# Presentation: 656493

## Particulate Handling inthe Human Lung

## Overview

******The Human Lung and Lung Compartments**
******Particles****	****	****Nomenclature**
**	****	****	****Characteristics that affect toxicity**
******Particle Deposition****	****Mechanisms**
**	****	****	****Factors that affect particle deposition**
******Particle Clearance****	****Mechanisms**
**	****	****	****Factors that affect particle clearance**
******Metrics used to evaluate particle dose****	****Mass**
**	****	****	****	****	****Volume**
**	****	****	****	****	****Surface area**
******General Model of Particle Toxicity**

## The Human Lung

**And**
**Lung Compartments**

## The Human Lung

**	****2 left lobes **
**	****	****superior and inferior**
**	****3 right lobes**
**	****	****superior, middle, and inferior**

_**The Human Lung**_

## Lung Compartments

_**Tracheobronchial**_**	****begins at larynx**
**	****trachea**
**	****bronchi**
**	****bronchioles**
**	****terminal bronchioles**
_**Pulmonary**_
**	****respiratory bronchioles**
**	****alveolar ducts**
**	****alveoli**

_**Lung Compartments**_

## Architecture of the Tracheobronchial and

**Tracheobronchial compartment**
**zones 1- 16**
**No gas exchange in this compartment.**
**Pulmonary compartment**
**zones 17-23**
**Gas exchange occurs in this compartment.**

_**Architecture of the Tracheobronchial and**_
_**Pulmonary Lung Compartments**_

## Properties of Particles

##             Respirable Particle Nomenclature

**Coarse particles > 2.5 ********m**
**Fine particles  0.1-2.5 ********m**
**Ultrafine (nano) particles  0.001-0.1 ********m**

##      Particle Characteristics that Affect Toxicity

**Size - determines, in part, lung deposition**
**Solubility:**
**   ****soluble particles - generally have low or no lung toxicity**
**	****	****          ****can have systemic toxicity**
**   ****insoluble particles – more likely to be toxic**
**                                      ****exhibit a wide range of toxicities**
**                                      ****dependent on other particle characteristics**

##      Particle Surface Chemistry Can Alter Toxicity

**Surface Chemistry**
**A=aged silica**
**B=freshly fractured silica**
**ESR signal from freshly fractured**
**silica is much greater than aged silica.**
**Freshly fractured silica is also more toxic.**

**A**

**B**

## Particle Deposition

##                 Particle Deposition Mechanisms

**Nasopharyngeal****	****impaction, sedimentation, electrostatic**
**	****	****	****	****particles > 1 ********m**
**Tracheobronchial****	**** impaction, sedimentation, diffusion**
**	****	****	****	****particles < 1 ********m**
**Pulmonary****	****	****sedimentation, diffusion**
**	****	****	****	****particles < 1 ********m**
**Airway branching pattern favors non-uniform (focal) areas of**
**deposition, especially when impaction is an important deposition  **
**mechanism.**

## Impaction

**The particle’s momentum in air stream prevents it from making turn at a bifurcation.**
**nasopharyngeal compartment**
**tracheobronchial compartment**

## Sedimentation

**When gravitational forces on a particle are greater than air**
**resistance and buoyancy, the particle will fall out of the air stream.**
**As air moves deeper into the lung, air flow**
**rate decreases.**

_**Sedimentation**_

**Sedimentation is proportional to:**
**particle time in airway**
**particle size and density**
**respiratory rate (breaths/minute)**

**nasopharyngeal compartment**
**tracheobronchial compartment**
**pulmonary compartment**

## Diffusion

_**Diffusion**_

**Particles have random motion, resulting in random impacts.**
**Diffusion coefficient is:**
**	****inversely related to particle size**
**	****independent of particle density**
**tracheobronchial compartment**
**pulmonary compartment**

##                      Electrostatic Precipitation

**A minor mechanism, but may be more important for freshly**
**generated particles because these particles tend to have greater**
**surface charge.**
**Particle surface charge induces an “image” charge on lung surface.**

## Particle Characteristics that Affect Deposition

**Size:**
**	****will effect location of deposition**
**	****sequential removal of particles as go through the lung**
**Particle hygroscopicity: **
**	****If a particle is hygroscopic, it can pick up water in the ****	****humidified air of the lung. **
**	****This will increase particle density and alter deposition.**
**Particle surface charge:**
**	****This will affect electrostatic deposition.**
**	**
**	**
**	**

## Ventilation Pattern can Affect Deposition

**Respiratory Rate (breaths/minute)**
**	****increase respiratory rate**
**	****increase air velocity in the conducting airways**
**	****enhance impaction**
**	****decrease sedimentation and diffusion**
**Tidal Volume (V****T****)****	****volume of air entering or leaving the lung ****	****	****	****	****in a single breath**
**	****Increased V****T**** results in deeper lung penetration by ****	****particles**
**	****Person with increase V****T**** will likely have a decreased  ****	****respiratory rate.  Thus, particles stay in lung longer ****	****making deposition more likely.**

## Particle Clearance

##               Particle Clearance Mechanisms

**The Nasopharyngeal Compartment**
**	****mucociliary clearance (transport back to nasopharynx )**
**	****mechanical clearance (sneezing, coughing, swallowing)**
**	****absorption into circulation (soluble particles)**
**The Tracheobronchial Compartment**
**	****mucociliary clearance (transport to oropharynx)**
**	****endocytosis into peribronchial region (insoluble particles)**
**	**** ****absorption into circulation (soluble particles)**
**The Pulmonary Compartment****	**
**	****alveolar macrophage mediated clearance**
**	****endocytosis by lung epithelial cells into interstitum**
**	****absorption into circulation (soluble particles)**
**	**

## The Mucociliary Escalator

**The mucocilliary escalator operates in the tracheobronchial region.**

## Clearance in the Pulmonary Compartment

_**Clearance in the Pulmonary Compartment**_

**AM-mediated particle clearance**
**endocytosis by lung epithelial**
**cells absorption into blood**

## Relationships Between Clearance Mechanisms

## Lung and Lymph Node Silica Burdens

**As lung silica burden decreased, the lymph**
**node silica burden increased.**

##            Factors that Affect Particle Clearance

**	****Gender****	****	****no differences**
**	****Age****	****	****increasing age associated with decreased ****	****	****	****	****clearance**
**	****Exercise****	****	****exercise may increase clearance**
**	****Influenza****	****	****decreased clearance up to 3 months**
**	****Pneumonia****	****decreased clearance up to 1 year**
- Adapted from D. Pavia et al.  Bull. Eur. Physiopathol. Respir. 16, 353, 1980.

## Summary of Particle Deposition and Clearance

**       ****lung**
_**compartment**_**       **_**deposition mechanisms**_**	****      **_**clearance mechanisms**_
**Nasopharyngeal****	****     impaction****	****	****	****  mechanical**
**	****	****	****     ****sedimentation****	****	****  mucociliary**
**	****	****	****     ****electrostatic****	****	****  absorption**
**Tracheobronchial****	****     impaction****	****	****	****  mucociliary**
**	****	****	****     ****sedimentation****	****	****  endocytosis**
**	****	****	****     ****diffusion****	****	****	****  absorption**
**Pulmonary****	****	****     sedimentation****	****	****  AM-mediated**
**	****	****	****     ****diffusion****	****	****	****  endocytosis**
**	****	****	****	****	****	****	****  ****absorption****	**

## Metrics Used to Evaluate Particle Dose

## Particle Mass Model

**Dust Overloading - Defined as a condition where the mass of **
**particles deposited reduces their clearance, and thereby increases**
**toxicity.**

##                  Particle Volume Model

**Particle volume****	****It is possible to estimate the total volume ****	****	****	****	****of particles deposited in the lung using ****	****	****	****	****particle size and mass deposited.**
**AM volume****	****	****It is also possible to estimate total lung**
**	****	****	****	****AM volume based on AM size and ****	****	****	****	****number of cells/lung.**
**Volumetric Overloading**
**	****The volume of  particles phagocytized by AMs reduces AM-mediated clearance by decreasing AM motility, thereby increasing particle toxicity.**

##                 Particle Surface Area Model

**Particle Surface Area**
**	****For equivalent mass doses of fine and ultrafine particles of the same composition, ultrafine particles exhibit more toxicity in comparisons to fine particles.**
**	****For equivalent particle surface areas, ultrafine particles do not exhibit more toxicity in comparison to fine particles.**

## General Model of Particle Toxicity

**in the Alveolar Lung Compartment**

## Slide 32

## Slide 33