Pathophysiology Exam 3

Phase 1 of wound healing

inflammatory phase

Tissue repair following injury

Blood clot forms

3-4 days, foreign material and cell debris removed by phagocytes

Neutrophils, lymphocytes, macrophages, dendritic cells, and mast cells gather at injury site and tissue is inflamed as part of normal injury response

Phase 2 wound healing

granulation phase

Days to weeks after injury.Varies on health status of patient.

Granulation tissue grows

New connective tissue and tiny blood vessels from on surfaces of wounds during healing

Granulation tissue grows on base of wound and fill to wounds of almost any size

Highly vascular, very fragile

Epithelial cells undergo mitosis and extend across wound

Collagen is produced by fibroblasts to provide strength for new tissue repair

Phase 3 wound healing

Gradual cross linking and shortening of collagen fibers promotes formation of tight scar tissue

Color of scar tissue gradually fades

Scar tissue is not normal functional tissue nor does it contain specialized structures such as hair follicles or glands

Scar tissue merely fills in the gap in damaged tissue

Small gaps = Less likely to be a scar

Large gaps = Leaves scar

How does diabetes affect wound healing?

-Decreased collagen synthesis

Glycation of proteins
Glucose reacts with proteins to form a glycoprotein

Glycoproteins are highly reactive

The more of these proteins the more reaction they will have with endothelial cells

-Impaired phagocytosis

-Reduces oxygen and nutrients due to vascular damage

-increased risk of infection with blood glucose elevations

Complications due to scar tissue formation

Loss of function

Contractures and obstructions

Adhesions

Hypertrophic scar tissue

Ulceration

Scar tissue complication: loss of function

Loss of normal cells that lack specialized structures

Loss of normal organization of tissue

If scar tissue replaces normal skin, area will lack hair follicles, glands and sensory nerve endings.

Highly organized tissue replacement scar tissue will not provide normal function

Scar tissue complication: Contractures and obstructions

Scar tissue is non-elastic and tends to shrink

Shrinkage Results in restricted movement. Joint fixation or deformity. This is known as contracture.

Shortening or narrowing of structures (Stenosis)

Can result in hiatal hernia

Esophageal contracture

Narrowing of esophagus can result in obstruction during swallowing

Chronic heartburn can scar the esophagus with gastric acid and result in narrowing

Stratified squamous tissue transforms into columnar tissue in attempt to defend against gastric acid

Risk factor for esophageal cancer

The process of esophageal shrinking can also pull the stomach upward through the hiatus in the diaphragm (hole through which the esophagus travels)

This is known as a hiatal hernia

This increases the incidence of GERD

Positive feedback loop

Scar tissue complication: Adhesions

Bands of scar tissue joining two tissue surfaces that are normally separated

Adhesions are common Between loops of intestine or between pleural membranes

Usually result in inflammation of infection in the body cavities

Can restrict normal movement of structures and may cause distortion of twisting of tissue

Common complication of abdominopelvic surgery

Adhesions cause problems for a lifetime because they impact quality of life

Scar tissue complication: Hypertrophy

Keloid masses may be disfiguring and cause severe contractures

Keloids are an overgrowth of fibrous tissue and are defined as extreme hypertrophic scar formation

Excessive collagen leading to hard ridges of scar tissue

Etiology not well understood: Deficiency in melanocyte stimulating hormone?

Scar tissue complication: Ulceration

Blood supply can become impaired around scar tissue

Results in further tissue breakdown and ulceration

Scar tissue is not very vascular. Reduced blood flow. Reduced immune cells and nutrients.

Breakdown of skin or mucous membrane

Resulting in loss of normal surface tissue and the presence of inflamed and disintegrated necrotic tissue. Example: Gastric ulcer

Burn

Transfer of energy from a source to the body tissue

Burn pathophysiology

inflammation leads to release of vasoconstrictive substances and increased capillary permeability

leads to a protein leakage and decrease in plasma osmotic pressure (fluid shift)=loss of cap seal and depletion of intravascular blood volume...edema at burn site

very hypovolemic quickly due to fluid shift...hypovolemic or "burn shock" results

fluid shift leads to low protein and low electrolytes

this causes increased HR and decreased BP

Loss of normal skin function results in water loss via evaporation

1st degree burn

Superficial burn

Epidermis and maybe upper region of dermis

Skin appears red, is painful but heals quickly

2nd degree burn

Deep partial thickness burn

Epidermis and part of dermis

Red, painful, blistered, easily infected

Grafting may be required

3rd degree burn

Full thickness burn

May involve underlying connective tissue and muscle layers

Skin grafts are required. No skin cells left for regeneration.

Treatment for hypovolemic shock

Plasma Expanders:

Crystalloids:

1. Normal saline

2. Ringer's lactate

Colloids: "Heavy guns" Increase solute concentration of blood to preserve volume Examples: Haemaccel, Gelofusion, Albumin (Natural plasma protein, Quickly metabolized, Very expensive)

Burn patient metabolic needs

Increased need of nutrition (protein, calories)

Hypermetabolism:
Burn patients Higher metabolic rate

Protein loss continues at site until healed

The cell wall of Gram-positive bacteria

combination of:

Peptidoglycan layer

Inner membrane

Top of plasma membrane

Pili

Large projections of the bacterial membranes

Used for horizontal gene transfer

The cell wall of Gram-negative bacteria

Lipopolysaccharide layer

Small peptidoglycan layer inside of a larger periplasmic space than that of a gram positive bacteria

hemolysin

an enzyme that lyses red blood cells

Released by E.coli to gain access to iron in blood cells

Collagenase

breaks down collagen

Released by clostridium

Streptokinase

dissolves blood clots

released by streptococci to make movement through blood vessels easier

Endotoxin

A toxic component of the outer membrane of certain gram-negative bacteria that is released only when the bacteria die.

Enteric fever

Includes typhoid fever. Bacteria gets into lymphatic system.

Caused by Salmonella

Norovirus

RNA virus

Vomiting bug

Highly contagious

Remain contagious for up to 2 weeks
Symptoms begin in 1-2 days and last 3-5

Listeria

Listeriosis is a serious infection caused by the germ Listeria monocytogenes. People usually become ill with listeriosis after eating contaminated food.

Bacteria that cause foodborne illness

Campylobacter

Salmonella

E. coli

Staphylococcus

Clostridium perfringens

Listeria

Norovirus

Hepatitis A

Beta-lactams

penicillins, cephalosporins, carbapenems

Central line

Catheter placed into a large vein in the neck (internal jugular vein), chest (subclavian vein or axillary vein) or groin (femoral vein) for central venous access

Central line infection microbes

Yeast

Enterococci

Staph aureus (MRSA)

Klebsiella

Microbe most implicated in central line infections

Yeast, 27% of cases

Main culprit of catheter associated UTIs

E. coli (36%) of cases

Hospital acquired clostrium difficile colitis

Can result from long term antibiotic therapy.

Healthy gut bacteria normally keep this bacteria at bay

Can cause life threatening diarrhea and is easily spread

Treated with flagyl/metronidazole

Hospital acquired MRSA infections

Includes MDR (Multi drug resistant) staph aureus

Resistant to Methicillin, Oxacillin, Cefoxitin

Main culprit of surgical site infections

Enterococci (33% of cases)

Ventilator-associated pneumonia

Risk increases with number of days attached to ventilator

Most common hospital acquired infection

Highest rate of mortality: Pseudomonas
Very hard to treat/high mortality

Clostridium tetani (tetanus)

Nerve makes contact with muscle cells via terminal bulbs

Within these terminal bulbs is the neurotransmitter Acetylcholine

Ach reaches the muscle cell receptors in order to contract

Acetylcholinesterase turns this off to prevent spastic (constant) contraction

The toxin produced by tetani inhibits

acetylcholinesterase and induces spastic contractions

Spores are found in soil, dust, and animal feces

Clostridium botulinum (botulism)

Neurotoxin botulinum

Severe paralytic disease

Most potent toxin known to humans Lethal dose is in nanograms/kg of bodyweight

Spores found in soil and able to survive adverse conditions

Heat resistant endospores

Clostridium difficile

Colitis

Opportunistic

Most common nosocomial

Component or normal fecal flora in healthy people

Related to high antibiotic use

Shigella

Shigellosis

Fecal/oral transmission

Diarrhea, fever, and stomach cramps Resolves in 5-7 days

Rheumatic fever

Caused by strep pyogenes

Antibiotics generated against M protein or cell wall will cross react with body's own cardiac protein myocin resulting in a systemic inflammatory disease

Often causes acute endocarditis

Damages heart valves especially mitral valve

Mitral valve regurgitation

When mitral valve fails to close completely due to scarring or prolapse, blood leaks backwards

Can be caused by heart damage:Heart attack

Different from endocarditis induced by strep

Neisseria gonorrhoeae

10% of males and 80% of females asymptomatic

Men who have had a gonorrhea infection has increase chance of prostate cancer

Wide ranging symptoms

Leptospirosis

Caused by spirochete

Zoonotic disease transmitted through urine

Survives for months in soil and water

Entry is ingestion or opening in skin

Borreliosis

Caused by Borrelia spirochete

Lyme disease

Tick and some lice transmission

12 of 52 known species of borrelia can cause borreliosis

Only 70-80% of bites produce the erythema migrans bullseye rash

Syphilis

Caused by Treponema spirochete

3 stages

3rd stage is incurable but also non contagious

Chlamydia, Rickettsia, and Mycoplasma are called

Parasitic bacteria

Chlamydia

STD main cause of PID
Trachomatis species is main concern
Sterility in humans
Blindness in infants
Damages uterus

Rickettsia

Rocky mountain spotted fever

3% mortality rate

Distinctive rash and small hemorrhages

Mycoplasma pneumonia

"Walking pneumonia"

Mild pneumonia

Resistant to antibiotics but self limiting

Pathogenic fungi

Tinea pedis (foot) [Also capitis (head)] Athlete's foot Ringworm

Candida albicans
Oral and genital yeast infections
Oral=Thrush. Normal oral flora

Opportunistic. Can cause chronic infections that spread systemically.

Pathogenic protozoa

Trichomonas: STD

Trichomoniasis causes a foul-smelling vaginal discharge, genital itching, and painful urination in women. Men typically have no symptoms.

Treated with metronidazole.

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Plasmodium:

Transmitted by female anopheles mosquito

Most virulent is P. falciparum due to high resistance to antimalarial drugs

Treated with Hydroxychloroquine

Viral latency

Viral latency is the ability of a virus to remain dormant within the host cell

• Can be reactivated by stressful stimuli and hormonal changes

• Many latent viruses hide in nerve tissue since immune cells do not travel there

Pathogenicity

Capacity of a microbe to cause disease

Virulence

The degree of pathogenicity of a specific microbe

Focal infection

Microbe spreads from local infection to other tissues

Systemic infection

Infection spreads to several sites and tissue fluids, typically through circulation

Septicemia

Caused by multiplication of pathogen in blood

Causes sepsis, toxic inflammatory condition arising from system-wide spread of pathogen

Bacteremia

Presence of bacteria in blood

Viremia

Presence of viruses in blood

Antibiotics

Old term used to refer to drugs derived from organisms

Example: penicillin from mold penicillium rubens

Antimicrobials

Refers to drugs that are active against a specific type of microbe

Examples:
Antivirals
Antibacterials
Antifungals

Bactericidal

Drugs that destroy bacteria

Bacteriostatic

Drugs that decrease the microbe's rate of reproduction, but rely on host's defenses to destroy microbe

Broad spectrum antibiotics

Antibacterial drugs effective against both gram negative and gram positive organisms

Narrow spectrum antibiotics

Antibacterial drugs effective against either gram negative or gram positive bacteria but not both

Inflammation

Non-specific response to injury

Prostaglandins

A group of bioactive, hormone-like chemicals derived from fatty acids that have a wide variety of biological effects including roles in inflammation, platelet aggregation, vascular smooth muscle dilation and constriction, cell growth, protection of from acid in the stomach, and many more.

Bradykinins

Chemicals produced by the body and responsible for inflammation and pain

Cytokines

Hormone-like chemicals facilitating communication between brain and immune system.

Bradykinins stimulate endothelial cells to release

Nitric oxide

Nitric oxide causes

Vasodilation, which improves blood flow and enhances oxygen delivery

How do ACE inhibitors and bradykinins interact?

ACE inhibitors inhibit the breakdown of bradykinin

Remains longer due to the ACE

Bradykinin releases nitric oxide

Nitric oxide causes vasodilation

Hyperemia

redness of the skin due to increased blood flow. Also increases heat.

Function of swelling in inflammation

Allows for spaces for neutrophils and complement proteins to move into tissue

Cytokines are released by:

a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells

cytokine storm

A potentially fatal immune reaction caused by highly elevated levels of various cytokines

C-reactive protein

A nonspecific protein, produced in the liver, that becomes elevated during episodes of acute inflammation or infection.

Hypothalamus

a neural structure lying below the thalamus; directs eating, drinking, body temperature; helps govern the endocrine system via the pituitary gland, and is linked to emotion

Stage 1 of fever

Cold and chills

Hypothalamus resets to higher temperature

Vasoconstriction

Piloerection

Epinephrine secretion

Shivering

Stage 2 of fever

Hot phase

Fever running its course

Flushed, warm, thirsty

Drowsiness, headache, restlessness, convulsions

Stage 3 of fever

Fever breaks

Hypothalamus resets to normal temperature

Fever resolves

Non-specific changes seen during inflammatory process

Leukocytosis

Elevated erythrocyte sedimentation rate

Elevated C-reactive protein

Increased plasma proteins, cell enzymes

Specific changes seen during inflammatory process

Neutrophilia

Eosinophilia

Lymphocytosis

Alanine aminotransferase

Creatine phosphokinase

periodontal disease

inflammation and degeneration of gums, teeth, and surrounding bone

As bacteria grow, gums become inflamed and initiate immune response

Infection can eventually reach the periodontal ligament.
This eventually can progress further to bone loss.

The bacteria responsible for this infection then have direct access to the bone and blood, leaching toxins into the body

Aspirin MOA

Decreases prostaglandin synthesis at site of inflammation, reducing pain and fever

Cholera

an acute intestinal infection caused by ingestion of contaminated water or food

What is one of the health concerns (dangers) of not properly treating strep throat?

Endocarditis

Endocarditis

inflammation of the inner lining of the heart

PID

pelvic inflammatory disease

pelvic inflammatory disease

inflammation and infection of organs in the pelvic region

caused by chlamydia and gonorrhea

Mycoplasma pneumoniae

Causes walking pneumonia

Has potential for antibiotic resistance

Walking pneumonia

a milder but longer-lasting form of pneumonia caused by the bacteria Mycoplasma pneumoniae.

Herpes 1 vs. Herpes 2

• Herpes simplex 1 causes "cold sores" around the mouth and infects over 90% of adults

• Herpes 1 typically infects around the mouth and lips

• Herpes 2 typically infects the genitalia

• Herpes 1 is very similar to Herpes 2 and Herpes 2 can infect humans around the mouth while Herpes 1 can infect genitalia

• Oral sex can result in Herpes 2 infection around the mouth and herpes 1 infection of the genitalia

schistosomiasis

Helminth infection acquired from contact with water containing infected snails.

cystitis

inflammation of the bladder

erythema

redness of the skin due to capillary dilation

Trichomoniasis

an infection caused by the protozoan parasite Trichomonas vaginalis