Download SYSTEMIC PATHOLOGY

2014-2015
Prerequisite
GENERAL PATHOLOGY
Books...Books...Books...
 Robbins Basic Pathology
 Editörler: Vinay Kumar, Abul K. Abbas, Nelson Fausto
 Türkçesi:
 Robbins Hastalığın Patolojik Temeli - ISBN 9789752771802
 Robbins Temel Patoloji – ISBN: 9781416029731
 Robins Review of Pathology (Türkçesi) - ISBN :975-8531-21-2
 Rubin's Pathology: Clinicopathologic Foundations of Medicine
 Editör(ler) :Raphael Rubin , David S Strayer
 ISBN :0781795168
 Essential Pathology
 Editör:Emanuel Rubin
 ISBN :0781723957
 Temel Patoloji
 Editör:Prof. Dr. Gamze Mocan KUZEY
 ISBN :975-277-104-1
Pathology
The most important field of Medical Science
 General Pathology
 Special Pathology or Systemic Pathology
 Systemic Pathology
 Clinical pathology
 Pathophysiology
 The preclinical curriculum (3rd Phase)
 Pathophysiology & Pathology
(students learn about basic mechanisms of disease) in
such fields
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Cardiovascular system
Respiratory system
Gastrointestinal system
Endocrinology
Hematology
Genital & Urinary systems
Diseases of Bones & Joints
Central Nervous System
 The course provides the educational experiences
utilizing both lectures and interactive lab discussions.
 This course is the basis provided to the students for
understanding various disease processes, as they
proceed thereafter to the core clinical clerkships.
Systemic Pathology
 Requires the knowledge of General Pathology
 Requires correlation between normal Anatomy and
Physiology and the process resulting in the
manifestations of disease
 The Systemic Pathology lectures were updated with
Pathophysiology and “must” information will be given
all year long
 Pathology lectures will guide you to enhance your
understanding of disease.
never forget...
There are 4 aspects of a disease process
that form the core of pathology
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2.
3.
4.
Etiology (the cause),
Pathogenesis (the mechanism),
Morphology (the alterations),
Clinical significance (the consequences).
1. Etiology (the cause):
Finding the primary cause(s)  diagnosis 
treatment
2. Pathogenesis (the mechanism) refers to the
sequence of events in the response of the
cells or tissues to the cause from the
beginning (initial stimulus) to the end (the
manifestations of disease)
3. Morphology (the alterations):
The morphologic changes refer to the
structural and functional alterations in cells
and tissues:
 either characteristic of the disease or
 diagnostic of the etiologic process
4. Clinical significance (the consequences):
The nature of the morphologic changes and their
distribution in different organs determine
 Signs and Symptoms
 Course & Prognosis of the disease.
The Pathology of
Infectious Diseases
Introduction
Tissue Responses to Infections
Infectious agents
 Focus on PATHOGENESIS
 Know basic steps in the pathogenesis of:
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Viruses
Rickettsiae
Chlamydiae
Mycoplasma
Bacteria (incl.spirochetes&mycobacteria)
Fungi
Protozoa
Helminths
Definitions
 Infection
The ability of an organism to invade and establish
itself in a host.
 Note: All infections DO NOT represent DISEASES !!!
 Infectious Disease Agent:
Organisms found in the environment that are
 capable of replication (either independently or with the
host)
 capable of provoking an adverse response in the host
Infectivity and Virulence
 Virulence refers to the complex of properties that
allows an organism to achieve infection and cause
disease of different degrees of severity.
 The organism must
(1) gain access to the body,
(2) avoid multiple host defenses,
(3) accommodate to growth in the human milieu,
(4) parasitize human resources.
 Virulence reflects both the structures inherent to
the offending microbe and the interplay of those
factors with host defense mechanisms.
Epidemiology of Infectious Disease
Example: Leismaniasis cutis (oriental sore)
 Reservoirs (cave)
 Vector (sandfly)
 Susceptibility of the host (common)
 Method(s) of Control (sanitation)
 Microbial Virulence Factors (antigens)
 Host Defense Mechanisms (cellular)
 Chemotherapy (amphotericin B paromomycin,
miltefosine)
HOST BARRIERS TO INFECTION
 I. Local Barriers
 II. Humoral Immunity
 A. Antibody
 B. Complement
 III. Cell-mediated Immunity
 A. T-helper
 B. T-suppressor
 C. Cytotoxic lymphocyte
 IV. Phagocyte
 A. Neutrophil
 B. Monocyte, macrophage
The destruction of
Local Barriers
 Skin
 Normal flora
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Staphylococcus epidermidis
Candida albicans
 Dry keratinized epidermis
 Acidic pH
 RISK OCCURS WHEN
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Cuts
Lacerations
Bites
Indwelling lines
Invasive procedures
 Urogenital Tract
 Urine is normally sterile primarily due to constant flow
 Peristaltic motion and valves are designed to maintain unidirectional
flow
 UT Infection rate  Female : Male = 10 : 1
 Acidic Ph of vagina
 RISK OCCURS WHEN
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Loss of the Acidic pH of Vagina
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Polygamy
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Candida abicans
HPV
SexTransmtd Dis
Urinary Tract Obstructions
Exposure to pathogens which adhere to urothelium
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Some strains of E. coli
Proteus
Pseudomonas
Gonococcus
Staphyloccous saprophyticus
 Respiratory tract
 Constant exposure to thousands of potential pathogens
 Unique defense structure: Mucociliary escalator
 Particles >5 micron : cleared by mucociliary escalator
 Particles <5 micron: cleared by macrophages & PMNs
 RISK OCCURS WHEN
 Mucociliary system is damaged (smoking, COPD, pathogens)
 There is an attack of infectious agents (capable to adhere to the
respiratory epithelium)
 Immunocompromised Patient
 Gastrointestinal tract
 Constant contact with organisms via food & water
 Defense systems:
 Mucus
 Gastric acid
 Pancreatic Fluids
 Bile salts
 IgA
 RISK OCCURS WHEN:
 Exposure to virulent organism
 Decrease in gastric acid production
 Antibiotic therapy
 Abnormal GI motility
 Barriers....
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Skin
Tears
Normal bacterial flora
Gastric acid
Bile
Salivary and pancreatic secretions
Filtration system of nasopharynx
Mucociliary blanket
Bronchial, cervical, urethral, and prostatic secretions
Neutrophils
Monocytes
Complement
Stationary mononuclear phagocyte system
Immunoglobulins
Cell-mediated immunity
PATHOGENESIS
 HOW CAN INFECTIOUS AGENTS CAUSE
DAMAGE?
 Direct damage
 Release of Exotoxins, Endotoxins and/or irritant
enzymes/proteins
 Induction of host immune response
VIRAL INFECTIONS
IMMUNE RESPONSE TO VIRAL INFECTIONS
 Natural Killer Cell
 Cytokine Release
 boosts the immune response
 directly inhibits viral replication
 Cytotoxic T Cell
 B cells - Neutralizing antibodies
BACTERIAL INFECTIONS
 Virulence
 Endotoxins
 Exotoxins
 Potent enzymes (Flesh-eating bacteria, Group A Strep)
 Ability to survive and proliferate intracellularly (Tb)
 Spread in the Host
 Macrophages may aid in spread (Tb)
 Bloodstream and Lymphatics (almost all bacteria)
 Motility and Chemotaxis (Vibrio cholerae)
 Cell and Tissue Damage
Virulence Factors
 Adhesins
 Capsular material
 Proteins (Protein F, Protein M)
 Lipotechoic acids
 Fimbriae & Pili
 Endotoxins
 Gram negative LPS cell wall components (Lipid A and Core Sugars)
 Exotoxins
 Can be produced by either Gram (+) or Gram (-) organisms
Special consideration for Mycobacteria
 Distinctive waxy cell coat requiring Acid Fast Stains
 Virulence is related to cell wall ”cord factor” which
inhibits phagosome-lysosome fusion
 Lipid cell wall components help initiate delayed cellmediated hypersensitivity response in the host GRANULOMAS
 Special culture methods used; may take up to 6 weeks
FUNGAL INFECTIONS
 Only a few commonly infect man
 increasingly important with the rise in
immunocompromised patients
 Route of Infection - Almost always the LUNGS
 +/- clinical pulmonary symptoms & signs
 pulmonary disease may be subclinical, mild, or severe
 Fungi may produce toxins (mycotoxins)
 Immune Response: Essential in clearing infections CLASSICALLY GRANULOMATOUS
PARASITIC INFECTIONS
 MECHANISMS of INJURY
 Mechanical Injury (ie. hookworm larvae)
 Eliciting an Immune Response (ie. hookworm larvae in
the lungs cause eosinophilic pneumonia)
 Nutritional depletion
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Adult hookworms
Ascaris
Giardia lamblia
 Digestion of host tissues (ie. Entabmoeba histolytica)
 Toxins and toxic metabolites (ie. Plasmodium in Malaria)
 Combinations of the above are common
HOST RESPONSE TO INFECTIOUS AGENTS
 Acute Inflammatory Response (exudative;
suppurative)
 Necrotizing Inflammation
 Granulomatous Inflammation
 Mononuclear Inflammatory Response (Chronic
Inflammation & Scarring)
 Cytopathic-Cytoproliferative Inflammation
 Blood manifestations:
- Leukocytosis: an increase in the number of leukocytes in the
blood (mostly bacterial)
- Neutropenia: insufficient circulating neutrophils
(salmonelosis, brucellosis, pertussis, and some viral and rickettsial
infections)
- Anemia: insufficient circulating erythrocytes (clostridium,
malaria, mycoplasma, chronic infections)
- DIC: disseminated intravascular coagulation (bacteria, virus)
Organisms in blood:
Bacteremia: Few bacteria in the bloodstream,
whether or not they are causing disease
Viremia
Septicemia: Bacteria traveling around the body via
the blood
Infected blood causes severe disease
Pyemia: Pyemia is a seldom-used term which means
"pyogenic organisms" (staphylococcus,
streptococcus, gram-negative rods) infecting the
blood
 Renal manifestations
 Immune Complex Glomerulonephritis
 Hepatic manifestations
 Icter (Jaundice)
 Central nervous system manifestations
 Cerebral malfunctions (confusion, convulsions, coma)
 Cardiovascular manifestations
 Septic shock, endocarditis
 SYSTEMIC manifestations= multiorgan dysfunction
 Thank you….