BIO 307 PATHOPHYSIOLOGY

DR. GREENAMYER

BASIC TERMS

• Vocabulary– Hyper-- vs hypo--– --itis– --osis– --opathy– Idopathic, Iatrogenic, Nosocomial

• Disease (Syndrome) vs Normalcy

• Etiology: causes or reasons for a disease– Virus/bacteria, occupation, age, sex, nutritional status,

genetics

• Can be used to classify disease– Inherited, congenital, toxic, infectious, traumatic,

degenerative, neoplastic, metabolic

• Pathogenesis: development/evolution of disease

• Manifestations of Disease– Signs: objectively identifiable changes (fever,

BP, HR, PCV)– Symptoms: subjective feelings (nausea, pain)

FACTORS THAT INFLUENCE DISEASE

• Extrinsic factors—outside individual, may or may not be controlled– Diet, medication, exposure to harmful agents

• Intrinsic factors—rarely under individual control– Age, sex, genetic inheritance– Congenital vs inherited

• Most diseases are a combination (interaction) of factors

Genetic disorders

• Single gene disorders—may affect any tissue/organ system

• Autosomal dominant—need only one bad copy of gene– Equally prevalent in males and females– No skipping of generations, delayed onset common– Typically less severe than recessive, structural protein

defect– Huntingdon’s Disease, Adult polycystic kidney disease

• Autosomal recessive—need two bad copies of gene

• Equally prevalent in males and females

• May skip many generations, but often seen in siblings

• Early age onset, more often enzymatic deficiency

• Cystic fibrosis, sickle cell anemia

• Sex Linked disorders—carried on X (most often) or Y (rarely) chromosome

• X linked recessive most common

• More common in male; females are usually asymptomatic carriers unless unequal X inactivation or 2 copies of the mutated gene

• All daughters of affected men are carriers

• Hemophilia A, Duchenne’s muscular dystrophy

• Mitochondrial gene disorders—passed through maternal line– Extremely rare

Chromosomal abnormalities

• Aneuploidy—abnormal number of chromosomes• Down’s syndrome (trisomy 21) most common

• Result of nondisjunction

• Translocations—result in structural abnormalities– Genetic material exchanged between nonhomologus

chromosomes

– Robertsonian translocations most important clinically

– Philadelphia chromosome in chronic myelogenous leukemia

Fig. 4-18

Causes of Cellular Injury

• Hypoxic injury (ischemia is #1 cause)• Chemical injury (free radicals, heavy metals)• Physical injury (mechanical, thermal, radiation,

electric shock)• Infectious injury (bacteria, viruses, fungi,

parasites)• Immunological and inflammatory injury

Terminology of Cellular Changes

• Atrophy– Autophagy in malnutrition

• Hypertrophy vs hyperplasia

• Dysplasia (atypical hyperplasia)

• Metaplasia

• Senescence (aging) and death

Common themes/results (T 2-2)

• ATP depletion

• Defects in membrane permeability

• Increased intracellular calcium

• Increased free radicals

Manifestations of Cellular Injury

• Accumulate water (cloudy swelling, oncosis, hydropic degeneration)

• Accumulate lipids (steatosis), carbohydrates, or proteins

• Atrophy—requires autophagy– accumulation of pigments (brown atrophy)

Cloudy swelling (oncosis, hydropic degeneration)

Cell death (necrosis)

• Nuclear changes are most obvious– Pyknosis—shrunken, irregular, dark staining

nucleus– Karyorrhexis—fragmentation of nucleus

• Karyolysis—dissolution of nucleus

• Coagulative necrosis—most common type– Cells retain shape, tissue retains normal architecture– Indicates ischemia—dry gangrene

• Liquifactive necrosis—most common in brain– Can result from hydrolases from bacteria– Wet gangrene

• Caseous necrosis—cells degenerate but fragments remain--Mycobacterium infections

Apoptosis

• Active process of programmed cell death (scattered, single)– Deletes excess cells during development– Probably occurs in malignant cells or cells

damaged by chemotherapy

• NOT accompanied by inflammation– Should not stimulate an immune reaction

Apoptosis

Systemic Manifestations of Necrosis (Inflammation)• Fever (from pyrogens)

• Increased heart rate

• Increased WBCs

• Elevated presence of tissue specific enzymes

• CPK creatine phosphokinase

• LDH lactic dehydrogenase

• ALT alanine aminotransferase

• Loss of some organ function

• Pain

LOCAL INFLAMMATION

Purpose of Inflammation

• Destroy and remove insult

• Wall off and confine damage

• Stimulate immune response

• Promote healing

Causes of inflammation

• Infection

• Trauma—physical, chemical, thermal, radiation

• Immune hyper-sensitivity reactions

INFLAMMATION---types

• Acute– Redness, heat, pain, swelling (rubor, calor,

dolor, tumor)– Altered function (functio laesa) has been added

• Subacute• Chronic---Longer duration

– Granuloma formation—massive numbers of macrophages

Fig 6-3

Clotting

Cytokines in acute inflammation

Local Inflammatory Response

• Margination and diapedesis of WBC

• Vascular Response—increased permeability• Arterial dilation—increased local BP

• Endothelial cells of blood vessels (venules) separate

• Exudation—significant amounts of protein lost into interstitial space

• Water follows protein to maintain osmotic balance

Results of water movement• Interstitial swelling pulls flaps of lymphatic

capillaries apart• Increased flow of lymph

• Protein, cells enter lymphatics

• Lymphangitis/lymphadenitis (lymphadenopathy) may result

Mediators of inflammation

• Histamine—mast cells

• Activated Factor XII--Clotting System

• Arachidonic acid metabolites• COX and LOX pathways

• Complement cascade

• Miscellaneous cell factors

Fatty acids

Chronic inflammation

Exudates

• Serous—protein in interstitial fluid• Fibrinous—fibrinogen accumulates on serous

surfaces• Mucinous—mucous membranes—cellular

secretion• Neutrophillic—purulent—bacterial

infection/necrotic cells• pus is suppurative exudate of neutrophils and dead bacteria

Systemic Manifestations of Inflammation

• Fever

• Leukocytosis

• Increased Erythrocyte Sedimentation Rate

Wound Healing

• Healing by first intention

• Healing by second intention (granulation)

Fig 6-21

Indications of wound infection

• Abscesses, furuncles (boils), carbuncles• Cellulitis—widespread purulent

inflammation• Mixed exudate from wound

– Fibrinopurulent– Mucopurulent– Serofibrinous

Factors that Delay Wound Healing

• Oxygen deficiencies/ Ischemia• Nutrition deficiencies• Fluid/ electrolyte imbalances• Age• Medications or other disease• Extent of tissue damage

• Dehiscence/ evisceration may result from premature suture removal

Complications of healing

• Scaring– strictures, contractures

• Adhesions

• Keloids