Pulmonary Function Tests.

 

Pulmonary Function Tests

PKGhatak, MD

Pulmonary Function Tests (PFTs) are aptly named, the tests delineate the functional status of the lung and allow one to follow the progression of a disease or improvement. The tests are also sensitive in the early stages of a pulmonary disease when other tests, like chest x-ray, C scan and blood tests, are likely to be normal. The PFTs are an integral part of good management of asthma where patients themselves can adjust medications on a day to day basis. Tests are simple enough and can be repeated frequently.

A complete PFT is done in a pulmonary lab by a technician and the tests are done in stages but in one sitting. It can be a bit exhausting, particularly for those with a lot of disabilities.

From the patient's side, the patient has to breathe in and out, as best he/she can, into a mouthpiece attached to a machine. And there is no need for a blood sample or any injections.

The electronic machines are amazingly efficient and fast and can spit out numbers instantly. If the report is delayed that is likely due to the time taken to interpret those numbers by an expert.

Why PFTs are needed:

1. It is an essential test to monitor a lung diastase from day to day.

2. Patients use this device to detect early warning signs of trouble and seek proper help ahead of the problem begins

3. In certain pulmonary diseases, the functional state is more important than just a diagnosis. An example is asthma.

4. An essential tool for detecting very early cases of asthma. And then categorize asthma according to severity, in order to prescribe appropriate medications and dose adjustments.

5.PFTs are sensitive tests utilized in detecting the cause when the breathlessness of the patient is the only symptom.

6. These tests differentiate obstructive lung diseases from those diseases that prevent the lung to expand fully to its capacity (restrictive lung disease).

Normal breathing.

We breathe 12 times a minute, one cycle takes about 5 sec, which includes two phases, inhalation and expiration. If one listens with a stethoscope the movement of air during inhalation makes a gentle sound, whereas, expiration is very short and only in the early part of expiration is audible. That is due to the fact that the elastic recoil of the lungs and the chest wall do all the work during expiration.

Let's take a look at this test result together. Note there is a small oval graph within the larger one, and a horizontal line is running across the graphs. The horizontal line is the baseline. The lower half of the graph represents the movement of air into the lungs, and the upper part is air moving out of the lung. For the lower half, the pen inscribes from Right to Left. The pen inscribes on the upper part from Left to Right.

The smaller graph depicts the air moving in and out of the lungs during normal breathing.

The larger graph is inscribed when the patient took in as much air in his lungs as possible and then forced out air as fast as he could and continued to push out air from his lungs with the constant cheering of the technician. This graph represents Forced vital capacity, or simply the Vital Capacity.

The horizontal line within the graphs represents the Volume of air in Liters, the vertical line depicts the Flow Rate of air in Liters per Second.

The difference between the two graphs is the Reserve Volume of the lungs, both in the inspiratory and expiratory phases.

FEV1.

The amount of air that expired under maximum efforts in the First second is known as the forced expired volume in the first one second (FEV1). A normal person can expel 80 % or more at the first second. In obstruction of the airway (COPD) the FEV1 is less than 75%. In asthma, the FEV1 should return to a normal level after a brief inhalation of a bronchodilator. In suspected cases of asthma, the initial EFV1 may be normal but the FEV1 will fall below 80% after a Methacholine challenge test, also known as Bronchial Provocation Test

The results of the PFT are reported with the actual patient's performance numbers and also as a percentage of his performance when compared with a normal person with his age/ sex/ethnic background/ height/ and ideal weight for the age and height.

Methacholine Challenge test.

A forced vital capacity is recorded first. Only if PFT is normal, then the methacholine challenge test is performed; because this test is a test to document hyperactive airways, if that is already demonstrable, then there is no point in doing the test.

The subject is asked to breathe in and out normally a nebulizing solution starting with a dose of 1 to 3 micrograms of methacholine and observing and documenting changes in flow rates of the forceful expiration. The test is continued with an increased dose of methacholine till the maximum dose is given or a reduction of flow rate is observed. 

A decrease of 20% of FEV1 is necessary to call a test positive.

Total Lung Capacity.

After a maximum expiratory effort, a significant amount of air is still left in the lungs, because the lungs cannot be squeezed further as the chest wall will not yield because of rigidity. The amount of air that will not be expelled is called Residual Volume.

On adding the residual volume to the forced vital capacity volume, the Total Lung Capacity (TLC) number is obtained.

Direct measurement of TLC.

To determine the TLC, a known amount of inert gas, Helium (harmless, non-absorbable, not soluble in water or blood) is used. A mixture of oxygen and helium is inhaled from a closed system and the subject is allowed to breathe in and out within the closed system to ensure the proper distribution of helium in the lungs. Then the expired air is analyzed for the final concentration of the helium gas. Knowing the initial gas concentration and the final gas concentration of helium, the volume of the Total Air present in the lungs is easily calculated.

In emphysema, the reserve volume increases at the expense of inspiratory reserve volume and the TLC also increased due to the loss of the elastic tissue and the chest expands outwards, commonly referred to as a Barrel Chest.

In chest wall deformities, e.g. Kyphoscoliosis, and in pulmonary fibrosis, the TLC and the FVC are reduced.

Diffusion Capacity.

The diffusion capacity of the lung is also known as the transfer factor, DLCO (diffusion of carbon monoxide), TLCO. The diffusion capacity is a measure of the health of the delicate tissue at the junction of air sacs (alveoli) and pulmonary capillaries where the oxygen molecules from the alveoli move across the membrane and bind with the Hemoglobin in the RBCs.

In a biological system, multiple factors are at play, so also in DLCO. One has to accept that under the condition of the test, just one factor is variable. After the result is obtained a correction is made, if necessary. As an example, significant anemia will appear as decreased DLCO due to less hemoglobin available to bind oxygen and not due to a damaged membrane.

To test DLCO, the subject exhales forcefully first, then inhales a known amount of a mixture of oxygen, nitrogen, helium and carbon monoxide (CO) from a closed system, and holds breath for 10 seconds. The expired air is sampled at the mid portion of expiration and analyzed by a rapid CO analyzer. The amount of CO transferred is calculated and expressed in CO mmol/min/k Pa or SI units. And a ratio of the expected normal value.

DLCO is reduced in pulmonary emphysema, pulmonary fibrosis, loss of lung tissue from lung surgery, or other diseases. Also damage to the pulmonary capillaries from platelet microthrombi, Pulmonary embolism, poison gases, radiation, etc.

Very Useful gadgets developed from PFT.

Peak Flow Meter.

A peak flow meter is easy to use, and the inexpensive gadget is an integral part of asthma management.

A maker on a tube records the highest flow generated with forceful expiration. A sudden fall in the Peak Flow indicates fatigue is setting in a sustained asthma attack - also called Status Asthmatics. Patients are well coached to seek medical attention right away.

Vitalograph.

A simple vital capacity measuring device uses a rubber bag to collect expired air and a pen records the volume and flow rates on graph paper. Patients with neurological conditions like Gillian Barre syndrome, ascending paralysis, or ALS and their caregivers are taught to use the gadget and call their doctors when detect deterioration. The use of these devices prevents time intervention and avoids ER trips unnecessarily.

Volumetric Incentive Spirometer.

It is still a simpler gadget than a vitalograph, but basically performs the same function of alerting a patient's caregivers of any diverse changes.

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Diabetes Mellitus and Microvascular Changes.

 Diabetes Mellitus Causing Microvascular Changes

                 PKGhatak, MD

Diabetes mellitus is a disease that lasts lifelong. People with diabetes follow their fasting blood sugars and some also understand the value of HbA1c in the management of diabetes. However, there is a silent killer working incessantly and burning away the smallest arterial branches like a smoldering brush fire. This killer is called Microvascular complications of diabetes.

Diabetes is actually of two types. Type I diabetes is due to a complete lack of Insulin. Type II diabetes is much more complex to categorize in one sentence. There are several reasons why a person develops diabetes in adult life; some due to insulin resistance, others the presence of insulin antibodies, and still there are more causes. But no matter which one is responsible for diabetes, in the long run, diabetics are at risk of developing one or more organ damages, which may happen in 50% of cases. It may result in visual impairment, renal failure, peripheral neuritis, skin ulcers and loss of a foot, heart disease and many other diseases.

Pathological changes in organs from diabetes are well described, but the way the changes happen is still not fully understood. Scientists experiment on lab animals, usually on mice, and not all their findings are squarely applicable to humans.

Blood sugar is Glucose. Besides blood glucose, the liver and muscles store glucose in a different chemical form called glycogen. The liver also turns excess fat and some amino acids into glucose. The heart uses glucose for energy and also uses fatty acids and ketones for the same purpose.

The blood sugar is kept between 80 to 100 mg in a fasting state by the interactions of several hormones. The chief among them is Insulin. Insulin combines with certain components of the cell membrane and makes a passage for glucose molecules to enter the interior of cells. The glucose molecule goes to mitochondria where the oxygen molecule reacts with glucose to release energy.

Like anything in excess amount does not always bring happiness, excess sugar has a dark secret. It burns the tissue, slowly and steadily.

In the biological system, all chemical reactions are the results of enzyme actions similar to Catalysts in chemical reactions. In diabetes, due to high blood glucose, the Superoxide, Sorbitol and Glycation of the substrate are overproduced. These substances are responsible for the thickening of the basement membrane, increased endothelial permeability, extravascular protein deposition and coagulation.

The microvascular changes in the eyes can be observed under direct vision with an Ophthalmoscope and so it is well documented but similar changes are also happening in other organs but the severity varies from individual to individual. In addition to the eyes, kidneys, Peripheral nerves, autonomic nerves the heart and skeletal muscles are affected.

Researchers have identified multiple biochemical pathways through which microvascular changes take place. The important among them are Protein Kinase C (PKC), Mitogen Activated Protein Kinase (MAPK), Diacylglycerol Kinase (DAG), Activated Protein Kinase (AMPK), Polyop pathway, and non-enzymatic Glycation End Products (GEPs), Kallikrein-Bradykinin system, Renin-Angiotensin system, and others. Hypertension acts as an accelerator of change.

PKC.

PKC is a family of closely related enzymes active with messenger calcium irons and DAG. PKC upregulates the Endothelial Growth Factor (EGF) through NADPH (nucleotide adenosine dehydrophosphatase hydrogen). The final result is the increased production of endothelin I, Vascular endothelial growth factor and connective tissue growth factor IV. The functional alterations are endothelial leaks, increased vascular permeability, angiogenesis, cell growth and apoptosis. And deregulation of cellular functions, dilation of small vessels, extracellular matrix expansion, and altered fatty acid metabolism.

MAPK.

MAPK is involved in the direct cellular response to mitogen, osmotic stress, gene expression, cell differentiation, mitosis, and cell survival.

DGK

DGK is an enzyme family, used in the phosphorylation of diacylglycerol (DG) and transforming it to phosphatidic acid (PA). Both DG and PA are important signal molecules.

AMPK.

AMPK acts as a master switch regulating glucose and fatty acid metabolism. It is capable of sensing energy needs. It is activated by skeletal muscle contraction and cardiac ischemia. In the liver, it enhances fatty acid oxidation and decreases the production of glucose, cholesterol and triglycerides.

NAD/NADH and NADP/NADPH systems.

These are coenzymes, which act as hydrogen ions and electron donors and receivers. NADP/NADPH is issued in anabolic (formation of new products) reactions and NAD/NADH is active in catabolic reactions.

Dextrose Monophosphate Shunt.

This is an alternate but parallel path through which glucose is utilized to 5-carbon pentose sugars. As the pentose is metabolized it generates Ribose and deoxyribose used in nucleoprotein synthesis.

Polyol / Sorbitol Pathway.

In diabetes, the hyperactive stage of this pathway leads to the accumulation of NADPH and reduced glutathione which are responsible for the overproduction of collagen fibers.

In diabetes, the above enzyme systems are overactive. The consequence is the following - Cell signaling dysfunction. Toxic AGE, Oxidants and Methyl glycol accumulation in the tissues. Altered osmols and redox potentials.

These are stressful situations within the cells and the response is manifested by the release of inflammatory cytokines and leukotrienes, decreased Insulin effectiveness, Kallikrein-Bradykinin activation. The end results are vascular changes of diabetes.

Organ changes in Diabetes mellitus.

Kidneys.

The initial change is the expansion of the mesangium and increased matrix production. The thickening of the basement membrane of the glomeruli is the result of it. Glomerular sclerosis and hyalinization of glomeruli lead to glomerular atrophy and hypertension and renal insufficiency.

Eyes.

Retinal changes are observable by an ophthalmoscope or retinoscope.

Micro aneurysm formation, retinal flame shaped hemorrhage, exudate and arterial atrophy, and macular edema are usual in various combinations and seventies in individual cases. This is the primary cause of visual loss and blindness.

Nervous system

The central, peripheral and autonomic nervous systems are affected in diabetes.

The changes are in the tiny arterioles supplying blood to the nervous tissues. Lack of oxygen and nutrients break down myelin sheath and in advanced cases, the axon is also damaged.

Cranial nerve palsy leads to double vision, and paralysis of the lateral rectus muscle is seen. The long peripheral nerves supplying the toes and fingers are the first to suffer damage. Loss of pain, touch and vibration sensations are lost initially then temperature sensations. Muscle weakness may develop due to motor nerve palsy. Neuritis pain in the legs is distressing for patients. Skin cuts and bruises and cigarette burns produce chronic ulcers and ultimately may end up requiring an amputation. Autonomic nervous system involvement produces impotence in men and postural hypotension. Nonspecific Gastric and intestinal symptoms may occur, and some also develop bladder and bowel evacuation difficulties.

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The changes in the heart, muscles and pancreas, liver and other organs can be found in previous blogs.

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