25 March 2010

Urinary Tract Infections



Urinary Tract Infections
By:Lourdes Lozano Vargas

Urinary Tract Infections
* Leading cause of morbidity and health care expenditures in persons of all ages.
* An estimated 50 % of women report having had a UTI at some point in their lives.
* 8.3 million office visits and more than 1 million hospitalizations, for an overall annual cost > $1 billion.

Acute Uncomplicated Cystitis
* Sexually active young women.
* Causes: anatomy and certain behavioral factors, including delays in micturition, sexual activity, and the use of diaphragms and spermicides tract.
* Aggressive diagnostic work-ups are unwarranted in young women presenting with an uncomplicated episode of cystitis.

Acute Uncomplicated Cystitis
* The microbiology is limited to a few pathogens.
* 70%- 85% are caused by Escherichia coli
* 5-20%are caused by coagulase-negative Staphylococcus saprophyticus
* 5-12% are caused by other Enterobacteriaceae such as Klebsiella and Proteus.

Acute Uncomplicated Cystitis
* Clinical Features: dysuria, frequency, urgency, suprapubic pain, hematuria.
o Fever >38C, flank pain, costovertebral angle tenderness, and nausea or vomiting suggest upper tract infection.

Acute Uncomplicated Cystitis
* Diagnosis: direct history and PE
* PE: Temperature, abdominal exam, assessment of CVA tenderness, pelvic exam.
o H/o STD’s, new sexual partner, partner with urethral symptoms, gradual onset.

Acute Uncomplicated Cystitis
* Guidelines for tx of acute cystitis recommend empiric antibiotic tx.
* Unnecessary antibiotic use??
* Clinical criteria for Dx:

Dysuria, presence of > trace urine leukocytes, and presence of nitrites or...
Dysuria and frequency in the absence of vaginal discharge.
Acute Uncomplicated Cystitis
* UA: Evaluation of midstream urine for pyuria.
o White blood cell casts in the urine are Dx of upper tract infection.
* Urine Culture: Not necessary
o Warranted in: Suspected complicated infection, persistent symptoms following tx, symptoms recur < 1 mo after tx. Acute Uncomplicated Cystitis * Urine dipsticks: o Leukocyte esterase (pyuria), sensitivity 75-90%, specificity 95% o Nitrite (Enterobacteriacea), sensitivity 35-85%, specificity 95%, false positive with phenazopyridine, beets. o Microscopic evaluation for pyuria or a culture is indicated in pt with negative leukocyte esterase that have urinary symptoms. Acute Uncomplicated Cystitis * Susceptibility: o E.coli o S.saprophyticus Acute Uncomplicated Cystitis * Treatment: o Short course vs. prolonged tx + Short course preferred except with beta-lactam agents o TMP-SMX (160/800mg BID x 3) first-line tx if: no allergy to the drug, no antibiotics in the past 3 mo, no recent hospitalization. o Nitrofurantoin (100mg BID x 5 days) o Analgesia: Phenazopyridine 200mg TIDx2 Acute Urethral Syndrome * Acute symptomatic women with dysuria and frequency with a midstream culture containing < 10(5) CFU/mL. * > 10(2) CFU/mL in women with acute symptomatic pyuria = UTI
* Tx as an uncomplicated UTI
* Mycoplasma genitalium, Ureaplasma urealyticum

Acute Complicated Cystitis
* UTI when/with structural, functional or metabolic abnormalities (polycystic, solitary, transplant kidney;DM, CRF, indwelling cath, neurogenic bladder) or elderly, male, child, pregnant or h/o recurrent UTI)
* E.coli accounts for fewer than one third of complicated cases.
* Clinically, the spectrum of complicated UTIs may range from cystitis to urosepsis with septic shock.

Acute Complicated Cystitis
* Urine culture and susceptibility are necessary.
* These infections are usually associated with high-count bacteriuria (> 10(5) CFU/mL).
* MO: Proteus, Klebsiella, Pseudomonas, Serratia, and Providencia, enterococci, staphylococci and fungi AND E.coli

Acute Complicated Cystitis
* Empiric therapy for these patients should include an agent with a broad spectrum of activity against the expected uropathogens: fluoroquinolone, ceftazidime, cefepime, aztreonam, imipenem-cilastatin. (Obtain Ucx prior to Tx)
* Tx x 7-14 days
* Follow-up urine culture should be performed within 14 days after treatment???

Recurrent Cystitis
* Up to 27% of young women with acute cystitis develop recurrent UTIs.
* The causative organism should be identified by urine culture.
* Relapse: infection with the same organism (multiple relapses = complicated UTIs).
* Recurrence: infection with different organisms.

Recurrent Cystitis
* >3 UTI recurrences documented by urine Cx within one year can be managed using one of three preventive strategies:
* Acute self-treatment with a three-day course of standard therapy.
* Postcoital prophylaxis with one-half of a TMP-SMX double-strength tablet (80/400 mg).
* Continuous daily prophylaxis TMP-SMX one-half tablet per day (40/200 mg); nitrofurantoin 50 to 100 mg per day; norfloxacin 200 mg per day.

Uncomplicated Pyelonephritis
* Suspect if:
o Cystitis-like illness and accompanying flank pain
o Severe illness with fever, chills, nausea, vomiting, abdominal pain
o Gram-negative bacteremia.

Uncomplicated Pyelonephritis
* DX: Clinical, confirm with:
o UA: pyuria and/or WBC casts
o UCx with > 10 (5) CFU/mL (80%)
* Tx: 14 days total
o Oral: TMP/SMX, fluoroquinolones
o IV: 3rd gen cephalosporin, aztreonam, quinolones, aminoglycoside

Uncomplicated Pyelonephritis
* Pt with symptoms after 3 days of appropriate antimicrobial tx should be evaluated by renal US or CT for obstruction or abscess.

UTI in Men

* At risk: Older men with prostatic disease, UT instrumentation, anal sex, or partner colonized with uropathogens.
* UCx: 10 (3) CFU/mL sensitivity and specificity 97%.
* Additional studies?
o Not necessary in young healthy men who have a single episode.

UTI in Men
* Tx:
o Uncomplicated cystitis:
+ TMP/SMX or fluoroquinolones x 7 days
o Complicated cystitis:
+ Fluoroquinolones x 7-14 days
o Bacterial prostatitis:
+ Fluoroquinolone x 6-12 weeks

Catheter-Associated UTI
* Risk of bacteriuria is ~ 5%/day (long term catheter bacteriuria is inevitable).
* 40% of nosocomial infections
* Most common source of gram-negative bacteremia.
* Dx: Ucx 10 (2) CFU/mL
o MO: E.coli, Proteus, Enterococcus, Pseudomona, Enterobacter, Serratia, Candida

Catheter-Associated UTI
* Mild to mod: oral quinolones10-14days
* Severe infection: IV/oral 14-21days
* Asymptomatic bacteriuria in pt with an indwelling Foley should not be Tx unless they are immunosuppressed, have risk of bacterial endocarditis or pt who are about to undergo urinary tract instrumentation.

Asymptomatic Bacteriuria
* UCx: > 10(5)CFU/mL with no symptoms
* Three groups of pt with asymptomatic bacteruria have been shown to benefit from tx:
o Pregnant
o Renal transplant
o Pt who are about to undergo urinary tract procedures.

Pregnant patients

* Asymptomatic bacteriuria: two consecutive voided urine specimens with isolation of the same bacterial strain >10(5) or a single cath urine specimen.
o Nitrofurantoin 100mg BID x 5-7 days
o Amoxi/Clav 500mg BID or 250 TID x 7days
o Fosfomycin 3g PO x 1

Interstitial Cystitis
* Frequency, urgency, urge incontinence with periurethral and suprapubic pain on bladder filling that is improved by voiding. Terminal hematuria may be present.
* Etiology. Unclear (autoimmune, altered glycosaminoglycal layer, allergic)

Interstitial Cystitis
* TX
o Refer to urology for cystoscopy.
o Dietary modifications
o Behavioral modifications
o Rx:
+ Pyridium
+ Pentosan polysulfate 100mg TID x 6mo to 2 years.
+ Amitriptyline 10-75mg QHS

Interstitial Cystitis
* Intravesical therapies
o Dimethyl Sulfoxide instillations q1-2 wks
o BCG instilled q1wk x 6-8 wks
o Hyaluronic acid instilled q1wk x 4-6wk.

References

Urinary Tract Infections.ppt

Read more...

Oral Cavity



Oral Cavity
By:Robert Scranton© 2008

The Tissues
Lining Mucosa
Masticatory Mucosa
* NKSS (nonkeratinized stratified squamous)
* Lamina Propria- loose CT w/ collagen bundles
o Mucous and serous glands
o Fordyce Spots
* Location?
* KSS/PKSS (keratinized/parakeratinized stratified squamous)
* Variable Lamina Propria
* Location?

Lining Mucosa
Don’t forget the soft palate
Diagrams are important

Identify:
* vermillion zone
* Hair follicle
* Epithelium, what type?
* Skeletal muscle
o what is the name?

Special Mucosa
* Filiform
o Most abundant
o Dorsal surface
* Fungiform
o Occasional tasebuds, CN-VII
* Vallate
o 8-12 along sulcus terminalis
o Crypt
o Serous glands of Von Ebner
o CN- IX, taste buds
* Foliate
o Dorsolateral surfaces, taste buds?

Identify filiform and fungiform
Vallate/ circumvallate

Teeth
* We origionally have __ baby (________) teeth. Adults have ___ teeth.
* What are the three cell types that form the teeth and what parts do they form?
* What do dentin and enamel have in common?
* Which is acellular?

Mesenchymal CT pulp cavity
Odontoblasts (mesenchyme) Dentin
ameloblasts (ectoderm) Enamel
Avascular
Ca2+ Hydroxyapatite (calcified organic Matrix
Enamel
Teeth
* The little tubules in the teeth, what is their story?
* Damage to What three things can lead to loss of a tooth?
* Dentinal tubules- the tubule that the cytoplasmic process of odontoblasts extend through for nociception
* Canaliculi- the tubules that cementocytes use to maintain cementum
* Bony Socket
* Peridontal ligament
* Cementum

Identify:
* Alveolar Bone
* Free Gingiva
* Attached Gingiva
* Alveolar Mucosa
* Gingival Ligament
* Gingival Sulcus
* Alveolar Bone
* Dentin
* Peridontal ligament
* Pulp Cavity
* Gingiva
* Odontoblasts
* Predentin
* Dentin
* Cementocytes
* Peridontal Ligament

Salivary Glands
Intrinsic
Extrinsic
* AKA minor
* Serous
* Mucous
* Mixed
* Means w/in lamina propria
* AKA Major
* Serous
* Serousmucous
* Outside oral cavity
* Has large ducts

Important words
* Serous amylase
* Serous demilunes bacteriolytic lysozyme
* IgA bacteriostatic, resistant to degradation
* Nasopharynx Respiratory Epithelium
* Oropharynx lining mucosa, NKSS
* Laryngopharynx transitional zone so KSS, NKSS

Oral Cavity.ppt

Read more...

Chemical composition and functions of saliva



Chemical composition and functions of saliva
By:Dennis E. Lopatin, Ph.D.

Chronology of defining salivary components and functions
* Beginning in 1950’s whole saliva evaluated (antimicrobial properties, role in microbial attachment, mineralization, taste, lubrication)
* Secretions of major glands (parotid and submandibular/sublingual)
* In 1970’s individual components isolated and biochemically characterized
* In mid-1980’s beginning to map functional domains (peptide synthesis and recombinant approaches)

Major salivary components
Mucin 1 (MG1)
sIgA
Mucin 2 (MG2)
Lactoferrin
Peroxidases
Amylases
Carbonic anhydrases
Proline-rich proteins
Lysozyme
Statherins
Histatins

Current concepts regarding the functional features of salivary macromolecules
* Recent structure/function studies have identified general principles regarding function
* Based on in vitro studies of purified molecules
* Additional studies required to evaluate concepts in situ

Conformational requirements
* Conformation or shape of a molecule is critical for its biological function
* Examples
o Proline-rich proteins interact with A. viscosus and St. gordonii only when adsorbed onto mineralized surface
o Statherins and histatins require -helical conformation
o Human salivary amylase require 5 inter-chain disulfide bonds

Multifunctionality
Salivary
Families
Anti-Bacterial
Buffering
Digestion
Mineralization
Lubrication &Viscoelasticity
Tissue
Coating
Anti-Fungal
Anti-Viral
Carbonic anhydrases,
Histatins
Amylases,
Mucins, Lipase
Cystatins,
Histatins, Proline rich proteins,
Statherins
Mucins, Statherins
Amylases,
Cystatins, Mucins,
Proline-rich proteins, Statherins
Histatins
Cystatins,
Mucins
Amylases, Cystatins,
Histatins, Mucins,
Peroxidases
Redundancy
* Saliva has built-in redundancy in regard to its protective functions.
* Example - Many salivary molecules can inhibit the precipitation of calcium phosphate salts.
o strong inhibitors such as statherin and acidic proline-rich proteins
o moderate inhibitors such as histatins and cystatins
o weak inhibitors such as mucins and amylase

Amphifunctionality
* A molecule may have both protective and detrimental properties - “double-edged sword”.
* May depend on molecule’s location or site of action
o Amylases
+ In solution, they facilitate clearance of viridans streptococci
+ Adsorbed to tooth surface, they can promote adherence of these bacteria and digest starch to dietary maltose and production of acid
o Statherin and acidic proline-rich proteins
+ At enamel surface, they play an important role in mineralization by inhibiting the formation of primary and secondary calcium phosphate salts. When adsorbed to the enamel surface, they promote attachment of cariogenic microorganisms.

Complexing
* Functional relationships exist between different molecules in saliva
* Two types of complexing (covalent and non-covalent)
o homotypic (between similar molecules)
o heterotypic (between different molecules)
* Example: Mucins
o homotypic complexes necessary for lubrication and viscoelastic properties
o heterotypic complexes with sIgA, lysozyme and cystatins concentrate these anti-microbials at tissue interfaces
Salivary Protein Functions
Mucins
* Lack precise folded structure of globular proteins
* Asymmetrical molecules with open, randomly organized structure
* Polypeptide backbone (apomucin) with CHO side-chains
* Side-chains may end in negatively charged groups, such as sialic acid and bound sulfate
* Hydrophillic, entraining water (resists dehydration)
* Unique rheological properties (e.g., high elasticity, adhesiveness, and low solubility)
* Two major mucins (MG1 and MG2)

Mucin Functions
* Tissue Coating
o Protective coating about hard and soft tissues
o Primary role in formation of acquired pellicle
o Concentrates anti-microbial molecules at mucosal interface
* Lubrication
o Align themselves with direction of flow (characteristic of asymmetric molecules)
o Increases lubricating qualities (film strength)
o Film strength determines how effectively opposed moving surfaces are kept apart
* Aggregation of bacterial cells
o Bacterial adhere to mucins may result in surface attachment, or
o Mucin-coated bacteria may be unable to attach to surface
* Bacterial adhesion
o Mucin oligosaccharides mimic those on mucosal cell surface
o React with bacterial adhesins, thereby blocking them

Amylases
* Calcium metalloenzyme
* Hydrolyzes (1-4) bonds of starches such as amylose and amylopectin
* Several salivary isoenzymes
* Maltose is the major end-product (20% is glucose)
* “Appears” to have digestive function
* Why is it also present in tears, serum, bronchial, and male and female urogenital secretions?
* A role in modulating bacterial adherence?

Lingual Lipase
* Secreted by von Ebner’s glands of tongue
* Involved in first phase of fat digestion
* Hydrolyzes medium- to long-chain triglycerides
* Important in digestion of milk fat in new-born
* Unlike other mammalian lipases, it is highly hydrophobic and readily enters fat globules

Statherins
* Calcium phosphate salts of dental enamel are soluble under typical conditions of pH and ionic strength
* Supersaturation of calcium phosphates maintain enamel integrity
* Statherins prevent precipitation or crystallization of supersaturated calcium phosphate in ductal saliva and oral fluid
* Produced by acinar cells in salivary glands
* Also an effective lubricant

Proline-rich Proteins (PRPs)
* Like statherin, PRPs are also highly asymmetrical
* Inhibitors of calcium phosphate crystal growth
* Inhibition due to first 30 residues of negatively-charged amino-terminal end
* Present in the initially formed enamel pellicle and in “mature” pellicles

Role of PRPs in enamel pellicle formation
* Acquired enamel pellicle is 0.1-1.0 µm thick layer of macromolecular material on the dental mineral surface
* Pellicle is formed by selective adsorption of hydroxyapatite-reactive salivary proteins, serum proteins and microbial products such as glucans and glucosyl-transferase
* Pellicle acts as a diffusion barrier, slowing both attacks by bacterial acids and loss of dissolved calcium and phosphate ions

Remineralization of enamel and calcium phosphate inhibitors
* Early caries are repaired despite presence of mineralization inhibitors in saliva
* Sound surface layer of early carious lesion forms impermeable barrier to diffusion of high mol.wt. inhibitors.
* Still permeable to calcium and phosphate ions
* Inhibitors may encourage mineralization by preventing crystal growth on the surface of lesion by keeping pores open

Calculus formation and calcium phosphate inhibitors
* Calculus forms in plaque despite inhibitory action of statherin and PRPs in saliva
* May be due to failure to diffuse into calcifying plaque
* Proteolytic enzymes of oral bacteria or lysed leukocytes may destroy inhibitory proteins
* Plaque bacteria may produce their own inhibitors

Calcium phosphate precipitation inhibitors and plaque
* Statherin and PRPs might be expected to occur in plaque, have not been detected
* Plaque bacteria produce calcium phosphate inhibitors
* Might be necessary to prevent calcification of bacteria -- happens with dead cells
* Immobilized crystal growth inhibitors can function as nucleators of crystal growth
* Immobilization may occur in plaque, encouraging calculus formation

Interaction of oral bacteria with PRPs and other pellicle proteins
* Several salivary proteins appear to be involved in preventing or promoting bacterial adhesion to oral soft and hard tissues
* PRPs are strong promoters of bacterial adhesion
o Amino terminal: control calcium phosphate chemistry
o Carboxy terminal: interaction with oral bacteria
* Interactions are highly specific
o Depends on proline-glutamine carboxy-terminal dipeptide
o PRPs in solution do not inhibit adhesion of bacteria

These anti-microbial proteins will be discussed in a later lecture
* Secretory Immunoglobulins
* Lactoferrin
* Lysozyme
* Sialoperoxidase
* Cystatins
* Histatins

Summary - Clinical Highlights
* Understanding of salivary mechanisms at fundamental level a prerequisite for
o effective treatment of salivary gland dysfunctions
o modulation of bacterial colonization
o development of artificial saliva other “cutting edge” approaches to salivary dysfunctions and diseases

Chemical composition and functions of saliva.ppt

Read more...
All links posted here are collected from various websites. No video or powerpoint files are uploaded on this blog. If you are the original author and do not wish to display your content on this blog please Email me anandkumarreddy at gmail dot com I will remove it. The contents of this blog are meant for educational purpose and not for commercial use. If you use any content give due credit to the original author.

This site uses cookies from Google to deliver its services, to personalise ads and to analyse traffic. Information about your use of this site is shared with Google. By using this site, you agree to its use of cookies.

  © Blogger templates Newspaper III by Ourblogtemplates.com 2008

Back to TOP