Download Blood and Lymphatic Diseases

Blood and Lymphatic
Diseases
Chapter 28
Nester 4th. Ed.
Topic Overview


Anatomy & Physiology
Bacterial Diseases of the Blood Vascular
System

Endocarditis
Subacute Bacterial Endocarditis
 Acute Bacterial Endocarditis


Septicemia

Gram Negative (-) Septicemia
Topic Overview

Bacterial Diseases of the Lymph Nodes &
Spleen

Zoonoses
Tularemia
 Brucellosis
 Plague

Topic Overview

Viral Diseases of Lymphoid & Blood
Vascular Systems




Infectious Mononucleosis (Mono)
Yellow Fever
Dengue Fever
Protozoan Diseases

Malaria
The Blood Vascular System

Normal flora


There are NONE.
Diseases




Systemic
Can produce disease in vital organs
Can cause circulatory system itself to stop
functioning
Can be rapidly fatal
Lymphatic System

Lymphatic vessels


Readily permeable
Take up foreign material
Invading microbes
 Microbial toxins
 Other antigens

Lymphatic System

Lymph Nodes



Act to trap foreign material
Contain phagocytic cells & antibody
producing cells
Lymphangitis

Demonstrates ability of lymph nodes to clear an
infection (even if only temporarily)
Bacterial Diseases of the Blood
Vascular System
Bacterial Endocarditis

What is it?

Infection of heart valves or endocardium


usually localized to one of the heart valves on the
left side
Acute


Starts abruptly (sudden and severe onset)
Virulent infection of the heart

Starts with abrupt fever
ABE

Pathogenesis




Usually an infection is seen somewhere else
or IV drug abuse is evident
Virulent bacteria
Invasion of heart and both normal & abnormal
valves
Rapid progression leading to permanent
damage or heart failure
ABE

Organisms




Staphylococcus aureus
Streptococcus pneumoniae
Neisseria gonorrhoeae
other bacteremia producing bacteria
Sub-acute Bacterial Endocarditis

What is it?

Infection of the endocardium




Usually localized to one of the heart valves on the left side
Caused by less virulent organisms
More protracted course
Commonly occurs in abnormal heart valves most
often resulting from



birth defect
rheumatic fever
other diseases
Sub-acute Bacterial Endocarditis
(SBE)

Causative Agent(s)

Usually normal flora of the mouth and skin
viridans Streptococci
 Staphylococcus epidermidis


General Symptoms



marked fatigue
slight fever
become ill and lose energy gradually over
weeks to months
SBE

Pathogenesis

organism gets into blood
dental procedures
 tooth brushing
 other trauma



abnormal valve forms a thin clot on it
clot traps organisms forming a biofilm

Protects organism from phagocytes and antibiotic
treatment
SBE

Pathogenesis




Antibiotics can make the bacteria clump together &
adhere to the clot
more clot forms
cycle - growth, clot, growth, clot, etc.
builds up a mass called a vegetation




bacteria continually wash off
pieces of the mass may come off too
Weakens the vessel – can lead to an aneurysm
Circulating immune complexes can lodge in eyes,
skin, organs, etc. causing damage
SBE

Pathogenesis

can burrow into the heart valve
abscesses
 damaged valve leaks


Diagnosis


venous blood from two anatomical locations
culture on blood agar
SBE

Epidemiology

cases with viridans Streptococci decreasing


antibiotics for people with valve problems before
dental work
cases with Staphylococcus epidermidis
IV drug abusers
 hospitalized people with plastic IV catheters in
place for a long time
 people with artificial heart valves

SBE

Prevention





no proven method
antibiotics before bacteremia causing
procedures
aseptically inserting catheters
moving IV catheters every few days
take out catheters ASAP
SBE

Treatment with bactericidal agent

Usually two or more together for prolonged
period

Penicillin & gentamicin 1 or more months
Septicemia




Systemic infection (blood poisoning)
Acute disease
~400,000 cases / year in U.S.
Caused by




Gram (-) bacteria (30% of all cases)
Gram (+) bacteria
viruses
fungi
Septicemia

Symptoms





violent shaking chills
fever
anxiety
rapid breathing
as septic shock develops
urine output decreases
 respirations & pulse increase
 vasoconstriction occurs

Gram (-) Septicemia

Pathogenesis

uncontrolled infection somewhere
due to some alteration in body defenses
 alternation in normal immune response (surgery,
trauma, subluxations) may allow infection to occur


endotoxin released from outer cell wall
from organism in blood or at local site of infection
 antibiotics that effect the cell wall enhance the
release of endotoxin

Gram (-) Septicemia

Pathogenesis

macrophages and circulating leukocytes
respond defensively to endotoxin



Intense response
good response if the infection is localized
bad if the endotoxin enters circulation
Gram (-) Septicemia

Pathogenesis

endotoxin causes triggering of macrophages
throughout body resulting in a systemic
reaction
intense immune response
 Hypersensitivity
 Cascade of harmful events (fig. 28.3 p. 720)


Macrophages important in defenses but play
a key role in septic shock
Gram (-) Septicemia

Pathogenesis

Interaction of endotoxin with macrophages
cause the cell to produce & release cytokines

tumor necrosis factor – TNF


induces fever
induces inflammation (PMNs -polymorphonuclear
neutrophils)
Gram (-) Septicemia

interleukin-1



acts with TNF to cause fever & release of leukocytes
from bone marrow
causes release of enzymes from polymorphonuclear
leukocytes
complement


attracts leukocytes and causes them to release tissue
damaging lysosomal enzymes
causes capillaries to leak plasma
Gram (-) Septicemia

Pathogenesis

endotoxin induces clotting
disseminated intravascular coagulation (DIC)
 uses up clotting factor
 leads to hemorrhaging


cytokines

decrease muscle tone of heart and vessels


hypotension
shock - not enough oxygen in vital organs
Gram (-) Septicemia

Pathogenesis

Lung - most susceptible to permanent
damage from endotoxemia

can lead to death even infection is cured and
shock is reversed
Gram (-) Septicemia

Epidemiology

Mainly a nosocomial infection

General trend of increasing incidence





increased life span
antibiotic suppression of normal flora
immuno-suppression drugs
equipment susceptible to biofilm formation
Prevention

Prompt ID and treatment of localized infections
Gram (-) Septicemia

Treatment


appropriate anti-microbial agent
measures to control shock


immunotherapy



death rate is still 30-50%
monoclonal antibody directed against endotoxin or TNF
Some benefit if given early before shock develops
Studies looking at recombinant technology protein
(Drotrecogin alpha)

Acts to oppose effects of cytokines
Bacterial Diseases of Lymph
Nodes and Spleen


Characterized by enlarged lymph nodes
and spleen
Three examples



All three are zoonoses
All three are uncommon in human disease in
U.S.
Seen a threat due to presence in animal
population
Tularemia (Rabbit’s Fever)

incubation period - (usually 2-5 days) following
bite of tick or insect or handling wild animal

Usual symptoms




skin - steep-walled ulcer
enlarged regional lymph nodes
fever, chills and achiness
Unusual symptoms


eye - conjunctivitis
lung - pneumonia



two routes of entry
GI tract - vomiting, diarrhea
Usually clears in 1-4 weeks, sometimes months
Tularemia

Causative agent

Francisella tularensis
pleomorphic, non-motile, Gram (-) rod
 needs cysteine to grow


Tularemia is widespread in animals in the
U.S.
rabbits, muskrats, bobcats
 “Rabbit Fever”

Tularemia

Pathogenesis - skin example



organism enters skin
lymph vessels carry the organism to the
lymph nodes
lymph nodes enlarge (lymphangitis)
fill with pus
 drain


organism spreads via lymphatics and blood
vessels
Tularemia

Pathogenesis – pneumonia

Occurs in 10-15% of cases
Enters lungs from bloodstream or inhalation
 High mortality – 30%


Most pneumonias occur among lab workers
Tularemia

Pathogenesis

organism ingested by phagocytic cells and
grows
Why it can persist fro months despite high
Antibody levels
 cell-mediated immunity cures
 90% survive without treatment

Tularemia

Epidemiology

portals of entry
unnoticed scratches
 mucous membranes
 oral cavity via food
 lung by inhalation

Tularemia

Epidemiology


150-250 cases per year
Eastern U.S.
winter
 from skinning rabbits (rabbit fever), squirrels,
muskrats, beavers


Western U.S.
summer
 tick and deer fly bites

Tularemia

Prevention




standard practices to prevent vector borne diseases
gloves, goggles, face masks for people skinning
animals
vaccine for lab workers and those of high risk of
infection
Treatment


tetracycline
gentamicin
Brucellosis


“Undulant Fever” or “Bang’s Disease”
Organism

Brucella melitensis
abortus - cattle
 melitensis - goats
 canis - dogs
 suis - pigs


strict aerobe, nonmotile, pleomorphic, small
Gram (-) rods
Brucellosis

Symptoms

Usually gradual and vague
Mild fever
 Sweating
 Weakness
 Aches & pains
 Enlarged lymph nodes
 Weight loss


Recurrence possible over few weeks to
months
Brucellosis

Pathogenesis




organism enters breaks in skin
organism penetrates mucous membranes
disseminated by lymphatic and blood vessels
organism grows inside phagocytes



infection persists for months
mortality - endocarditis - 2%
frequent serious complication - osteomyelitis
Brucellosis

Epidemiology



~150 cases / year in U.S.
10-20 times that number go unreported
usually a chronic infection of domestic animals



60% of cases


mammary glands - contaminate milk
uterus - abortions but not in humans
meat packing industry
less than 10% of cases

contaminated milk or unpasteurized milk products
Brucellosis


Worldwide – major problem causing yearly losses in
millions of dollars
In U.S. infections have been acquired from elk,
moose, bison, caribou & reindeer


~20% of Yellowstone bison population is infected
Prevention




pasteurization
inspection of animals
goggles, gloves
live attenuated vaccine for domestic animals
Brucellosis

Treatment





Most cases resolve within 2 months w/o
treatment
~15% symptomatic more than 3 months
If needed
tetracycline with rifampin ~ 6 weeks
may use streptomycin or gentamicin with
rifampin
Plague

“Black Death”



Killed 1/4 of Europeans between 1346 & 1350
Crowding and large rat population played
major role
Basis for
“Ring around the Rosie”
 “Would not touch them with a 10 foot pole”


Potential bioterrorism disease
Plague

Symptoms develop abruptly 1-6 days after
bite by infected flea

Bubonic plague
enlarged and tender lymph nodes – buboes
 high fever, shock, delirium, patchy bleeding under
skin


Pneumonic plague

Cough and bloody sputum
Plague

Organism - Yersinia pestis




facultatively, intracellular enterobacterium
small, oval, pleomorphic, non-motile, Gram (-)
rod
grows best at 25 degrees Celsius
bipolar staining - safety pin
Plague

three distinguishable plasmids

Smallest codes for protease “Pla”



Causes blood clots to dissolve by activating plasminogen
activator
Destroys C3b and C5a components of complement
Mid-sized plasmid codes for




(1) proteins that interfere with phagoyctes
(2) regulators of proteins’ expression
Proteins called Yops (Yersinia outer membrane proteins)
Bacteria loses virulence if this plasmid is lost
Plague

Plasmids

Largest plasmid codes for antigen F1


This protein becomes part of an antiphagocytic capsule
and is important component of plague vaccine
Virulence factors - Table 28.4, p. 724
Plague

Pathogenesis





fleas bite infected human or rat
flea body temp is 25 degrees Celsius
organism grows well and blocks flea’s GI tract
hungry flea bites human many times and
regurgitates
chronically infected fleas excrete organism
Plague

Pathogenesis


Protease Pla is essential for spread of organisms to lymph
nodes
Organism taken up by macrophages and are not killed


Macrophages die & release bacteria (now encapsulated)


multiply & release F1 capsular material
Fra 1 - gene for non-phagocytic capsule
After several days – acute inflammation & tenderness of
lymph nodes – bubonic plague

Lymph nodes necrose – spread to bloodstream – Septicemic
plague

Endotoxin release results in shock and DIC
Plague

Pathogenesis

organism can get to lungs 10-20% of the time
resulting in pneumonic plague


organism passed person to person via respiratory
droplets is extremely dangerous - organism is
easily transmitted
mortality - untreated
bubonic - 50-80%
 pneumonic -100% within a few days

Plague

Epidemiology


Endemic in all continents except Australia
In U.S. mostly confined to wild rodents in ~15
western states
Disease in prairie dogs, rock squirrels, and their
fleas - reservoirs
 Rats, rabbits, dogs, and cats - maybe
 Hundreds of species of fleas carry plague


~15 CASES / YEAR
Plague

Prevention




rat control
Insecticides
rope guards on moored ships
killed vaccine available
short term immunity
 to control epidemics
 high risk people - labs and endemic areas

Plague

Treatment



Tetracycline used prophylactically for
exposures
Alone or with gentamicin effective if given
early in disease
Can be used to control epidemics
Viral, Protozoan and Multi-Cellular
Diseases
Infectious Mononucleosis
“Mono”, “kissing disease”

Symptoms

Usually appear after incubation period of 3060 days
Fever
 Sore throat (pus covered)
 Marked fatigue
 Enlargement of spleen and lymph nodes



Most cases fever & sore throat gone in ~2 weeks
Enlarged lymph nodes in 3
Infectious Mononucleosis

Causative Agent

Epstein-Barr virus (now called Human herpes
virus type 4)
Linear ds DNA virus – Herpesviridae family
 enveloped
 Unknown until the 1960s


Originally isolated originally from a patient with Burkitt’s
lymphoma
Infectious Mononucleosis

Pathogenesis

Primary disease – throat infection



Replication in epithelium of mouth, glands & throat
Virus carried to lymph nodes via lymphatics
Infects B lymphocytes (up to 20% are infected during illness)


Infection can be productive
 Virus replicates in cell & kills B cell
Infection can be non-productive
 Virus establishes a latent infection existing either as
extrachromosome circular DNA or integrated into the host
cell chromosome at random sites
Infectious Mono

Latent infection occurs in other B-cells
B-cells differentiate
 Make IgM heterophile Ab






Antibody against antigens of another animal sheep,
horse, ox)
Used for diagnosis
No pathologic significance
Does not react with Epstein-Barr virus
Latently infected B-cells are immortal
Infectious Mononucleosis

Activation of T-lymphocytes occurs
T-cells kill infected productive cells
 T-cells appear abnormal - diagnostic for “mono”
 Occasionally misdiagnosed as leukemia


Enlargement of spleen and lymph nodes
reflects active replication of lymphocytes.
 In rare cases where death occurs



Splenic rupture
Most likely within 3-4 weeks of onset of illness
Infectious Mononucleosis

Epidemiology




worldwide
saliva transmission - “kissing”
most people of middle age have Ab
virus in saliva of 20% of the people previously
infected- carriers
Infectious Mononucleosis

Epidemiology

economically disadvantaged parts of the
world
even in the U.S. - especially urban areas
 infection occurs earlier in life
 no significant illness
 90% are infected by 6 years of age

Infectious Mononucleosis

Epidemiology

more affluent societies

infections occurs later in life


adolescents, teenagers, young adults
15-24 yoa
half those infected actually get “mono”
 no disease in the other half

Infectious Mono

Epidemiology



Virus present in salvia up to 18 months
following infection
Can occur intermittently for life
No animal reservoir
Infectious Mononucleosis

Prevention

don’t share objects contaminated with saliva


soda cans, tooth brushes, drinking glasses, etc.
Treatment

Acyclovir


Inhibits productive infection by virus
No activity against latent infection



For serious cases only
Those with liver and spleen enlargement
Those with prolonged disease
Chronic EBV Infection

Chronic EBV infection

severe disease after the primary disease
pneumonitis
 hepatitis
 hematological abnormalities
 prolonged relapsing course
 sometimes death
 not associated with chronic fatigue syndrome

Epstein-Barr Virus

Burkitt’s lymphoma



children in east Africa and New Guinea
viral DNA is found in > 90% of the tumors
malaria may be a cofactor
increases chances of tumor formation
 EBV found in only 20% of Burkitt’s lymphoma that
occurs in other parts of the world

Epstein-Barr Virus

Nasopharyngeal carcinoma



males of Chinese origin (southeast Asia)
viral DNA is found in > 90% of the tumors
EBV in immunodeficient hosts


lymphoproliferative diseases
not the Burkitt’s type
Yellow Fever

First recognized in 1648


Flaviviridae


Arbovirus
Yellow fever virus


Epidemic in Yucatan, Mexico
ss RNA genome
Vector

Aedes aegypti mosquito
Yellow Fever

Mild disease


Fever
Headache

Very severe disease






High fever
Nausea
Bleeding from nose
and mouth
G.I. Bleeding - “black
vomit”
jaundice - hence name
Mortality - 50%
Yellow Fever

Pathogenesis



mosquito with virus bites human
virus gets to blood and lymphatic vessels
viremia
liver - jaundice
 small blood vessels - petechiae throughout body
 heart - direct damage to heart muscle
 blood vessel injury - DIC

Yellow Fever

Epidemiology


Reservoir - mosquitoes and primates
Recognized in 1648 (Yucatan, Mexico)


Central and South America




1989 Bolivian epidemic in poor people who moved to the
jungle to grow coca
Africa


Imported from Africa
1960’s Ethiopian epidemic of 100,000
30,000 dead
Any of the tropical jungles
No U.S. outbreaks since 1905
Yellow Fever

Epidemiology

Control
Urban areas - insecticides sprayed in breeding
areas
 Jungles - almost impossible
 Live attenuated vaccine



highly effective for traveler’s to endemic areas
No proven antiviral treatment
Yellow Fever

Prevention




Insect repellent
Protective clothing
Mosquito netting
Vaccine - Know Before You Go

Certain countries require vaccine


Live virus vaccine, single dose, confers immunity for 10
years or more
Information found at the CDC website
Dengue Virus

Cause

Flavivirus genus (related to yellow fever virus)
Transmitted by Aedes aegypti mosquitoes
 Composed of single-stranded RNA





Has 4 distinct serotypes (DEN-1, 2, 3, 4)
Each serotype provides specific lifetime immunity, no cross
over immunity
All serotypes can cause severe and fatal disease
 Genetic variation within each serotypes
 Some genetic variants - more virulent
Incubation – 2 – 15 days
Dengue Fever (DF) & Dengue
Hemorrhagic Fever (DHF)

Clinical Characteristics (can include)






Fever
Headache
Muscle and joint pain
Nausea/vomiting
Rash
Hemorrhagic manifestations






Skin hemorrhages: petechiae, purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding: hematemesis, melena, hematochezia
Hematuria
Increased menstrual flow
Dengue Fever & Dengue
Hemorrhagic Fever

Incidence


Variable, depending on epidemic activity
Globally
~50-100 million cases of DF
 Several hundred thousand cases of DHF
 Fatality rate of DHF ~5%
 Americas




1995 – 250,000 cases DF
7,000 cases of DHF
~100-200 cases in U.S. each year (by travelers)
Dengue Fever & Dengue
Hemorrhagic Fever

Costs


~ $250 million estimate in Puerto Rico in past
10 years
Risk Groups



Residents or visitors to tropical urban areas
Children under 15 yoa
No cross-immunity from each serotype
Malaria



Protozoan
Sporozoan
Plasmodium




vivax - most U.S. cases
falciparum - 30% of cases in U.S.
malariae
ovale
Malaria

Plasmodium species

differ in:
microscopic appearance
 life cycle
 type of disease
 severity
 treatment

Malaria

Anopheles mosquito - vector


bites human and picks up gametocytes
Life cycle



parasites (sporozoites) enter RBC’s
sporozoites develop and multiply in RBC’s
RBC’s burst releasing merozoites
merozoites infect more RBC’s - cycle
 some merozoites become male and female
gametocytes - don’t contribute to symptoms

Malaria

Life cycle (Fig. 28.11, pg. 732)






gametocytes enter mosquito intestine
there they fuse to form a zygote and then a cyst
the cyst ruptures releasing sporozoites
sporozoites travel to the mosquito salivary gland
mosquito bites a human
sporozoites in saliva enter blood
Malaria

Life cycle



sporozoites travel to the liver and multiply there
(called hypnozoites in the liver)
 P. vivax and P. ovale hypnozoits responsible for
relapse
leave the liver and return to the blood (now called
merozoites)
merozoites enter RBC’s - back to first step of cycle
Malaria

Symptoms and pathogenesis



recurrent bouts of fever followed by feeling
healthy
tied to cycle of RBC’s bursting releasing
merozoites
infections of RBC’s become synchronized

each batch of infected RBC’s ruptures at the same
time
Malaria

Symptoms and pathogenesis

time frame until RBC’s burst
malariae - 72 hours - fever every 4th day
 other species - 48 hours - fever every 3rd day


RBC susceptibility to merozoites

falciparum infects all red cells


more severe disease
other species infect only young and old cells

less severe disease
Malaria

Consequences

RBC’s become rigid







clog capillaries
decrease oxygen to organs
cerebral malaria = stroke
malaria of heart = failure
spleen enlarges trying to filter out the parasites
anemia due to bursting of RBC’s
Immune system over stimulated by large amount of Ag - gets
overworked
Malaria

Epidemiology





Malaria may be a cofactor for Burkitt’s
lymphoma
tropical climates mostly
300,000,000 infected worldwide
1,000,000 deaths per year
20-30% of deaths of African children are due
to malaria
Malaria

Epidemiology

in the U.S.
recognized in 1648
 imported from Africa
 eliminated from the continental U.S. in the 1940’s
 now it’s back



CA - organism found in mosquitoes
FL - natural infection in a person bitten in FL
Malaria

Treatment





different treatments are needed for different
stages of the life cycle
chloroquine for the RBC stages
primaquine for the exoerythrocyte stages
mefloquine or doxycycline for chloroquine
resistant falciparum and vivax
I.V. quinine, quinidine, sulfa drugs,
tetracycline
Malaria

Prevention and control





vaccine being developed
increase access to treatment
earlier diagnosis
faster treatment
travelers
chloroquine weekly stops symptoms not infection
 primaquine needed to stop infection

Conclusion

What organisms
cause the following
diseases:




Bacterial Diseases





Sub-acute bacterial
endocarditis
Gram-negative
septicemia
Tularemia
Bruscellosis
Plague
Viral Diseases


Infectious
Mononucleosis
Yellow Fever
Dengue
Protozoan Diseases

Malaria
Conclusion

What are the
symptoms of the
following diseases:




Bacterial Diseases





Sub-acute bacterial
endocarditis
Gram-negative
septicemia
Tularemia
Bruscellosis
Plague
Viral Diseases


Infectious
Mononucleosis
Yellow Fever
Dengue
Protozoan Diseases

Malaria
Conclusion

What is the epidemiology
and pathogenesis of the
following diseases:




Bacterial Diseases





Sub-acute bacterial
endocarditis
Gram-negative septicemia
Tularemia
Bruscellosis
Plague
Viral Diseases


Infectious
Mononucleosis
Yellow Fever
Dengue
Protozoan Diseases

Malaria
Conclusion

What is the prevention
and treatment of the
following diseases:




Bacterial Diseases





Sub-acute bacterial
endocarditis
Gram-negative septicemia
Tularemia
Bruscellosis
Plague
Viral Diseases


Protozoan Diseases


Infectious
Mononucleosis
Yellow Fever
Dengue
Malaria
Multi-cellular Parasitic
Diseases

Schistosomiasis