Etiology of Disease- PRELIMS L5

ETIOLOGY

Is the study of the causes, origins, or reasons behind the way that things are, or the way they function, or it can refer to the causes themselves

GENETIC DISEASE

A disease caused by an abnormality in an individual's genome.

GENETIC ABNORMALITIES

• Affects the structure and function of proteins

• Disrupts cellular homeostasis and contributes to disease

GENETIC ABNORMALITIES MAY BE CAUSED BY

• Mutations in Protein-Coding Genes

• Alterations in Protein-Coding Genes

MUTATIONS IN PROTEIN- CODING GENES

• Mutations

• Those that affect germ cells are transmitted to the progeny and may give rise to inherited diseases.

MUTATION

Refers to permanent changes in the DNA

ALTERATIONS IN PROTEIN- CODING GENES

• Structural variations copy number changes (amplifications or deletions)

• Translocations

TRANSLOCATIONS

Resulting in aberrant gain or loss of protein function.

THREE MAJOR CATEGORIES OF GENETIC DISORDERS

• First category

• Second category

• Third Category

FIRST CATEGORY

• Referred to as Mendelian Disorders

• Most of these conditions are hereditary and familial.

SECOND CATEGORY

• Most common disorders of humans

• Hypertension and diabetes mellitus

• “Multifactorial inheritance”

THIRD CATEGORY

Disorders that are the consequence of numeric or structural abnormalities in the chromosomes

HEMODYNAMIC DISORDERS

• Is a disorder in relation with blood flow circulation.

• Changes in intravascular volume, pressure, or protein content, or alterations in endothelial function can be the cause

• The functions are not regulating property.

• The factors and chemicals being transported are altered

TYPES OF HEMODYNAMIC DISORDERS

• Hyperemia and congestion

• Edema

• Hemorrhage

• Hemostasis

• Thrombosis

HYPERMIA AND CONGESTION

Both are the result of excessive blood in a part of the body.

HYPEREMIA

Is an excess of blood contained within blood vessels in a part of the body due to an active process.

CONGESTION

Is an excess of blood contained within blood vessels in a part of the body due to a passive process

ACTIVE HYPEREMIA

Active process happens when there’s an increase in the blood supply to an organ. This is usually in response to a greater demand for blood.

CAUSES OF ACTIVE HYPEREMIA

• Exercise

• Heat

• Digestion

• Inflammation

• Menopause

• Release of a blockage

PASSIVE HYPEREMIA (CONGESTION)

Passive process is when blood can’t properly exit an organ, so it builds up in the blood vessels.

CAUSES OF PASSIVE HYPEREMIA (CONGESTION)

• Heart failure or ventricular failure.

• Deep vein thrombosis (DVT).

• Hepatic vein thrombosis (HVT), also called Budd-Chiari syndrome.

EDEMA

Is an abnormal accumulation of fluid in the interstitium, located beneath the skin and in the cavities of the body, which can cause severe pain. Clinically, edema manifests as swelling

FOUR MAJOR CAUSES OF EDEMA

1. Increased intravascular hydrostatic pressure causes edema.

2. Decreased Intravascular Osmotic Pressure (hypoproteinemia).

3. Increased Vascular Permeability.

4. Lymphatic Obstruction (lymphangiectasia).

LOCALIZED EDEMA

Edema is usually localized to one area

GENERALIZED EDEMA

Infrequently it affects most or all of the body

ANASARCA

Is a term that means general edema but in common usage, this term is only used for fetuses.

TYPES OF EDEMAS

1. Transudate

2. Exudate

TRANSUDATE EDEMA

Fluids that pass- through a membrane or squeeze through tissue or into the extracellular space of tissues

EXUDATE EDEMA

Fluids or cells or any other cellular substances that are slowly discharged from the blood vessels. Involved in inflamed tissue, typically have higher protein concentration.

HEMORRHAGE

An escape of blood from a ruptured blood vessel, especially when profuse defined as the extravasation of blood from vessels

RISK OF HEMORRHAGE

Is increased in a wide variety of clinical disorders collectively called hemorrhagic diatheses .

HEMORRHAGE MAY BE MANIFESTED BY DIFFERENT APPEARANCES AND CLINICAL CONSEQUENCES

• Hematoma

• Petechiae

• Purpura

• Ecchymoses

HEMATOMA

A solid swelling of clotted blood within the tissues

PETECHIAE

Are minute (1 to 2 mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces.

PURPURA

Are slightly larger (3 to 5 mm) hemorrhages; can result from trauma, vasculitis, and increased vascular fragility.

ECCHYMOSES

Are larger (1 to 2 cm) subcutaneous hematomas (colloquially called bruises).

CLASSIFICATIONS OF HEMORRHAGE DEPENDS ON

• Nature of the vessel involved

• Timing of the hemorrhage

• Duration of the hemorrhage

• Nature of the bleeding

• Type of intervention

THE CLINICAL SIGNIFICANCE OF ANY PARTICULAR HEMORRHAGE DEPENDS ON

• Volume of blood lost

• The rate of bleeding

THROMBOSIS

Is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system.

VEGETATIONS

Thrombi on heart valves

THREE PRIMARY ABNORMALITIES THAT LEAD TO THROMBUS FORMATION (CALLED VIRCHOW’S TRIAD)

• Endothelial injury

• Stasis or turbulent blood flow

• Hypercoagulability of the blood

ENDOTHELIAL INJURY

e.g., by toxins, hypertension, inflammation,or metabolic products

ABNORMAL BLOOD FLOW

e.g., due toaneurysms, atherosclerotic plaque

HYPERCOAGULABILITY

It is loosely defined as any alteration of the coagulation pathways that predisposes affected persons to thrombosis, and can be divided into:

A. Primary (inherited) hypercoagulability

B. Secondary (acquired) hypercoagulability

PRIMARY HYPERCOAGULABILITY

Inherited

SECONDARY (ACQUIRED) HYPERCOAGULABILITY IS SEEN IN

• Prolonged bed rest or immobilization

• Myocardial infarction

• Atrial fibrillation

• Tissue injury (surgery, fracture, burn)

• Cancer

• Prosthetic cardiac valves

• Disseminated intravascular coagulation

• Heparin-induced thrombocytopenia

• Antiphospholipid antibody syndrome

EMBOLISM

An embolism is a detach intravascular solid, liquid or gaseous mass that is carried by the blood from point of origin.

• Pulmonary embolism

• Systemic thromboembolism

• Fat embolism

• Amniotic fluid embolism

• Air Embolism

INFARCT

Is an area of ischemic necrosis cause by occlusion of vascular supply to affected tissue.

CLASSIFICATION OF INFARCT

1. Red infarcts

2. White infarcts

3. Septic infarcts

FACTORS THAT INFLUENCE INFARCT DEVELOPMENT

1. Anatomy of vascular supply

2. Rate of occlusion

3. Tissue vulnerability to ischemia

4. Hypoxemia

NUTRITIONAL DISEASE

• Malnutrition

• Marasmus

• Kwashiorkor

MALNUTRITION

• Primary Malnutrition

• Secondary Malnutrition

• Protein- Energy Malnutrition

PRIMARY MALNUTRITION

One or all of the components are missing in the diet

SECONDARY MALNUTRITION

Results from nutrient malabsorption, impaired storage, excess losses, or increased requirements

PROTEIN-ENERGY MALNUTRITION

Range of clinical syndromes, all resulting from a dietary intake of protein and calories that is inadequate to meet the body’s needs .

MARASMUS

• Growth retardation and loss of muscle mass as a result of catabolism and depletion of somatic protein compartment

• Extremities are abnormally thin and weak

• Multivitamin deficiency

• Immune deficiency

• Concurrent infections

KWASHIORKOR

• Protein deprivation is greater than the reduction in total calories

• Sever loss of visceral protein compartment

• Increased fluid retention (edema)

• Skin lesions with hyperpigmentation, desquamation, and hypopigmentation

• Bands of pale and dark colored hair

• Enlarged fatty liver

SECONDARY PROTEIN- ENERGY MALNUTRITION

Common in chronically ill or hospitalized patients

• Cachexia

• Proteolysis-inducing factor

• Tumor-necrosis factor

CACHEXIA

Severe form of secondary PEM

PROSTEOLYSIS- INDUCING FACTOR

Directly stimulates the degradation of skeletal muscle proteins

TUMOR- NECROSIS FACTOR

Stimulates fat mobilization from lipid stores

ANOREXIA NERVOSA

Self-induced starvation resulting in marked weight loss

• Amenorrhea

• Dehydration and electrolyte imbalance

• Decreased bone density

AMENORRHEA

Resulting from decreased GRH

MAJOR COMPLICATION OF ANOREXIA NERVOSA

Cardiac arrhythmia and Sudden death

BULIMIA

The patient binges on food and then induces vomiting

• Electrolyte imbalances

• Pulmonary aspiration of gastric contents

• Esophageal and stomach rupture

VITAMIN A DEFICIENCY

• Depleted stores of Vitamin A due to infection in children

• Poor absorption in newborns

• In adults, malabsorption syndromes may develop (celiac disease, Crohn disease, and colitis)

• Toxicity occurs from overuse of supplements and high vitamin A in foods such as liver

MANIFESTATIONS OF VITAMIN A DEFICIENCY

1. Impaired vision (night blindness)

2. Xerophthalmia (dry eye)

VITAMIN D DEFICIENCY IN CHILDREN

Rickets

VITAMIN D DEFICIENCY IN ADULTS

Osteomalacia

VITAMIN D DEFICIENCY CAUSES

• Limited exposure to sunlight

• Heavily veiled women

• Children born to mothers who have frequent pregnancies followed by lactation

• Inhabitants of northern climates with scant sunlight

• Renal disorders

• Malabsorption disorders

VITAMINS D TOXICITY

Hypervitaminosis

HYPERVITAMINOSIS

Megadoses of orally administered vitamin D

VITAMIN D TOXICITY IN CHILDREN

Metastatic calcifications of soft tissues (kidney)

VITAMIN D TOXICITY ADULTS

Bone pain and hypercalcemia

VITAMIN C DEFICIENCY SCURVY

• Hemorrhages and healing defects in children and adults

• Appears in patients undergoing peritoneal dialysis and hemodialysis and among food faddists

VITAMIN C DEFICIENCY EXCESS

Excreted in urine but may cause uricosuria and increased absorption of iron (iron overload)

OBESITY

• A state of increased body weight, due to adipose tissue accumulation which produce adverse health effects

• Disorder of energy balance

METABOLIC DISEASES

Can happen when abnormal chemical reactions in the body alter the normal metabolic process.

NEOPLASIA

• New growth

• An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persist in the same excessive manner after cessation of the stimuli that evoked the change.

GENERAL PATHOGENESIS OF TUMORS

• Initiation

• Promotion

• Progression

INITIATION

• A carcinogen induces non-lethal mutation(s) in a cell.

• Point at which an irreversible alteration, usually genetic, is introduced to a target cell.

PROMOTION

Transformed cell under the effect of PROMOTERS, begins to multiply, giving the beginning to the clone of daughter cells

PROGRESSION

Continual accumulation of multiple mutations results in an invasive phenotype and distant metastasis

CLASSIFICATION OF NEOPLASIA

• Benign Tumor

• Malignant Tumor

BENIGN TUMOR

• Fibroma

• Chondroma

FIBROMA

Benign tumor arising in fibrous tissue

CHONDROMA

Benign cartilaginous tumor

BENIGN TUMOR CLASSIFIED BY

• Basis of their microscopic pattern

• Basis of their macroscopic pattern

MALIGNANT TUMOR

• Arising in “solid” mesenchymal tissues or its derivatives are called sarcomas

• Commonly called Cancer; They invade and destroy the surrounding tissue and may form metastases, and if left untreated or unresponsive to treatment, will prove fatal.

METAPLASIA AND DYSPLASIA

METAPLASIA

Abnormal change in nature

DYSPLASIA

The presence of cells of an abnormal type within a tissue , which may signify a stage preceeding the development of cancer.

ETIOLOGY/CAUSES OF CANCER: CARCINOGENIC AGENTS

Three classes of carcinogenic agents

1. Chemicals

2. Radiant Energy

3. Microbial products

INFECTIOUS DISEASES

Is the steps or mechanisms involved in the development of disease.

CLASSIFICATION OF INFECTIOUS DISEASES

• PARASITIC INFECTION

• FUNGAL INFECTION

• BACTERIAL INFECTION

• VIRAL INFECTION

STEPS IN THE PATHOGENESIS OF INFECTIOUS DISEASES

• ENTRY

• ATTACHMENT

• MULTIPLICATION

• INVASION/ SPREAD OF THE PATHOGEN

• EVASION OF HOST DEFENSE

• DAMAGE TO HOST

ENVIRONMENTAL DISEASE

The term environmental disease refers to the lesions and disease caused by exposure to chemical or physical agents in the ambient, workplace, and personal environments, including disease of nutritional origins.

EXOGENOUS CHEMICALS MECHANISMS OF TOXICITY

Known as xenobiotics are absorbed by the body through inhalation, ingestion, and contact skin , and can either be eliminated from the body or accumulated in the fat, bone, brain, and other tissues.

XENOBIOTICS

Can be converted into non-toxic products, or be activated to generate toxic compounds, through a two-phase reaction process that involves the cytochrome P-450 system.

ENVIRONMENTAL POLLUTION

• Airborne microorganisms have long been major causes of morbidity and mortality.

• More widespread are the chemical and particulate pollutants found in the air, especially in industrialized nations.

OUTDOOR AIR POLLUTION

• The ambient air in industrialized nations is contaminated with an unsavory mixture of gaseous and particulate pollutants

• In the USA, the Environmental Protection Agency (EPA) monitors and sets allowable upper limits for six pollutants : Sulfur dioxide, Carbon monoxide, Ozone, Nitrogen dioxide, Lead, and particulate matter