Histology #4 (Respitory) Flashcards
Functions of Respitory system
- Gas exchange (Main function)
- Regulates blood pH
- Sense of smell
- Phonation
- Air filtration
- Extretes watere and heart
Respitory = works closley with the cardiovascular system
- Respitory = Gas exchnage
- Cardiovascular = distrubutes O2 throughout the body and collects CO2 from the tissues
Divisions of Respitory system
Structural divisions - Upper vs. Lower Respitory
- Upper - Nose + Nasal cavity + Oral Cavity + Pharynx
- Lower - Trachea + Primary Bronchi + Lungs + Larynx
Functional dividions - Conducting vs. Respitory
- Conducting -
- Respitory - Respitry bronchials + Aveoli Ducts + Aveolar sacs
Lungs and Tracheobronchial Tree
Lung Plura
Covering of the lungs - Plura
- Composed of Visceral and Parietal Plura (between the two have the Plura space filled with fluid)
Image - see visceral plura on inside + parietal plura on outside
Visceral Plura
Layer that intimatley covers the lungs (wraps around all of the fissues on the lung surface)
- Wraps the lungs
- Closer to lung parachyma
Function - Sceretes plueral fluid –> fluid reduces friction as the lungs expand
Dividied into 5 Layers:
Mesothelial (most superficial) –> Submesothelial –> External elastic –> Interstitial –> Internal Elatic
- Interstial layer contains capilaries and lymphatics
Image - see the 5 layers
Visceral Plura (Images)
Right - HPS stain –> college is stained yellow/orange + see the lymphatic system in the middle
- Astrics = show the lymphatic system
Parietal Plura
Layer that lines the chest wall and covers the diaphram and mediastinum
- Outter layer
- Runs paraell to the chest
Function - Protection (Very fiberous -> provides support to the lung structure)
Consists of 5 Layers:
Mesothelial (outtermost) –> Subesothelia –> Fibradipose –> Interstitial –> Internal Elastic
- Interstitial layer = has collegen fibers
Image - See adipose cells in teh Fibroadipose layer
Parietal Plura (Images)
Right - Top most layer = mesothelial layer THEN the lower layers is connective tissue THEn have adipose cells
Left - See the collegen organization
Lung Lobule
Overall - Fundemental respitory unit of the lungs (functional unit)
- Plura = covers and prtects the lung lobules
Function - Gas exchnage
Made up of 10-30 Acini
- Acini = Composed of Alveolar Ducts + Aveolar Sacs + Aveoli
Relationship between lung lobule and pluera
Each lobule lies beneath the visceral plura
- Plura = supports the expansion and contraction of the lung lobule
- Plura = close to the parachyma – have blood vessles going through + have plura fluid in the plura cavity which provides cushioning for aveoli
The plural fluid in the cavity between the visceral and parietal pleura ensure that each lobule expands and contracts without friction or resistence
Trachea + Brinchi
Trachea + Bronchi = forms the tracheobronchi tree (part of the conducting zone)
Trachea = moves air from nose and mouth to the lungs
Bronchi = disrtubutes air to the lobes of the lungs
Layers of the walls of Trachea and Bronchi
Mucosa –> Submucosa –> Cartilagenous layer –> Adventitia
Mucosa - innermost layer lines with epithelia cells (contains goblet and basal cells)
Submucosa - connective tissue suporting the mucosa
- Helps with conrtraction
Cartilagenous layer - cartileganois rings and intervening smooth muscle
- Smooth muscle = structrual support
- Function - structural support and integrity
Adventitia - More internal fibroelastic layer of connective tissue
- Function - connects submucosa to other tissue
Mucosa layer specific to bronchi
In the muscosa layer. have part that is ONLY found in Bronchi –> have a layer of muscle cels that move mucosa
Muscle cells = also help constrict and dilate during breath
Trachea Epithelia cells
Psudostratified epithelum line trachea (cilated + has goblet cells + basal cells)
- Cilia help move the muscus to the Pharynx
- basal cells line under the psudostratified epithelum
- basal cells = stem cells –> differeniate into epitheliam cells
Mucous = traps dust (first line of defense) + moisturizes the air + brings the air to the right temperature
Bronchi Epithelia cells
Psudostratified epithelium (cilitaed + has goblet and basal cells)
Image - see the goblet cels (Cicular sacs)
Submucosal glands and ducts
Overall - Secretory structure found in submucosa that line cartilagenous airways
Location - Larynx + trachea + primary bronchi
Function - Defends against inhaled and exhaled pathogens
- Have water + ions + proteins accuminated in colecting ducts)
- Ciliated region at the top = connects to epithelial surface = moves things to the epithelial layer
- Has a role in innate immunity
- Physically secreates pathogens to move out of lungs
Strcuture – tubuloacinar secrtroy rehions joined by ducts (See sceretrtor regiion at the botted and collecting duct cells in green fiurther up)
- Connected ducts are at the to
What happens if have issue in submcosal ducts
Have issue in submucosal ducts = get cystic fibrosis
Submucosal glands and ducts (histology)
Left - in trachea - see it boarders cartilegenous layer + closer to the surface
Cartilage rings
Overall - C shaped rings composed of hyaline cartiage
Location - Trachea
Structure - 16-20 C shaped rings that line the entire length of the trachea
- NOT fully round (connected at the posterior end by smooth muscle)
- Smooth muscle = near the asphogus (sophage needs to be able to move to transport food.= have soft tissue in back of trachea)
Function - Support the trachea and allow it to move and flex without collapse while breathing
Cartilage plates
Overall - Hyline cartilege structures located within bronchial walls
Location - Bronchi
- In the Primary bronchi here are still cartilagnous rings BUT in the secondary bronchi the rings become cresent shaped plates or islands
Function - Keeps the airway open and the bronchi from collapsing during inhilation and exhalation
Structure - Cresent shaped plates or islands
Image -
Bottom - see irregularly shaped plates + has smooth msucle at the bottom
Top - see cartilege lining top of bronchi + smooth muscle
Adventitia
Overall - most superfivial layer of the trachea and the bronchi
Structure - Loose connectve tissue (collegen)
Function - anchors the trachea and bronchi to adjacent tissues
- Provides elastcity + strength + support
- Allows for seperation between structures (important because trachea and brocnhi are part of conducting system = don’t want things to come in)
Adventitia (Trachea histology)
Right - see loos arangment of fibers in adventia
Left - Adventitia anchors the trachea + loos arangments allows the trachea to expand
Adventitia (Bronchi histology)
See similar to trachea
Bronchioles
First structure in the respitory portion
Function - Direct air movement into aveoli
- Also block and clear debris + secret proteins to protect epithelium + degrade airborn toxins + regerate epithelum
Contains ciloated and non ciliated columnar and cuboidal cels + contain clara cells (non-ciliated)
Contains smooth msucle cells and elastic fibers –> allows for dontraction and dilation to control airflow
Does NOT contain cartilege and glands (as oppose to bronchi that do)
Images:
Top left - clara cells
Bottom Left and right - cross sectio of bronchiooles (see smooth muscle cells around epithelium –> controls air flow)
Clara cells
Non ciliated dome cells –> improtant for secreting proteins + creating epithelium + maintain bronchioles
Types of bronchioels
- Terminal brocnhioles
- Respitory bronchioles
Branching Function – increases surface area = optimizes gas exhnage + decreases air veolicty as air flows through
Image - se the terminal bronchiols branch into the respitory
Terminal bronchioles
Most distal conducting airways
Each branch of Terminal bronchiole gives rise to 2-5 respotroy bronchioles (terminal bronchioles branch into respitory bronchioles)
Resptory Bronchioles
Intial airways into where gas exchnage ahppens
Contains Alveoli (allows for gas exchnage to occur)
Bronchiole Histology
TB = Terminal bronchiole
AD = Alveolar Duct
RB + Respirtpry Bronchiole
Left - terminal have a distict epithelium then have trasnitiion to respitory (as transition to respitory you have aveoli)
Alveoli
Overall - Thin Walled sac
Contain Type 1 and Type 2 Pnumocytes
Function - Site of gas exchange
Contains Elstic and Reticular fbers –> provide structural supoort + allow for expansion and contraction as air flows through
Conatins Pores of Kohn –> promote collateral circulation + Route for alveolar macrophages
Contains smooth musckes at opening – smoth muscle controsl opening of Alveoli
Image -
Bottom left = see cross section of alveoli ducts
Bottom Right - have cross section of alveoli (share a commmon wall where exchnage occurs) ; knobs at the top are smooth muscle cells controling opening
Pores of Kohn
Pores of Kohn = small opening that connects airspace of adjacent alveoli –> creates collateral circulation + route for macrophages to travel
Alveoli Histology
RB = Rspitory bronchioles
AD = Aveolar duct
ALV = Alveoli
Left - Alveoli throughout (Cup and circular shaped)
Right - See bronchi
Type I Pnumocyte
Function - Facilitates gas exchnage between Alveoli and capilaries
- Exchnage occurs when deoxygenated blood is brought to the lungs –> Swap CO2 and O2 –> Blood goes to heart
Thin squamous cell shape
Covers 97% of lung (avleoli) surfaces BUT only composes 10% of total lung cell population
Type 1 Pnumocyte sturctural relevaace basal lamina
Type 1 Pnumocytes - have basal lamina
Tyoe 1 basal lamina are fused with the lamimae of pulminary capillaries that run in interalveolar septa
Image - see flat cell (Tyoe 1 pnumocyte) – cell is in communication with the aveoli space (Impritant for gas exchnage)
Type 1 Pnumocyte sturctural relevaace tight junctions
Tyoe 1 cells join other cells via tight junctions
- Tight junctions = prevent fluid from leaking into alveolar space
Type II Pnuemocyte
Function - Secretes surfactant
- Surfactnat = a mixture of proteins + phospholipids + Glycoaminoglycans
Type I Pnumocyte = also functions as a stem cell that can differentiate into both Type 1 and Tye II Pnuemocytes (1% of cells are replaced on a daily basis)
Has a large cuboidal cell shape
Compse of 30% of the lung cells in the Alveoli
Type II Pnumocyte sturctural relevaace
Tyoe II Pnemocytes = have numerous memebrane bound multi lamellar bodies in the cytoplasm
- Lamelar bodies = make surfactnat
- Pnumocytes = found at sites where alveoli walls join
Type II Pnuemocytes = joined to type I pnuemocytes by tight junctions and desmosomes
Image - swiry structure - lamalar bodies (secrete substances)
Surfactant
Fluid that covers the alveolar epithelium
Function - Reduces the surface tension in the alveoli
- facilitates alveoli epxansion during respiration + Prevents a;veolar collapse during expiratiion
Alveolar macrophaes
Derived from monocytes in the blood
Most numerous cell in the lung (90%-95%)
Function - Clean up crew for Aveolar –> Patrol air spaces to phagocytose debris and bacteria
- Called Dust cells - because they engulf particles
Location - Found in the interveolar septa and on the surface of alveolar lumen
- Macrophages in the lumen will make their way to the brinchioles and be released in the mouth
Alveolar Structures
- Interalverlar septa
- Blood-Air Barrier
Interalvelar Septa
Alveolar wall shared by adjacent alveoli
Contains a dense capilary network for gas exchange (contains the pulminary capilaries)
Perferated by pores of Kohn
Function - provides the structural basis for gase exchnage in the lung
Componetnts of the Interalveola septa
- Epithelum (of adjacent alveoli)
- Interstitium (collegen and elastic fibers)
- White color in image
- Capilary endothelium - has capilaries
Have sandwhich of epithelium with interstium between and sandhwich of the capilayr epitheliam with interstitium between (seen in image)
Function of septa
Septra structure gives the basis for gas exchange in the lung
Interalveolar Septa Histology
Left - shows alveoli - Arrows show the inter alveolar septa
Right - Arrows show the pores of Kohn (pores are connection around air spaces)
- Pores = equilize the pressure between adjacent alveoli
Blood Air Barrier
Overall - Barrier between capilary blood and alveolar air
Function - Specilized region of the Alveolar wall across which gas exchnage occurs
- O2 enters the blood
- CO2 enters the alveoli
Blood Air Barrier sturcture
- Alveolar epithelium (composed of type I pnuemocytes)
- Have a thin layer of surfactant that cover the Alveola Epithelium
- Capilary endothelium (endothelial cells)
- Fused basal laminae of the two cells
Have a thin layer of surfactnat that covers the apical side of the Type 1 Pnumocytes
Blood Air Barrier Type I Pnumocytes
Blood Air barrier Type I pneumocytes form a simple squamous epithelium lining the majorty of the surface area of the alveoli
Capilaies - single layer endothelium
IMage - aveolar wall – see Type 1 Pnumocytes form stromas epithelum lining air spaces see pulminary capilzaries inside alveolar wall
Blood Air Barrier Cytoplams
The cytoplasm of the Type I pnumocytes and the endothelial cells is HIGHLY attenuated + The two cells types share a fused basement mmebrane –> BOTH factors minimize the barrier = increase gas exchnage efficiencey
Why does gas exchnage happen in the alveoli
Cytoplasm of Type 1 and Capilary endothelial cells is attentuated (dcereased) - thickness of the cytoplas is 0.5-15 um
ALSO twi cells share a fused babsement memberane= air can difuse more easily = increases gas exhnage efficiencey
NOTE - air does not go through nucei 0 air goes across the cytoplpas
Movment of O2 through the Blood Air barrier
O2 in teh Alveoli –> O2 goes to the cytoplasm of the Type 1 Pneumocyte –> O2 goes across the basement memebrane –> O2 goes to the cytoplasm of the endothelial cell –> O2 goes to the Blood
CO2 does the same but it goes in the opposite direction
Disease of lungs:
- Malignent Mesothelioma
- Chronic Brinchitus
- Respitory Distress Syndrome
Maligenent meothelioma
Overall - cancerous growth of the mesothlium (Arrow in image)
Occurs in simply epitheliam cells derived from the mesoderm
Could occur in simple epithilial cells in teh Serous memebranes (serosa) of Pericardium (heart) + Pleura (Lungs) + Peritenium (GI system) + Tunica Vaginalis (Testicles)
- Occurs in the serous meembranes of all of these linings
80% of cases is due to Asbestos exposres
Malignenet Mesothelioma statistics
Rare - only 4,000 cases per year
Majority of cases in men 50-70 YO (because industrial occupations + disease takes 20 years to develop)
Agressive cancer (almost always fatal = poor prognosis)
- With treatment - survival is <10% at 5 years
Pleural form is most common ; paritenial is the second most common
Symptons:
1. Diffuculty breathing
2. Painful cough
3. Unitended weight loss
Image - see different forms _ subtypes
How do the Abestos fibers reach the pluera
Still an open question - some posisblities:
1. Driven by negative plural pressire + inflimantion from fbers + increasing permability of epithelial layer of aveoli —> fibers can go to pleural cavity
2. Cells are peirced by the fibers
3. Aveolar macrophages phagocytose the fibers and then travel to the plural space (controversial hypothesis)
Why does Malignent meothelaoma affect parietal plura
Drainage of the plueral fluid occurs predominatley thrugh the parietal side through stoma
- Fibers are bigger than the stoma = can clog the stoma on parietal sde = cancer usually forms on the parietal pleura (NOT visceral)
- Asbestos fobers = very durable
Image:
Left - black arrounds show plueral fluid turnover
Meothelaoma affect parietal plura (Images)
Malignenet mesothelioma + Abestos
Asbestos can’t be effectivley dgeraded
Size can prevent phagocytosis
Malignenet mesothelioma Mechanism
Asbests fibers are tracked to the pleura –> Asbestos fibers cause frustrated phagocytosis –> Mutagenic envirnment on the pareital mesothelum results in cancerous transfermation
Asbestos fibers = very durable
Phagocytosis = makes a mutigenic envirnmenta due to ROS and inflmation = causes cancer
Chronic bronchitis
Overall - severe long term inflamation of the bronchi
Diagnosis - chronic cough for a least 3 month over the course of 2 years
Chronic bonrchitus = a form of Chronic obsturctuve pulminary disease (COPD)
Caused by cigarette smoking or noxious polutants
- Noxious pollutants = second hand smoke or occupational polutants or pollustion –> al risk factors)
Image - shows healthy (open passage of air) vs chronic bornchitus (have inflamation + Mucous)
Forms of COPD
- Chronic bronchitus
- Emphyzema
Emphyzmea + chronic bronchitus = often co-occur
Chronic bronchitus systmptims and diagnosis
Symptoms:
1. Coughing and Wheezing
- Cough out a lot of flem
2. Cyanosis (blue colro in skin - espeically in the extremities because reduced oxygen)
3. Shortness of breath
4. Lungs appear hyper inflated
5. Barrel shape chest –> because not exhaling air properly
Diagnosis - do pulminary function spirometry tests
- Test - have patient take a deep breath - measure FEV and the FVC
- FEC = meausre volume of air that you ca forcfully exhale
- Diagnose if have a decline in FEV/FVC) –> have less air leaving the lungs
- Lower FEV/FVC ratio in obstruvtive disease = redced in chronic bronchitus
- Can also do CT Imaging
- Can also do pulse oximertry (monitor O2 in blood)
Chronic bronchitus Pathophysiology
cellular chanages = lungs trying to defend against harmful stimuli
- Have inflmation
Get Goble cell hyperplasia (increase in number of goblet cells) –> get excess mucous production –> get luminal occulsion
Have squamous cell metaplasia
Cilia is damaged (clipped short) –> mucous accumilates
- Pateints need to cough to get mucous out (because cilia is not moving it)
Immunosupression of alveolar macophages by tobacco smoke = immunosupresive envirnment
Have predisposition to lower respitory tract infection because the mucous acts as a bacterial growth medium
Squamous cell metaplasia in Chronic bronchitus
Chronic bronchitus –> get squamous cell metaplasia
Metaplasia = chnage from one type of epithelial cell to another (tyically occurs in response to an irritatiion)
In bronchitus - have Psudostratified cillitaed columnar cells –> tranistions to squamous epitheliam
- Lung = normaly psudeostratified columnar epithelium –> metaplasia occurs as an immune respinse to iritant (from exposure to toxin) –> epithelum chnages to squamous
- Get increase in number of layers of cells
If irritants are adressed the process can be revered
Metaplasia can be part of larger process to neoplastic chnages
Image - shows chnage in epithelial cells
- left - see cialia and columnar formation –> right have squamous layer
Chronic bronchitus + goblet cells
Chronic bronchitus –> can lead to goblet cell hyperplasia
- Goblet cell hyperplasia + squamous cell metaplasia usually occur together
Have proliferation of goblet cells
Increase numver of goblet cells –> get increased production of mucus –> leads to narrower airways
Image - Have non-smoker = have small amount of goblet cells –> see more goblet cells in COPD
Chronic bronchitus treatment options
Damage is irreversible so treatments usually try and stop progression
Goal = stop progression and manage symptoms
- Stop porgression by stopping smoking
Can give bronchodialtors to relax airways and increase airflow (Beta-2 agonists + antocholinergenics + theopylline)
- Ca be short or long acting
Give inhaled steroids to rduce inflamation
Give Suplemental O2
Respiratory Distress sundrome (RDS)
Lack of surfactant in the lungs –> have Aveoli collapse –> leads to wax build up around lungs –> abstructs gas exhchange
Kown as Hyaline memebrane disease
- Cell debris accuminaltes in the airway
60-80% of infants born before 28 weeks (common in pre mature infants)
- 90% survival rate
- Prevelane decreases with gesttional age
Symptims:
1. Diffuculty breathuing
2. Cyanosis (blue color from poor oxygen exchnage
3. Rib muscles pulling inwards on inhale
4. CO2 –> leads to Acidosis –> causes dysfunction
Diagnosis:
1. CT Scans
2. Blood tests for acidosis
RDS Physiology
Overall: Dirven by Type II Pnumocytes
Normally type II pnuemocytes (alveolar cells) secrete surfactant
- Surfactant secretion starts around 28 weeks = premature babies do not have surfactant production
Surfactant - contains phospholipids + prteins + glycosaminoglycans
- Surfacant covers alveolar epitheluum
- Surfacatant reduces surface tension in aveoli + barrier between airspace and water space of inner lungs
- When inhale surfactnat facilitates Aveolar expansion and orevents aveolar collapse during exhale
If lack surfactant = have problems inhaling and aveoli collapse (issues expanding and keeping lungs open)
RDS Histology
Upper left - healthy lung - aveoli are open and have thin walls
Lower left - aveoli are smaller and walls are thicker/inflamed
Right - white aveoli spaces
- Black arrows show hylin memebrane (around aveolei - impede gas exhnage by acting as a membrane)
RDS treatment
CPAP - continous positive airway pressue –> pushes air into the lungs to inflate the aveoli
Surfactant replacement - implant synthetc surfactant through endotracheal tube
Mechanical ventilaion
- Only in severe cases
- Can cause airway or lung injury
Glucocotricoids –> given to the mother before premature delivery
- Stimulates lung maturation + surfactant productionin baby
Acute Respitory distress syndrome (ARDS)
Results from a viral infcetion in lugs –> have inflmatory cells –> get nuertophil relased inflmaatry molcules –> leads to damage of aveolar papailary memebrane –> causes pulmenary adema + increase in permeability
Inflmation in lungs from COVID19 or sepsis or flu
- Pnumocytes - releases inflamatory cytokines
- Nuertophils - release proteases + ROS
- Occurs in adults
Injury to alveolrar capilary memebrane = more permable
Pulminary edmea –> washes away surfactant –> leads to aveoli collapse
40% moretality (high mortaility rate ; have few treatments)
