Spirometer: measures an individual’s pulmonary functio

• Allows you to record lung volume measurements
  – Generates a graph (spirogram) to analyze the efficiency of an individual’s lung function.
• Here, we analyze the spirogram of an average adult male
  y-axis = volume (liters) → spirograms record air volume (between 0 – 6 liters)
  x-axis = time (seconds) → spirograms record over time.

Key Values and Spirogram Analysis:

Tidal volume (TV):

Volume of air inspired during quiet breathing → 0.5 liters

Inspiratory reserve volume (IRV):

Forced inhalation → 3.0 liters

Maximal (peak) inspiration

= 6.0 liters lung volume

Expiratory reserve volume (ERV):

The volume of forceful exhalation → 1.0 liter

Maximal expiration

= 1.5 liters lung volume

Residual volume (RV):

The volume of air still in the lungs after maximal expiration

Lung capacity = sum of two or more lung volumes

Vital capacity (VC): The difference between maximal inspiration and maximal expiration.

VC = TV + IRV + ERV

Total lung capacity (TLC): the total volume of air that the lungs can hold.

TLC = VC + RV

Inspiratory capacity (IC): the maximum volume of air that the lungs can inspire.

IC = IRV +TV

Functional residual capacity (FRC): the volume that remains in the lungs after a single quiet breath.

FRC = ERV + RV 

Pulmonary Ventilation and Alveolar Gas Exchange:

Conducting portion:

Trachea → left, right bronchi → terminal bronchioles

• Only air conduits, do not participate in gas exchange.
• This is the anatomic dead space*
• Gas exchange primarily occurs in the respiratory bronchioles and alveoli.

Healthy Lungs vs. Emphysema

Healthy lungs:

Physiologic dead space = anatomic dead space.

Emphysema:

Physiological dead space > anatomic dead space.

• Lungs lose elasticity → insufficient recoil → air is trapped in lungs, unable to be exhaled
• Air now part of the physiologic dead space *
• Increase in RV (volume of air remaining in the lungs after maximal expiration)
• Decrease in vital capacity.
• Individuals have “barrel chest” → accommodates increased RV

2 Functional Divisions

The conducting portion

• Conducts air, and comprises: the nose, nasal cavity, pharynx, larynx, trachea, bronchi, and bronchioles.
• No gas exchange occurs in these structures.
• Terminal bronchiole terminates the conducting portion of the respiratory tract.
  The respiratory portion
• Site of gas exchange, and comprises: the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli.

Nose

• Opens the respiratory system to the outside environment.

Nasal cavity

• Its mucosal lining moistens, warms, and cleans the inhaled air.

Pharynx

• Muscular tube that lies behind the nasal cavity, oral cavity, and larynx; it is open to them, and acts a conduit for air and food/liquid. Thus, it serves both the respiratory and digestive systems.

Esophagus

• Continues posteriorly to carry food to the stomach.

Larynx

• The cartilaginous structure that prevents food and liquid from entering the lower respiratory tract, and produces and modifies sounds (and is often referred to as the “voice box”).

Tracheobronchial tree

• Collective term for trachea and its bronchial branches.

Trachea (the “windpipe”)

• Descends through the neck to the thorax, and comprises C-shaped (vertically-stacked) cartilaginous rings.

Primary Bronchi

• First divisions of tracheobronchial tree
• Aka, main bronchi

Secondary bronchi

• Serve lobes of the lungs
• Aka, lobar bronchi

Tertiary bronchi

• Serve lung segments, called bronchopulmonary segments.
• Aka, segmental bronchi

With each successive division, the branches get narrower and the walls of the branches get thinner.

Bronchioles

• Terminal bronchioles are last portion of conducting division.

Respiratory bronchioles

• Beginning of respiratory division

Alveolar sacs

• Comprise small out pockets called alveoli, which have specialized walls to facilitate gas exchange with surrounding pulmonary capillaries.
• The hundreds of millions of alveoli within give the lungs a light, spongy texture.

Lungs

• Right lung comprises three lobes (divisions) and the left lung has only two lobes.
• The heart nestles into the medial aspect of the left lung, which makes it slightly smaller than the right.

HISTOLOGICAL FEATURES

Tracheal ring

• Comprises thick layer of purple-staining hyaline cartilage, which is covered by perichondrium on both sides.
• Lamina propria and submucosa; though not visible in our sample, the submucosa contains seromucous glands and blood vessels.
• Mucosal folds, which are lined with pseudostratified epithelia.

Bronchi

• Lumen is surrounded by mucosal pseudostratified epithelium.
• Submucosal glands
• Bundles of smooth muscle
• Large plates of hyaline cartilage distinguish the larger bronchi.

Smaller tertiary bronchi

• Characterized by highly fractured and thin pieces of hyaline cartilage.

Respiratory bronchioles

• Thinner walls that lack cartilage and comprise simple cuboidal epithelial cells.
• Alveolar outpockets arises directly from the respiratory bronchioles.
• Club cells (formerly known as Clara cells), are cuboidal, non-ciliated cells in the bronchioles that secrete proteins.
• Respiratory bronchiole gives rise to the alveolar ducts, which open to alveolar sacs.

Alveoli

• Type I pneumocytes (aka, alveolar cells), which are squamous epithelial cells.
  • Type I cells provide a thin surface for easy gas exchange with nearby pulmonary capillaries, which we can identify by the presence of red blood cells in their lumens.
• Type II pneumocytes, which are rounder and bulge into the alveolus.
  • Type II cells produce and secrete surfactant, which reduces surface tension and prevents alveolar collapse in exhalation; they also maintain and repair the alveolar wall.
  • Alveolar macrophages, aka, dust cells, fibroblasts, and mast cells are also present.

Clinical Correlation

Asthmatic airway:

• Prolific goblet cells, lumen-obstructing mucous, and thickened basement membrane.
  • Allergic asthma is caused by hypersensitivity to allergens that trigger inflammatory responses, including mucous over-production, in the lungs and obstruct air flow.
  • Non-allergic asthma, on the other hand, is caused by pathological neural regulation of bronchiole diameter, and, therefore, air flow.

By now you may already know that the kidneys filter your blood. Microscopically speaking, it is structures known as the glomeruli (singular ‘glomerulus’) inside of the kidney that perform the actual filtration. If they, like the car and fridge filter, are damaged, then they will leak stuff into your urine that normally shouldn’t be there.

A glomerular disorder that causes hypoalbuminemia, proteinuria, and edema is known as nephrotic syndrome. All sorts of glomerulopathies (diseases of the glomerulus) can result in nephrotic syndrome, including: 

• Minimal change disease 
• Focal segmental glomerulosclerosis 
• Membranous nephropathy 
• Diabetic nephropathy 

CAUSES OF NS

Minimal change disease:

• PRIMARY CAUSE: IDIOPATHIC (10–15% of idiopathic NS in adults, but 70–90% of NS in children.)
• SECONDARY CAUSE: HIV
• CAUSED BY DRUGS: NSAIDS, Rifampicin interferon
• NEOOPLASMIC: Hodgkin’s lymphoma
• mc in children

Membranous nephropathy 

• PRIMARY CAUSE: IDIOPATHIC (30% of idiopathic adult NS.)
• SECONDARY CAUSE: Chronic Hep B/C, Syphillis, Leprosy, Hydatid disease
• CAUSED BY DRUGS: NSAIDS, Gold, Penicillamine, Probenecid, Captopril
• NEOOPLASMIC: Paraneoplastic syndrome (IgG) and Ca of breast, lung, ovary and colon.
• mc in elderly and malignant lesions
• maximum risk of renal vein thrombosis

Focal segmental glomerulosclerosis 

• PRIMARY CAUSE: IDIOPATHIC (30% of idiopathic adult NS.)
• SECONDARY CAUSE: Chronic Hep B, Parvo B-19
• CAUSED BY DRUGS: NSAIDS, Heroine intake, Lithium and Panidronate
• NEOOPLASMIC: Non- Hodgkin’s lymphoma
• mc in adults
• mc lesion in HIV

I don’t want you to really get bogged down in remembering the causes of nephrotic syndrome so much as understanding what actually happens. Any of those diseases damage the glomerulus. The glomerulus is the filter that is supposed to keep large things, such as proteins, inside of the blood while filtering out smaller toxins that get excreted in the urine. If the pores of the glomerulus, the little holes that allow for things to pass through the glomerulus and into the urine, are damaged, they get bigger. Bigger pores in any filter means that things that should’ve been kept out are now leaking into the urine and out of the blood. 

You can reproduce this point at home. Take out some dirty old rag you no longer need. If you look really closely, you will see that there are small holes in the rag. They’re truly tiny. This rag will represent our glomerulus, the filter. Turn on the faucet in a sink and place a couple of golf balls or something similar into the rag. Now place all of this under the running faucet. You’ll note that the golf balls aren’t filtered through, but the water and all the microscopic parts of it easily pass through to the other side. 

Now go ahead and cut some big holes into the rag, mimicking the damage glomerulopathies cause. Repeat what you did before. This time around, not only will the water leak through but the golf balls will pass through as well. 

In the case of nephrotic syndrome, a protein called albumin is like a golf ball that leaks out of the blood and into urine when it normally shouldn’t. This leakage results in decreased levels of albumin in the blood, termed hypoalbuminemia and increased levels of protein in the urine, known as proteinuria.

SERUM ALBUMIN= Normal Value is 3.5-5.5 but in NS the value decreases to 2.5 g/dl
PROTENURIA
Old= more than 3.5 g/dl
Children= More than 2g/dl
Adult= More than 3g/dl
Proteinuria during nephrotic syndrome is in the range of three grams per day or more. This is in contrast to other causes of proteinuria, such as a kidney infection, which results in less than that (up to two grams per day, normally). 

You should note that the protein albumin, now leaking out of blood and into the urine, is important in keeping fluid within the blood vessels and out of the body tissues. Albumin is like a sponge that sucks up water into the vasculature. Since there’s less albumin in the blood during nephrotic syndrome, there are fewer sponges in the blood vessels. This means water leaks out of the blood vessels and into the tissues. This is what is known as edema. Edema causes a person to literally swell up with fluid. Keeping this in mind, lets understand:
Initiating Mechanism of Edema:
Decrease in oncotic pressure due to albumin loss —> Fluid shift from intravascular to extravascular—> causing effective decrease in intravascular volume.
Hence, increase in renin and aldosterone leading to increase in water and sodium retention.