Pathophysiology: Exam 1

Define pathophysiology

functional changes within the body caused by disease or injury

Etiology

root cause of a disease

Pathogenesis

how the disease develops overtime

Clinical manifestation

visible signs and symptoms

Treatment implication

how we intervene based on the mechanism

Osmosis

movement of water across a membrane from low to high concentration

Osmolality

How crowded/measurement of weight

Osmolarity

exact number of particles based on volume

Osmotic Activity

how strong particles like glucose or Na attract others

Clinical example of osmosis imbalance

cerebral edema

Homeostasis

body’s ability to keep internal environment stable and within normal ranges

3 “command centers” in the CNS that regulate homeostasis

1. Hypothalamus/Pituitary gland

2. Medulla Oblongata

3. Reticular Formation

How does the hypothalamus/pituitary gland contribute to homeostasis?

Endocrine regulation by hormone release and fluid balance; also a “thermostat”

How does the medulla oblongata contribute to homeostasis?

autonomic control that regulates involuntary functions (heart rate and breathing)

How does the reticular formation contribute to homeostasis?

Manages alertness, sleep/wake cycle, temp, vital system regulation (blood pressure)

*Reticular Activating System (RAS)

3 Mechanisms of a Feedback Loop

1. Sensor/Receptor: detects disruptions

2. Control Center/CNS: receives distress signal and regulates body’s response

3. Effector: organ or tissue that physically acts to correct disruption

Describe a negative feedback loop

Stops or inhibits an action (hormone release, etc)

Prime example of negative feedback loop

Thyroid regulation

Describe a positive feedback loop

“keep going”; stimulates more hormone release; short term

Clinal examples of a positive feedback loop

1. Oxytocin release during labor

2. Luteinizing hormone release during ovulation

3. Blood Clotting

Adaptation

reversible response to normal or adverse conditions to maintain homeostasis

Atrophy

decrease in cell size

Hypertrophy

Increase in cell size

Hyperplasia

Increase in number of cells by mytosis

Metaplasia

Reversible replacement of one mature cell type by another (change in cell type) caused by tissue damage, repair, or regeneration

Dysplasia (atypical hyperplasia)

abnormal changes in cell size, shape, or organization

Physiologic atrophy vs. Pathologic

Physiologic: thymus in childhood and ovaries post-menopause

Pathologic: ischemia, malnutrition, disuse

Physiologic vs. Pathologic Hypertrophy

Physiologic: Increased demand, hormone stimulation, growth factors

Pathologic: chronic hemodynamic overload

Ischemia

reduced blood supply

Hypoxia

lack of sufficient oxygen to the cell

Metabolic Shift

cell is forced into anaerobic metabolism

Oxidative stress

accumulation of oxygen-derived free radicals

Most common cause of cellular injury?

Hypoxic Injury

What can hypoxic injury result from?

*Ischemia, reduced oxygen content, decreased production of RBCs, respiratory disease, etc

Perfusion

flow of blood through body’s blood vessels to deliver oxygen and nutrients and carry away waste

Oxygenation

process of supplying oxygen to cells and tissues

Ischemia-Reperfusion Injury: define and mechanisms by which it occurs

1. restoration of blood flow and oxygen after ischemia

2. Inflammation, apoptosis, increase in ROS

How do free radicals contribute to oxidative stress?

Contain unpaired electrons that interact with and disrupt plasma membrane

Chemical injury

injury caused by toxic substances or poisons

4 external and chemical injury mechanisms

1. Trauma

2. Chemical threats

3. Infectious agents

4. Immunologic and Inflammatory

Apoptosis

active, programmed cell death

Autophagy

removal of damaged cells that promotes homeostasis

Necrosis

rapid loss of plasma membrane structure, extreme organelle swelling, and complete mitochondrial dysfunction

Fatty necrosis

destruction of fat tissue (pancreatitis)

Coagulative Necrosis

caused by ischemia or infarction of organs like heart of kidneys

Liquefactive necrosis

tissue becomes liquid (seen in brain or absesses)

Caseous Necrosis

cheese-like appearance associated with TB

Gangrenous necrosis

Caused by severe and prolonged ischemia, infarction, and necrosis of extremities

Gas gangrene

Caused by clostridium perfringens that thrive in low O2 environments and emit gas as they destroy tissue

Pallor mortis

skin becomes pale/yellow

Algor Mortis

cooling of the body

Rigor mortis

postmortem stiffening

Livor mortis

discoloration of dependent portions due to settling of blood from gravity

Putrefaction and autolysis

cell/tissue breakdown

Purge Fluid

fluid exudes from oral.nasal cavities

Primary consumers of oxygen

Mitochondria

Damage to proteins, lipids, and DNA is a result of _____.

Oxidative stress

During ischemia, which cellular event occurs first and contributes most directly to cellular swelling?

Failure of sodium/potassium pump

Which pathophysiologic process contributes to ischemia-reperfusion injury by promoting inflammation and microvascular obstruction?

Neutrophil adhesion to endothelial cells

First Line of Defense

Innate immunity: physical, mechanical, and biochemical barriers

Second Line of Defense

Inflammation

Third line of defense

Adaptive Immunity

Define innate immunity

the body’s first non-specific defense present at birth; has a rapid response with no memory

Epithelial Barriers in Innate Immunity

skin + mucous membranes

Chemical barriers in innate immunity

Sweat, tears, saliva, acidic stomach environment (all contain lyzozymes)

Physical Barriers in innate immunity

Cilia in lungs, mucous, normal flora

How does “washing” contribute to innate immunity?

Handwashing, urine flushes, saliva flushes

Functions of normal flora of the body

1. Produce enzymes for digestion

2. Compete with pathogens for nutrients

3. Produce antibacterial substances

Purpose of the inflammatory response

limits injury, prevents infection, and prepares for healing

5 Cardinal Signs of Localized Inflammation

1. Redness

2. Heat

3. Swelling

4. Pain

5. Loss of function

In the process of inflammation, why does the skin become red and warm?

Caused by vasodilation and increased blood flow

In the process of inflammation, why does the skin swell?

Caused by increased vascular permeability and fluid leakage

In the process of inflammation, why might there be pain?

Caused by pressure from swelling and fluid leakage

Why might there be loss of function with inflammation?

Results from pain and tissue edema

Stages of the Vascular Response of Inflammation

1. Hemostasis (coaggulation)

2. Vasodilation

3. Increased Permeability

4. Migration

Explain hemostasis stage in the vascular response to inflammation.

Bleeding is stopped to contain initial injury.

Explain the Vasodilation stage in the vascular response to inflammation.

Inflammatory mediators cause blood vessels to widen, slowing blood velocity and increasing localized volume

Explain the Increased Permeability stage in the vascular response to inflammation.

Capillaries become porous, allowing exudative fluid to leak into surrounding tissue

Explain the Migration stage in the vascular response to inflammation.

WBCs adhere to inner walls of vessels and migrate through enlarged junctions into damaged tissue.

What is the role of histamine?

An inflammatory mediator that causes vasodilation, increased permeability, and responds to trauma or immune reaction.

4 Phagocytic cells in the innate system

1. Neutrophils

2. Monocytes

3. Macrophages

4. Dendritic Cells

First responder in innate immunity

Neutrophils

Cells released from bone marrow that migrate to tissues and mature into macrophages

Monocytes

Cells that engulf and digest microbes that attach to cell membrane

Macrophages

Cell that presents antigens to the T Cells to initiate adaptive immunity and release cytokines

Dendritic Cells

Cell found in areas where pathogens commonly enter

Dendritic Cells

Non-phagocytic cells that contain histamine and are involved with allergic reactions

Eosinophils and Basophils

Non-phagocytic cells that live in tissues and are associated with allergic reactions and hypersensitivity

Mast Cells

Complement System

30+ proteins found in blood that circulate in inactive form; when infection occurs, proteins activate via cascade system

Functions of the Complement System (OIL)

1. Opsonization: coat pathogen for destruction

2. Inflammation

3. Lysis: MACs (membrane attack complex) poke hole in pathogen membrane

Acute Inflammation

Early rapid response the is specific to a local site

Cells involved in acute inflammation?

Granulocytes and Monocytes

Chronic inflammation

Persistent inflammation that lasts days/weeks/months that results in tissue destruction

Cells involved in chronic inflammation?

lymphocytes and macrophagesS

Serous exudate

watery

Fibrinous exudate

thick and clotted

Purulent Exudate

pus

Hemorrhagic Exudate

erythrocytes

System manifestations of acute inflammation

Fever (by pyrogens that act directly on hypothalamus), Leukocytosis (increased WBCs), increased plasma protein synthesis, sepsis, lymphadenitis

Non-pharm ways to reduce inflammation

Ice packs, heat, packs, herbs, exerciseP