

Peritoneal Dialysis
* Fluid placed into peritoneal cavity by catheter
* Glucose provides solvent gradient for fluid removal from body
* Can vary concentration of electrolytes to control hyperkalemia
* Can remove urea and metabolic products
* Can be intermittent or continuously cycled
* Simple to set up & perform
* Easy to use in infants
* Hemodynamic stability
* No anti-coagulation
* Bedside peritoneal access
* Treat severe hypothermia or hyperthermia
* Unreliable ultrafiltration
* Slow fluid & solute removal
* Drainage failure & leakage
* Catheter obstruction
* Respiratory compromise
* Hyperglycemia
* Peritonitis
* Not good for hyperammonemia or intoxication with dialyzable poisons

Intermittent Hemodialysis
* Maximum solute clearance of 3 modalities
* Best therapy for severe hyperkalemia
* Limited anti-coagulation time
* Bedside vascular access can be used
* Hemodynamic instability
* Hypoxemia
* Rapid fluid and electrolyte shifts
* Complex equipment
* Specialized personnel
* Difficult in small infants

Continuous Hemofiltration
* Easy to use in PICU
* Rapid electrolyte correction
* Excellent solute clearances
* Rapid acid/base correction
* Controllable fluid balance
* Tolerated by unstable patients
* Early use of TPN
* Bedside vascular access routine
* Systemic anticoagulation (except citrate)
* Frequent filter clotting
* Vascular access in infants

SCUF:Slow Continuous Ultrafiltration
* Pros
* Cons
Continuous Venovenous Hemofiltration
Dialysis Fluid
Continuous Venovenous Hemodialysis
Continuous Venovenous Hemodialysis with Ultrafiltration
Is there a “Best” Method?
Indications for Renal Replacement Therapy
Indicators of Circuit Function
Filtration Fraction
QP: the filter plasma flow rate in ml/min
Blood Flow Rate & Clearance
Pediatric CRRT Vascular Access: Performance = Blood Flow!!!
Urea Clearance
Solute Molecular Weight and Clearance
Cytokines (large) adsorbed minimal clearance
Replacement Fluids
Physiologic Replacement Fluid
Mechanisms of Filter Thrombosis
Heparin - Problems
Sites of Action of Citrate
Anticoagulation: Citrate
What are the targets?
Unknowns of Hemofiltration for Sepsis
Pediatric CRRT in the PICU
Renal Replacement Therapy in the PICU Pediatric Literature

Renal Replacement Therapy.ppt


Renal Replacement Therapy

Renal Replacement Therapy
Trauma Conference
By:Amanda Wheeler, MD

4 Main Modalities in ICU
* HD
* PD

Definition of Terms
* SCUF- Slow Continuous Ultrafiltration
* CAVH- Continuous Arteriovenous Hemofiltration
* CAVH-D- Continuous Arteriovenous Hemofiltration with Dialysis
* CVVH- Continuous Venovenous Hemofiltration
* CVVH-D- Continuous Venovenous Hemofiltration with Dialysis

Indications for Continuous Renal Replacement Therapy
* Volume Overload
* Electrolyte Imbalance
* Uremia
* Acid-Base Disturbances
* Drugs

Hemodialysis vs Hemofiltration Membrane
The hemofiltration membrane consists of relatively straight channels of ever-increasing diameter that offer little resistance to fluid flow.
Hemodialysis membranes contain long, tortuous inter-connecting channels that result in high resistance to fluid flow.
Hemodialysis allows the removal of water and solutes by diffusion across a concentration gradient.

* maximum solute clearance
* best tx for severe hyper-K+
* ready availability
* limited anti-coagulation time
* bedside vascular access
* hemodynamic instability
* hypoxemia
* rapid fluid + solute shifts
* complex equipment
* specialized personnel


Peritoneal Dialysis
* simple to set up + perform
* easy to use
* hemodynamic stability
* no anti-coagulation
* bedside peritoneal access
* unreliable ultrafiltration
* slow fluid + solute removal
* drainage failure, leakage
* catheter obstruction
* respiratory compromise
* hyperglycemia
* peritonitis


* 1. near-complete control of the rate of fluid removal (i.e. the ultrafiltration rate)
* 2. precision and stability
* 3. electrolytes or any formed element of the circulation, including platelets or red or white blood cells, can be removed or added independent of changes in the volume of total body water

* easy to use in ICU
* rapid electrolyte correction
* excellent solute clearances
* rapid acid/base correction
* controllable fluid balance
* tolerated by unstable patients
* early use of TPN
* bedside vascular access routine
* systemic anticoagulation *
* citrate anticoagulation new
* frequent filter clotting
* hypotension


Renal Replacement Therapy.ppt


29 April 2010

Bacteria Pathogenicity Ability to Cause Infection

Bacteria Pathogenicity Ability to Cause Infection

Infectious Diseases
* Encounter-bug meets host (reservoir)
* Bug adheres to host
* Entry-bug enters host
* Multiplication- bug multiplies in host
* Damage to host
* Outcome- bug or host wins or
* Coexist- chronic infection

* Exposure to microbe
Virulence Factors
* Prevent infection
* Influenza changes adhesions over time
* Neisseria gonorrhoeae -variety of adhesions

Portals of Entry
* Mucous membranes
* Conjunctiva
* Skin
* Bugs have preferred portal
* C. tetani spores in soil --- anaerobic wound


* Number of microbes-dose
* Greater dose, more chance infection will occur
* ID50 or LD50 expresses virulence

* Adherence of microbe to surface
* Activates factors that let microbe in-penetration
* Microbes produce invasins (proteins)
* Endocytosis
* Requires multiplication
* Compete with normal flora for space & nutrients
* Overcome local host defenses
* Avoid IgA

* Need Fe to multiply
Avoid Phagocytosis
* Components of cell wall –virulence
Surviving Within Phagocyte

* Ancient disease
* 1/3 of world population infected
* 8 million develop active TB each year
* 2 million die each year
* AIDs increases activation of latent TB
* Dependent upon virulence of strain & host resistance
* Produces cell mediated immunity which prevents active disease in many people
* Multi drug resistance has developed

S & S of Pulmonary TB
* Chronic disease
* Progressive weight loss
* Night sweats
* Chronic cough
* Hemoptysis
Mycobacterium tuberculosis
* Acid fast bacillus (AFB)
* Resistant to drying
* Aerobic, slow growth
* Airborne transmission
* Inhale airborne droplets
* Ingested by alveolar macrophages
* Multiply in macrophages even with ongoing immune response

TB Response
* Host immune response-delayed type hypersensitivity reaction
* Tissue damage DT Inflammatory response
TB Conversion
* TST skin reaction is positive
* Occurs within 24 – 48 hours after exposure to TB antigens
* Purified protein derivative of bacillus
* Cell mediated immunity
* Sensitized T cells react with proteins
* Blood test
* Detects interferon gamma

How to Confirm Diagnosis
* Sputum cultures for AFB smear & culture
* Chest xray
* LTBI (latent TB infection)
Active Disease

* Low resistance

TB Outcomes
* Primary infection- positive skin test
* 10% progressive primary infection-not controlled
Secondary or Reactivation Infection
* Reinfection-2nd exposure or
* Bacteria escape immune system-reactivation
* Activated macrophages release cytokines
* Delayed hypersensitivity reaction

Prevention of Transmission
* Negative pressure rooms
* Respirator masks-fit tested
* Admit staff aware of symptoms of TB
* Yearly TST of staff
* Conversions treated with 6-9 months of INH

* INH for LTBI or TB conversion
* TB disease-active TB
* 9- 12 months of treatment
Resistant TB
* DT improper treatment

* Live culture of M. bovis
Latent vs Active
* Latent TB
* Active TB
* Hanson’s disease- discovered in 1873
* Seen in tropics and underserved countries
* U.S.-150 new cases per year
* Infection of nervous system
* Infects the peripheral nerves within skin
* 2 forms of disease dependent upon immune response

M. leprae
* Tuberculoid form
Lepromatous Form
* Weak immune response & microbe spreads
* Skin & nerve cells infected
* Shed large #s in nasal secretions and oozing sores-more infectious
Invasion via Enzymes
Invasion via Toxins
A-B Toxins
Naming of Exotoxins
S & S
S. aureus
Successful Pathogen
Skin Infections
Invasion via Toxins
Toxic shock syndrome
S. aureus Intoxication
Outbreaks in Community
PVL Gene
Preventing Transmission
Clostridium botulinum
Botulism-Foodborne Disease
Clostridium tetani
Clostridium difficile
Range of Disease
Pathogenesis of CDI
New Issues

* Clean and disinfect surfaces in close proximity of the patient
* Patient care equipment.
* Use bleach for C. difficile
* Privacy drapes

Bacteria Pathogenicity Ability to Cause Infection.ppt


Microbial Interactions with Humans

Microbial Interactions with Humans

Types of Interactions: Symbiosis
* Symbiotic Relationships

Overview of Human-Microbial Interactions
* Pathogens
* Pathogenicity
* Virulence
* Opportunistic Pathogen

Infection Versus Disease
* Infection
* Disease

Opportunistic Pathogens
* Don’t normally cause disease, but may under some circumstances
* 3 circumstances for gaining control/disease

Types of Interactions:
Normal Flora
* Normal Flora
* Factors that influence normal flora

Normal Flora
* Hundreds of different niches associated with human
* Some normal flora are pathogenic
* Resident versus transient flora
* Considered part of the first line of defense!
* Microbial antagonism
* Competitive exclusion

Portals of Entry
* Skin
* Mucous membranes

Preferred Portal
* Many microorganisms have to enter in a specific way and in a certain place to cause disease.
* Skin Portal

* Epidermis and Keratin
* Hair often deters microbial contact with skin
* Dermis and subcutaneous tissue
* Apocrine and sebaceous glands
* Eccrine glands (sweat)

Skin as a Barrier
Mucous Membranes
* Found in mouth, pharynx, esophagus, GI, respiratory, and urinary tracts
* Epithelial cells coated with protective glycoprotein layer (mucous)
* Less protection than skin
* Cilia and mucous produced by goblet cells

Mucous Membranes
* Respiratory tract Portal
* Respiratory Normal Flora
* Respiratory Barrier Mechanisms
* Gastrointestinal tract portal
* GI Normal Flora

Gastrointestinal Tract
* Large intestine
* GI Barrier
* Genitourinary tract Portal
* Genitourinary Tract Normal Flora
* Genitourinary Tract Barrier

LD50 and ID50
* LD50: Number of microbes in a dose that kill 50% of the organisms infected in a sample
* ID50: Number of microbes in a dose that causes disease in 50% of the organisms infected
* The higher the virulence the lower the ID50 or LD50

Microbial Virulence
Microbe Versus Host
* To cause disease a microbe must…
* Why it is difficult for microbes…
o Skin, antimicrobial sweat
Microorganisms and Mechanisms of Pathogenesis

Line of Defense
* First line: Skin and mucous membranes, normal flora
* Second line: phagocytes, inflammation, fever and antimicrobial substances
* Third line: (specific response) special lymphocytes (B and T cells) and antibodies

Step One: Adherence
* Specific adherence
* Pathogens have attachment structures
* Pathogens have attachment structures

Step 2: Invasion/Colonization
* Increase in numbers beyond the point of attachment.
* Three goals

Step 2: Invasion/Colonization
* Localized versus Systematic infections
* Bacteremia, viremia, toxemia
* Septicemia

Step 3: Cause Damage
* Virulence
* Three Ways to cause damage

Virulence Factors
* Usually help organism colonize and grow
* Coagulase
* Siderophores
* Collagenase
* Protease

Another Way to Classify Exotoxins
* Descriptive classifications
A-B toxin
* Cholera toxin (Vibrio cholera)—cholera

The Action of Chlorea Enterotoxin
More A-B toxin examples
Botulinum Toxin
Tetanus Toxin
Membrane Disrupting Toxins
* Gram type negatives
* Part of outer portion of cell wall (outer membrane)
* Lipid A portion
* Exert effects when G- microbe lyses
* Same symptoms for different species of microbe
* No antitoxins produced by host
* Very stable—can’t destroy easily
* Rarely fatal
* Disseminated intravascular clotting
* General symptoms

Pyrogenic Response
* Macrophage ingestion
* Release of interleukin-1 in bloodstream
* Interleukin-1 to hypothalamus and production of prostaglandins
* Resetting of bodies thermostat

Susceptibility/Resistance of Host
* Species specificity
* Tissue specificity
* Age
* Stress
* Diet
* Pre-existing disease (Genetic and Infectious)
* Gender
* Behavior
* Weather?
* Your first line of defense—Review this

Microbial Interactions with Humans.ppt


21 April 2010


By: Henry Wormser, Ph.D.

* Definition: water insoluble compounds
+ Most lipids are fatty acids or ester of fatty acid
+ They are soluble in non-polar solvents such as petroleum ether, benzene, chloroform
* Functions
+ Energy storage
+ Structure of cell membranes
+ Thermal blanket and cushion
+ Precursors of hormones (steroids and prostaglandins)
* Types:
+ Fatty acids
+ Neutral lipids
+ Phospholipids and other lipids
Fatty acids
* Carboxylic acid derivatives of long chain hydrocarbons
o Nomenclature (somewhat confusing)
+ Stearate – stearic acid – C18:0 – n-octadecanoic acid
o General structure:
* Common fatty acids
n = 4 butyric acid (butanoic acid)
n = 6 caproic acid (hexanoic acid)
n = 8 caprylic acid (octanoic acid)
n = 10 capric acid (decanoic acid)
* common FA’s:

n = 12: lauric acid (n-dodecanoic acid; C12:0)
n = 14: myristic acid (n-tetradecanoic acid; C14:0)
n = 16: palmitic acid (n-hexadecanoic acid; C16:0)
n = 18; stearic acid (n-octadecanoic acid; C18:0)
n = 20; arachidic (eicosanoic acid; C20:0)
n= 22; behenic acid
n = 24; lignoceric acid
n = 26; cerotic acid

Less common fatty acids
* iso – isobutyric acid
* anteiso
* odd carbon fatty acid – propionic acid
* hydroxy fatty acids – ricinoleic acid, dihydroxystearic acid, cerebronic acid
* cyclic fatty acids – hydnocarpic, chaulmoogric acid

A plant derived fatty acid with 16 carbons and branches at C 3, C7, C11 and C15. Present in dairy products and ruminant fats.
A peroxisome responsible for the metabolism of phytanic acid is defective in some individuals. This leads to a disease called Refsum’s disease
Refsum’s disease is characterized by peripheral polyneuropathy, cerebellar ataxia and retinitis pigmentosa
Less common fatty acids
These are alkyne fatty acids
Fatty acids
* Fatty acids can be classified either as:
o saturated or unsaturated
o according to chain length:
Unsaturated fatty acids
* Monoenoic acid (monounsaturated)
Double bond is always cis in natural fatty acids.
This lowers the melting point due to “kink” in the chain
* Dienoic acid: linoleic acid
* Various conventions are in use for indicating the number and position of the double bond(s)
* Polyenoic acid (polyunsaturated)
* Monoenoic acids (one double bond):
* Trienoic acids (3 double bonds)
* Tetraenoic acids (4 double bonds)
* Pentaenoic acid (5 double bonds)
* Hexaenoic acid (6 double bonds)
Both FAs are found in cold water fish oils
Typical fish oil supplements
Properties of fats and oils
* fats are solids or semi solids
* oils are liquids
* melting points and boiling points are not usually sharp (most fats/oils are mixtures)
* when shaken with water, oils tend to emulsify
* pure fats and oils are colorless and odorless (color and odor is always a result of contaminants) – i.e. butter (bacteria give flavor, carotene gives color)
Examples of oils
* Olive oil – from Oleo europa (olive tree)
* Corn oil – from Zea mays
* Peanut oil – from Arachis hypogaea
* Cottonseed oil – from Gossypium
* Sesame oil – from Sesamum indicum
* Linseed oil – from Linum usitatissimum
* Sunflower seed oil – from Helianthus annuus
* Rapeseed oil – from Brassica rapa
* Coconut oil – from Cocos nucifera.....

Websites on lipids

* http://www.cyberlipid.org/ web site deals mainly with an overview on all lipids
* http://www.lipidsonline.org – this website focuses mainly on disease processes (atherosclerosis) and treatment
* http://www.lipidlibrary.co.uk/ -There are two main divisions in this website, one dealing with the chemistry and biochemistry of lipids and the other with the analysis of lipids



Inborn Errors of Metabolism

Inborn Errors of Metabolism
By:Namrata Singh M.D

Introduction to IEM
* Usually a single gene defect that causes a block in metabolic pathways.
* Problems are because of accumulation of enzyme substrate behind the metabolic block or deficiency of the reaction product.
* In some instances the substrate is diffusible & affects distant organs & in some there is just a local effect ( lysosomal storage disease ).
* Clinical presentation is varied  mild to severe forms ( mutations even in the same gene may be different in different people ).
* Can present at any time.
* Can affect any organ system.

IEM General approach
* DIAGNOSIS : Some clinical presentations:-
o Consider in DDx . when dealing with :-
+ Critically ill infant
+ Seizures
+ Encephalopathy (Reyes like syndrome )
+ Liver disease
+ MR or developmental delay or regression
+ Recurrent vomiting
+ Unusual odor
+ Unexplained acidosis
+ Hyperammonemia
+ hypoglycemia
* Some clues to look for :-
o *Symptoms accompany changes in diet.
o *Developmental regression.
o *History of food preferences or aversions.
o *History of consanguinity in parents.
o *Family history of MR , unexplained deaths in cousins or siblings etc.
* Physical exam:- common findings—
o Alopecia or abnormal hair
o Retinal cherry red spot
o Cataracts or corneal opacities
o Hepatosplenomegaly
o Coarse features
o Skeletal changes ( gibbus)
o Ataxia
o Micro or macrocephaly
o Rash / jaundice /hypo or hypertonia
* Lab tests:- almost always needed—
o Serum electrolytes
o Ph ( anion gap & acidosis )
o Se lactate
o Se pyruvate
o Ammonia
o Serum & urine amino acids
o Urine organic acids
o DNA probes
o Glycine in CSF (glycine encephalopathy)
o Urine ketones
+ If + in neonates  IEM
+ If – in older child  IEM ( defect in f.a. oxidation )

IEM – Clinical situations
* MR or dev delay
o Can occur alone.
o Seen in urea cycle ,a.a disorders.
o Also in organic acidemias ,peroxisomal & lysosomal storage disorders.
o Serum & urine a.a .
o Urine for mucopolysacchiduria.
* Ill neonate :-
o Clinically indistinguishable from sepsis.
o Usually disorders of protein & CHO metabolism.
o Acidosis or altered mental status out of proportion to systemic symptoms.
o Labs:
+ Lytes , NH3, gluc , ketones , urine ph ,glycine in CSF.
+ Se & urine for a.a & o.a (* before oral intake is stopped or pt is transfused)

IEM – Clinical situations
* Vomiting & encephalopathy :-
* Hypoglycemia :-
o Seen in fatty acid oxid defects ,glycogen storage diseases ,hereditary fructose intolerance & organic acidemias.
o Other labs:-
Urine ketones ~(+) in GSD & organic acidemias. ~(-) in HFI & f.a. oxidation disorders
o Other labs:-
+ NH3 elevated in organic acidemias & fatty acid oxidation defects.
+ Urine reducing subst.– (+) in galactosemia ,HFI.
+ Urine organic acids
* Hyperammonemia :-
o initially – poor appetite , irritability . Then , vomiting , lethargy , seizures & coma.
o Tachypnea – direct effect on resp. drive.
o Seen in (1)- urea cycle disorders (2)- organic acidemias (3)- transient hyperammonemia of the newborn.
o Resp alkalosis : urea cycle disorders & transient hyperammonemia of newborn.
o Acidosis : organic acidemias

* Acidosis :-
o With recurrent vomiting.
o With elevated NH3.
o Out of proportion to clinical picture.
o Difficult to correct.
o Seen in organic acidemias , MSUD ,GSD , disorders of gluconeogenesis.
o Increased anion gap (ketoacids ,lactic acid , methylmalonic acid.)

* Acidosis :- additional tests—
o Se glucose
o NH3
o Urine pH
o Ketones
o Amino & organic acids
o Blood lactate & pyruvate
* Lactate & pyruvate—
o Measure in arterial blood.
o Normal Ratio is 10:1 to 20:1.
o High ratio
+ Mitochondrial disorders.
+ Pyruvate carboxylase deficiency.
o Normal or low ratio
+ Glycogen storage disease.
+ Pyruvate dehydrogenase deficiency
* Broad management :-
o Problems severe acidosis , hypoglycemia , hyperammonemia . Can lead to coma & death!
o Stop all oral intake.
o Give I/V glucose to stop catabolism.( most respond favorably to glucose – some do not eg. Primary lactic acidosis in pyruvate dehydrogenase deficiency .)
o Bicarb.
o Hyperammonemia – may need dialysis .
* Specific interventions :-
o Urea cycle disorders-
+ * preventing protein catabolism ( high calorie diet , arginine supplementation )
+ * decreasing NH3 load (protein restriction )
+ * utilizing NH3 scavengers ( benzoate ,phenylbutyrate)
o PKU-
+ *Avoid enzyme substrate in diet.
+ *Diet low in phenylalanine ( Lofenelac , Phenylfree, Analog XP , Maxamaid XP )
+ *Protein restriction.
o Galactosemia-
+ *galactose free diet ( soy formulas contain sucrose rather than lactose )
o Isovaleric acidemia-
+ Pharmacotherapy to remove accumulated substrate –( glycine treatment).
o Methylmalonic acidemia-
+ Provide co-enzyme ( vit B12)
o Gauchers disease-
+ Provide normal enzyme (enzyme infusions)

IEM Some associations

Inborn Errors of Metabolism.ppt


Complex Carbohydrates

Complex Carbohydrates

- Know the structural components and differences between the glycoconjugate types
- Know the general biosynthetic and catabolic strategies and molecules involved
- Know the general function of each class of glycoconjugate
- Know the general biochemical principles associated with diseases resulting from defects in the catabolic pathways of the glycoconjugates

* Marks, Marks and Smith Chapter 30, primary source, Harper’s Ch 56 supersecondary source. Review Ch. 15,16 for sugar and lipid structural properties

General Biosynthetic and Catabolic Themes for Glycoconjugates
* An initial sugar residue is attached to a core protein or lipid, usually through a serine or asparagine residue.
* Sugar residues are added sequentially from nucleotide diphosphate sugar donors by specific glycosyltransferases in the endoplasmic reticulum and golgi.
* Glycosidases (sugar specific hydrolases) in the lysosome are responsible for degradation and catabolism
* Almost all diseases related to glycoconjugates result from defective lysosomal glycosidase function

UDP-Glucose Glycosyltranserase Reaction
Sugar Nucleotide Conversions
* Consist of a core protein, that is either transmembranous or secreted. Via serine residues, long, unbranched, repeating disaccharides of uronic acid (glucuronic or iduronic) and hexosamine (N-acetylglucosamine or N-acetylgalactosamine) are covalently attached to the protein on the (on the extracellular surface if membrane attached).
* These residues are frequently sulfated following polymer formation. Thus they possess a large net negative charge, are highly hydrated, and occupy a large amount of space extracellularly (good for their role as lubricants and molecular sieves). They also provide a large surface area for binding of other matrix components and some growth factors.
* Major components of the extracellular matrix, also in joint synovial fluid, vitreous humor of the eye, arterial walls, bone and cartilage

The main classes of disaccharide repeats found in glycosaminoglycans attached to protein
GAG-Carbohydrate Core Linkage to Protein

Sequential Biosynthetic Pathway for GAGs
There are three major classes of glycoproteins – those with carbohydrate chains that are N-linked (via an Asn), O-linked (via Ser or Thr) or linked via a glycosylphosphatidylinositol (GPI) lipid. These are primarily transmembranous proteins with the carbohydrates positioned extracellularly, and they are also secreted.

* For N-linked, the carbohydrate core structure is synthesized processively on an activated lipid carrier, dolichol phosphate, and transferred co-translationally to membrane proteins synthesized in the endoplasmic reticulum.

Three Main Types of Glycoprotein Structures
GPI = glycosylphosphatidylinositol
Also: targeting signal for removal of damaged or mis-folded proteins from the cell
And: generally function to aid in the proper conformation and stability of membrane-associated proteins
Dolichol-linked Donor Oligosaccharide Synthesis for N-linked Glycoproteins
O-linked Glycoproteins (Mucins most common)
* Carbohydrates are attached to ceramide (a sphingolipid: sphingosine plus fatty acid). Involved in cell-cell contact/interactions. The terminal carbohydrates can frequently be identical to carbohydrate chains on glycoproteins (Ex: blood group antigens)
* Cerebrosides – glycolipids with one or two sugars (glucose and galactose); if sulfated, are termed sulfatides, found in high concentrations in the brain
* Gangliosides – glycolipids that contain sialic acid residues, longer and branched relative to cerebrosides

Glycolipid Structural
Sulfate donor
R = protein or ceramide
Bacteria sp. with binding proteins (lectins) for Lactosylceramide
I-Cell Disease Summary
Tay-Sachs Disease (Ex.)
* The most common form of GM2 gangliosidosis; the GM2 ganglioside accumulates due to a defect in hexosaminidase A. Causes swelling and loss of ganglion cells in the cerebral cortex, proliferation of glial cells, and demyelination of peripheral nerves.
* Rare defect in general population, but occurs 1 in every 3600 births in the U.S. Jewish population descended from Eastern Europe (ex: 1 in 28 Ashkenazi Jews carry the defect).
* No effective treatments; genetic counseling and screening are the primary approaches used to minimize occurrence.

Complex Carbohydrates


Sphingolipid Disorders

Sphingolipid Disorders
by:Eric Niederhoffer

Sphingolipids (phospho- or glycolipids)

General Structure
Generalized gangliosidosis
Tay-Sachs disease
Niemann-Pick disease
Metachromatic leukodystrophy
Krabbe’s disease
Gaucher’s disease
b-hexosaminidase A
GM2 activator
b-hexosaminidase A&B
a-galactosidase A
arylsulfatase A
Targeting of Lysosomal Enzymes to Lysosomes
Addition of M6P to lysosomal enzymes
Recognition by MPRs
M6P independent pathways

Review Questions

* How do you interpret ganglioside names (G, D, M, 1, 2, 3)?
* What do the different lysosomal enzyme names mean in the context of removing saccharides?
* Where does ganglioside degradation occur?

Sphingolipid Disorders


11 April 2010

Infectious Diseases of the Respiratory System

Infectious Diseases of the Respiratory System

Infections of the Respiratory tract
* Most common entry point for infections
* Upper respiratory tract
* Lower respiratory tract

Protective Mechanisms
Normal flora: Commensal organisms
* Limited to the upper tract
* Mostly Gram positive or anaeorbic
* Microbial antagonist (competition)

Other Protective Mechanisms
* Nasal hair, nasal turbinates
* Mucus
* Involuntary responses (coughing)
* Secretory IgA
* Immune cells

Selected Bacterial Infections

Pneumonia - Streptococcus pneumoniae
Diphtheria - Corynebacterium diphtheriae
Tuberculosis - Mycobacterium tuberculosis
Whooping cough - Bordetella pertussis
Streptococcus pyogenes
Group A Strep
Strep Throat
Scarlet Fever
Bacterial Pneumonia
Streptococcus pneumoniae
Bacterial Pneumonia
Streptococcus pneumoniae
* Transmitted by droplets or fomites
* Infects the upper respiratory tract
* Begins with severe sore throat, low-grade fever and swollen lymph nodes or with skin rash, 1-6 days after infection

Corynebacterium diphtheriae
* Aerobic Gram + bacillus
* Toxin inhibits protein synthesis of cells to which it binds
* Destroyed cells and WBC form "pseudomembrane" which blocks airways
Bordetella pertussis
Pertussis (Whooping Cough)
Mycobacterium tuberculosis
Tubercule formation
Multi-Drug Resistant
TB Skin Test
Virus infections
Fungal Infections
Respiratory Syncytial Virus
* Enveloped (membrane) RNA virus
* Spread by respiratory droplets
* Community outbreaks in late fall to spring
* Upper respiratory tract infection – epithelial cells
* May be fatal in infants
Influenza Virus
An enveloped RNA virus
Coccidioides immitis
Valley Fever is an Endemic Disease
Coccidioides immitis

Infectious Diseases of the Respiratory System.ppt


Anatomy of Respiratory System

Anatomy of Respiratory System

Organization and Functions of the Respiratory System
* Consists of an upper respiratory tract (nose to larynx) and a lower respiratory tract ( trachea onwards) .
* Conducting portion transports air.
- includes the nose, nasal cavity, pharynx, larynx, trachea, and progressively smaller airways, from the primary bronchi to the terminal bronchioles

* Respiratory portion carries out gas exchange.
- composed of small airways called respiratory bronchioles and alveolar ducts as well as air sacs called alveoli

Respiratory System Functions
* supplies the body with oxygen and disposes of carbon dioxide
* filters inspired air
* produces sound
* contains receptors for smell
* rids the body of some excess water and heat
* helps regulate blood pH

* Breathing (pulmonary ventilation). consists of two cyclic phases:
* inhalation, also called inspiration - draws gases into the lungs.
* exhalation, also called expiration - forces gases out of the lungs.

Upper Respiratory Tract
* Composed of the nose and nasal cavity, paranasal sinuses, pharynx (throat), larynx.
* All part of the conducting portion of the respiratory system.
Respiratory mucosa
* A layer of pseudostratified ciliated columnar epithelial cells that secrete mucus
* Found in nose, sinuses, pharynx, larynx and trachea
* Mucus can trap contaminants
o Cilia move mucus up towards mouth

Upper Respiratory Tract

* Internal nares - opening to exterior
* External nares opening to pharynx
* Nasal conchae - folds in the mucous membrane that increase air turbulence and ensures that most air contacts the mucous membranes

* rich supply of capillaries warm the inspired air
* olfactory mucosa – mucous membranes that contain smell receptors
* respiratory mucosa – pseudostratified ciliated columnar epithelium containing goblet cells that secrete mucus which traps inhaled particles,
* lysozyme kills bacteria and lymphocytes and
* IgA antibodies that protect against bacteria

provides and airway for respiration
• moistens and warms entering air
• filters and cleans inspired air
• resonating chamber for speech
detects odors in the air stream
rhinoplasty: surgery to change shape of external nose

Paranasal Sinuses
* Four bones of the skull contain paired air spaces called the paranasal sinuses - frontal, ethmoidal, sphenoidal, maxillary
* Decrease skull bone weight
* Warm, moisten and filter incoming air
* Add resonance to voice.
* Communicate with the nasal cavity by ducts.
* Lined by pseudostratified ciliated columnar epithelium.

Paranasal sinuses

* Common space used by both the respiratory and digestive systems.
* Commonly called the throat.
* Originates posterior to the nasal and oral cavities and extends inferiorly near the level of the bifurcation of the larynx and esophagus.
* Common pathway for both air and food.
* Walls are lined by a mucosa and contain skeletal muscles that are primarily used for swallowing.
* Flexible lateral walls are distensible in order to force swallowed food into the esophagus.
* Partitioned into three adjoining regions:

* Superior-most region of the pharynx. Covered with pseudostratified ciliated columnar epithelium.
* Located directly posterior to the nasal cavity and superior to the soft palate, which separates the oral cavity.
* Normally, only air passes through.
* Material from the oral cavity and oropharynx is typically blocked from entering the nasopharynx by the uvula of soft palate, which elevates when we swallow.
* In the lateral walls of the nasopharynx, paired auditory/eustachian tubes connect the nasopharynx to the middle ear.
* Posterior nasopharynx wall also houses a single pharyngeal tonsil (commonly called the adenoids).

* The middle pharyngeal region.
* Immediately posterior to the oral cavity.
* Bounded by the edge of the soft palate superiorly and the hyoid bone inferiorly.
* Common respiratory and digestive pathway through which both air and swallowed food and drink pass.
* Contains nonkeratinized stratified squamous epithelim.
* Lymphatic organs here provide the first line of defense against ingested or inhaled foreign materials. Palatine tonsils are on the lateral wall between the arches, and the lingual tonsils are at the base of the tongue.

* Inferior, narrowed region of the pharynx.
* Extends inferiorly from the hyoid bone to the larynx and esophagus.
* Terminates at the superior border of the esophagus and the epiglottis of the larynx.
* Lined with a nonkeratinized stratified squamous epithelium.
* Permits passage of both food and air.

Lower Respiratory Tract
* Conducting airways (trachea, bronchi, up to terminal bronchioles).
* Respiratory portion of the respiratory system (respiratory bronchioles, alveolar ducts, and alveoli).
* Voice box is a short, somewhat cylindrical airway ends in the trachea.
* Prevents swallowed materials from entering the lower respiratory tract.
* Conducts air into the lower respiratory tract.
* Produces sounds.
* Supported by a framework of nine pieces of cartilage (three individual pieces and three cartilage pairs) that are held in place by ligaments and muscles.
* Nine c-rings of cartilage form the framework of the larynx
* thyroid cartilage – (1) Adam’s apple, hyaline, anterior attachment of vocal folds, testosterone increases size after puberty
* cricoid cartilage – (1) ring-shaped, hyaline
* arytenoid cartilages – (2) hyaline, posterior attachment of vocal folds, hyaline
* cuneiform cartilages - (2) hyaline
* corniculate cartlages - (2) hyaline

epiglottis – (1) elastic cartilage
* Muscular walls aid in voice production and the swallowing reflex
* Glottis – the superior opening of the larynx
* Epiglottis – prevents food and drink from entering airway when swallowing
* pseudostratified ciliated columnar epithelium

Sound Production
* Inferior ligaments are called the vocal folds.
- are true vocal cords because they produce sound when air passes between them
* Superior ligaments are called the vestibular folds.
- are false vocal cords because they have no function in sound production, but protect the vocal folds.

* The tension, length, and position of the vocal folds determine the quality of the sound.

Sound production
* Intermittent release of exhaled air through the vocal folds
* Loudness – depends on the force with which air is exhaled through the cords
* Pharynx, oral cavity, nasal cavity, paranasal sinuses act as resonating chambers that add quality to the sound
* Muscles of the face, tongue, and lips help with enunciation of words

Conducting zone of lower respiratory tract
* A flexible tube also called windpipe.
* Extends through the mediastinum and lies anterior to the esophagus and inferior to the larynx.
* Anterior and lateral walls of the trachea supported by 15 to 20 C-shaped tracheal cartilages.
* Cartilage rings reinforce and provide rigidity to the tracheal wall to ensure that the trachea remains open at all times
* Posterior part of tube lined by trachealis muscle
* Lined by ciliated pseudostratified columnar epithelium.
* At the level of the sternal angle, the trachea bifurcates into two smaller tubes, called the right and left primary bronchi.
* Each primary bronchus projects laterally toward each lung.
* The most inferior tracheal cartilage separates the primary bronchi at their origin and forms an internal ridge called the carina.
Bronchial tree
* A highly branched system of air-conducting passages that originate from the left and right primary bronchi.
* Progressively branch into narrower tubes as they diverge throughout the lungs before terminating in terminal bronchioles.
* Incomplete rings of hyaline cartilage support the walls of the primary bronchi to ensure that they remain open.
* Right primary bronchus is shorter, wider, and more vertically oriented than the left primary bronchus.
* Foreign particles are more likely to lodge in the right primary bronchus.
* The primary bronchi enter the hilus of each lung together with the pulmonary vessels, lymphatic vessels, and nerves.
* Each primary bronchus branches into several secondary bronchi (or lobar bronchi).
* The left lung has two secondary bronchi.The right lung has three secondary bronchi.
* They further divide into tertiary bronchi.
* Each tertiary bronchus is called a segmental bronchus because it supplies a part of the lung called a bronchopulmonary segment.
* Secondary bronchi tertiary bronchi bronchioles terminal bronchioles
* with successive branching amount of cartilage decreases and amount of smooth muscle increases, this allows for variation in airway diameter
* during exertion and when sympathetic division active bronchodilation
* mediators of allergic reactions like histamine bronchoconstriction
* epithelium gradually changes from ciliated pseudostratified columnar epithelium to simple cuboidal epithelium in terminal bronchioles

Respiratory Zone of Lower Respiratory Tract
Conduction vs. Respiratory zones
* Most of the tubing in the lungs makes up conduction zone
o Consists of nasal cavity to terminal bronchioles
* The respiratory zone is where gas is exchanged
o Consists of alveoli, alveolar sacs, alveolar ducts and respiratory bronchioles

Respiratory Bronchioles, Alveolar Ducts, and Alveoli
* Lungs contain small saccular outpocketings called alveoli.
* They have a thin wall specialized to promote diffusion of gases between the alveolus and the blood in the pulmonary capillaries.
* Gas exchange can take place in the respiratory bronchioles and alveolar ducts as well as in the alveoli, each lung contains approximately 300 to 400 million alveoli.
* The spongy nature of the lung is due to the packing of millions of alveoli together.

Respiratory Membrane
* squamous cells of alveoli .
* basement membrane of alveoli.
* basement membrane of capillaries
* simple squamous cells of capillaries
* about .5 μ in thickness

Gross Anatomy of the Lungs
* Each lung has a conical shape. Its wide, concave base rests upon the muscular diaphragm.
* Its superior region called the apex projects superiorly to a point that is slightly superior and posterior to the clavicle.
* Both lungs are bordered by the thoracic wall anteriorly, laterally, and posteriorly, and supported by the rib cage.
* Toward the midline, the lungs are separated from each other by the mediastinum.
* The relatively broad, rounded surface in contact with the thoracic wall is called the costal surface of the lung.

Left lung
* divided into 2 lobes by oblique fissure
* smaller than the right lung
* cardiac notch accommodates the heart
* divided into 3 lobes by oblique and horizontal fissure
* located more superiorly in the body due to liver on right side

Pleura and Pleural Cavities
* The outer surface of each lung and the adjacent internal thoracic wall are lined by a serous membrane called pleura.
* The outer surface of each lung is tightly covered by the visceral pleura.
* while the internal thoracic walls, the lateral surfaces of the mediastinum, and the superior surface of the diaphragm are lined by the parietal pleura.
* The parietal and visceral pleural layers are continuous at the hilus of each lung.

Pleural Cavities
The potential space between the serous membrane layers is a pleural cavity.

* The pleural membranes produce a thin, serous pleural fluid that circulates in the pleural cavity and acts as a lubricant, ensuring minimal friction during breathing.
* Pleural effusion – pleuritis with too much fluid
Blood supply of Lungs
* pulmonary circulation -
* bronchial circulation – bronchial arteries supply oxygenated blood to lungs, bronchial veins carry away deoxygenated blood from lung tissue  superior vena cava
* Response of two systems to hypoxia – pulmonary vessels undergo vasoconstriction bronchial vessels like all other systemic vessels undergo vasodilation

Respiratory events
* Pulmonary ventilation = exchange of gases between lungs and atmosphere
* External respiration = exchange of gases between alveoli and pulmonary capillaries
* Internal respiration = exchange of gases between systemic capillaries and tissue cells

Two phases of pulmonary ventilation
* Inspiration, or inhalation - a very active process that requires input of energy.The diaphragm, contracts, moving downward and flattening, when stimulated by phrenic nerves.
* Expiration, or exhalation - a passive process that takes advantage of the recoil properties of elastic fiber. ・The diaphragm relaxes.The elasticity of the lungs and the thoracic cage allows them to return to their normal size and shape.

Muscles that ASSIST with respiration
* The scalenes help increase thoracic cavity dimensions by elevating the first and second ribs during forced inhalation.
* The ribs elevate upon contraction of the external intercostals, thereby increasing the transverse dimensions of the thoracic cavity during inhalation.
* Contraction of the internal intercostals depresses the ribs, but this only occurs during forced exhalation.
* Normal exhalation requires no active muscular effort.

Muscles that ASSIST with respiration
* Other accessory muscles assist with respiratory activities.
* The pectoralis minor, serratus anterior, and sternocleidomastoid help with forced inhalation,
* while the abdominal muscles(external and internal obliques, transversus abdominis, and rectus abdominis) assist in active exhalation.

Boyle’s Law
* The pressure of a gas decreases if the volume of the container increases, and vice versa.
* When the volume of the thoracic cavity increases even slightly during inhalation, the intrapulmonary pressure decreases slightly, and air flows into the lungs through the conducting airways. Air flows into the lungs from a region of higher pressure (the atmosphere)into a region of lower pressure (the intrapulmonary region).
* When the volume of the thoracic cavity decreases during exhalation, the intrapulmonary pressure increases and forces air out of the lungs into the atmosphere.

Ventilation Control by Respiratory Centers of the Brain
* The trachea, bronchial tree, and lungs are innervated by the autonomic nervous system.
* The autonomic nerve fibers that innervate the heart also send branches to the respiratory structures.
* The involuntary, rhythmic activities that deliver and remove respiratory gases are regulated in the brainstem within the reticular formation through both the medulla oblongata and pons.

Respiratory Values
* A normal adult averages 12 breathes per minute = respiratory rate(RR)
* Respiratory volumes – determined by using a spirometer

* TIDAL VOLUME (TV): Volume inspired or expired with each normalハbreath. = 500 ml
* INSPIRATORY RESERVE VOLUME (IRV): Maximum volume that can be inspired over the inspiration of a tidal volume/normal breath. Used during exercise/exertion.=3100 ml
* EXPIRATRY RESERVE VOLUME (ERV): Maximal volume that can be expired after the expiration of a tidal volume/normal breath. = 1200 ml
* RESIDUAL VOLUME (RV): Volume that remains in the lungs after a maximal expiration.ハ CANNOT be measured by spirometry.= 1200 ml

* INSPIRATORY CAPACITY ( IC): Volume of maximal inspiration:IRV + TV = 3600 ml
* FUNCTIONAL RESIDUAL CAPACITY (FRC): Volume of gas remaining in lung after normal expiration, cannot be measured by spirometry because it includes residual volume:ERV + RV = 2400 ml
* VITAL CAPACITY (VC): Volume of maximal inspiration and expiration:IRV + TV + ERV = IC + ERV = 4800 ml
* TOTAL LUNG CAPACITY (TLC): The volume of the lung after maximal inspiration.ハ The sum of all four lung volumes, cannot be measured by spirometry because it includes residual volume:IRV+ TV + ERV + RV = IC + FRC = 6000 ml

Anatomy of Respiratory System.ppt

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