HUMAN AND

DISEASE

PROF. TOPO HARSONO

(EMERITUS PROFESSOR OF
PATHOLOGY)

ULTIMATE GOAL OF MEDICAL PRACTICE:

1. RESPECT TO LIFE AND HUMAN BEING
2. PROMOTION OF HEALTH AND
LONGIVITY
3. REDUCTION OF MORBIDITY AND
PREVENTION OF DISEASE
4. RELIEVE OF SUFFERINGS

1. RESPECT TO LIFE AND HUMAN BEING

ONLY GOD DECIDE ON THE FATE OF

LIFE OF EVERY HUMAN BEING.

2. PROMOTION OF HEALTH AND

LONGEVITY.
IT IS THE TASK OF EACH INDIVIDUAL TO
MAINTAIN THE BEST CONDITION OF GODS
CREATION.

3. REDUCTION OF MORBIDITY AND

PREVENTION OF DISEASE.
THIS IS THE MAIN TASK OF A MEDICAL
DOCTOR

4. RELIEVE OF SUFFERINGS
A MEDICAL DOCTOR SHOULD NOT BE
TEMPTED TO AGREE ON EUTHANASIA
IN RELIEVING HIS PATIENTS SUFFERINGS

PROMOTIVE

PREVENTIVE

PREVENTIVE

HEALTH

REHABILITATIVE
BODY DEFENCE
MECHANISM

INJURY

REGENERATION

EXOGENOUS
ENDOGENOUS

POTENTIAL

DISEASE
CURATIVE

CURATIVE

DEATH

DISEASE
Any deviation from or interruption of the
normal structure or function of a part, organ
or system of the body as manifested by characteristic symptoms and signs; the etiology, pathology and prognosis may be known
or unknown (DORLANDS MEDICAL
DICTIONARY)

MORBID:
1. Pertaining to, affected with, or inducing disease;
diseased.
2. Unhealthy or unwholesome.
3. Characterized by preoccupation with gloomy or
unwholesome feelings or thoughts

MALFORMATION
Primary error of morphogenesis, intrinsic abnormal
developmental process.
Usually multifactorial rather than the result of a single
gene or chromosomal defect.
Some, such as congenital heart disease involve a single
body system. Multiple malformations involving many
organs may coexist.

Causes of Congenital Anomalies in Humans

Genetic
Chromosomal aberrations
10 15 %
Mendelian inheritance
2 10 %
Environmental
Maternal / placental infections:
%
Rubella
Toxoplasmosis
Syphilis
Human Immunodeficiency Virus
Maternal disease states:
Diabetes
Phenylketonuria
Drugs and chemicals:
Alcohol
Androgenes

23

68%

1%

 Multifactorial (Multiple genes ? Environment)

%
Unknown

20-25

40-60 %

DISORDER
A derangement or abnormality of function;
A morbid physical or mental state

SYNDROME
A set of symptoms which occur together.
A symptom complex
The sum of signs of any morbid state

PAIN
A more or less localized sensation of discomfort, distress or agony, resulting from
the stimulation of specialized nerve endings.
Subjective feeling of discomfort.
Other similar words: sore ache hurt
numb illness - sickness

WHO Definition of HEALTH

Health is a state of optimal physical, mental
and social well-being, and not merely the
absence of disease or infirmity.

UU No: 32 1992:
Kesehatan adalah keadaan sejahtera dari badan, jiwa dan sosial yang memungkinkan
setiap orang hidup produktif secara sosial
dan ekonomis.

PATHOLOGY:
That branch of medicine which treats of the
essential nature of disease, especially of the
structural and functional changes in tissues
and organs of the body that cause or are
caused by disease (Dorlands Medical
Dictionary)

PATHOLOGY:
A bridging discipline involving both science
and clinical practice devoted to the study of
the structural and functional changes in cells,
tissues and organs that underlie diseases
(ROBBINS: Pathologic Basis of Diseases)

PATHOLOGY:
That specialty of the practice of medicine dealing
with causes and nature of disease which contribute
to diagnosis, prognosis and treatment, through
knowledge gained by laboratory application of the
biologic, chemical or physical sciences to man or
material obtained from man (AMERICAN
PATHOLOGY SOCIETY)

PATHOGENESIS
ETIOLOGY

(DISEASE PROCESS)

ANATOMICAL
PHYSOLOGICAL
MICROBIOLOGICAL
CHANGES
PATHOLOGY
DIAGNOSIS
PROGNOSIS

PATHOLOGY
CLINICAL
ANATOMICAL FORENSIC
PATHOLOGY PATHOLOGY PATHOLOGY
PATHOBIOLOGY GYNAECOPATHOLOGY
IMMUNOPATHOLOGY
SURGICAL PATHOLOGY
NEUROPATHOLOGY
DERMATOPATHOLOGY
GEOGRAPHICAL PATH. ONCOPATHOLOGY
PALEOPATHOLOGY
GASTERO-ENTERO PATH.
PEDIATRIC PATHOLOGY ORTHOPEDIC PATHOLOGY

GROWTH AND DEVELOPMENT

Growth and Development are essentially synonymous terms
that describe the series of changes an organism goes
through to attain maturity.
In practice: Growth signify the increase in size attendant
upon maturation.
Development indicate the increase of
functional capacities.

THE NEWBORN

The newborn period is a unique moment in the life of the

individual. The change in status from a parasitic to an independently existing organism, the change in environment, and
the exposure to exogenous insults and trauma and the
changes in function of the various organs are of a nature and
magnitude which are never again encountered in life.
The stress imposed by these adjustments is of such a
degree that the mortality rate in the neonatal period is higher
than at any other time during life. The problems of the
newborn comprise a very special field for medical endeavor,
and this is as true of pathology as it is of other branches of
medical science

The following factors must be taken into account in any discussion of the pathology of the newborn period:
The status of the infant at the time of birth and the time of
death,
The size of the infant as an indicator of maturity,
Whether the infant is viable or within the range considered
nonviable,
The health status of the mother and the infant of specific
anatomic abnormalities incompatible with life,
The effects of the birth process on the infant, with special
attention to the question of birth trauma and the immediate
postnatal care of the infant relative to such matters as
anoxia,
hyperoxydation, administration of artificial respiration etc.

Aside from these rather basic items, there are problems peculiar
to the newborn per se:
There are diseases that only occur in the newborn period,
such as hyaline membrane disease, generalized infection by
the herpes virus or some consequences of neonatal care like
retrolental fibroplasia.
There are indications that some conditions are misleading,
such as the general designation of anoxia, or as it is sometimes
called abnormal pulmonary ventilation as a cause of death. Anoxia is rarely primary. In a very few instances the cause of anoxia is evident, such as deep anesthesia of the mother, premature separation of the placenta or intracranial hemorrhages
due to birth trauma. In truth, all infants die of anoxia, for
when
pulmonary and circulatory functions begin to fail, anoxia supervenes.

RETROLENTAL FIBROPLASIA
Caused by exposure of the infant to oxygen concentrations
of more than 40 % for excessive periods of time. Retinal vascularization is incomplete at birth in premature infants.
High concentration causes constriction of the retinal vessels
and if this persists for 3 or 4 days they become irreversibly
damaged.
The disturbance of nutrition and oxygenization of the retina
resulting from occlusion of these vessels, causes a tissue
reaction similar to granulation tissue, that is an irregular proliferation of capillaries and fibrous tissue, leading to hemorrhage
and transudation of fluid extending in to the vitreous and complete detachment of the retina and blindness.

Antepartum death: > infants who died during the period

before birth, no obvious cause found
> 15 % associated with congenital anomalies
> small number incompatibility of
maternal and fetal blood group
> disease of the mother
> prematurity
Intrapartum death: > infants who died during the period
of onset of labor and delivery
> more frequently in infants at, near or
beyond labor
> 35 % related to premature separation of
placenta, placenta previa or abruptio
placenta.

 Neonatal death: > any death occuring within the first 28 days
of life
Perinatal death: > infants who died just prior to birth and
within the first week of life
> 70 % of neonatal death occurs within the
the first week of life
> prematurity 80 % of infants dying within
first 48 hours of life
Postmortem Examination:
Technique of postmortem examinaton of fetus and newborn
does not differ markedly from that of the older child and
adult, but it calls for special emphasis to examination of the
umbilical cord and placenta.

Fetal distress:
The principal symptoms of fetal distress during intrauterine life
are irregularity of the fetal heart, a brief period of increased activity of the fetus and the relaxation of the anal sphincter with release of meconium into the amniotic fluid.
When an infant is born after a prolonged period of fetal distress
and is still alive, there may be slow heart beat, pallor, poor muscle tone, and yellow staining of the skin and nails. These children
usually fail to establish respiration and the heart ceases to beat
shortly after birth. This condition is called asphyxia pallida.
Even in instance where there has been no evidence of fetal distress the infant may fail to breath spontaneously at birth. This is
mostly associated with pathological conditions like:
intracranial hemorrhage due to birth trauma, with pressure or
damage to the respiratory centers of the brain stem,
mechanical interference with the respiratory system, such
as in diaphragmatic hernia or pleural effusion,

Prematurity and Postmaturity.

Prematurity: > birth weight less than 2500 gm
> crown-heel length under 47 cm
> gestation less than 37 weeks
Immature : > birth weight between 500 1000 gm
> length between 28 46.9 cm
> gestation between 22 and 28
weeks
> in USA immature infants
are just called
fetus or abortus and is not
considered a
living individual
Prematurity recognized as complication of toxemia,
placenta previa and premature separation of placenta.
Prematurity also closely linked to cigarette smoking.

Hyaline Membrane Disease

Single disease associated with prematurity.
Histologically the lungs are seen to contain relatively little air
and the walls of many of the alveolar ducts are collapsed. The
outstanding feature is the presence of eosinophilic, homogenous,
acellular refractile masses lining the air spaces. There is intense
engorgement of the capillaries.
Current theory suggest the presence of a resorption ateletasis
and presence of amniotic fluid in the lungs

Postmaturity

Infant with gestational length of more than 42 weeks.

Mother of postmature baby are classified as the elderly
primipara mother who has her first child after the age of
30.
Giant fetuses has no direct correlation with the length of
gestation, rather than with the tendency of the mother having
diabetes or having a genetic constitution of diabetes.

 hypoplasia or malformation of the lungs,

depression of the respiratory center by excessive
analgesia or anaesthesia given to the mother before
delivery,

Birth Trauma:
Birth trauma is associated with trauma resulting from mechanical force (molding of the head during labor) and is associated with
hemorrhages.
Intracranial haemorrhage is more frequent in premature infants
and probably is related to the physical character of the brain substance.

Major discoveries in Microbial Pathogenesis

1796
1843
1865
1882
1884
1902
1906
1908
1933
1945
1949
1983
1997

Edward Jenner
Wendell Holmes

Vaccination against Smallpox

Discovery of the iatrogenic nature
of black death of childhood
Louis Pasteur
Proof of germ theory and the beginning of modern biology
Robert Koch
Kochs postulate (4)
Elie Metchnikov
Description of phagocytosis by macrophages
Ronald Ross
Identification of mosquito vector for
Plasmodium falciparum malaria
Paul Ehrlich
Description of chemotherapeutic
agents
Ellermann & Bang
Viral oncogenesis in chicken pox
Rebecca Lancefield
Serotyping of organisms and association of bacterial clones with disease
Avery
Identification of DNA as genetic material
and start of Molecular biology revolution
John Franklin Enders
Culture of viruses and production of
& Weller
poliovirus vaccine
Luc de Montagnier &
Identification of HIV as cause of AIDS
Robert Gallo
Venter
Sequence of genome of Haemophilus
influenzae

New Emerging Infectious Diseases

1973
1975
1977

1980
1981
1982

1983
1985
1988
1989
1992
1993
1995
2002
2004

Rota virus
Cryptosporidium parvum
Ebola virus
Hantaan virus
Legionella pneumophila
Campylobacter jejuni
HTLV-I
Staphylococcus aureus
HTLV-II
Escherichia Coli
(O157:H7)
Borrelia burgdorferi
HIV
Helicobacter pylori
Enterocytozoon bieneusi
HHV-6
Hepatitis E
Hepatitis C
Vibrio cholerae (O139)
Encephalitozoon cuniculi
KSHV (HHV-8)
Corona virus
N5H1 virus

Infantile diarrhea
Acute and chronic diarrhea
Epidemic haemorrhagic fever
Hemorrhagic fever with renal disease
Legionnaires pneumonia
Enteritis
T-cell lymphoma or leukemia
Toxic shock syndrome
Hairy cell leukemia
Hemorrhagic colitis hemolytic-uremic
syndrome
Lyme
AIDS
Chronic gastritis
Chronic diarrhea
Roseola subitum
Enterically transmitted hepatitis
Non-A and Non-B hepatitis
New epidemic cholera strain
Opportunistic infections
Kaposi sarcoma in AIDS
Severe Acute Respiratory
AVIAN FLU Syndrome

KOCHS POSTULATE
1. Microorganism must be observed in every case of the
disease.
2. Microorganism must be isolated and grown in pure
culture.
3. The pure culture must, when inoculated into a
susceptible animal, reproduce the disease.
4. The microorganism must be observed in, and recovered from, the experimentally diseased animal.

CATEGORIES OF INFECTIOUS AGENTS

I. PRIONS:
Composed of modified host protein
Cause

transmissible spongioform encephalopathies:

-> kuru, associated with human cannibalism
-> Creutzfeldt-Jakob disease, associated with
corneal transplants
-> Bovine spongioform encephalopathy (BSE)
mad cow diseaese
-> atypical C-J disease transmitted to humans from
BSE

II. VIRUSES:
All viruses depend on host cell metabolism for their replication
Obligate intracellular parasites
Classified by the nucleic acid content of their core (DNA or RNA)
and their shape of coat or capsid
More than 400 species inhabit humans but only some cause acute
iIlnesses to humans: common colds or influenza.
Others are capable of lifelong latency and of long-term reactivation
(Herpes viruses) or may give rise to chronic diseases (Hepatitis
viruses)

III BACTERIOPHAGES, PLASMIDS

AND TRANSPONS
Mobile genetic elements that encode bacterial virulence factors:
adhesins, toxins or enzymes that confer antibiotic resistance.
Ability to infect bacteria and incorporate themselves into their genome:
toxin genes of Vibrio cholerae and Shigella flexneri.
Exchange of these elements between bacterial strains and species
endows the recipients either with survival potentials or capacity to
cause disease

IV. BACTERIA
Bacterial cells lack nuclei and endoplasmic reticulum
Cell walls are rigid, composed either of two phospholipid bilayers
with a peptidoglycan layer in between (Gram-negative species) or
of a single bilayer covered by peptidoglycan (Gram-positive bacteria)
Bacteris synthesize their own DNA, RNA and proteins but depend on
the host for favorable growth conditions.
Some thrive mainly on the bodys surface layers (skin), including
staphylococcus and propioni bacteriums, the agent responsible for
adolescent pimples
A large amount reside inside the gastrointestinal tract of which 99 %
are anaerobe

V. CHLAMYDIAE, RICKETTSIAE AND MYCOPLASMAS

Has similarities with bacteria divide by binary fission
susceptible to antibodies
but lack of certain structures:
lack of cell wall or lack of certain
metabolic capabilities (ATP synthesis)
Most rickettsiae are transmitted by insect vectors (lice, ticks and mites) and
are obligate intracellular agents, replicating in cytoplasm of endothelial cells
cause a hemorrhagic vasculitis often visible as skin rash, transient pneumonia, hepatitis, CNS injuries and death.
Mycoplasma pneumoniae spreads from person to person by aerosols, binds
to the surface of epithelial cells in the airways by an adhesin (P1) and causes
an atypical pneumonia.

VI. FUNGI
Fungi possess thick, ergosterol-containing cell walls and grow as perfect, sexually
reproducing forms in vitro and as imperfect forms in vivo, including budding yeast
cells, hyphae and conidia.
Tinea group of fungi are confined to superficial layers of the skin (athletes foot).
Other dermatophytes damage the hair shaft or nails. Some fungal species invade
subcutaneous tissue causing granulomas or spread systemically destroying vital
organs in immunocompromised hosts

VII. PROTOZOA
Parasitic protozoa are single-celled organisms endowed with motility, pliable
plasma membranes and complex cytoplasmic organelles.
Trichomonas vaginalis is transmitted sexually from person to person.
Intestinal protozoas are spread by the fecal-oral route: Entamoeba histolytica
and Giardia lamblia.
Blood-bourne protozoa (Plasmodium, Tryponema and Leishmania specieses)
are transmitted by blood-sucking insects, in which they undergo a complex succession of life stages before passed to new human hosts.
Toxoplasma gondii is acquired either by contact with oocyst-shedding kittens or
by eating cyst-ridden undercooked meat.

VIII. HELMINTHS
Parasitic worms are highly differentiated multicellular organisms with a complex
life cycle: alternation of sexual reproduction in the definitive host and the asexual
multipliacation in an intermediary host or vector.
Thus, depending on the parasitic species, humans may harbor either adult worms
(Ascaris) or immature stages (Toxocara canis) or asexual larval forms (Echino
coccus).
Adult worms, once residing in humans, do not multiply in number but generate
eggs or larvae destined for the next phase of the cycle.

VIII. HELMINTHS (Cont.)

Important consequences of the lack of replication of adult worms:
disease often caused by inflammatory responses to the eggs or larvae
rather than to the adult forms
disease is in proportion to the number of organisms infecting the individual
Parasitic worms are of three classes:
[1] First class: Nematodes (roundworms) Intestinal: Ascaris and Strongyloides
Tissue invaders: Filariae and Trichinella
[2] Second class: Cestodes (flat worms) Tapeworms and cystic tapeworm larvae:
Cysticerci and hydatid cyst
[3] Third class: Trematodes (flukes)
oriental liver and lung flukes

IX. ECTOPARASITES
Ectoparasites are arthropods (lice, ticks, bedbugs and fleas) that attach to and live
on the skin.
Scabies: example of severe dermatitis caused by mites burrowing into the stratum
Corneum.
Arthropods can be vectors for other pathogens: Lyme disease caused by spirochetes
(Borrelia burgdorferi) transmitted by deer ticks

HUMAN VIRAL DISEASES AND THEIR PATHOGENS

RESPIRATORY
Adeno virus
Echo virus
pharyngitis
Rhino virus
Coxsackie virus
Influenza virus A-B
Parainfluenza virus

Upper/lower Resp Tr Inf.

Upper Resp Tr Inf,
Upper Resp Tr Inf
Hand-foot-mouth disease
Influenza
Upper/lower Resp Tr Inf.

DIGESTIVE
Mumps virus
Mumps,pancreatitis,orchitis
Rota virus
Childhood diarrhea
Hepatitis A virus
Acute viral hepatitis
Hepatitis virus
Acute or Chronic hepatitis
Hepatitis C virus
Acute or Chronic hepatitis
Hepatitis D virus
Acute or Chronic hepatitis
Hepatitis E virus
Enterically transmitted
hepatitis

SYSTEMIC WITH SKIN ERUPTIONS

Measles virus
Measles (rubeola)
Rubella virus
German measles (rubella)
Parvo virus
Erythema infectiosum
Vaccinia virus
Smallpox vaccine
Varicella-zoster virus Chickenpox, HerpesZoster

Herpes simplex v.1

Herpes simplex v.2

Cold Sore
Genital herpes

SYSTEMIC WITH HEMATOPOIETIC

DISORDERS
Cytomegalovirus
Epstein-Barr virus
HTLV-I
HTLV-II
HIV-1 and HIV-2

Cytomegalic Inclusion Dis

Infectious mononucleosis
Adult T-cell leukemia
Role uncertain
AIDS

ARBOVIRAL AND HEMORRHAGIC

FEVERS
Dengue virus 1-4
Yellow Fever virus
Colorado tick fever
Regional Hemorrhagic
Fever viruses

Dengue, hemorrh. Fever

Yellow fever
Colorado tick fever
Ebola, Marburg disease
Hantaan HF

CENTRAL NERVOUS SYSTEM

Polio virus
Poliomyelitis
Arboviral encephalitis Encephalitis
Rabies virus
Rabies