Pathophysiology of Asthma

It is a chronic disorder of the airways, characterized by bronchoconstriction, airway edema and airway hyper-responsiveness and airway remodeling. During the acute exacerbation of asthma, the bronchial smooth muscles contract due to its exposure to a varieties of allergens or irritants. Inspissated mucus plugs can be formed including structural changes such as hyperplasia and hypertrophy in the airway of the smooth muscles (Hackett 2012). Furthermore sub epithelial fibrosis, thickening of the basement membrane can lead to narrowing of the airway causing respiratory distress. The mechanism involving the airway hyper-responsiveness includes the neuro-regulation and airway inflammation (Doeing and Solway, 2013).

Inflammation plays the central role in the clinical progression of asthma. The inflammation of the airway involves the interaction of several types of inflammatory cells like the lymphocytes, mast cells, Eosinophil, dendritic cells, neutrophils and the epithelial cells. There are several inflammatory mediators like cytokines, Chemokines, Cysteinyl-leukotrienes, Nitric oxide (NO).  The inhaled allergen stimulates the T helper type 2 (Th2) cell proliferation, leading to the release of the Th2 cytokines, interleukin (IL)-4, IL-5 and IL-13 by the activation of  the mast cells, eosinophil and the neutrophils (Kudo et al. 2013).IgE is the antibody that is accountable for the hypersensitivity reactions. The antibody attaches to the surface of the cell via high affinity receptors that release the chemical inflammatory mediators. The allergens can be taken up by the dendritic cells that process the  antigenic molecules and present them to the naïve T –cells. Finally the allergen specific Th2 cells are activated.

Mode of action- It is normally used as an anti-inflammatory and immunomodulating agent. After the attachment of the cell surface receptor, the drug enters the nucleus of the cells where specific nuclear receptors are being bound that modifies the gene expression and inhibits the cytokine production.

Class-Ipratropium

Mode of action-It is used as a bronchodilator. It works as an anticholinergic agent. It blocks the muscarinic cholinergic receptors. It decreases the formation of cyclic guanosine monophosphate (cGMP). The effect of cGMP on the intracellular calcium ions, the contractility of the smooth muscle is decreased (LIU et al. 2013).

Pharmacokinetics- the drug is absorbed through the nasal mucosa having minimal systemic absorption. The drug is absorbed rapidly from the GI tract and the lungs.

Distribution- about 15 -10 % of the inhaled drug is deposited in the respiratory tract and the remaining drugs is deposited in the mouth and the oropharynx. 87 % of the drug bounds to the plasma proteins.

Metabolism- Metabolism of the drug takes place inside the liver. The portion hat is inhaled in to the respiratory tract is metabolized before its absorption in the systemic circulation.

Excretion- The metabolites are mainly excreted through the feces and some through the urine.

Pharmacodynamics

The drug stimulates the enzymes that are required to decrease the inflammatory action. It is used to prevent bronchiole asthma, avoid the recurrent of the nasal polyps after the surgery.

Pharmacokinetics-

Absorption- It is not readily absorbed in to the systemic circulation either from the GI tract or the lungs. The inhaled dose is normally swallowed.

Inflammatory Response Mechanisms in Asthma

Distribution- Not applicable

Metabolism- Hepatic metabolism and the half-life of elimination is 2 hours.

Excretion- The absorbed drug is normally excreted through bile and urine.

Pharmacodynamics-

Anticholinergic action- It antagonizes the action of acetyl choline, thus inhibiting the reflexes that is vagally mediated. The Anticholinergic inhibits the augmentation of the intracellular cyclic guanosine-monophosphate resulting in the interaction of the acetyl choline with the muscarinic receptor present on the bronchia smooth muscles.

1. Atrovent might not work during an acute asthmatic attack as Atrovent is normally categorized as a long acting anticholinergic agent that requires time for the medicine to come in to effect. Although these drug can be used for the prevention but no during the attack. Vanceril is an anti-inflammatory drug but the maximum effectiveness is found after a continued use for about 48-72 hours.
2. Prevention of the asthma requires strict adherence to the medication regimen on a long term basis and use of bronchodilators during attacks. Other education that can be given to the patient are the use of masks, while working in the mill to avoid exposure to dust, smoke and harmful chemicals. A month follow up is also needed as that will help in the regular monitoring of the patient’s health.

1. The four most critical elements in the  physical assessment of Mr. Needaire are :-

• Productive cough and yellowish thick sputum
• Decreased breath sounds in LLL, anteriorly and posteriorly that signifies pneumonia.
• Coarse crackles, which is associated with the infection or inflammation of the bronchioles.
• Oxygen saturation- 84 % that is much less than the normal value.

1. The most critical element that is of concern is the low oxygen saturation in the patient as value below 90% can lead to hypoxia (Mukandala et al. 2016). The patient is an elderly patient and hypoxia can be associated with depression of the synaptic activity and neuronal loss.
2. The physician has ordered to maintain an oxygen saturation level greater than 90 % as less than that may cause hypoxia in the patient. The decrease in the amount of the oxygen level per unit volume of the air may result in an insufficient amount of oxygen entering the blood stream. Hypoxia can have hazardous effect on the organ system and acute episodes of hypoxia may cause anaerobic metabolism and increase the respiratory rate in order to increase the oxygen intake and may give rise to angiogenesis and erythropoiesis for promoting oxygen delivery to the peripheral tissues (Mukandala et al. 2016). Inadequate supply of oxygen to the neuronal tissue may decrease the synaptic signaling due to anaerobic metabolic changes. Hence oxygen saturation should always be maintained above 90 %.
3. A sputum culture and sensitivity test is normally done for identifying the pathogen that is responsible for the illness. A sputum sample is cultured to allow the growth of the microorganisms present on it and then after 24 hours, the bacterial strain is identified by the process of gram staining. That will help the doctor to initiate the type of medications required or the type of antimicrobial that has to be used. Fluorescent microscopy is also used in sputum test.
4. A blood culture is collected at or around the time of the elevation of the temperature in the patient because it increases the likelihood of detecting the any significant bacteremia present in the blood (Riedel et al. 2008). Temperature hikes, chills are symptom of bacterial infection in the blood, although temperature spike due to bacteremia can be complicated if the patient is an elderly as they may remain hypothermic at the time they are bacteremic or may be unable to mount any febrile reaction. Another concern is that, fever can be caused by other factors other than bacteremia, hence to differentiate that blood culture is done.
5. Blood culture should be done by taking blood from two different sites of the body as multiple site blood culture helps in the appropriate detection of sepsis of bacteremia. Taking blood from a single may give erroneous results due to contamination with other microorganism. Some of the major contaminants that can give wrong results are the coagulase-negative staphylococcus species. Hence blood culture from multiple sites would facilitate accurate results.
6. A chest x- ray helps in determining the clinical conditions like cancer, infection in the pneumothorax, cystic fibrosis, accumulation of fluid in the lungs. Air bronchograms can be noticed in an x ray as it can be caused due to the accumulation of fluid in the alveoli (Bourcier et al. 2015). Silhouetting can be noticed in the right heart border which refers to the loss of the normal borders between the thoracic structures, which is a common phenomenon is case of pneumonia (Bourcier et al. 2015). Hence chest x-ray is ideal for diagnosing pneumonia although it does not give information regarding the type of germ present.

Intervention	Rationale
Elevation of the head of the bed  and changing the position frequently	It promotes chest expansion, mobilization and expectoration of the mucus, aeration of the segments of lungs (Juthani-Mehta et al 2016).
Teaching deep breathing exercises, splinting of chest and effective coughing remaining upright.	It helps in the  maximum expansion of the lungs. Splinting and effecting coughing decreases the chest discomfort.
Warm fluids to should be given	Warm fluids helps in mobilization and expectoration if the secretions.
Mucolytics, bronchodilators, expectorants, analgesics can be given	Medications would reduce the bronchospasms and mobilize the secretions.
Continuous monitoring of the ABGs , pulse oximetry	Helps to understand the progression of the disease facilitating modifications in the pulmonary therapy (Juthani-Mehta et al .2016).
Administration of the oxygen therapy	The PaO2level should be maintained above 60mm Hg.
Administration of the analgesics, assisting the patient in the chest splinting, providing comfort such as position changes, backrubs, massage (Juthani-Mehta et al. 2016).	Analgesic measures as well as non –analgesic measures can be useful in relieving pain.
Diabetes management by medications and nutritional assessment	Diabetic are at increased risk of compromised immunity and infections

• To get vaccinated  by pneumococcal vaccines, influenza vaccines
• To maintain cleanliness and hygiene.
• To keep the immune system strong by getting plenty of physical activity and following a healthy diet.
• To avoid smoking as it damages the ability of the lungs to filter out and defend against the pathogens.

Assignment 2

HEPATITIS B

• The differentials in the diagnosis of Hepatitis B are Cholangtitis, Autoimmune hepatitis, Cirrhosis, drug induced liver injury, Hemochromatosis, Hepatitis D, Hepatitis E, Hepatocellular Carcinoma, Primary, Wilson disease (De Paula 2012).
• The differential diagnoses for hepatitis A is Alcoholic hepatitis.
• The differential diagnoses for hepatitis c are Steatohepatitis, Hemochromatosis. In case of Steatohepatitis, there are no such differentiating signs and symptoms. In that case liver biopsy can show Steatohepatitis. Patients with Hemochromatosismay also have arthritis, cardiomyopathy or diabetes.

Mode of transmission –It is transmitted by fecal oral route, Ingestion of water or food that has been contaminated with the infected person’s feces. It can also be transmitted by unsafe sex practice, avoidance of undercooked raw shellfish.

Prevention- Maintenance of cleanliness and proper sanitation, use of protection during sex.

Modes of transmission- It is transmitted through exposure to infected blood, semen or other body fluids. It can also be transmitted from the mother to the child during birth or from the family members to the baby. It can also be transmitted during blood transfusion or being exposed to contaminated syringes and equipment (Bayliss et al. 2013). Health care workers can be accidently subjected to needle stick injury while taking care of the HAV patients.

Prevention- Safe handling of the contaminated equipment and body fluids, avoiding sharing of personal items like razors and tooth brushes and effective vaccination (Bhattarai et al. 2015).

Modes of transmission- It is mostly spread through the exposure to infected blood. It can occur during transfusion of the blood or blood products contaminated with the virus. Sexual transmission might be possible but is less likely (Jadoul and Barril, G. 2012).

Prevention- Maintaining Safety precautions while carrying out surgical procedures or while handling the blood products. There is no vaccine for this virus (Linas et al 2013).

Peter Mark has been diagnosed with hepatitis B and caring for hepatitis B patient without appropriate precaution might lead to transmission of the infection. Hepatitis B vaccine is recommended for those caring for the hepatitis B patient. Gloves, should be worn while taking care of the patient or dealing with used things of the infected patient. Gowns could be worn in case the clothing gets soiled. Proper hand hygiene should be maintained after touching the patient or any contaminated equipment. Used syringes and used articles by the patient should be discarded in labelled bags. If the hygiene of the patient is poor then he/she should be shifted to a separate room. Employee having a direct fecal –oral exposure should receive immune globulin as a preventive measure.

The period of incubation of the HBV ranges from 28 to 180 days. In most of the infections, the period of incubation is about 60- 100 days. The infection route has very less influence on the incubation period. A prodromal viral illness follows the incubation period which is again followed by afebrile jaundice. HBsAg can be detected in the serum 2±8 weeks before the raise of aminotransferases (Bayliss et al.2013). As the illness progresses, the level of the aminotransferases rise and the viral products can be easily detected including the viral DNA polymerase and HBeAg. Anti-HBc IgM can be detected at the outset of the disease.

Drug Classifications and Actions of Vanceril and Atrovent

Long term complications like hepatic encephalopathy, anorexia, decreased liver function and increased jaundice may occur. Further deterioration may lead to bacterial or fungal infection, pulmonary failure, renal failure and other electrolytic complications (Ngo-Metzger et al. 2013). In acute liver function failure, a liver transplant may be required. Very less percentage of the patients develop fulminant hepatitis.

• Abdominal pain, especially in the upper right part of the abdomen, due to the inflammation of the liver.
• Myalgia, can be a symptom for viral hepatitis.
• Nausea, vomiting tendency and mild jaundice can be the clinical manifestation of hepatitis B.
• An increased level of conjugated bilirubin implies the presence of liver disease.

Hand hygiene: The patient should be educated regarding the importance and the ways of proper hand washing, use of alcohol based hand rubs.

Patient should be recommended not to donate blood, body organs or other things or sharing of razors or tooth brushes.  

Vaccination- 2 dose hepatitis B vaccine schedule ; Heplisav-B (Dynavax) should be given one month apart.

Practice safe sex- Protection should be used while having unsafe sex. Avoiding close contact with the infected individual.

References:

Bayliss, J., Nguyen, T., Lesmana, C.R.A., Bowden, S. and Revill, P., 2013, May. Advances in the molecular diagnosis of hepatitis B infection: providing insight into the next generation of disease. In Seminars in liver disease (Vol. 33, No. 02, pp. 113-121). Thieme Medical Publishers.

Bhattarai, S., Smriti, K.C., Pradhan, P.M., Lama, S. and Rijal, S., 2014. Hepatitis B vaccination status and Needle-stick and Sharps-related Injuries among medical school students in Nepal: a cross-sectional study. BMC research notes, 7(1), p.774.

Bourcier, J.E., Paquet, J., Seinger, M., Gallard, E., Redonnet, J.P., Cheddadi, F., Garnier, D., Bourgeois, J.M. and Geeraerts, T., 2014. Performance comparison of lung ultrasound and chest x-ray for the diagnosis of pneumonia in the ED. The American journal of emergency medicine, 32(2), pp.115-118.

De Paula, V.S., 2012. Laboratory diagnosis of hepatitis A. Future Virology, 7(5), pp.461-472.

Doeing, D.C. and Solway, J., 2013. Airway smooth muscle in the pathophysiology and treatment of asthma. Journal of applied physiology, 114(7), pp.834-843.

Franco, E., Bagnato, B., Marino, M.G., Meleleo, C., Serino, L. and Zaratti, L., 2012. Hepatitis B: Epidemiology and prevention in developing countries. World journal of hepatology, 4(3), p.74.

Hackett, T.L., 2012. Epithelial–mesenchymal transition in the pathophysiology of airway remodelling in asthma. Current opinion in allergy and clinical immunology, 12(1), pp.53-59.

Jadoul, M. and Barril, G., 2012. Hepatitis C in hemodialysis: epidemiology and prevention of hepatitis C virus transmission. In Hepatitis C in Renal Disease, Hemodialysis and Transplantation (Vol. 176, pp. 35-41). Karger Publishers.

Juthani-Mehta, M., Van Ness, P.H., McGloin, J., Argraves, S., Chen, S., Charpentier, P., Miller, L., Williams, K., Wall, D., Baker, D. and Tinetti, M., 2014. A cluster-randomized controlled trial of a multicomponent intervention protocol for pneumonia prevention among nursing home elders. Clinical Infectious Diseases, 60(6), pp.849-857.

Kudo, M., Ishigatsubo, Y., and Aoki, I. 2013. Pathology of asthma. Frontiers in Microbiology, 4, 263.

Linas, B.P., Barter, D.M., Leff, J.A., Assoumou, S.A., Salomon, J.A., Weinstein, M.C., Kim, A.Y. and Schackman, B.R., 2014. The hepatitis C cascade of care: identifying priorities to improve clinical outcomes. PloS one, 9(5), p.e97317.

LIU, C.D., DONG, P.P. and WANG, L.J., 2013. The Clinical Observation on the Efficacy of Oxygen Atomized Inhalation of 5% Hypertonic Saline and Atrovent in the Treatment of Bronchiolitis in Children. Chinese and Foreign Medical Research, 3, p.022.

Mukandala, G., Tynan, R., Lanigan, S., and O’Connor, J. J. 2016. The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS. Brain Sciences, 6(1), pp.6.

Ngo-Metzger, Q., Ward, J.W. and Valdiserri, R.O., 2013. Expanded hepatitis B virus screening recommendations promote opportunities for care and cure. Annals of internal medicine, 159(5), pp.364-365.

Riedel, S., Bourbeau, P., Swartz, B., Brecher, S., Carroll, K. C., Stamper, P. D., …Doern, G. V. 2008. Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia .Journal of Clinical Microbiology, 46(4), 1381–1385Trépo, C., Chan, H.L. and Lok, A., 2014. Hepatitis B virus infection. The Lancet, 384(9959), pp.2053-2063.