Week 1: Pathophysiology of Body Systems

Pathology

Study of all aspects of disease

Patients are usually caught in a ____ feedback loop

positive

Clinical scope of pathology

-Hematology

-Immunology

-Bacteriology

-Virology

Anatomical scope of pathology

-Morgue

-Surgical

-Forensic

Incidence

The number or rate of new cases of a particular condition during a specific time.

Prevalence

Occurrence of new causes in a population

Symptoms

Subjective characteristics of disease felt by the patient

Signs

Objective and measurable. BP

Etiology

cause of a disease

Lesion

abnormality in the structure. Ex: Calcification, fibrotic material, cancerous

Diagnosis

ID of an injury or disease often at the cellular level

Do PT's give medical diagnosis

NO

Pathogenesis

How the disease manifests itself. Ex: Hypertension may accelerate atherosclerosis

Prognosis

Expected outcome from the disease/disorder

Treatment

medication, pharmacological, radiation, exercise, etc.

PT's treatment is more on the ____ level

systems

morbidity

what happens with the disease

mortality

death rate

Two leading causes of death in the US

heart disease and cancer

Classifications of disease

-Hereditary

-Environmental

-Intrinsic (endogenous)

-Idiopathic

-Latrogenic

environmental disease

toxins, over-eating

intrinsic disease

from within, autoimmune

idiopathic disease

any disease without a known cause

Latrogenic disease

disease produced by medications

Causes of cell injury or death

Hypoxia, Anoxia, Ischemia, Infarction, physical agents, chemicals, bio-agents, immune mechanisms, genetic derangements, nutritional imbalances.

Hypoxia

Reduced oxygen

Anoxia

No oxygen

Ischemia

Lack of blood supply

Infarction

death of tissue

biological agents

bacteria and viruses

what is reversible cell death

cells have not been killed

what tends to happen to damaged tissues?

Cellular swelling (hydropic swelling)

What happens to the rough endoplasmic reticulum with sub-lethal cell injury

ribosomes dissociate, and cells can no longer make protein.

What happens to plasma membrane with sub-lethal cell injury

As cell swells, surface of cells stretches out and creates "Blebs." Clot forms, RBC gets trapped in the clot.

with sub-lethal cell injury, what happens when a stressor is removed?

Body goes back to normal

what happens when a healthy cell is deprived of oxygen

-Sodium accumulates, and water follows - cell swells.

-Ribosomes dissociate

-Plasma membrane Blebs.

What happens in response to too much drinking, and alteration to hepatocyte

RER dissolution, can't make protein and can't package fat, causing an enlarged fatty liver.

Chronic adaptations to cell injury

-Induction of the ER

-Sequestration of focal injury

-Atrophy of tissues

-Hypertrophy of tissues

-Hypoplasia

-Hyperplasia

-metaplasia

-Dysplasia

How could medication use lead to chronic adaptation?

could increase the size of the endoplasmic reticulum, which will break down the drug faster and lead to tolerance.

Example of hyperplasia when moving to higher elevation

Body not getting enough oxygen, leads to release of erythropoietin and increased RBC's

Metaplasia

changing of one cell type to another

Dysplasia example

cells don't look normal and may not act normal

what may dysplasia lead to?

Neoplasia or aplasia

Neoplasia

New cell growth, cancer.

Aplasia

lack of development of cells.

Permanent cell types

Do not regenerate. CNS, PNS, cardiomyocytes.

Stable cell types

Cells that don't undergo mitotic division unless called upon (skeletal muscle, kidney, lung, liver)

Labile cell types

cells constantly dividing. Skin, GI tract lining, blood cells.

Irreversible cell injury ultrastructural changes may occur to what structures?

-Mitochondria

-Lysosomes

-Nucleus

what occurs to mitochondria in irreversible cell damage

takes in excess amount of calcium causing densities to form, cell might die, making it unable to perform metabolism

what occurs to lysosomes during irreversible cell damage

ruptures, releasing digestive enzymes into the cell.

Pyknosis

Clumping of the nucleus due to lysosomal digestive enzymes acting on it

Karyorrhexis

Nucleus starts to break

Karyolysis

Nucleus starts to dissolve.

Necrosis

death of tissue

Apoptosis

programmed cell death

Purpose of inflammation

-Pain limits further damage by decreasing function

-Removal of necrotic tissue and microorganism.

-Sets up repair or regeneration of tissue

possible consequence of inflammation

may lead to damage of un-injured cells.

Cardinal signs/symptoms of inflammation

-Rubor (redness)

-Calor (temp)

-Tumor (swelling)

-Dolor (pain)

-Functio Laesa (decreased movement)

-Pus formation

causes of inflammation

-Tissue trauma

-Ischemia

-Neoplasm

-Infection biological agent

-Foreign particles

-Chemicals

What are chemotactic factors?

Produced during inflammation. Recruits, attracts, and stimulates inflammatory cells.

Examples of chemotactic factors

-Complement proteins

-Lipoxygenase products

-Lymphokines

-Monokines

Cells found in acute inflammation

-PMN's (neutrophils)

-platelets

-monocyte/macrophage

Cells found in chronic inflammation

-monocyte/macrophages

-lymphocytes

-plasma cells

-fibrocytes/fibroblasts

-endothelial cells

What do vasoactive mediators do

Increase vascular permeability, blood flow, and lead to edema

Examples of vasoactive mediators

-Histamine

-Serotonin

-Bradykinins

-Anaphylatoxins

-Leukotrienes/prostaglandins.

How does edema occur?

Capillaries increase vascular permeability, plasma proteins leak out, causing edema.

How do vasoactive mediators cause increased temperature during inflammation?

Arterioles open, leading to redness and increased blood flow.

Arterioles feed into

capillaries

RBC's flow through

capillaries

How do capillaries prevent RBC's and WBC's from leaving?

Have tight junctions that trap plasma proteins inside

Forces causing fluid to leave capillary

-Capillary hydrostatic pressure

-Interstitial hydrostatic pressure

-Interstitial oncotic pressure

Forces bringing fluid into capillaries

Capillary oncotic pressure

Starling law of the capillary

what is filtered out at the capillary is almost equal to what gets returned.

What is the mechanism by which excess filtrations gets returned to the blood?

lymphatic system

Hemodynamic changes during acute inflammation

short lived vasoconstriction occurs first and then overriding vasodilation kicks in

Increased capillary hydrostatic pressure allows for what during acute inflammation

blood to rush into the capillary bed.

Transudate

Arteriole vasodilates, but the endothelial cells don't separate, hydrostatic pressure rises, water (TRANSUDATE) leaks into the interstitial.

Exudate

Endothelial cells separate, plasma protein leaks out, dragging more water (EXUDATE) with it.

What causes exudate

Increased vascular permeability to water and proteins.

What pressures are less with proteins leaking out, what pressures increase?

Capillary oncotic pressure is less because proteins have leaked, interstitial oncotic pressure has increased, dragging fluid with it.

Serosanguineous exudate

RBC's leak out as well as plasma proteins as a result of more severe micro-trauma and inflammation

Formed elements during acute inflammation

-WBC's

-Neutrophils

-Monocytes/macrophages

What are WBC's attracted to during acute inflammation

chemotactic substances

What is the first cell from the blood stream to show up to phagocytize debris, then die?

Neutrophils

Stages of chemotaxis

-recognition via receptors

-Calcium influx into the cell

-Cytoskeleton alterations via ATP

-Movement of WBC's toward chemotactic factors

How do WBC's move towards chemotactic factors?

Neutrophil crawls from the capillary, through the endothelial cells, and towards the chemotactic factor

Margination

WBC's sticks to the capillary wall

Migration

WBC finds an opening, migrates out of capillary into the interstitial space to get to the bacteria

Phagocytosis

Phagocytizes debris, or microorganisms.

stages of phagocytosis

-Phagosome forms around bacteria

-Attachment of lysosome to become a secondary lysosome, bactericidal activity released onto the bacteria, killing it.

-Antibody has an FC region that is a receptor for it.

-Complement protein have receptors on the phagocytic cell.

Factors limiting locomotion and or phagocytosis

-Diabetes

-Severe trauma or burns

-Overwhelming infection

-Chronic debilitating disease

-chemotherapy, immunosuppression

Sub-acute inflammation time frame

weeks to a month

Cells involved in sub-acute inflammation

-Monocyte/macrophage

-Fibrocyte

-Endothelial cell

what tissue involved in sub-acute inflammation

Granulation tissue

What is released during sub-acute inflammation

growth factor released by macrophages and platelets.

Chronic inflammation timeframe

months to years

Chronic inflammation function

contain or remove the persistent pathological agent.

Cell types involved in chronic inflammation

-Monocyte/macrophage

-Endothelial cell

-Lymphocytes

-Plasma cells

chronic injury activates what

T-lymphocytes