Tufts DPT - Physiology Week 2

ischemia

Insufficient Blood flow

decreased delivery of nutrients

decreased removal of waste products

Hypoxia

Low oxygen saturation of the body, not enough oxygen in the blood

Anoxia

Complete loss of Oxygen

Bacterial infectious Agents

Toxins

Viral infectious Agents

either directly or indirectly cytopathic

Cell injury or death: Immune reaction

- antibody attachment

- complement activation

-activation of inflammatory cells: macrophages, T&B lymphocytes, basophils, neutrophils

Cell Injury or death: Genetic Factors

- Chromosomal alterations

- Single or multiple mutation(s) of genes

Cell injury or death: Mechanical Factors

- Physical stress theory: chronic or single high magnitude event

- Failure of tissue when load exceeds failure tolerance

Cell injury or death: Physical Factors

Extreme:

- Temp

-Radiation

- Electricity

Cell Injury or death: Chemical Factors

- Direct injury (think mercury)

- Indirect (reactive oxygen species)

reactive oxygen species

highly reactive forms of oxygen due to loss of one electron creating a "free radical" which causes chain reaction of electron stealing

Nitric Oxide

important modulator in physiologic responses

increased bioavailability with exercise

Cell injury or death: Psychological Factors

Fear, tension, anxiety

Irreversible Cell damage characteristics

- Plasma membrane blebs

-Pyknotic Nucleus

-Swelling of cell

- Accumulation of fluid in Endoplasmic reticulum

- Release of ribosomes

Reversible Cell damage characteristics

- Plasma Membrane blebs

- Swelling

- Accumulation of fluid in Endoplasmic reticulum

- Release of ribosomes

Necrosis

Apoptosis

Organized and programmed cell death

Atrophy

Decrease in cell or orgran size

Hypertrophy

Increase in cell or organ size (striated and heart muscle)

Hyperplasia

Increase number of cells and organ size

Metaplasia

Change in cell morphology/function

Dysplasia

Increase in number of cells and change in cell morphology

Inflammation involves responses from these various levels:

- Vascular

- Humoral

- Neurologic

- Cellular

Inflammatory reaction functions: (3)

- inactivate injurious agent

- breakdown and remove dead cells

- initiate healing

Four Cardinal Signs of Inflammation

-Erythema

-Heat

-Edema

-Pain

Three outcomes of acute inflammation

- Resolution

- healing by Fibrosis

- Healing via chronic inflammation

Acute inflammation: resolution

- clearance of injurious stimuli

- replacement of injured cells

- normal function restores

Acute Inflammation: healing by fibrosis

- collagen deposition

- Loss of function

Acute Inflammation: healing by Chronic inflammation

- Angiogenesis

- mononuclear cell infiltrate

- fibrosis

Acute Inflammation: mechanism of injury

- Infarction

- Bacterial Infection

- Toxins

- Trauma

Chronic Inflammation: mechanism of injury

- Viral infections

- Chronic infections

- Persistent Injury

-Autoimmune diseases

Acute Inflammation cellular infiltrates

- Platelets

- Neutrophils

- Monocyte/macrophage

- Fibrocytes/Fibroblasts

-Endothelial cells

Chronic Inflammation cellular infiltrates

- Monocyte/macrophage

-Lymphocytes

-Plasma cells

- Fibrocytes/fibroblasts

-Endothelial cells

Histamine, Bradykinins, and Leuokotrienes/prostaglandins affect:

Blood flow

Lymphokines and Monokines

attract and stimulate cells

Extrinsic Pathway

- Tissue Injury

1. Thromboplastin (Factor IIa)

2. Thrombin (factor IIa)

3. Fibrinogen (factor I)

4. Fibrin (factor Ia)

Intrinsic Pathway

- Endothelial Injury

- Factor 12

2. Hageman Factor XII

3. Prothrombin (factor II)

4. Thrombin (factor IIa)

5. Fibrinogen (factor I)

6. Fibrin (factor Ia)

Fibrin (factor Ia)

mesh-like structure that forms blood clot

Internal bleeding activates both intrinsic and extrinsic pathway (T or F)

True

Tissue healing occurs by:

1. Regeneration

2. Repair

Components of Tissue Healing

- Fibronectin

- Collagen

- Proteoglycans and Elastin

Type 1 Collagen Characteristics

- Thick

-Predominant in strong tissues

- Mature Scar

(think tendons and bones)

Type 2 Collagen Characteristics

- Thin Supporting Filaments

- Predominant in cartilaginous tissue

Type 3 Collagen Characteristics

- Thin Filaments

- Makes tissue strong but supple and elastic

Phases of Tissue Healing

1. Hemostasis and Degeneration

2. Inflammation

3. Proliferation and migration

4. Remodeling and Maturation

Hemostasis and Degeneration Phase

- Seconds to hours

- Vasoconstriction

- Platelet aggregation

- Leucocyte migration

Inflammatory Phase

- Hours to days

- Phagocytosis and removal of foreign bodies/bacteria

-macrophages

Proliferation and Migration Phase

- Days to week

- ECM reorganization

- Angiogenesis

- Granulation Tissue Formation

- Epithelialization

Remodeling and Maturation Phase

- ECM Remodeling

- Increase in tensile strength of wound

- Collagen Fibril Cross linking

Tissue Healing overlap

Healing by Primary intention

- Clean cut and easily healed

-minimal scaring

Healing by Secondary Intention

- Edges cannot be approximated

- Cannot be closed surgically

- slower healing

- Large scar

Healing by Tertiary Intention

- Contaminated

- Delayed closure as wound needs to be closed

Wallerian Degeneration

Degeneration of the part of the axon distal to site of injury

Phases of skeletal muscle healing

- Hemostasis

- Phagocytosis

- Regeneration

Phase 1 Fracture Healing

- Hematoma formed

- Bleeding delivers fibroblasts, platelets and Osteoprogenitor cells

- stimulate initial hematoma into more organized granular tissue

Phase 2 Fracture Healing

- Inflammatory cells arrive

- Formation of granulation tissue

- Initial Fibrocartilage formation

Phase 3 Fracture Healing

- Soft callus formed

-endochondral ossification

Phase 4 Fracture Healing

- disorganized bone turns into mature lamellar bone

-excessive bony callus is resorbed and remodels according to stresses placed on it

Tendons and Ligaments are made up of __% water, __% collagen, and __% glycosaminoglycans

78, 20, 2

Which type of ligament has a poorer healing response ?

A.) extra-articular ligaments

B.) Intra-articular ligaments

Intro-articular Ligaments

Tendons and Ligaments regain normal strength in _____ to ______ weeks

40-50 weeks

Articular surface of cartilage resists which type of force

Sheer force

Radial zone of cartilage resists which type of force

Compressive force

Outer Annulus Collagen type

Type 1

Inner Annulus Collagen type

Type 2

Nucleus Pulpous Collagen type

Type 2

Peripheral Nervous System (PNS) branches

- autonomic nervous system (sympathetic and parasympathetic)

- somatic nervous system

Somatic nervous system controls

motor systems (concious)

Autonomic Nervous system controls

Visceral Function (involuntary)

Preganglionic neurons in sympathetic nervous system originate in

Thoracolumbar spinal cord

Preganglionic neurons in parasympathetic nervous system originate in

Brain stem and sacral spinal cord

Preganglionic neurons always release:

acetylcholine (ACH)

Cholinergic Neurons

release acetylcholine (all preganglionic neurons since they release ACH)

Andrenergic neurons

release norepinephrine

Postganglionic neurons of the sympathetic nervous system

can either be Adrenergic (release NE) or Cholinergic (release ACH)

Postganglionic Neurons of the Parasympathetic nervous system

Almost always Cholinergic (release ACH)

Cholinoreceptors

muscarinic and nicotinic receptors for ACH on effector organs (M)

Adrenoreceptors

Receptors for NE on effector organs (a1, a2, b1, b2)