Medical physiopath ( Bacterial Diseases, Sepsis, SIRS) exam1

Staphylococcus Aureus

Staphylococci are gram-positive aerobic organisms.

◦S. aureus is the most pathogenic.

◦Typically causes skin infections , but sometimes pneumonia, endocarditis, and osteomyelitis.

◦Commonly leads to abscess formation.

S. aureus is among the most

most ubiquitous and dangerous human pathogens, for both its virulence and its ability to develop antibiotic resistance.

◦Carried, usually transiently, in the anterior nares of about 30% of healthy adults and on the skin of about 20%.

◦From these locations, staph can cause infection in the host and others.

◦Carriage rates higher in hospital patients and personnel.

Most reservoir of staph is

the nose

People who are predisposed to staphylococcal infections include

◦Neonates and breastfeeding mothers.

◦Patients with influenza, chronic bronchopulmonary disorders (e.g., cystic fibrosis, emphysema), leukemia, tumors, chronic skin disorders, or diabetes mellitus.

◦Patients with a transplant, an implanted prosthesis, other foreign bodies, or an indwelling intravascular plastic catheter.

◦Patients receiving adrenal steroids, irradiation, immunosuppressants, or antitumor chemotherapy.

◦Injection drug users.

◦Patients who have chronic kidney disease and are being treated with dialysis.

Patients with surgical incisions, open wounds, or burns

Predisposed patients may acquire

antibiotic-resistant staphylococci from other patients, health care personnel, or inanimate objects in health care settings. Transmission via the hands of personnel is the most common means of spread, but airborne spread can also occur.

Staph aureus Disease is caused by

◦Direct tissue invasion (MC).

◦Exotoxin production.

Staph aureus Direct tissue invasion includes:

◦Skin infections.

◦Pneumonia.

◦Endocarditis.

◦Osteomyelitis.

◦Infectious (septic) arthritis.

Multiple exotoxins are sometimes produced by staphylococci.

Some have local effects; others trigger cytokine release from certain T cells, causing serious systemic effects (e.g., skin lesions, shock, organ failure, death

Staph areus Toxin-mediated diseases

◦Toxic shock syndrome.

◦Staph scalded skin syndrome.

Staph food poisoning

Methicillin-resistant Staphylococcus aureus.

In the 1940s, medical treatment for S. aureus infections became routine and successful with the discovery and introduction of antibiotic medicine, such as penicillin.

◦From that point on, however, use of antibiotics—including misuse and overuse—has aided natural bacterial evolution by helping the microbes become resistant to drugs designed to help fight these infections.

In the late 1940s and throughout the 1950s, S. aureus developed resistance to penicillin.

◦Methicillin, a form of penicillin, was introduced to counter the increasing problem of penicillin-resistant S. aureus.

◦Methicillin was one of most common types of antibiotics used to treat S. aureus infections; but, in 1961, British scientists identified the first strains of S. aureus bacteria that resisted methicillin.

◦This was the so-called birth of MRSA.

The first reported human case of MRSA in the United States came in 1968.

◦Subsequently, new strains of bacteria have developed that can now resist previously effective drugs, such as methicillin and most related antibiotics.

MRSA is actually resistant

to an entire class of penicillin-like antibiotics called beta-lactams.

◦This class of antibiotics includes penicillin, amoxicillin, oxacillin, methicillin, and others.

S. aureus is evolving even more and has begun to show resistance to additional antibiotics.

◦In 2002, physicians in the United States documented the first S. aureus strains resistant to the antibiotic, vancomycin, which had been one of a handful of antibiotics of last resort for use against S. aureus.

◦Though it is feared that this could quickly become a major issue in antibiotic resistance, thus far, vancomycin-resistant strains are still rare.

Rheumatic Fever (Acute Rheumatic Fever)

Group A streptococcal (GAS aka Strep pyogenes) pharyngitis is the etiologic precursor of acute rheumatic fever.

◦Host and environmental factors are important.

◦GAS M proteins share epitopes (antigenic-determinant sites that are recognized by antibodies) with proteins found in synovium, heart muscle, and heart valve, suggesting that molecular mimicry by GAS antigens from rheumatogenic strains contributes to the arthritis, carditis, and valvular damage.

Rheumatic Fever (Acute Rheumatic Fever) Risk Factors :

◦Undernutrition.

◦Overcrowding.

◦Lower socioeconomic status.

Acute Rheumatic Fever infection

Although GAS infections of both the pharynx and of other areas of the body (skin and soft-tissue structures, bones or joints, lungs, and bloodstream) may cause poststreptococcal glomerulonephritis, nonpharyngitis GAS infections do not lead to ARF.

◦The reason for this distinct difference in complications resulting from infection by the same organism is not well understood.

Which is the most affected by the rhumatic fever

The joints, heart, skin, and CNS.

ARF Acute rheumatic fever : Heart

carditis : ◦affects the heart from the inside out -Valve and endocardium

-then myocardium

-Finally pericardium

Sometimes followed years to decades later by chronic rheumatic heart disease.: ◦Valvular stenosis.

◦Regurgitation.

◦Arrhythmias.

Ventricular dysfunction

Rheumatic valvular disease most commonly involves

mitral and aortic valves

Tricuspid and pulmonic valves are seldom, if ever, affected in isolation

Characteristic of ARF

◦Aschoff bodies often develop in the myocardium and other parts of the heart.

◦Fibrinous nonspecific pericarditis, sometimes with effusion, occurs only in patients with endocardial inflammation and usually subsides without permanent damage.

◦Characteristic and potentially dangerous valve changes may occur.

◦Acute interstitial valvulitis may cause valvular edema.

chronic rheumatic fever

-Valve thickening, fusion, and retraction or other destruction of leaflets and cusps may occur : Leads to stenosis insufficiency

-Chordae tendineae can shorten, thicken, or fuse: - Worsens regurgitation of damaged valves -Causes regurgitation of an otherwise unaffected valve

-Dilation of valve rings may also cause regurgitation.

Manifestation of ARF

Nonspecific synovial inflammation : Bx to get small foci resembling Aschoff bodies with Granulomatous collections of leukocytes, monocytes, and interstitial collagen

Unlike the cardiac findings of ARF, the joint abnormalities are not chronic

◦Do not leave scarring.

◦Do not leave residual abnormalities.

◦"ARF licks the joints, but bites the heart."

ARF SKIN

-Subcutaneous nodules appear indistinguishable from those of juvenile idiopathic arthritis (JIA), but biopsy shows features resembling Aschoff bodies.

-Erythema marginatum differs histologically from other skin lesions with similar macroscopic appearance, e.g., the rash of systemic JIA, Henoch-Schönlein purpura, erythema chronicum migrans, and erythema multiforme.

-Perivascular neutrophilic and mononuclear infiltrates of the dermis occur

The rash typically appears on the trunk and extremities, especially the arms and legs, and is not itchy or painful

ARF: CNS

Sydenham chorea, the form of chorea that occurs with ARF, manifests in the CNS as hyperperfusion and increased metabolism in the basal ganglia.

◦Increased levels of antineuronal antibodies have also been shown.

Sydenham's chorea

a movement disorder that typically occurs in children and adolescents following a streptococcal infection or rheumatic fever. It is characterized by involuntary, jerky movements, emotional instability, and possible speech difficulties. The condition usually resolves on its own within a few months, but treatment may be needed for severe cases.

Botulism

Clostridium botulinum

Anaerobic gram-positive rod. ( Botulism)

◦Survives in soil and marine sediment by forming spores.

◦Under anaerobic conditions that permit germination, it synthesizes and releases a potent exotoxin.

Microbiologically, the organism stains gram-positive in cultures less than 18 hours old. The organism may stain gram-negative after 18 hours of incubation, potentially complicating attempts at diagnosis

Botulism : Pathophysiology of disease:

Toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers:

◦Inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions OR

◦Binding acetylcholine itself

Toxins are absorbed from the stomach and small intestine, where they are not denatured by digestive enzymes:

◦

◦Hematogenously disseminated and block neuromuscular transmission in cholinergic nerve fibers.

The nervous, gastrointestinal, endocrine, and metabolic systems are predominantly affected

Botulism aspect

Infant. :

◦Ingestion of spores.

◦Germinate in the intestines.

◦Produce toxins.

◦Typically come from bee honey or the environment.

Foodborne.:

◦Improperly canned or home-prepared foods.

Wound.: .

◦Contamination of a wound with toxin-producing C. botulinum.

Botulism is intresting because

It start as gram posotive but after cultute it turn down to gram -

Wound Botulism

when wounds are contaminated with C botulinum spores.

◦Following traumatic injury that involved soil contamination.:

◦Among injection drug users (particularly those who use black-tar heroin).

After cesarean delivery

The wound may appear deceptively benign.

Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and to produce neurotoxin, which then disseminates hematogenously.

The nervous, endocrine, and metabolic systems are predominantly affected.

Symptoms develop after an incubation period of 4-14 days, with a mean of 10 days

Tetanus

Clostridium tetani - Gram positive obligate anaerobic toxin-forming bacillus

Neurotoxin - tetanospasmin interferes with neurotransmission at spinal synapses of inhibitory neurons.

◦Minor stimuli result in uncontrolled spasms.

◦Reflexes are exaggerated.

Spores of the organism are ubiquitous in soil and may germinate when introduced into a wound.

Incubation period = 5 days - 15 weeks (average 8-12 days).

Most cases occur in unvaccinated individuals.

Clostridium tetani

Persons at risk for tetanus

◦Older adults.

◦Migrant workers.

◦Newborns.

◦Injection drug users.

Puncture wounds are particularly prone to infection.

◦Any wound, including bites or decubiti, may become colonized/infected.

Diphtheria (Corynebacterium diptheriae):

Gram positive, club-shaped bacteria.

Albert's stain.

◦Green club shaped.

◦Metachromatic granules: dark blue spots made of phosphate at the bacterial poles.

◦When they cluster together, they look like Chinese letters.

Subspecies can be toxigenic or not, depending on if they produce the diphtheria toxin (DT

◦Cytotoxic protein that damages host cells.

◦All subspecies start out non-toxigenic, but become toxigenic once they are infected by a beta-bacteriophage.

Beta-bacteriophage. ( Diptheria)

◦Virus that attaches to bacteria and merges its genome with the bacteria's.

◦Contains tox-genes that code for DT production.

Now the diphtheria bacteria can cause diphtheria

DT has two subunits

A and B, connected by a disulfide bond

, A and B group for DT are charactrize by

◦Subunit B attaches to host cell membrane.

◦Whole DT complex is engulfed, forming a sac inside the cell (endosome).

◦Medium inside the endosome becomes acidic, breaking the disulfide bond.

◦Subunit A leaves the endosome and goes to the host cell ribosomes.

◦Interferes with cell protein synthesis.

◦Leads to cell death.

Diptheria ( Unvaccinated or immunocompromised people.)

1- Transmitted mainly be respiratory droplets (coughing, sneezing).

2- Bacteria gradually invade deeper into the pharyngeal wall, into the bloodstream and to other locations in the

3-Transmitted through open skin lesions.

Transmitted mainly be respiratory droplets (coughing, sneezing).

◦Pharyngeal type.

◦Bacteria attaches to pharyngeal epithelial cells and releases DT toxin.

◦Leads to necrosis of the tissue.

◦Necrotic tissue builds up over the pharynx/larynx, forming a gray film.

◦Gray, adherent, leathery membrane (pseudomembrane).

◦May partially detach, get lodged in the trachea/bronchi, block airways.

◦Death by asphyxiation.

◦Bacteria gradually invade deeper into the pharyngeal wall, into the bloodstream and to other locations in the body.

◦Myocarditis.

◦Acute tubular necrosis.

◦Nerve demyelination, polyneuropathy.

◦Oculomotor nerve à palsy à impaired ocular movements.

◦Phrenic nerve à affects diaphragm à trouble breathing.

Transmitted through open skin lesions.

◦Cutaneous type.

Cholera ( gram -)

Contagious infection due to vibrio cholera.

◦Gastroenteritis, watery diarrhea-"rice water diarrhea"

◦Rapid dehydration, which can be fatal.

Gram negative, curved bacteria.

◦Flagellum.

Transmission.

◦Fecal to oral route.

◦Consuming untreated sewage water.

◦Raw or undercooked fish/shellfish.

◦Improper hygiene (not washing hands after BM).

More common in developing countries.

◦Africa, South America.

Once in the intestines cholera

◦Moves toward intestinal wall.

◦Propels through the mucous layer.

◦Attaches to villi on the surface of epithelial cells.

◦Multiplies, producing toxins.

◦V. cholera does not enter the cells, but the toxins do.

Toxins produced depend on the strain of bacteria.

◦Some toxins produce little or no symptoms.

Cholera enterotoxin (choleragen) à significant symptoms :( ◦Disrupts the osmotic balance between the intestines and the surrounding tissues.

◦Water, bicarbonate, and potassium rush into the lumen of the intestines.

◦Leads to voluminous amounts of watery diarrhea (rice water).)

Campylobacter jejuni

Campylo = curved.

Bacter = rod.

Jejuni = jejunum.

A comma-shaped bacteria.

◦Gram negative.

◦Has a flagellum; motile.

One of the most common causes of gastroenteritis worldwide.

Campylobacter jejuni transmission

◦Animals to humans.

◦Fecal-oral route (ingestion of stool particles containing bacteria).

◦GIT of birds (undercooked poultry).

◦Cows (unpasteurized milk).

◦Infected pets (puppies with infected stool).

May contaminate fresh water supplies

Campylobacter jejuni incubation peroid

1-7 day incubation period.

Once in the body Campylobacter jejuni

◦Attach to mucosa of small intestine and colon.

◦Uses spiral shape and flagella to drill into the mucosa.

◦Release toxins (cytolethal distending toxins-CDT).

◦Damage nearby epithelial cells, causing inflammation.

◦Colon can dilate, causing toxic megacolon.

◦Bacteria may keep drilling until they reach the blood stream (bacteremia).

◦Immune system may react by producing anti-ganglioside antibodies. - Attack peripheral nerves.- Cause Guillain-Barre syndrome.

◦May prompt an autoimmune reaction, attacking the joints. - Reactive arthritis.

Chlamydia (C. Trachomatis)

Gram-negative :

◦Cannot retain the crystal violet stain used during gram staining.

◦Unlike other GN bacteria, chlamydia has no layer of murein (peptidoglycan).

◦Cannot retain the pink safranin dye used in gram staining.

◦Best stained with giemsa stain, which colors them pinkish blue.

Chlamydia sterotypes

◦A-C à conjunctivitis in adults (trachoma).

◦D-K à genital infection (chlamydia).

◦L1, L2, L3 à infect lymph nodes (lymphogranuloma venereum)

Chlamydia conjunctivitis

◦Untreated, can progress to keratoconjunctivitis.

◦Infection of both the cornea and conjunctiva.

◦May lead to total blindness.

Chlamydia. aspect

◦Most common STD in men and women.

◦Men: - Urethritis, prostatitis.

◦Women:

◦Urethritis, vulvovaginitis, cervicitis, pelvic inflammatory disease, Fitz-Hugh-Curtis syndrome (once inflammation spreads to peritoneum).

Chlamydia during pregnancy

◦Can be passed to baby during vaginal delivery.

◦Late onset neonatal conjunctivitis.

◦Neonatal pneumonia if travel down respiratory tract.

In chlamydia =

Lymphogranuloma venereum which is Most commonly affects the inguinal lymph nodes

Neisseria gonorrhoeae

purulent infection of the mucous membranes

◦Gram-negative, intracellular, aerobic diplococcus.

Neisseria gonorrhoeae. spreads by

◦Sexual contact.

Transmission during childbirth (opthalmia neonatorum and systemic neonatal infection).- Neonatal prophylaxis is standard in the developed world

Gonococcal Infections

An important public health problem.

◦Major source of M/M worldwide.

Gonococcal Infections in Women

◦Endocervicitis.

◦Urethritis.

◦PID.

Gonococcal Infections in Men

◦Anterior urethritis.

Neisseria gonorrhea

Can also spread through the body to cause localized and disseminated disease.

"Gonorrhea" usually refers to urethritis and/or cervicitis in a sexually active person.

Gonoccocemia

The presence of N. gonorrhea in the blood stream.

◦Can lead to disseminated gonococcal infection (DGI).

◦Occurs in about 0.5-3% of patients with gonorrhea.

Gonoccocemia dissemination

Organisms spread from a primary site, such as the endocervix, the urethra, the pharynx, or the rectum, and disseminate to the blood to infect other end organs:

◦Usually, multiple sites, such as the skin and the joints, are infected.

◦Neisserial organisms disseminate to the blood due to a variety of predisposing factors, such as host physiologic changes, virulence factors of the organism itself, and failures of the host's immune defenses.

◦Changes in the vaginal pH during menses, pregnancy, puerperium make the environment more suitable for growth.

◦Defects in the host's immune defenses make certain patients more likely to develop this.

◦Certain strains are more virulent and are associated with DGI.

Sexually Transmitted Infection

Usually follows mucosal inoculation during vaginal, anal, or oral sexual contact.

◦It also may be caused by inoculation of mucosa by contaminated fingers or other objects.

The risk of transmission of N gonorrhoeae from an infected woman to the urethra of her male partner is approximately 20% per episode of vaginal intercourse and rises to 60-80% after 4 or more exposures.

◦In contrast, the risk of male-to-female transmission approximates 50-70% per contact, with little evidence of increased risk with more sexual exposures.

Gonococcal Infections: Pediatrics

Importance in pediatric population is 3-fold:

------------------------

Common, preventable STD in sexually active teens.

Perinatal infection at childbirth.

Forensic aid in investigating sexual abuse.

Neonatal and Pediatric Populations

Neonatal.

◦May follow conjunctival infection during passage through the birth canal.

◦Direct infection may occur through the scalp at the sites of fetal monitoring electrodes.

Pediatrics.

◦May occur from sexual abuse by an infected individual.

◦May occur through nonsexual contact in the household or in institutional settings.

Autoinoculation

Autoinoculation can occur when a person touches an infected site (genital organ) and contacts skin or mucosa.

Gonococcal Infection: Risk Factors

Sexual exposure to an infected partner without barrier protection (e.g., failure to use a condom or condom failure).

Multiple sex partners.

Male homosexuality.

Low socioeconomic status.

Minority status - Blacks, Hispanics, and Native Americans have the highest rates in the United States.

History of concurrent or past STDs.

Exchange of sex for drugs or money.

Use of crack cocaine.

Early age of onset of sexual activity.

Pelvic inflammatory disease (PID).

Use of an intrauterine device (IUD).

Rickettsia ricketsii

Intracellular pleomorphic coccobacillus

Tick-borne disease

◦The organism is endemic in parts of North, Central, and South America, especially in the southeastern and south-central United States.

◦Transmitted to humans by the bite of a tick.

◦Several hours of contact between the tick and the human host are required for transmission.

Native Americans are at high risk for infection

Sepsis

•is a life-threatening organ dysfunction

•caused by a dysregulated host response to infection.

•

Sepsis Updated Definition

•Sepsis-3 (2016) emphasizes organ

dysfunction, not just SIRS

Pathophysiology of sepsis

•Inflammatory cascade → vasodilation,

•capillary leakage, coagulation abnormalities.

Spesis Importance

•High mortality if untreated; early recognition

•saves lives.

Sepsis Etiology and Predisposing Factors

•Common Causes:

•Bacterial infections (e.g., pneumonia, urinary tract infections, intra-abdominal infections)

•Fungal or viral causes less common

•Risk Factors:

•Age (elderly, infants)

•Immunosuppression (HIV, chemotherapy, corticosteroids)

•Chronic illnesses (diabetes, liver/kidney disease)

•Indwelling devices (catheters, central lines)

Overview of Sepsis Pathophysiology

•Initial trigger: Infection by bacteria, virus, fungi, or parasites

•Host response: Immune system launches inflammatory response

•Key problem: Dysregulated immune response causes collateral damage

•Outcome: Widespread inflammation, coagulation, and tissue injury

Innate Immune Activation Step 1

Inflammatory Cascade

•Pathogen Recognition:

•PRRs (Pattern Recognition Receptors) detect PAMPs (Pathogen-Associated Molecular Patterns)

•Common PRR: Toll-like receptors (TLRs)

•Cytokine Storm:

•Massive release of pro-inflammatory cytokines (TNF-α, IL-1, IL-6)

•Results in fever, vasodilation, increased vascular permeability

Innate Immune Activation Step 2

Vascular and Endothelial Changes

•Vasodilation → Hypotension

•Increased capillary permeability → Fluid shifts into tissues → Edema

•Endothelial injury leads to:

•Leukocyte adhesion

•Microthrombi formation

•Reduced perfusion and oxygenation

Coagulation Abnormalities step 3

- Procoagulant State

•

•Activation of coagulation cascade

•Tissue factor expression increases

•Decreased anticoagulants (Protein C, antithrombin)

•

•Microvascular thrombosis

•Organ ischemia and dysfunction

•

•Risk of DIC: Disseminated intravascular coagulation

Cellular Dysfunction and Organ Failure Step 4

Mitochondrial and Organ Dysfunction

•Mitochondrial injury → impaired ATP production

•Cellular hypoxia despite normal oxygen delivery

•Apoptosis and impaired cellular repair

•Result: Multisystem organ failure (lungs, kidneys, liver, brain)

Resolution or Progression Step 5

Resolution or Progression to Septic Shock

•If controlled:

•Anti-inflammatory mediators (IL-10, TGF-β) restore balance

•Immune system regains regulation

•If uncontrolled:

•Persistent inflammation + immune paralysis

•Septic shock: profound hypotension, lactate >2 mmol/L, high mortality

Sepsis process

1- inflammatory cascade : pathigne recognition-cytokine casacde

2-Vasodiltion and enthothelial damage :- vasodilation ;increased permability ;endothelilal injury

3- Coagulation abnormalities ( Procoagulant state):

-Activation of coagulation -microvascular thrombis and risk of DIC

4- Mitochondrial and organ dysfunctionction: - mito injury ;cellular hypoxia;apoptosis;result in multisystem orhgan failure

5- Resolution or progession to septic shock : -if controlled >>>> anti inflammatory ;immune sysytem regulation

Definition of shock

Problem that results in failing of perfusion