Patho Exam 1 Chapters 1-5

Immune response

Third line of defense

Inflammatory response

Second line of defense

Skin and mucous membranes

First line of defense

Acute inflammation

Triggered by tissue injury

Goals of inflammation

• Increase blood flow to site

• Increase healing cells at site

• Prepare for tissue repair

Vascular response

• Facilitated by chemical mediators

• Induces vasodilation and increases capillary permeability

• The body’s goal is to get more blood flowing to the injured area

Cell derived inflammatory mediators

• White blood cells (mast cells)

• Platelets

• Endothelial or damaged tissue cells

Plasma derived inflammatory mediators

• Complement system

• Kinin system

• Clotting system

Cellular response

• Chemotaxis

• Cellular adherence

• Cellular migration

Chemotaxis

The movement of microorganisms toward or away from a chemical stimulus, driven by a chemical gradient in their environment

Cellular adherence

The process by which cells attach to their surrounding extracellular matrix or to other cells through specific adhesion molecules

Cellular migration

The process by which a cell moves from onle location to another, driven by internal cytoskeletal changes and external cues

Manifestations of inflammation

• Local manifestations include heat, incapacitation, pain, edema, redness

• Systemic manifestations may include fever and increased circulating leukocytes and plasma proteins

Treatment of inflammation

• Reduce blood flow

• Decrease swelling

• Block the action of chemical mediators

• Decrease pain

• RICE: Rest, Ice, Compression, Elevation

• Medication: Aspirin, NSAIDs, and Glucocorticoids

Inflammatory phase (H&TR)

• Acute inflammatory response

• Seal the wound

Proliferative phase (H&TR)

• Clear the debris (macrophages, polymorphonuclear neutrophils)

• Restore structural integrity

Remodeling phase (H&TR)

• Restore functional integrity

• Remodeling

Complications of healing

• Infection

• Ulceration

• Dehiscence

• Keloids

• Adhesions

Chronic inflammation

• Recurrent or persistent inflammation lasting several weeks or longer

• Monocytes, macrophages, and lymphocytes more prominently involved

• Formation of granulomas and scarring often occur

Burns pathophysiology

• Cause: direct contact with excessive heat or radiation, caustic chemicals, or electricity

• Result: acute inflammatory response

• Burn severity is correlated with exposure type and time

Burns pathophysiology: classification

• Superficial partial thickness = a type of burn injury that affects the top layer of the skin, the epidermis

• Deep partial thickness = a type of burn injury that affects the two top layers of the skin, the epidermis and dermis

• Full thickness = a type of burn injury that affects all the layers of the skin, the epidermis, dermis, and hypodermis

Burns clinical manifestations

• Superficial partial thickness burns

  • Heat, swelling, pain, redness, loss of function

• Deep partial thickness burns

  • Blistering, redness, heat, pain, edema, serous exudate

• Full thickness burns

  • Redness, eschar, edema, exudate

• All include inflammatory response

Burns diagnostic criteria

• Rule of nines

• American Burn Association has designated criteria for distinguising minor, moderate, and major burns based on:

  • Wound depth

  • Surface area

  • Required level of treatment

Burns treatment 

• American Burn Association criteria

• Remove source of injury and cool/rinse skin

• Airway, breathing, circulation (ABCs)

• Fluids, nutrition, antibiotics, analgesics

• Wound management may include:

  • Hydrotherapy

  • Skin grafting

RA pathophysiology

• Chronic inflammation of synovial membranes and synovial hyperplasia

• Etiology combines:

  • Genetics

  • Triggering event

  • Autoimmunity

• Remissions and exacerbations

• Pannus formation

• Cartilage erosion

• Fibrosis

• Ankylosis

RA clinical manifestations

• Mild to debilitating

• Symmetrical joints

• Pain, stiffness

• Redness, heat, swelling

• Decreased mobility

RA diagnostic criteria

• No definitive test

• Increased likelihood with positive findings

  • Erythrocyte sedimentation rate (ESR)

  • C-reactive protein (CRP)

  • Rheumatoid factor (IgG)

  • Antinuclear antibodies (ANA)

RA treatment

• Pharmacologic: drugs that induce remission

• Nonpharmacologic:

  • Rest/activity balance

  • Physical therapy exercises

  • Splints

  • Surgery

Acute pancreatitis pathophysiology

• Injury to:

  • Acinar cells

  • Zymogen

  • Pancreatic duct

  • Protexcive digestive feedback mechanisms

• …….. resulting in inflammation

• Caused by:

  • Duct blockage by gallstones

  • Excessive alcohol use

Acute pancreatitis clinical manifestations

• Upper abdominal pain

  • Sudden onset

  • Growing intensity

  • Dull, steady ache

  • Radiating to back

• Nausea

• Vomiting

• Anorexia

• Diarrhea

Acute pancreatitis diagnostic criteria

• History and physical examination

• Laboratory testing

  • Complete blood count, ESR, CRP

  • Serum amylase and lipase

  • Serum alkaline phosphatase

  • Total bilirubin

  • Aspertate aminotransferase (AST)

  • Alanine aminotransferase (ALT)

Acute pancreatitis treatment

• Intravenous hydration

• Analgesics

• Surgical removal of gallstones

• GI rest (NPO) if nausea and vomiting are present

Chronic pancreatitis pathophysiology

• Excessive alcohol use

• Duct obstruction by enzymes and proteins

• Ischemia

• Acinar cells become atrophic and fibrotic

• Loss of function

• Oxidation: cellular injury and organ damage

• Autoimmunity

Chronic pancreatitis clinical manifestations

• Abdominal pain

  • Severe, intermittent

  • Mid or upper right sided, radiating to back

  • Lasting several hours at unpredictable intervals

• Diarrhea

• Steatorrhea (fatty stools)

• Weight loss

Chronic pancreatitis diagnostic criteria

• Endoscopic retrograde cholangiopancreatography (ERCP)

• Serum amylase and lipase levels

• Direct aspiration of pancreatic duct or duodenum

Chronic pancreatitis treatment

• Pain management

• Behavior modification

  • Alcohol cessation

  • Smoking cessation

  • Exercise

  • Nutrition

• Surgery

Infection

• A state of cellular, tissue, and organ destruction resulting from invasion by microorganisms

• Penetration of three lines on defense

• Multiple drug-resistant microbes

• Globalization and spread of harmful microbes

Pathogens

Disease producing microbes

Mechanisms for causing disease

• Direct destruction of host cell by pathogen

• Interference with host cell’s metabolic function

• Exposing host cell to toxins produced by pathogen

Factors affecting pathogenicity

• Virulence

• Infectivity

• Toxigenicity

• Antigenicity

• Antigenic variability

• Pathogenic defense mechanisms

• Coinfection

• Superinfection

Types of pathogens

• Obligate vs facultative

• Bacteria

• Viruses

• Rickettsiae, mycoplasmas, and chlamydiae

• Fungi

• Protozoa

• Helminths

Infectious agent (COI)

• Bacteria

• Fungi

• Viruses

• Rickettsiae

• Protozoa

Reservoirs (COI)

• People

• Equipment

• Water

Portal of exit (COI)

• Excretions

• Secretions

• Skin

• Droplets

Means of transmission (COI)

• Direct contact

• Ingestion

• Fomites

• Airborne

Portal of entry (COI)

• Mucous membrane

• GI tract

• GU tract

• Respiratory tract

• Broken skin

Susceptible host (COI)

• Immunosuppression

• Diabetes

• Surgery

• Burns

• Elderly

Phases of acute infection

• Exposure

• Incubation

• Prodrome

• Acute clinical illness

• Convalescence

Complications of infection

• Septicemia

  • Bacteremia

  • Septic shock

• Chronic infection

Local manifestations of infection

• Heat

• Incapacitation

• Pain

• Edema

• Redness

• Lymphadenitis

• Purulent exudate

Systemic manifestations of infection

• Fever

• Weakness

• Headache

• Malaise

• Anorexia

• Nausea

Laboratory and diagnostic tests

• White blood cell count

  • Leukocytosis

  • Leukopenia

• Serum antibody levels

• Cultures

• Sensitivities

Antimicrobial drugs (TOI)

• Antibacterials - fight bacterias

• Antifungals - fight fungus

• Antivirals - fight viral infections

Symptom reduction (TOI)

• Fluids

• Rest

• Analgesics

• Antipyretics

Influenza pathophysiology

• Viral infection fo epithelial cells of the airway

• Respiratory droplet transmission

• Infected epithelial cell necrosis

• Reassortment: gradual change in genetic composition during replication in human host

Influenza clinical manifestations

• Cough

• Sore throat

• Nasal congestion/drainage

• Shortness fo breath

• Chills

• Fever

• Body aches

• Weakness

• Malaise

Influenza diagnostic criteria

• History and physical examination

• Rapid viral assays

Influenza treatment

• Prevention

  • Handwashing

  • Vaccinations

• Symptomatic care

  • Hydration

  • Nutrition

  • Analgesics

• Antiviral drugs

Viral hepatitis pathophysiology

• Acute or chronic inflammation of the liver caused by. infection with one or more hepatitis viruses

• Transmitted via fecal - oral route or direct contact with infected blood/body fluids

• Results in varying levels of hepatic necrosis

Viral hepatitis clinical manifestations

• Prodrome

  • Fatigue

  • Anorexia

  • Low grade fever

• Icterus

  • Jaundice

  • Hepatomegaly

  • Clay stools

  • Dark urine

• Recovery

  • Improvement with residual hepatomegaly

Viral hepatitis diagnostic criteria

• History and physical examination

• Detection of viral antibodies in blood

  • Anti-HAV

  • Anti-HCV

  • Anti-HDV

  • Anti-HEV

• Other labs

  • Urine bilirubin

  • Serum bilirubin

  • Clotting time

Viral hepatitis treatment

• Prevention

  • Vaccination

  • Handwashing

  • Avoidance of infected:

    • Fecal material

    • Blood

    • Body fluids

• Symptomatic care

  • Fluids

  • Rest

  • Analgesics

  • Low fat diet

• Antiviral drugs

Tuberculosis pathophysiology

• Most prevalent and deadly infectious disease worldwide

• Caused by infection with Mycobacterium tuberculosis

• Transmitted via inhaled airborne droplets

• Human are only know reservoir

• Lungs are primary site of infection

Tuberculosis clinical manifestations

• 90% of those infected are asymptomatic

• In 10% with progressive primary disease:

  • Malaise

  • Weight loss

  • Fatigue

  • Anorexia

  • Low grade fever

  • Night sweats

  • Severe chronic productive cough with hemoptysis

  • Site specific

Tuberculosis diagnostic criteria

• Tuberculin skin tests (screening)

• Chest radiograph

• Sputum culture

• Sputum nucleic acid amplification

Tuberculosis treatment

• Vaccinations (BCG)

• Transmission prevention

  • Isolation in private room

  • Negative air pressure

  • Droplet precautions (respirators)

• Directly observed therapy

Drug susceptible tuberculosis

• Treated with 

  • isoniazid (INF)

  • rifampin (RIF)

  • ethambutol (EMB)

  • pyrazinamide (PZA)

• Initial phase of 56 doses (8 weeks)

• Continuation phase of 126 doses (18 weeks)

• Total of 26 weeks (6 months)

Multi drug resistance tuberculosis

• Resistance to isoniazid and rifampin (first like drugs)

• Requires the use of more expensive and longer treatments with second line drugs

• Several sources reported 9 month treatment plan

Extensively drug resistant tuberculosis

• Resistance to isoniazid and rifampin (first line drugs)

• Resistance to any fluoroquinolone

• Resistance to at least one second line injectable drug

• MDR TB can become EDR TB when drugs misuse

UTI pathophysiology

• Ascending infection of urinary tract

• E. coli most common pathogen

• Results in cell necrosis in urinary tract epithelium

UTI clinical manifestations

• Dysuria

• Urgency

• Frequency

• Hematuria

• Cloudy urine

UTI diagnostic criteria

• History and physical examination

• Urinalysis and urine culture

• Leukocyte esterase dip test

UTI treatment

• Antibiotic drugs

• Increased fluid intake

• phenazopyridine (Pyridium)

Tinea pathophysiology

• A group of fungal infections

• Transmitted via direct contact

• Dermatophyte attaches to and produces thickening of keratinized cells

Ringworm

Corporis (body)

Hypopigmentation

Versicolor (skin)

Hair loss/breakage

Capitis (scalp)

Maceration between and around toes

Pedis (feet)

Erythema, itching

Cruris (groin)

Nail thickening, discoloration

Unguium (nails)

Tinea diagnostic criteria

• History and physical examination

• Microscopic examination

• Fungal cultures

• Wood light examination

Tinea treatment

• Prevention

  • Proper hygiene

  • Avoidance of contact with those infected

• Antifungal drugs (topical and oral)

Malaria pathophysiology

• Caused by infection with Plasmodium protozoa

• Transmitted by mosquito

• Incubation period of 1 month from exposure

• Currently eradicated in United States

• Worldwide, >1 million deaths per year

• Common in children from sub-Saharan Africa

Malaria clinical manifestations

• Headache

• Shivering and chills

• High fever

• Excessive sweating

• Cough

• Fatigue

• Malaise

• Joint/muscle aching

Malaria diagnostic criteria

• History of travel to an epidemic area

• Physical examination

• Laboratory testing

  • Hemoglobin level

  • Platelet counts

  • Liver function tests

  • Lactate dehydrogenase level

  • Lymphocytes

  • Peripheral blood smears

Malaria treatment

• Prevention

  • Avoiding mosquitoes

  • Using a bed net during sleep

  • Wearing long sleeve clothing

  • Using insect repellants (DEET)

• Antimalarial drugs

  • Quinolines

  • Antifolates

  • Artemisinins

  • Antimicrobials

• Antipyretics

Active immunity

Development of antibodies to an antigen and achieved by having a specific disease or vaccine

Passive immunity

Immunity transfer from host to recipient. Ex. mother to infant transfer from breastfeeding

Primary adaptive immune response

Activation with first recognition of a specific antigen

Secondary adaptive immune response

Reactivation with later recognition of the same antigen

Host defense failure

Antigenic variation, viral latency, and immunodeficiency

Hypersensitivity

• Type I (immediate) hypersensitivity reaction

• Type II antibody mediated hypersensitivity reaction

• Type III immune complex mediated reaction

• Type IV cytotoxic lymphocyte mediated hypersensitivity reaction

Autoimmunity

Failure to distinguish self from non self and causes damage to specific organs or to the entire system

Alloimmunity

• Graft rejection

• Graft vs host disease

This occurs with cells from another individual (organ or tissue transplant and blood donation)

AIDS pathophysiology

• Altered host defense resulting from secondary immunodeficiency

• Results in loss of cell-mediated and humoral immunity due to loss of CD4 TH1 lymphocytes

• Loss of immune response

AIDS clinical manifestations

• Immunosuppression

• opportunistic infections

  • Fungal infection

  • Pneumonia

• Kaposi Sarcoma

AIDS diagnostic criteria

• History and physical examination

• Laboratory analysis

  • Detection of antibodies to HIV

  • HIV viral load

  • CD4 T helper lymphocyte cell counts

AIDS treatment

• Antiretroviral therapy

  • Suppress viral load

  • Restore or preserve immune function

  • Reduce morbidity and mortality

• Drugs used in combination

  • Reduce the development of drug resistance

Anaphylactic reaction pathophysiology

• Exaggerated systemic immune response due to a type 1 hypersensitivity reaction

• Triggers:

  • Insect stings

  • Food allergies

  • Drug allergies

• Antigen exposure stimulates an IgE mediated response in a previously sensitized individual

• Degranulation of mast cells and basophils cause local and systemic responses

  • Dilation of vascular smooth muscle

  • Constriction of bronchial smooth muscle

  • Increase in vascular permeability

Anaphylactic reaction clinical manifestations

Phase 1

• Difficulty breathing

• Skin flushing and itching

• Angioedema

Phase 2

• Difficulty breathing

• Severe hypotension

• Severe edema