Week 2 Qs
Restrictive ventilatory impairment
- Characterized by reduced lung volumes (total lung capacity, FVC, FEV1) and relatively normal expiratory flow rates - Inferred from spirometry when FVC is reduced and FEV1/FVC is normal or > 80% - Pathologies include interstitial lung disease, pleural diseases, chest wall deformities, obesity, pregnancy, neuromuscular disease, and tumor
what are the major modes of HIV transmission in Africa?
1. (40%) breast feeding 2. perinatal transmission 3. heterosexual intercourse
at what point would a loading does reach steady state concentration?
4 half lifes
If tidal volume (VT) is 500 ml, respiratory rate (f) is 15 /min and the volume of the dead space (VD) is 160 ml, then alveolar ventilation is equal to
5.1 L/min To determine alveolar ventilation you need to multiply the amount of fresh gas entering the alveoli in each breath by the respiratory rate, i.e. (500-160) mL/breath x 15 breaths/min = 5100 mL/min.
how to measure residual volume
A gas dilution test. A person breathes from a container containing a documented amount of a gas (either 100% oxygen or a certain amount of helium in air). The test measures how the concentration of the gases in the container changes.
Which of the following cannot be measured by spirometry?a. Functional residual capacityb. Expiratory reserve volumec. Tidal volumed. Forced vital capacitye. Forced expiratory volume in one second
Answer: A. The functional residual capacity is the sum of the expiratory reserve volume and residual volume. The residual volume cannot be measured by spirometry because spirometry relies on airflow measurements and air in the residual volume does not move. Therefore it cannot be measured by spirometry. All of the other options can be measured using spirometry.
A 61 yo patient has been diagnosed with pulmonary fibrosis. Compared with a healthy patient of the same age, his lungs would be A. more compliant B. be easier to deflate C. require less work to inflate D. have less elastic recoil E. have greater airway resistance
B. be easier to deflate Pulmonary fibrosis increases elastin and collagen -- increased elastic recoil --> easier to deflate, but harder to inflate.
vomer bone
Flat, thin bone that forms part of the nasal septum
How does lymph move?
From higher to lower pressure: subscapular sinus to medullary sinus
will the resting tidal volume in a restrictive pulmonary disease be decreased?
No.
List 4 modes of transmission of HIV. Compare the major transmission modes in Eastern and Southern Africa and Australia (3 marks).
Sexual, Blood transfusion, Vertical, Sharing needles/IDU In Africa; primarily via heterosexual sex, vertical transmission. In Australia; primarily via homosexual sex. Heterosexual sex and IV drug use account for most of the rest.
the vast majority of T cells in a peripheral blood sample is
T cells and CD4 or CD8
pneumothorax
air in the pleural cavity caused by a puncture of the lung or chest wall
Which pathogen cannot be transmitted via placenta?a) Rubella virusb) Chlamydia trachomatisc) Treponema pallidiumd) Listeria monocytogenese) Toxoplasma gondii
b) Chlamydia trachomatis
Which of these is NOT part of the medial wall of the nasal cavity? a. Vomer bone b. Perpendicular plate of the ethmoid c. Nasal crest of the maxilla d. Nasal spine of the frontal bone e. Perpendicular plate of the palatine
e. Perpendicular plate of the palatine (part of the lateral wall of the nasal cavity)
what has the most influence on steady state concentration?
rate of metabolism.
oral tolerance
the characteristic tolerance of the immune system for 'foreign' antigens, such as food, ingested into the gastrointestinal tract. this is a normal characteristic of GALT
calculate minute ventilation
tidal volume x respiratory rate
Describe the conchae, meatuses, and other features of the lateral wall and roof of the nasal cavity.
- Conchae: the nasal conchae are 3 bony outgrowths of the maxilla (superior, middle and inferior concha) that protrude into the nasal cavity on the lateral side and are covered by respiratory epithelium. As air is breathed in, it is churned against these mucosa-lined conchae to receive warmth, moisture and cleansing (by reducing the airflow, larger foreign particles will drop before they reach the lower respiratory tract). The inferior nasal concha is most significant in warming, humidifying and slowing down inhaled air. It is also derived from the nasal bones, whereas the superior and middle are derived from cranial bones. - Meatuses: the meatuses are passages within the lateral wall of the nasal cavity that are formed by the conchae above it. These passages often receive drainage from other parts of the skull. The hiatus semilunaris is a crescent-shaped groove at the anterior of the middle nasal meatus. it receives drainage from the frontal sinus and anterior ethmoidal air cells (through the frontonasal duct), as well as the maxillary sinus (orifice of maxillary sinus). The nasolacrimal duct is a duct that drains tears from the eye into the nasal cavity at the inferior nasal meatus. When a person cries, or has watery eyes, the fluid drains through this duct and ends in the nasalcavity. - Auditory (Eustachian) tube: the auditory tube is a tube that connects the nasal cavity to the middle ear. The auditory tubes must be actively opened (e.g. by swallowing) when the surrounding air pressure drops, e.g. when an aeroplane ascends.
All of the following are significant contributors to changes in pharmacokinetics in the eldery except A. Changes in absorption from the gut B. Changes in renal function C. Changes in liver function D. Changes in blood albumin concentration E. Changes in water composition (and ratio) of the body
A. Changes in absorption from the gut whilst GIT absorption is reduced in the elderly, this does not affect pharmacokinetics (the time course for movement of a drug through the body)
HIV resistance to NNRTIs such as efavirenz is caused by:a. Mutations in viral reverse transcriptaseb. Mutations in viral aspartate proteasec. Mutations in the fusogenic domain of the gp41 regiond. Mutations in HIV-integrasee. Mutations in the V3 region of gp120
Answer: A. Resistance to NNRTIs would require structural changes to the reverse transcriptase enzyme that NRRTIs act on. If the structure of the reverse transcriptase enzyme changes, then efavirenz may no longer have a site where it can allosterically bind to. All NNRTIs except etravirine and rilpivirine are susceptible to high-level drug resistance caused by single-amino-acid changes in the NNRTI-binding pocket due to this they should always be combined with other active agents to avoid resistance. NNRTIs should never be used as the sole addition to a failing regimen. b. resistance to protease inhibitors (PIs) e.g. Darunavir c. gp41 transmembrane protein allows for fusion of virus to cell -- so resistance to HIV fusion inhibitors d. resistance to integrase inhibitors (INSTIs) e.g. Raltegravir e. gp120 is the envelope protein of the HIV-1 molecule, used to bind to the CD4 molecule. This means that mutations here will induce resistance to HIV fusion (entry) inhibitors
Regarding clearance rate (CL) of a drug, all of the following statements are true EXCEPT:a. The CL is constant for every type of drugb. Knowledge of CL is important to determine the therapeutic rangec. CL increases with a decrease in half lifed. CL decreases with increased bioavailabilitye. The area under the curve (AUC) is inversely proportional to CL
Answer: A. The clearance rate refers to the volume of blood that would be completely cleared of a drug per unit time due to metabolism or excretion. It can also be thought of as the volume of blood that would have a drug concentration of 0 if the remaining volume maintained the same plasma concentration as the drug was removed from circulation. The CL will be constant for a drug that undergoes zero order kinetics, where elimination mechanisms are saturated and metabolism of the drug occurs at a fixed, maximum rate. However, drugs that undergo first order kinetics will have a clearance rate that increases as more of the elimination mechanisms are recruited to metabolise the drug. Therefore CL is not constant for every drug. - Option B is a true statement: while the clearance rate strictly does not affect the therapeutic range (which is a pharmacodynamic parameter), it is important in determining the loading dose and maintenance doses needed to ensure that the drug remains in therapeutic range. - Option C is a true statement: the formula for CL is given as CL = Ke x Vd , where Ke (elimination constant) = ln(2)/t1/2. A decrease in half life means that the drug is removed from the body more quickly, suggesting a higher clearance rate. - Option D is a true statement: another representation of CL is CL = D/AUC, where AUC refers to the area under the curve of the plasma drug concentration vs time curve. With increased bioavailability, the plasma drug concentration is increased, increasing the overall AUC. As CL is inversely proportional to AUC if the dose is constant, increased bioavailability will reduce clearance. - Option E is a true statement: see option D.
Which of the following statements about lung volume and capacity is MOST correct? a. The expiratory reserve volume is the difference between functional residual capacity and residual volumeb. The vital capacity is the amount that is exhaled in a typical breathc. The vital capacity and functional residual capacity together make up the total lung capacityd. Inspiratory reserve volume is the maximum volume that can be inspired after maximal expiratione. The functional residual capacity consists of inspiratory reserve volume, tidal volume, expiratory reserve volume and residual volume
Answer: A. The functional residual capacity refers to the amount of air remaining in the lungs that can undergo gas exchange after a normal exhalation. The residual volume is the volume of air that remains after maximum expiration, and exists because the expiratory muscles cannot remove the same amount of air that the inspiratory muscles bring in. The difference between this is the expiratory reserve volume, i.e. the volume of air that can be exhaled further when performing a maximum expiration instead of a normal expiration. - Option B is incorrect: the vital capacity is the amount that is exhaled after performing a maximum inspiration and expiration. usual expired volume is tidal volume. - Option C is incorrect: combining the vital capacity and functional residual capacity double-counts the expiratory reserve volume, so it would give total lung capacity + expiratory reserve volume. - Option D is incorrect: inspiratory reserve volume, similar to expiratory reserve volume, refers to the additional amount of air that can be inspired when performing a maximum inspiration instead of a normal inspiration. - Option E is incorrect: the functional residual capacity is the sum of expiratory reserve volume and residual volume only.
You are assisting with the insertion of a nasogastric tube. Which of the following MOST correctly describes the order of structures that it will pass? a. Nasal vestibule, inferior concha, nasopharynx b. Vestibule, inferior meatus, superior olfactory mucosa c. Superior olfactory mucosa, nasal vestibule, nasal atrium d. Nasal atrium, nasopharynx, olfactory region e. Nasal vestibule, superior olfactory mucosa, nasopharynx
Answer: A. The nasal vestibule is the antero-inferior section of the external nose and the first section of the nasal cavity. The inferior concha is a feature of the respiratory region of the nasal cavity, which is further along the respiratory tract. The nasopharynx connects the nasal cavity to the larynx. - Option B is incorrect: the superior olfactory mucosa and the inferior meatus are approximately at the same level in the respiratory tract. A nasogastric tube should not be passing through the superior olfactory mucosa as it will contact the sphenoid sinus rather than move down through the pharynx. - Option C is incorrect: the nasal vestibule is found before the superior olfactory mucosa. - Option D is incorrect: the nasopharynx is found after the olfactory region. - Option E is not the best answer: while this is a correct order along the respiratory tract, a nasogastric tube should not be passing through the superior olfactory mucosa.
Which of the following statements about antiviral medications for HIV is MOST correct? a. Clinical efficacy involves inhibitory concentrations at the site of infection, which is usually inside the infected cell b. Most agents eliminate non-dividing or latent viruses. c. They have a broad spectrum of action, targeting many different viral proteins d. HAART must be maintained for life because latent HIV is not integrated into host DNA e. Single point mutations that cause significant amino acid substitutions are insufficient to cause resistance
Answer: A. This is a general principle that is applicable for all antimicrobial agents - in order to treat infection, the antiviral must reach a concentration that inhibits active replication of the virus. Since viruses infect host cells, these concentrations therefore must be achieved in the infected cells. - Option B is incorrect: current antiretroviral medication is unable to remove latent or non-dividing virus, which is one of the reasons why HIV remains incurable. - Option C is incorrect: each type of HIV antiretroviral medication available has a very specific target through which it is effective. There is no single drug that can target many different viral proteins simultaneously. - Option D is incorrect: HIV integration into host DNA is the main reason why HAART must be maintained for life. When HIV integrates into host DNA, there is always a potential that it will reactivate and cause an active infection. - Option E is incorrect: single point mutations are sufficient to alter the shape of the target that an antiretroviral drug may be targeting. For example, single point mutations in the gp41 protein can confer a 450x increase in resistance to enfuvirtide (a HIV entry inhibitor).
Live vaccines are more effective compared to inactivated vaccines, because they generate:a. Antibodies with higher affinityb. A stronger CD8+ cell responsec. A stronger CD4+ effector cell responsed. More abundant CD4+ memory cellse. More abundant B memory cells
Answer: B. A stronger CD8+ cytotoxic response is preferable for immunisation against a viral infection. Live vaccines (especially the live, attenuated influenza vaccine) tend to generate more CD8+ action, which help clear the infection by killing infected cells and preventing further spread of the virus. - Option A is incorrect: the same antigens are present in the live and inactivated virus, so antibodies with equal affinity will be generated in both cases. - Option C is incorrect: while CD4+ effector cells are important in coordinating an adaptive immune response, CD8+ cells (which contribute most to clearing viral infection) do not require coactivation from CD4+. The live, attenuated influenza vaccine is known to enhance CD8+ function. - Option D is incorrect: the role of CD4+ memory cells is unclear in active immunity. - Option E is incorrect: humoral immunity tends to be less important in a viral infection compared to a bacterial infection, so more abundant B memory cells would not be the main distinction between live and inactivated.
Which of the following statements MOST correctly describes the mechanism of action of non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz)? a. It inhibits viral reverse transcriptase and viral DNA synthesis, preventing HIV replication. b. It allosterically inhibits viral reverse transcriptase c. It mimics cleavage site of viral polyproteins by competitively inhibiting viral protease d. It prevents viral replication by stopping insertion of viral DNA into the host DNA e. It selectively inhibits HIV-mediated membrane fusion by binding to and blocking gp41
Answer: B. Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz) are a class of reverse transcriptase inhibitors that do not rely on competitive inhibition of reverse transcriptase. Instead, they are a chemically diverse range of allosteric inhibitors that induce conformational changes in the enzymes to prevent substrate-enzyme attachment. - Option A is not a good option: this is a description of the mechanism of action of reverse transcriptase inhibitors in general. - Option C is incorrect: this describes the mechanism of protease inhibitors. - Option D is incorrect: this describes the mechanism of HIV integrase inhibitors. - Option E is incorrect: this describes the mechanism of HIV entry inhibitors such as enfuvirtide.
Which of the following statements about the histology of the lung is MOST correct?a. The bronchioles are lined by stratified columnar epitheliumb. Alveoli are lined by type 1 alveolar cellsc. Terminal bronchioles lead to the alveolar ductsd. Type 1 pneumocytes produce surfactante. Bronchioles have numerous seromucous glands in the mucosa
Answer: B. Type 1 alveolar cells (also called type 1 pneumocytes) make up the epithelial layer of the alveoli. As they are very flat in shape (squamous), they facilitate diffusion of gases (O2, CO2) through the alveolar cells and the capillaries. - Option A is incorrect: bronchioles are lined with simple cuboidal epithelium. The respiratory tract is normally lined with pseudostratified columnar epithelium, however more distally the height of the epithelium reduces to become cuboidal by the bronchioles, and squamous by the level of the alveoli. - Option C is incorrect: terminal bronchioles (conducting zone) branch into respiratory bronchioles (respiratory zone) before forming alveolar ducts. - Option D is incorrect: type 2 pneumocytes produce pulmonary surfactant, which reduces surface tension in the alveoli. This prevents collapse of the alveoli during expiration. - Option E is incorrect: by the level of the bronchioles, the walls are no longer thick enough to house seromucous glands. Seromucous glands are present in the walls of larger bronchi, but not bronchioles.
An endocrinologist performs an experiment comparing the BMI of 18 women to that of 11 men. Which of the following should tests should she use to test for statistical significance?a. Chi-squared testb. Levene's testc. Independent t-testd. Fisher's exact teste. Z-test
Answer: C. An independent t-test is the appropriate statistical test when a scalar variable is compared in two small independent populations (n < 30). The BMI of the men and women in this sample are independent of each other. A t-test is more appropriate for determining whether there is a difference in a population variable (e.g. mean BMI, which is a continuous, numerical quantity) in two small populations (as long as the standard deviation of each population is known). - Option A is incorrect: a Chi-squared test looks for statistical significant differences in categorical data (e.g. expressed in a 2 x 2 table). However, BMI is a form of numerical data, not categorical data. - Option B is incorrect: Levene's test is a preliminary test that is done to check whether two samples have the same standard deviation, which is not what is being tested here. - Option D is incorrect: Fisher's exact test is used in 2 x 2 tables to determine whether two variables are independent or not. This requires bivariate data (each subject has a x and y coordinate etc.), which is not present here. - Option E is incorrect: a Z-test is used to look for statistically significant differences between a sample's variable and a known population parameter (e.g. comparing BMI of these men to the average BMI of the Australian population). It does not compare two groups.
Which of the following structures is MOST likely to be injured from perforation of the thyrohyoid membrane?a. Vocal cordb. Vestibular cordc. Epiglottisd. Arytenoid cartilagee. Cricoid cartilage
Answer: C. The epiglottis lies posterior to the thyrohyoid membrane and therefore is most likely to be injured from a thyrohyoid membrane perforation. - Option A is incorrect: the vocal cords lie inferior to the thyrohyoid membrane and therefore would not be likely to be injured from a direct perforation of the thyrohyoid membrane. - Option B is incorrect: the vestibular folds lie inferior to the thyrohyoid membrane. They arise from the inner surface of the thyroid cartilage and attach to the anterolateral arytenoid surfaces. - Option D is incorrect: the arytenoid cartilages are located inferior to the thyrohyoid membrane and are one of the more posterior structures in the laryngopharynx, making them unlikely to be injured. - Option E is incorrect: the cricoid cartilage is the most inferior of the unpaired cartilages, below the thyroid cartilage. It would not be injured from a direct perforation of the thyrohyoid membrane.
Which of the following statements about the larynx is MOST correct?a. The vocal cord contains a smooth muscle (vocalis) which alters the length and tension of the vocal ligamentb. It is located below and the pharynx and above the oesophagusc. It holds the true vocal cords lined with stratified squamous epitheliumd. It has false vocal cords that are devoid of mucous glandse. It is a hollow structure surrounded by a ring of small bones
Answer: C. The true vocal folds are the free edges of the cricothyroid ligaments that vibrate in phonation. They are lined with stratified squamous epithelium, unlike the rest of the respiratory tract, because this resists abrasion better than respiratory epithelium. - Option A is incorrect: the vocalis is a skeletal muscle. It does alter the length and tension of the vocal ligament during speech. - Option B is incorrect: the larynx is located below the pharynx, but anterior to the oesophagus. - Option D is incorrect: the vestibular folds (or false vocal folds) are lined with respiratory epithelium and have mucoserous glands. These secrete lubricating substances into the laryngeal ventricle to lubricate the rapidly vibrating vocal folds.- Option E is incorrect: the larynx is defined as the section of the respiratory tract extending from the tongue to the trachea. There are paired and unpaired cartilages, and the only bone in the larynx is the hyoid bone.
Where is a tumour of the vocal fold most likely to spread to first?a. Epiglottic cartilageb. Hyoid bonec. Vocal process of arytenoid cartilaged. Muscular process of arytenoid cartilagee. Anterior arch of cricoid cartilage
Answer: C. The vocal process of the arytenoid cartilage is the structure that has the closest relation to the vocal fold. The vocal fold attaches to the vocal process of the arytenoid cartilage posteriorly and to the thyroid cartilage anteriorly. Local spread of a vocal cord tumour is therefore most likely to affect the vocal process of the arytenoid cartilage first. - Option A is incorrect: the epiglottic cartilage is a feature of the laryngeal inlet, located superior to the vocal fold. It is connected to the thyroid cartilage anteriorly like the vocal fold, but to the arytenoid fold posteriorly (not the arytenoid cartilages directly). - Option B is incorrect: the hyoid bone is located too superior to the vocal fold to be the first structure affected by a vocal cord tumour. It is found superior to the thyroid cartilage (separated by a thyrohyoid ligament). - Option D is incorrect: the muscular process of the arytenoid cartilage does not directly connect to the vocal fold. Instead, the muscular process serves as an attachment point for muscles such as the posterior and lateral cricoarytenoid muscles. The muscular process is a lateral projection of the arytenoid cartilage while the vocal process is an anterior projection. - Option E is incorrect: since the vocal fold connects to the thyroid cartilage, the anterior arch of the cricoid cartilage would be located too inferiorly to make it the first structure affected by a vocal cord tumour.
Which of the following changes occurs in moderate exercise?a. PaO2 decreasesb. PaCO2 increasesc. Oxygen consumption increasesd. Oxygen extraction from blood decreasese. Ventilation-perfusion ratio worsens
Answer: C. Oxygen consumption would have to increase in moderate exercise, since more oxygen is required to facilitate aerobic cellular respiration in the muscles (and therefore produce ATP). This is reflected as increased oxygen extraction, where the venous partial pressure of O2 is lower than normal. - Option A is incorrect: the PaO2 should increase in exercise. Increase in tidal volume and respiratory rate when exercising increases ventilation, allowing more O2,to be taken from the air and into the blood. - Option B is incorrect: the PaCO2 should decrease in exercise. As tidal volume and respiratory rate increases, more CO2 is blown off in expiration, reducing PaCO2. - Option D is incorrect: oxygen extraction by the muscles from the blood increases to meet the increased oxygen demand of the exercising muscles. - Option E is incorrect: the ventilation/perfusion ratio will trend to a 1:1 ratio in exercise. This is ideal as this means the oxygen supplied by ventilation is just enough to fully saturate the blood's oxygen-carrying capacity.
Which of the following statements about the unique structure of the spleen MOST correctly describes its immune function?a. In the medullary section, there are no interlobular septa b. The blood-splenic barrier enables positive selection c. In the red and white pulp, there are macrophages and fenestrated endothelial cells for the removal of old and senescent erythrocytes d. Blood enters via afferent vessels and passes into the splenic sinusoids e. The white pulp has periarteriolar lymphoid sheaths and B cells in the peripheral white pulp
Answer: E. The white pulp refers to the regions of the spleen immediately surrounding the arterioles. White pulp is arranged as a peri-arterial lymphatic sheath of T lymphocytes immediately adjacent to the central arteriole, with B cells located closer to the periphery of the white pulp. These B cells produce antibodies against antigens detected in the blood passing through the central arteriole. - Option A is incorrect: a medullary region and interlobular septa are features of lymph nodes, not the spleen. - Option B is incorrect: positive selection of lymphocytes does not occur in the spleen. Positive selection of T cells occurs in the thymus, and selection of B cells occurs in the bone marrow. - Option C is incorrect: macrophages and fenestrated endothelial cells (splenic sinuses) are a feature of the red pulp only, not white pulp. - Option D is incorrect: afferent vessels receive blood entering the spleen, and these first pass into the white pulp with the peri-arteriolar lymphatic sheath.
Which of the following statements is NOT listed as part of the UNAIDS 90-90-90 goal? a. By 2020, 90% of all people living with HIV will know their HIV status. b. By 2020, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy. c. By 2020, 90% of people living with HIV will be screened for TB. d. By 2020, 90% of all people receiving antiretroviral therapy will have viral suppression. e. Aim to end the HIV epidemic as a major global health threat by 2030
Answer: the aims of the UNAIDS goals are: - By 2020, 90% of all people living with HIV will know their HIV status. - By 2020, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy. - By 2020, 90% of all people receiving antiretroviral therapy will have viral suppression. - End the AIDS epidemic by 2030. This makes option C the only statement not listed as part of the UNAIDS 90-90-90 goal. This goal primarily focuses on the HIV epidemic, not tuberculosis.
Which is not characteristic of a low CD4 count from HIV infection?a. CMV retinitisb. Infection with strep pneumoniaec. Pneumocystis pneumoniad. Kaposi sarcomae. Burkitt's lymphoma
B strep
Which of the following options regarding pharmacokinetics is wrong: A. Bioavailability is 100% with i.v. B. Maintenance dose does not involve Css C. Bioavailability is not included for clearance D. Loading dose helps achieve Css faster
B. Maintenance dose does not involve Css
What is NOT the normal function of GALT a) to promote oral tolerance b) respond to foreign antibodies in food/diet and intestinal flora c) have activated memory lymphocytes d) have migrating lymphocytes e) secrete copious amounts of IgA
B. respond to foreign antibodies in food/diet and intestinal flora. - alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders.
Sam is fallen off a tree and has a laceration on his forearm and has had his tetanus immunisations and boosters. Which of the following is MOST CORRECT about the subsequent immune response?A) The antigen is carried to the lymph nodes via the efferent lymphatic vessels.B) The antigen is presented to CD4 T cells on MHC Class 1.C) T cells migrate from the bloodstream to the interstitium then to the lymphatics.D) B cells proliferate in germinal centres in axillary lymph nodesE) B cells differentiate into plasma cells, then travel in lymphatics to become lodged in the spleen.
C) T cells migrate from the bloodstream to the interstitium then to the lymphatics. A is wrong because it'd be carried by the afferent, not efferent.B is wrong because it's MHC Class 2 that presents to CD4.D is wrong as B cells proliferate wherever they get presented with antigen E is wrong as plasma cells lodge in bone marrow, not spleen
John is a patient with 10 years of HIV with [CD4+] = 250 ´ 106 cells/L (reference range = 500 - 1000 ´ 106 cells/L). Which of the following statements is most true? A. The immune response is so suppressed that the antibodies are likely to be undetectable. B. He is at high risk of prostate cancer C. He is at high risk of non-hodgkin lymphoma D. CD4 count is higher than CD8 count E. HIV viral load is very low
C. He is at high risk of non-hodgkin lymphoma AIDS patients have a high incidence of certain tumors, particularly Kaposi sarcoma (KS), non-Hodgkin lymphomas, and cervical cancer.
Which of the followwing are NOT indicative of an AIDS defining opportunistic illess: A. Pneumocystis Jirovecii based pneumonia B. Karposi's Sarcoma C. Cytomegalovirus Retinitis D. Burkitt's Lymphoma E. Influenza based Steptococcal Pneumonia
E. Influenza based Steptococcal Pneumonia AIDS defining features: 1. Pneumocystic jirovecii pneumonia (PJP or PCP) 2. Oesophageal candidiasis 3. Kaposi sarcoma (HHV-8 infection) 4. Wasting syndrome 5. Mycobacterium avium infection ... and more, such as TB which is more prevalent in developing countries
Describe the development of cytotoxic T cells and neutralising antigens and their role in viral infections (10 marks)
Early development: 1. Small numbers of very immature cells, derived from haematopoietic stem cells, leave the bone marrow, travel via the blood, and enter the thymus (so they are called T cells). 2.The cells proliferate in the thymus, and the DNA of their T cell receptor (Tc R ) genes rearranges. 3. Their TCR proteins are tested. Only cells with intact TCRs that do not bind to self antigens are allowed to mature. Cells with unsatisfactory TCRs (the majority) are deleted. 4. Mature T cells of the 2 major subsets (CD4 and CD8) then leave the thymus via the blood, and do not return. Most migrate to secondary lymphoid organs, whilst some others stay in the circulation. Antigen presentation and viral infection role. - Dendritic cells use MHC Class I to initiate CD8 T cell response, class II for CD 4 T cell response - Both CD8 and CD4 T cells will proliferate upon dendritic cell antigen presentation, with the co-activation of CD 28. This produces clones that can be either effector cells that continue to neutralise pathogens, and long-lived memory cells for subsequent re-infections. - Antigen peptides bound to MHC Class I molecules is presented to CD8 T cells via their TcR. This also requires co-stimulation for optimal activation e.g. CD28. This allows for the CD4 cells to initiate apoptosis in the infected cell.
The rates of HIV and AIDS diagnoses in Australia are diminishing. In the space below, give reasons for this trend.
First, levels of testing for HIV in people at risk of HIV in Australia are among the highest in the world.• Coupled with the second factor, the emergence of effective therapies for HIV, this means that a large proportion of people with HIV in Australia are diagnosed, and are receiving HIV therapy. More than 50 percent of people with HIV attending medical practices in Australia have undetectable viral loads, and this has probably led to decreased infectivity of people with HIV.• Third, the homosexual community in Australia played an active role in promoting safe sex among its members. Despite behavioural studies which suggest that over recent years many Australian homosexual males have reverted to having unprotected sex with casual partners, this has occurred in situations of modified risk, such as HIV-negative men assuming the insertive position in anal sex. Other reasons include (0.5 marks each):• Screening of blood donors by questionnaire• Testing of blood supply to prevent the use of contaminated blood products;• Needle exchange programs for intravenous drug users, helping to reduce the incidence of needle sharing;• An effective safe sex campaign throughout the whole community.
What techniques or instruments can you use to distinguish different cells (CD4+ and CD8+ T cells, B cells, NK cells etc.) on a blood film? (3 marks)
Lymphocyte immunophenotyping by flow cytometry can be used to determine the numbers of different lymphocytes in a conventional blood smear. Monoclonal antibodies are created for unique surface markers on each lymphocyte (e.g. CD3 and CD4). These monoclonal antibodies are also tagged with a fluorescent marker. When the antibodies are mixed in excess with the lymphocytes, they will bind to the specific lymphocyte. The amount of fluorescence is directly proportional to the amount of lymphocytes within that blood smear, allowing an estimation of the proportion of lymphocytes in the subject's blood.
Vital capcity (VC)
The amount of air that can be forcibly expelled from the lungs after breathing in as deeply as possible.
Describe the bone and cartilage structure of the nasal cavity.
The nasal cavity is a large air-filled space above and behind the nose, in the middle of the face. Structurally, it is bound by the nostrils (nares) and septal cartilage anteriorly , superiorly by the ethmoid bone, laterally by the maxilla, inferiorly by the maxilla and palatine bone and posteriorly by the choanae. It is also separated medially by the perpendicular plate of the ethmoid bone superiorly and vomer bone inferiorly.
Describe the three regions of the nasal cavity.
The nasal cavity is divided into three regions: the nasal vestibule, olfactory region and respiratory region. - Nasal vestibule: this is the anteroinferior section of the external nose lined with skin It acts as a dust and pathogen barrier. Coarse hairs help to trap large particulate matter that may be inhaled. - Olfactory region: this is the posterosuperior region of the nasal cavity (roof of the nasal cavity), at the ethmoid bone before the sphenoidal sinus. It is lined by olfactory epithelium, a special form of respiratory epithelium that includes olfactory receptors. These olfactory receptors are the endings of olfactory nerves that pierce through the cribriform plate of the ethmoid bone before they pass into the olfactory bulb, the major nervous structure involved in smell.
steady state concentration
The point where drug accumulation equals drug elimination.
Describe two HIV prevention strategies in the HIV Prevention Revolution and describe their mechanism. (6 marks)
Treatment as prevention (TasP) is the usage of ARTs to prevent sexual transmission of HIV to an HIV-negative partner. Multiple studies have shown the efficacy of TasP in serodiscordant couples, decreasing transmission by 93%. Later phylogenetic analysis showed that there were no linked transmission during viral suppression of the HIV positive partner. To this effect, the WHO is pursuing the 90-90-90 goal of virally suppressing as much of the population as possible to reduce HIV transmission. Pre-exposure prophylaxis (PrEP) refers to the administering of ARTs to a HIV negative person to prevent the acquiring HIV. Whilst initial studies showed moderate efficacy in reducing HIV transmission, this was shown to be due to poor adherence within the participant groups. Since the ARTs must reach minimum plasma concentrations to confer risk reduction for HIV, less than 2 tablets/week provides no reduction in HIV transmission, but at daily usage, PrEP is 99% effective. Currently, limitations include the moderately expensive PrEP course, reduced risk perception amongst PrEP users, as well as poor adherence, particularly in at risk groups (IV drug users etc.).
With regard to the trachea in an adult, indicate which of the following statements is/are TRUE, and which are FALSE. a) It contains 16 to 20 "U" shaped cartilages b) It has the left vagus nerve as an immediate relation in the thorax c) It has a soft posterior wall to allow for dilation of the oesophagus d) It usually begins at the level of the 4th cervical vertebra
a) It contains 16 to 20 "U" shaped cartilages The first statement is TRUE. The trachea is strengthened by these cartilages which are discontinuous posteriorly where the trachealis smooth muscle completes the posterior wall. b) It has the left vagus nerve as an immediate relation in the thorax The second statement is FALSE. The left vagus is separated from the trachea by the arch of the aorta c) It has a soft posterior wall to allow for dilation of the oesophagus The third statement is TRUE. Particularly at the level of the narrow thoracic inlet, dilation of the oesophagus during swallowing needs to be accommodated by the soft posterior wall of the trachea. d) It usually begins at the level of the 4th cervical vertebra The fourth statement is FALSE. The trachea begins at the sixth cervical vertebra level at the inferior margin of the cricoid cartilage of the larynx.
Which of the following statements about volume of distribution is LEAST correct? a. Lipophilic drugs have a low volume of distribution b. Metabolism increases the drug's hydrophilicity c. The mode of delivery of a drug can affect its peak plasma concentration d. Ophthalmic administration of a drug can lead to systemic effectse. Most drugs are lipophilic, aiding their distribution in the tissue
a. Lipophilic drugs have a low volume of distribution Answer: A. The volume of distribution is the theoretical volume needed to contain the total amount of administered drug at the same concentration as plasma drug concentration, i.e. Vd = Amount of drug / Plasma concentration. A high volume of distribution suggests that the drug has a tendency to leave the plasma and enter extravascular compartments of the body. Lipophilic drugs are able to cross lipid bilayers of cells and leave the bloodstream more readily than hydrophilic drugs. This means they have a higher volume of distribution. - Option B is a true statement: metabolism of a drug aims to change the drug into a form where it can be excreted, e.g. in the urine. For this to happen, the end product of drug metabolism must not be able to cross lipid bilayers, or else it will diffuse out of its excretion route. Hydrophilic substances cannot lipid bilayers and are easier to excrete, so metabolism should increase the drug's hydrophilicity. - Option C is a true statement: the mode of delivery is an important determinant of a drug's bioavailability, i.e. the proportion of the drug that avoids first pass metabolism and enter the plasma. Intravenous delivery achieves peak plasma concentrations instantly with no first pass metabolism, while other routes (oral, intramuscular, subcutaneous etc.) all have varying degrees of first pass metabolism. - Option D is a true statement: while rare, it is possible for unwanted systemic effects to occur from ophthalmic administration. Drugs administered through this route can enter circulation by draining into the nasolacrimal canal and into the nasal mucosa, where it is absorbed into circulation. - Option E is a true statement: since most drugs have a site of action outside of the bloodstream, they have to be lipophilic so that they can exit the bloodstream and reach their target tissue.
what happens to the CD4 and CD8 T cell levels in an untreated HIV infection?
as viral load begins to peak soon after primary infection, CD4+ cells start to drop. HIV targets CD4+ T cells specifically cuasing their dyregulation and death. in primary infection CD4 cells will drop close to 500/ul. During this time CD8+ lymphocytes will begin to spike in reaction to overload of viral antigens, they will kill antigens as well as infected CD4 cells which further contributes to decline of CD4+. - during the asymptomatic phase there is a slight increase in CD4+ count but ut never returns to normal and will again begin to decline as we progress into symptomatic AIDS.
Regarding immunodeficiency, which is MOST CORRECT?a. Pneumocystic pneumonia (PCP) is an uncommon feature of AIDS.b. When PCP does occur, the CD4 T cell count is >200 cells/mm3.c. Deficiencies of antibody are associated with an increased susceptibility to infection with pyogenic bacteria.d. Deficiencies of complement are associated with an increased susceptibility to mycobacterial infection.e. Incidence of prostate cancer is increased in immunodeficient men.
c. Deficiencies of antibody are associated with an increased susceptibility to infection with pyogenic bacteria. (a) PCP is a common features of AIDS - an AIDS defining illness (b) often PCP occurs when CD4 cells count is <200/mm3 (d) complement deficiency is vulnerable to: neisseria, haemophilus, strep, pneumococcus (e) predominantly skin and virally induced (e.g. cervical cancers are increased)
Regarding pharmacokinetics which one is not correct a. Decrease in Ke of a drug reduces clearance b. CYP450 enzymes are heme-containing proteins c. Inhibiting CYP450 would increase drug metabolism d. Clearance is inversely proportional to the area under the curve
c. Inhibiting CYP450 would increase drug metabolism
which stage of lung development occurs during the second trimester?
canalicular
Concerning the development of the diaphragm, which of these structures become the central tendon.a. Ventral Pleural Sacb. Mesentery of the oesophagus c. Septum Transversumd. 3rd to 5th Somitee. Pleuroperitoneal membranes
d. 3rd to 5th Somite forms the musculature of the diaphragm a. Ventral Pleural Sac (becomes connective tissue) b. Mesentery of the oesophagus (becomes the connective tissue around oesophagus) c. Septum Transversum (becomes the central tendon)d. 3rd to 5th Somite (becomes the musculature of the diaphragm)e. Pleuroperitoneal membranes (becomes connective tissue)
All of the following statements about pharmacokinetics are true, EXCEPT: a. Cardiac insufficiency can result in changes to drug clearance (CL) b. The maintenance dose of a drug is dependent on volume of distribution (Vd) c. Genetic polymorphisms in CYP450 enzyme can result in an increase in drug metabolism d. The alpha phase refers to the elimination phase of a drug e. Zero order kinetics assumes enzymatic saturation of a drug
d. The alpha phase refers to the elimination phase of a drug Answer: D. In the two-compartment model of pharmacokinetics for lipophilic drugs, the alpha phase refers to the distribution phase where the drug is being distributed from the blood into a peripheral compartment. The beta phase refers to the elimination phase of the drug, where the drug is removed from the circulation. - Option A is a true statement: cardiac insufficiency and congestive heart failure can cause a reduction in drug clearance. For example, it can cause hypoperfusion of the liver and kidneys, the main organs responsible for drug clearance. - Option B is a true statement: one of the most important utilities of volume of distribution is that it can determine the loading and maintenance dose of a drug. While the maintenance dose is primarily dependent on the clearance rate, clearance rate is still affected by volume of distribution (CL = Ke x Vd ), so maintenance dose is still affected by Vd . - Option C is a true statement: genetic variations in CYP450 expression can either cause an increase in drug metabolism (e.g. if there are more CYP450 enzymes than normal) or reduction in drug metabolism (if there are less CYP450 enzymes than normal). - Option E is a true statement: zero order kinetics describes drug clearance that occurs at a constant rate. This occurs when elimination mechanisms are completely saturated (e.g. metabolic enzymes are saturated), and there is no potential for clearance to proceed any faster. This means that drug elimination occurs at a fixed, maximal rate.
Regarding HIV in Australia, the following statements are true, EXCEPT:a. STI infection increases the risk of HIV transmissionb. The rate of HIV incidence has been decreasing in the last 15 yearsc. In recent years more gay men are engaging in unprotected anal sexual intercoursed. Prophylactic treatment of HIV-negative individuals has reduced the transmission of HIV by over 90%e. Intravenous drug transmission accounts for 10% of new cases of HIV
e. Intravenous drug transmission accounts for 10% of new cases of HIV In 2019, 59% of HIV notifications were attributed to sexual contact between men. 23% of cases were attributed to heterosexual sex, 7% to a combination of sexual contact between men and injecting drug use, 3% to injecting drug use alone, and 8% to other/unspecified. Rates of HIV incidence reached a peak in 2014 and has been declining since. Before that it had been increasing since 2000.
Ke
elimination rate constant
how do you differentiate between types of lymphocytes in sample
flow cytometry
Function of CD4 cells
help macrophages and neutrophils phagocytose bacteria and help Bcells make antibodies, help CD8 tcells in absence of DC as APC. stimulate function of other Tcells, B cells, and macrophages/granulocytes
reduced lung capacity in restrictive airway diseases is more apparent during rest or exercise?
restrictive impairment does not greatly affect airflow or gas exchange, and so at resting levels of ventilation there are likely to be few signs of the disorder. However, the reduced lung capacity becomes significant when greater demands are placed on the respiratory system
how do b and t cells enter the lymph nodes?
via blood vessel hilum to endothelial venules then to lymph nodes.
will the vital capacity be decreased in restrictive pulmonary diseases?
yes! the vital capacity is the maximal volume of gas that can be expelled from the lungs by forceful effort following max insporation. VC = VT + IRV + ERV. The definition of restrictive impairment is decrease in total lung capacity
is HIV medication recommended during pregnancy?
yes, to reduce risk of perinatal transmission and to improve maternal health
Adam is a man who was found to have HIV infection and Pneumocystis carinii pneumonia.Explain how HIV infection is affecting Adam's immune system. Define opportunistic infection. Apart from AIDS, what other conditions can cause immunocompromise?
• HIV infects CD4 (helper) T cells and over time (usually several years) leads to a serious decline in the number of CD4 T cells. This is most easily measured by determining the blood concentration of CD4 T cells. Adam is likely to have a seriously reduced number of blood CD4 T cells. • Helper T cells have a normal role in co-ordinating the immune system and providing help to cytotoxic T cells, macrophages and B cells. When helper T cells are reduced in number, the immune system is less effective in responding to infections.• In people with advanced HIV infection, the function of the immune system is seriously impaired. They are at serious risk of opportunistic infection.• Opportunistic infections are caused by micro-organisms that do not cause disease in people with normal immune systems. As well, there is increased incidence of certain malignancies: lymphoma, Kaposi's sarcoma, cervical cancer (linked to viral triggers). • Other causes of immunocompromise include malnutrition, effects of anti- inflammatory, immunosuppressives or cytotoxic drugs, radiation therapy, diabetes mellitus, burns and primary (congenital) immunodeficiency.