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TITLE:A Multiple Choice Geriatric Examination Assessing the Integration of

Clinical and Underlying Sciences

AUTHORS:Steven Denson, MD, Kathryn Denson, MD, Edmund Duthie Jr, MD, Diane

Brown, MS, Deborah Simpson, PhD

CORRESPONDING AUTHORDeborah Simpson, PhD

PARTIALLY FUNDED BY:Donald W. Reynolds Foundation and the Wisconsin Geriatrics

Education Center

CONTENTS:1. 26 Item Examination

a. 13 Clinical Items Paired with 13 Underlying Science Items2. 2 Versions

a. Questions each annotated with answer keyb. Handout version of questions

Wednesday, May 10, 20239/12/2013 V3 AAMC iCollaborate from Version MCQ 3 27.13 with Annotate V2.1 – 1 | P a g e

Source: https://www.mededportal.org/icollaborative/resource/843

https://www.mededportal.org/icollaborative/resource/843

ANNOTATED ASSESSING CLINICAL GERIATRICS & UNDERLYING SCIENCE TOOL

1. Pulmonary function tests were ordered on an 85 year old patient. When reviewing the report, which of the following factors would you expect to decline compared to a healthy normal 25 year old man of the same size?

A) A-a gradient B) PCO2 C) Residual volume D) Total lung capacity E) Vital capacity

ANSWER: E) Vital capacityPulmonary function changes as a result of aging. The pCO2 is unchanged; the main effect on gas exchange is declining pO2 and an increase in the A-a gradient. These changes can be accelerated by smoking, but are also seen among non-smoking patients. Total lung capacity is unchanged with aging. With aging, mechanical changes of lung function are associated with some air trapping and a rise in residual volume resulting in a decline in the vital capacity with aging.

TOPIC: Normal agingTHEMES: Connective tissue changes REFERENCE: Pisani M, Ely EW. Respiratory Diseases and Disorders. In: Pacala JT, Sullivan GM.

Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine, 7th ed. New York: American Geriatrics Society; 2010.

2. What is the underlying science that best explains these age-related pulmonary changes? A) Altered immunity B) Connective tissue changes C) Growth hormone decline D) Osteoporosis of the ribs E) Smoking

ANSWER: B) Connective tissue changesANNOTATIONS: An important underlying mechanism involves changes in the connective tissue

(collagen cross linking, elastin degeneration) affecting the pulmonary parenchyma as well as the chest wall. Bone loss of the ribs is not the important chest wall connective tissue change that affects pulmonary function (kyphoscoliosis, calcification of costal cartilages play a larger role). Sarcopenia of the diaphragm also plays a role. These changes can be accelerated by smoking, but are not all due to smoking and are seen among non-smoking subjects. Although there is growth hormone decline with aging and altered immunity, these would not explain the pulmonary changes.


Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine, 7th ed. New Medical College of Wisconsin – September 12, 2013 2 | P a g e




York: American Geriatrics Society; 2010.3. You are caring for a geriatric woman with urinary incontinence who is sexually active. A pelvic exam was

done to better understand her incontinence. The examination reveals thin vaginal mucosa with decreased rugae and reduced vaginal secretions.

The most likely explanation for these findings is: A) Age-related connective tissue changes B) Estrogen decrease C) Impact of urinary leakage on surrounding vaginal mucosae D) Sexual activity

ANSWER: B) Estrogen decrease

ANNOTATIONS: The decline in estrogen influences target tissue (such as the vaginal mucosae) resulting in the atrophic changes seen in this patient. This anatomic change is not solely age related as estrogen hormone replacement can restore tissues to their prior status. Sexual activity should not result in tissue atrophy. Urinary leakage is a condition not uncommonly seen with aging and can lead to vaginal tissue changes, but these changes would more likely be inflammatory and not simply atrophy.

TOPIC: Endocrinologic changes with agesTHEMES: Cellular replicationREFERENCE: Timiras PS, ed. Physiological basis of aging and geriatrics. Boca Raton, FL: CRC

Press; 2003.

4. The underlying science that best explains the pelvic findings is: A) Autoimmunity associated with aging B) Cellular senescence C) Loss of cellular structural integrity D) Neurodegenerative central pituitary failure E) Neurodegenerative hypothalamic failure

ANSWER: B) Cellular senescenceANNOTATIONS: Menopause is a classic example of aging changes. The primary etiology of

menopause problem is cellular senescence with ovarian failure and the loss of follicles that are able to develop and result in ovulation. This follicular loss results in the loss of steroid hormones. The hypothalamus and pituitary do not primarily drive ovarian loss and pituitary hormones, in fact, luteinizing (LH) and follicular stimulating hormone (FSH) are both initially elevated in response to ovarian failure. Chronic inflammatory changes in the ovary are not considered to be the cause of this follicular loss. Cellular structural integrity is not the cause of ovarian failure.


Medical College of Wisconsin – September 12, 2013 3 | P a g e




Press; 2003.

5. An 88 year old patient comes to your clinic with a chief complaint of memory loss, which has been gradual and progressive over the past two years. More recently, the patient notices difficulty with finding the “right” words and has more difficulty managing work at home. The patient’s spouse mentions that the patient has had some problems with getting lost while driving, has made some errors in balancing the checkbook and has lost interest in some of the activities that used to be enjoyed. Clinically the patient seems to have a flat affect. Given this history, the most likely etiology of the patient’s symptoms is:

A) Age-related memory loss B) Alzheimer’s dementia C) Delirium D) Mild cognitive impairment E) Vascular dementia

ANSWER: B) Alzheimer’s dementiaANNOTATIONS: This patient has symptoms of Alzheimer’s Dementia. This includes cognitive

impairment in memory and other areas of cognitive functioning that impair normal home, work, or social functioning. These cognitive and resulting functional changes occur slowly over time. Age-related memory loss is described by mild changes or occasional impairment in word finding, recall, or information retrieval. Delirium is distinguished from dementia in part, by its onset and course. Dementia’s gradual onset and general constancy differs from the medical condition of delirium, which is an acute, potentially reversible, decline in cognition and function as a response to a medical or systemic illness or event. Mild cognitive impairment is a decrease in some areas of memory, such as new task learning or difficulty making new memories. This loss is mild, and, unlike dementia, does not contribute to functional decline and loss. Vascular dementias are the second most common cause of dementia, causing cognitive loss through direct injury to cognitive portions of the brain. Vascular dementia may present in a “step-wise” manner, with periods of abrupt cognitive decline, then stabilization, and further abrupt decline over time.

TOPIC: Genetics – basic science principles of agingTHEMES: Post-mitotic tissue predilection for age changesREFERENCE: Budson AE, Solomon PR. New criteria for Alzheimer’s disease and mild cognitive

impairment: implications for the practicing clinician. Neurologist. 2012;18(6):356-363.

6. The underlying science that explains the cognitive complaints and decreased function is that there are genetic mutations leading to:

A) Decreased blood perfusion to neuronal cells in the brain B) Decreased serotonin levels in the brain with aging C) Increased amyloid proteins D) Increased acetylcholine in the brain





E) Increased oxidation, free radicals, and neuronal cell damage

ANSWER: C) Increased amyloid proteinsANNOTATIONS: Genetic mutations leading to Increased amyloid proteins is the underlying etiology

of the patient’s dementia. The aging brain develops amyloid plaques and neurofibrillary tangles, and undergoes both synaptic and neuronal loss. Plaques can develop extracellularly throughout the nervous system, and is thought to induce cell death by the development of free radicals and inflammatory products. Neurofibrillary tangles develop from tau proteins, and deposit within neuronal cells. When tangles developing within the hippocampal, medial temporal, parietotemporal and frontal cortices reach a critical point, they can lead to neuronal cell death and impair cognitive and brain function. This constitutes the most common form of dementia, with prevalence increasing with age. While periods of decreased blood perfusion to neurons in the brain may result in cognitive loss from stroke (vascular dementia), this etiology of dementia is not due to clear genetic mutations. Serotonin is a neurotransmitter in the brain that is associated with depression. Acetylcholine levels in the brain do not increase with genetic mutations, and may, in patients with increased amyloid and tau proteins decrease as a result of neuronal cell death. Increased oxidation, free radicals and neuronal cell damage are occurring in the process of Alzheimer’s dementia, but this is not a direct result of a genetic mutation.



7. A 70 year old presents to clinic for routine follow-up and an annual physical exam. The patient has a history of hypertension, hypercholesterolemia, and coronary artery disease. The patient is a retired farm hand, having worked on several large ranches in Texas, New Mexico, and Arizona. On exam, the patient has moderately pigmented, very wrinkled skin.

Also notable is a small scaly red plaque lesion on the helix of the right ear, and several small lesions on the scalp where the hair is thinning. There is a history of extensive sun exposure, but rarely of blistering burns. The most likely lesion is:





ANSWER: B) Squamous cell cancer ANNOTATIONS: This lesion is most characteristic of a squamous cell skin cancer. Squamous cell

cancer is the second most common type of skin cancer, mainly caused by lifetime of cumulative UV exposure. Seven hundred thousand squamous cell cancers are diagnosed annually, with approximately 2500 annual deaths. It is characterized by red, elevated scaly patches often with a central depression. A melanoma skin cancer is characterized as a dark lesion, potentially multicolored, with variation in color and roughness of lesion borders. Seborrheic keratosis is a non-malignant skin lesion which is frequently confused with melanoma in appearance. It darkens in appearance over time, appears rough in texture and “stuck on” in appearance. Tophus is a lesion which may be seen in cartilaginous areas of the body and is associated with gout.

TOPIC: Environmental: UV solar radiation, ionizing radiation, etc.THEMES: Connective tissue changesREFERENCE: Stulberg DL, Crandall B, Fawcett RS. Diagnosis and Treatment of Basal Cell and

Squamous Cell Carcinomas. Am Fam Physician. 2004;70(8):1481-1488.

8. The underlying science that best explains the pathology of this skin lesion is: A) Thymidine dimer damage in the p53 tumor suppressor gene preventing repair of mutated

keratinocytes B) Damage to melanocyte tumor suppressor gene p16 C) Mutation to gene CDKN2A on 9p21 resulting in melanocyte suppressor damage to p16 and p14ARF D) Autosomal dominant mutation to the PTEN tumor suppressor gene E) Purine nucleotide metabolism end-product deposition in joints and soft tissues

ANSWER: A) Thymidine dimer damage in the p53 tumor suppressor gene preventing repair of mutated keratinocytes

ANNOTATIONS: The underlying pathophysiology of squamous cell cancer is thought to be thymidine dimer damage at the p53 tumor suppressor gene, which then prevents the genetic repair of UV damaged keratinocytes. The melanocyte tumor suppressor gene p16 has been implicated in melanoma formation. CDKN2A on 9p21 is a tumor suppressor gene that is associated with a number of tumors, including melanoma. PTEN is a tumor suppressor gene linked to glioblastoma, endometrial cancer, and prostate cancers.. Purine nucleotide end-products are associated with gout, which can form tophi.



A) Melanoma B) Squamous cell cancer C) Seborrheic keratosis D) Psoriasis E) Tophus





9. A patient is interested in maximal longevity. She asks you for the current best evidence in animal studies that supports increasing the life span. Which of the following factors has the best data to support its efficacy to increase mammalian life span?

A) Acetylcholinesterase -Inhibitors B) Caloric restriction C) Exercise D) HMG-CoA reductase inhibitors E) Stress reduction

ANSWER: B) Caloric restriction ANNOTATIONS: Caloric restriction has the best experimental evidence in animals to support

increasing life span. The other measures (ACE inhibitors, exercise, HMG-CoA redutase inhibitors) may contribute to increased life expectancy but do not explain maximal longevity associated with caloric restriction.

TOPIC: TOR-Target of Rapamycin-signaling conserves cellular energy (beneficial to aging)THEMES: Cellular replication and control of mitotic processesREFERENCE: . Kapahi P, Vijg J. Aging — Lost in Translation? N Engl J Med. 2009;361:2669-2670

10. Drawing upon your basic science knowledge, which of the following genetic pathways is felt to modulate longevity?

A) Hedgehog pathway B) Rapamycin (now known as sirolimus)(TOR) pathway C) Ras-regulated signal pathway D) Transforming growth factor ß (TGF ß) Pathway

ANSWER: B) Rapamycin (now known as sirolimus)(TOR) pathway ANNOTATIONS: On the molecular level, caloric restriction inhibits the TOR pathway. A downstream

target of the TOR pathway is ribosomal protein S6 kinase. Deletion of this kinase gene leads to an increased life span. Inhibition of TOR has a similar effect. The other pathways listed do not explain longevity associated with caloric restriction.

TOPIC: TOR-Target of Rapamycin-signaling conserves cellular energy (beneficial to aging)THEMES: Cellular replication and control of mitotic processesREFERENCE: Kapahi P, Vijg J. Aging — Lost in Translation? N Engl J Med. 2009;361:2669-2670

11. Mrs. Golden is an 85 year old woman who presents to your clinic with excruciating, new onset mid-back pain that is constant and non-radiating. She states she fell on the ice yesterday while walking her dog. Her pain has not decreased with acetaminophen and ibuprofen. What would be the next step you would take with this patient?

A) Obtain calcium and 25(OH) D levels Medical College of Wisconsin – September 12, 2013 7 | P a g e




B) Order DEXA scan C) Order bed rest and increase ibuprofen dosage D) Obtain physical therapy consultation E) Order radiograph of the thoracic vertebrae

ANSWER: E) Order radiograph of the thoracic vertebrae ANNOTATIONS: The best next step in the evaluation of this patient with osteoporosis risk factors

and unremitting pain after a fall is to image the area of pain, specifically the back. A result of a vertebral fracture will give the etiology of the pain and will guide treatment decisions. Calcium and 25 (OH) D levels may indicate an underlying etiology for possible osteoporosis or low bone mass, and should be done as a secondary step in overall bone health and osteoporosis prevention and treatment. A DEXA scan is used to further quantify, radiographically, bone mass. It may be helpful in understanding bone health, but will not diagnose the cause of the back pain. Bed rest can increase symptoms and risks associated with immobility, and ibuprofen may lead to renal and gastric side effects. Physical therapy will likely be of benefit, but the first step is diagnostic with a radiograph of the thoracic vertebrae

TOPIC: OsteoporosisTHEMES: Impaired homeostasis, connective tissue changesREFERENCE: Lewiecki EM. Current and emerging pharmacologic therapies for the management

of postmenopausal osteoporosis. J Women's Health. 2009;18(10):1615-1626.

12. The underlying science that explains the etiology of the patient’s pain is: A) A homeostatic imbalance between osteoclastic and osteoblastic activity B) A physiological decrease in parathyroid hormone secretion with aging C) Connective tissue cross-linking of collagen decreases with aging D) Horizontal trabeculae of trabecular bone of vertebrae are lost with aging E) Insulin-like growth factor-1 (IGF-1) over activity

ANSWER: A) A homeostatic imbalance between osteoclastic and osteoblasticANNOTATIONS: Osteoporosis is caused by a homeostatic imbalance between osteoclastic and

osteoblastic activity. Risk factors for osteoporosis include being female, thin, small framed, family history, post-menopausal estrogen deficiency, low testosterone [in males], Asian or Caucasian, and old. Secondary conditions like parathyroidism can induce bone resorption, typically this is seen with low parathyroid states and is not a part of normal aging. Collagen cross-linking does not decrease with aging. Growth hormone and IGF-a overactivity are associated with acromegaly and not osteoporosis.







13. A 75 year old is evaluated for a 2 year history of progressive pain in the left knee that worsens with activity and decreases with rest. It is worst along the medial aspects of the joints, but does not lock or give way. There is neither swelling nor any morning stiffness. On exam, there is a no evidence for an effusion, but passive range of motion is painful for flexion and extension. Plain radiography and lab work (including CRP, ESR, and CBC) are normal. Which of the following is the most appropriate next step in management?

A) Arthrocentesis B) MRI of the knee C) Physical therapy D) Rheumatoid Factor E) Uric acid level

ANSWER: C) Physical TherapyANNOTATIONS: In a patient with pain in a load bearing joint without evidence for infection,

effusion, or severe inflammation, the most prudent course of action is physical therapy. Arthrocentesis would not be considered a first line treatment for pain in a joint, especially a joint without an effusion noted on clinical exam. An MRI is unlikely in this situation to provide actionable information beyond the clinical exam, and is an expensive first step. Without symptoms of rheumatoid arthritis or active gout, laboratory studies for rheumatoid factor, and uric acid levels are not warranted and will be of low clinical yield diagnostically.

TOPIC: OsteoporosisTHEMES: Impaired homeostasis, connective tissue changesREFERENCE: Ramiro S, Radner H, et. al. Combination therapy for pain management in

inflammatory arthritis. Cochrane Database of Systematic Reviews. (10):CD008886, 2011.

14. The underlying basic science that explains the patient’s clinical problem is: A) Defective repair, inflammatory infiltrates and synovitis, and cytokine mediated cartilage degradation B) HLA-DRB1*0401 and *0404 histocompatibility loci on synovial macrophages acting as antigen

presenting cells C) Immune-complex mediated deposition and tissue destruction D) Purine nucleotide metabolism end-product deposition in joints and soft tissues

ANSWER: A) Defective repair, inflammatory infiltrates and synovitis, and cytokine mediated cartilage degradation

ANNOTATIONS: The mechanisms for arthritic pain in a joint are inflammatory infiltrates and synovitis with cytokine medicated cartilage degradation and defective repair. . HLA-DRB1*0401 and *0404 histocompatibility loci are related to genetic risks of developing rheumatoid arthritis and are not associated with osteoarthritis. Immune complex mediated deposition and tissue destruction is a hallmark of immune mediated or reactive arthritis Purine nucleotide metabolism end-product deposition in joints and soft tissues is the pathophysiology of gout and does not





explain the patient’s condition.TOPIC: OsteoporosisTHEMES: Impaired homeostasis, connective tissue changesREFERENCE: Ramiro S, Radner H, et. al. Combination therapy for pain management in


15. An 85 year old woman is admitted to your ward service. She has isolated systolic hypertension. Her carotid pulse upstroke is bounding. Which of the following aging changes accounts for these findings?

A) Adrenal Medullary Catecholamines B) Arteriosclerosis C) Atherosclerosis D) Cardiac Output E) Renal Function

ANSWER: B) ArteriosclerosisANNOTATIONS: Arteriosclerosis is the process by which blood vessels stiffen due to deterioration

of the elastin and collagen in the media of the vessel wall associated with calcium deposition over time. Atherosclerosis is a disease of the intima and is responsible for vessel occlusion; it would not cause the changes in the pulse contour described in this case nor the blood pressure findings. Cardiac output overall does not change substantially with aging alone, although is frequently decreased, and occasionally increased, as a result of disease processes. Age related changes in renal function would not be expected to change arterial pulse contour.

TOPIC: Arterial aging - w/age the arterial walls stiffen. Eventually, the transmission of flow pulsations downstream to organs (brain and kidney’s first). Elastin comprises 90% of arterial fibers.

THEMES: Connective tissue changes with agingREFERENCE: Rich MW. Cardiovascular Disorders and Diseases. In: Pacala JT, Sullivan GM eds.


16. The underlying science that best explains these blood pressure and blood vessel findings is: A) Neural aging B) Connective tissue changes of the vessel media C) Blood vessel intimal plaque formation D) Renal-hormonal changes associated with aging E) Catecholamine depletion with aging

ANSWER: B) Connective tissue changes of the vessel media ANNOTATIONS: Arteriosclerosis is the process by which blood vessels stiffen with aging due to

deterioration of the elastin and collagen in the media of the vessel wall associated with calcium deposition. These changes can cause vessel rigidity and can





contribute to systolic blood pressure increase and an increased upstroke when palpating the pulse. With aging, renin typically declines as a result of renal aging changes. Renal aging will not explain the findings. Beta receptors are blunted as a function of age. Catecholamine levels are maintained and do not explain these findings.

TOPIC: FIBERS. Arterial aging - w/age the arterial walls stiffen. Eventually, the transmission of flow pulsations downstream to organs (brain and kidney’s first). Elastin comprises 90% of arterial



17. A 70 year old man wishes to conceive a child with his 37 year old wife. This would be their third child, the other two being healthy. Both parents are healthy with no diagnosed medical conditions. The wife continues to have normal menses. Despite a 12 month course of fertility drugs, the couple is unable to conceive.

What is the most likely male factor preventing conception? A) Benign prostatic hyperplasia B) Chronic UTIs C) Diminished sperm concentration in the ejaculate D) Diminished sperm viability

ANSWER: D) Diminished sperm viability ANNOTATIONS: An estimated 15% of couples are infertile, of which 20-40% is related to male

infertility problems. Male infertility can be broadly divided into abnormal sperm production, sperm function, and obstruction to outflow. Of these, diminished sperm viability is the most common cause, as androgens are central in both cell division and in seminal fluid production. Other common medical causes include varicocele, infections (gonorrhea, chlamydia, prostatitis, or mumps orchitis), retrograde ejaculations (from diabetes, spinal injury, meds, surgical changes), auto-antibodies to sperm, tumors, undescended testes, hormone imbalances, sperm duct defects, chromosomal abnormalities, erectile dysfunction, celiac disease, and certain medications .Environmental causes include chronic overheating of the testicles, radiation exposure, lead and other heavy metals as well as benzene, toluene and other organic industrial chemicals. Lifestyle causes include illicit drug use, alcohol, tobacco, stress, prolonged bicycling or horseback riding, and obesity.

TOPIC: Telomeres – role of telomere shortening in infertilityTHEMES: Post mitotic tissue, age changes.REFERENCE: Wiener-Magnazi, Auslender R, Dirnfeld M. Advanced paternal age and

reproductive outcomes. Asian J Andrology. 2012;14(1):69-76.





18. The science underlying the patient’s infertility is: A) Age-related degeneration of the Leydig and Sertoli cells B) Age-related impairment in production of seminal fluid C) Epididymal amyloid deposition preventing mature sperm transport D) Germ cell degeneration and loss during meiosis and mitosis E) Impaired inflammatory response in bladder mucosa

ANSWER: D) Germ cell degeneration and loss during meiosis and mitosisANNOTATIONS: Androgens are central in both cell divisions and in seminal fluid production, and

would cause germ cell degeneration and loss in both meiosis and mitosis. This is the most likely cause of infertility of the choices offered. While age related changes in seminal fluid and in Sertoli cells (that help mature spermatozoa) and Leidig cells (which release androgens) would impact spermatogenesis, it would not impact fertility as directly as germ cell degeneration. The bladder mucosa is part of the urologic system but does not impact the reproductive system in this way.



19. A 90 year old with a history of dementia was brought to the emergency department after a fall at home, and was noted to be confused and agitated by the daughter. The patient was recently started on risperidone as an outpatient. The patient complains of cough, rhinorrhea and myalgias. EMR indicates all immunizations are current. Patient’s vitals showed temp 102.5F, RR 24, HR 90, ox sat 96% on RA. Cardiac and abdominal examinations were unremarkable, pulmonary exam showed bilateral wheezes. Pertinent Lab values showed: Na 132, WBC 14.0. CXR was negative. UA showed positive nitrates, 0-5 WBC, hyaline casts and moderate bacteria. What is the most likely ROOT CAUSE of the patient’s change in condition?

A) Delirium B) Hyponatremia C) Influenza D) Neuroleptic malignant syndrome E) Urinary tract infection

ANSWER: C) InfluenzaANNOTATIONS: While this patient is presenting with delirium (an acute change in cognitive

function and attention), this is a syndrome and does not represent the root cause of her clinical complaints and findings. Of the listed choices, influenza is the only choice that would meet the symptoms of an upper respiratory infection, fevers, and cough. Although she was vaccinated, immunosenescent changes in vaccine response commonly decrease the protective effects of influenza vaccines, and this patient has the typical clinical presentation of influenza. The patient’s hyponatremia is not severe, and is unlikely to be at a level to cause her clinical condition. There is no evidence for a urinary tract infection on testing, and she has





no evidence of neuroleptic malignant syndrome given her respiratory complaints.TOPIC: Immune system changes with aging (atypical presentation of infection/decreased

leukocytosis)THEME: ImmunologyREFERENCE: Gravenstein S, Fillit HM. Clinical Immunology of aging. In: Tallis R, Fillit H, eds.

Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 6th Ed. London, England. Churchill Livingstone Press. Pgs: 113-124; 2003.Lang PO, Govind S et al. Immunosenescence: Implications for vaccine programes in adults. Maturitas. 2011;68(4):322-330.

20. The underlying science that explains the change in the patient’s condition is: A) Age related increase in AVP release B) CNS neuroendocrine changes with aging C) Decreased cytotoxic T lymphocyte activity D) Drug related side effect E) Increased proliferative capacity of lymphocytes in response to antigens

ANSWER: C) Decreased cytotoxic T lymphocyte activity ANNOTATIONS: Decreased cytotoxic T lymphocyte activity is the most likely cause of the patient’s

symptoms. Common changes in the immune system with aging include slower immune response to infection and vaccination, impaired healing, tumor and malignancy management, and increased risks of autoimmune disorders. Immunosenescence manifests through changes in antigen presentation, decreased specific antibody responses, and altered cytokine functions. Changes to T and B cells see both rises in pro-inflammatory cytokines and autoimmune antibodies, and decreases in T and B cell activity and function. There is also a decrease in neutrophil, macrophage, NK, and dendritic cells. Studies have demonstrated up to a 50% decline in antibody response to vaccines in persons over the age of 65. The end result is increased susceptibility to infection, and decreased vaccination efficacy. AVP would have more impact on sodium and water balance and does not affect the immune system directly in this way. CNS neuroendocrine changes with aging, while perhaps contributing to the patient’s underlying cognitive loss and predisposing the patient to delirium, are not the acute etiology behind the patient’s current presentation. Risperidone may contribute to the patient’s cognitive decline and agitation but would not explain her pulmonary disease and fever.

TOPIC: Immune system changes with aging (atypical presentation of infection/decreased leukocytosis)

THEME: ImmunologyREFERENCE: Gravenstein S, Fillit HM. Clinical Immunology of aging. In: Tallis R, Fillit H, eds.

Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 6th Ed. London, England. Churchill Livingstone Press. Pgs: 113-124; 2003.





Lang PO, Govind S et al. Immunosenescence: Implications for vaccine programes in adults. Maturitas. 2011;68(4):322-330.

21. A 79 year old woman presents to the clinic with a chief complaint of back pain. The pain has been present for the past four months. On ROS the patient is found to have a 20 lb unintentional weight loss. Physical examination shows some point tenderness over the spine where here pain is. Lab studies reveal a hematocrit of 30. What is the next step in the patient’s management?

A) Bone marrow biopsy B) CT of the spine with contrast C) Parathyroid level D) Radionuclide bone scan E) SPEP/UPEP (Serum & Urine Protein Electrophoresis)

ANSWER: E) SPEP/UPEP (Serum & Urine Protein Electrophoresis) ANNOTATIONS: The patient’s medical presentation is most consistent with a disease of multiple

myeloma. Multiple myeloma is the second most common hematologic malignancy after non-Hodgkin’s lymphoma. The most common symptoms of multiple myeloma include bone pain, often in the spine and ribs, infection (related to impaired immune response; often a pneumonia), renal failure (due to nephrotoxic effects of light chains within the kidneys), anemia (usually a normocytic and normochromic anemia), and neurological symptoms (fatigue, confusion, headache, weakness).

Initial evaluation is usually serum and urine electrophoresis looking for paraproteins (for example, Bence-Jones proteins in the urine). The most common serum paraprotein is IgG, followed by IgA and IgM. This first step is ideal in that it begins with relatively non-invasive and less expensive diagnostic tests. A bone marrow biopsy is helpful and can be diagnostic, but is also invasive and not a first line test. A CT of the spine may demonstrate lytic lesions that would raise suspicion for multiple myeloma, but would not be diagnostic of it. A parathyroid level is non-diagnostic for multiple myeloma. Skeletal surveys and radionucleotide bone scans are helpful to identify abnormalities in the bone but are usually non-specific and need to be combined with the electrophoresis data to be more diagnostic of multiple myeloma.

TOPIC: antioxidants, mitotic processes, cell damage, repair mechanismsTHEME: cellular replication and control of mitotic processes (neoplasia in the elderly)REFERENCE: Terpos E. Dimopoulos MA. Myeloma bone disease: pathophysiology and

management. Annals of Oncology. 2005;16(8):1223-1231.

22. One underlying basic science theory that may explain the clinical findings in this case is: A) Continuously mitotic cells are more prone to oncogenic transformation B) Increased tumor growth due to a decline in humoral immune function C) Oxidative damage to cell membranes occurs over time D) Tumor suppressor genes are auto-regulated in elderly patients





ANSWER: A) Continuously mitotic cells are more prone to oncogenic transformation ANNOTATIONS: The basic science underlying multiple myeloma, and many cancers in general, is

that continuously mitotic cells are more prone to genetic injury and oncogenic transformation than those cells that are less frequently mitotic. While the other three answer choices are related to cancer development, they are not the primary basic science underlying the oncogenic transformation of healthy cells into the oncogenic cells of multiple myeloma



23. A 70 year old is brought into the Emergency Department at midnight following a motor vehicle crash on the way home from a restaurant. The patient has a history of diabetes, hypertension, and hyperlipidemia. The patient often has vision problems at night, with seeing halos around lights, and visual acuity is a bit “hazier” lately. The patient has recently started limiting night driving, wears glasses, and was wearing them at the time of the incident. On exam there are no visual field deficits. The most likely visual impairment contributing to the accident is:

A) Age-related macular degeneration B) Diabetic retinopathy C) Cataract formation D) Glaucoma

ANSWER: C) Cataract formation ANNOTATIONS: Cataracts are a formed by a chronic opacification of the lens of the eye, leading to

decreased visual acuity. The visual changes are caused by spatial density fluctuations, scattering and absorption of light, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment. The result is a gradual decrease of visual acuity, clouding of vision resulting in glare and nighttime/ low light transmission through the eye. The causes include age (most common cause), ultraviolet radiation exposure, especially uv-B, trauma, cigarette smoking, medications, and certain diseases. There are genetic conditions that are associated with cataract formation, notably Down’s and Turner’s syndromes, and trisomy 18. Macular degeneration is a loss of central vision due to damage of the macular portion of the retina. Diabetic retinopathy is damage to the retinal caused by systemic (including the eye) vascular disease and may present with blurred vision. Glaucoma describes an ocular disorder with increased intraocular pressure, which may clinically present as a loss of peripheral vision with remaining, “tunnel vision”.

TOPIC: Environmental Stochastic changesTHEME: Post mitotic tissue, age changes





REFERENCE: Harvery PT. Common eye diseases of elderly people: identifying and treating causes of vision loss. Gerontology. 2003;49(1):1-11.

24. The underlying science that explains the visual impairment is: A) Drusen deposition, geographic atrophy, serous detachment of the retinal pigment epithelium, and

neovascularization B) Gradual changes in retinal microvasculature leading to retinal nonperfusion, increased vascular

permeability, and uncontrolled neovascularization C) Age-related spatial density fluctuations, light scattering and absorption, formation of opaque lens

fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment D) Intraocular pressure causing blockade of the lamina cribrisa of axonal protein transport, causing

neuronal retinal ganglion cell death by trophic insufficiency

ANSWER: C) Age-related spatial density fluctuations, light scattering and absorption, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment

ANNOTATIONS: The underlying science of cataract formation is age-related spatial density fluctuations, light scattering and absorption, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment. Age related macular degeneration is a leading cause of blindness that affects the macula faster than the peripheral retina. It is related to drusen deposition, geographic atrophy, and serous detachment of the retinal pigment epithelium as well as neovascularization. Diabetic retinopathy is caused by microvascular retinal changes that lead to non-perfusion and increased vascular permeability; this can cause a hypoxic or anoxic state within the retina, which in turn stimulates uncontrolled neovascularization. Glaucoma causes gradual vision loss often beginning in the periphery and causing tunnel vision. It is related to increased intraocular pressure causing blockage of the lamina cribrisa and impairing axonal protein transport and causing neuronal retinal ganglion cell death by trophic insufficiency.

TOPIC: Environmental Stochastic changesTHEME: Post mitotic tissue, age changesREFERENCE: Harvery PT. Common eye diseases of elderly people: identifying and treating

causes of vision loss. Gerontology. 2003;49(1):1-11.

25. An 88 year old patient is under your care in the hospital. The patient develops delirium and is found to have a serum glucose level of 750 mg/dl. There was no prior history of diabetes. The patient had received a glucose infusion post operatively. Which of the following age-related changes most likely contributed to the patient’s risk of developing hyperglycemia?

A) Accelerated glycogenolysis B) Growth hormone excess C) Hypercortisolism D) Insulin resistance





E) Pancreatic endocrine failure

ANSWER: D) Insulin resistance ANNOTATIONS: Diabetes is a major health problem and has an increased prevalence in later life.

Type 2 diabetes can result in patients developing very high blood glucose levels. The fundamental problem is insulin resistance which can be traced to cellular changes beyond the insulin receptor. Patients may be asymptomatic at baseline but the stress of illness and hospitalization, as well as the challenge of IV glucose and some medications (e.g., glucocorticoids) or infection, may result in an increase in serum glucose levels. Growth hormone excess and hypercortisolism are not endocrinological changes of normal aging. Additionally, a decrease or lack of insulin from pancreatic endocrine dysfunction is not typically seen with aging alone.

TOPIC: Diabetes MellitusTHEME: Impaired homestasisREFERENCE: Blaum CS. Diabetes mellitus. In: Pacala JT, Sullivan GM eds. Geriatrics Review

Syllabus: A Core Curriculum in Geriatric Medicine, 7th ed. New York: American Geriatrics Society; 2010.

26. While the basic science underlying body composition is not yet clear, which of the following changes in body composition contributes to glucose intolerance with aging?

A) Increased cross linking of connective tissue B) Increased hepatic size accelerating insulin breakdown C) Increased lipofuscin deposition in the pancreas D) Reduced lean body mass E) Reduced renal mass with altered glucagon excretion

ANSWER: D) Reduced lean body mass ANNOTATIONS: With age there are important changes in body composition. There is loss of lean

mass which can result in sacropenia. There is also a loss of body water and cell solid. Body potassium, an indirect marker of lean body mass, also declines with age. Body fat increases as a function of age. Although these body composition changes are important contributors to relative insulin resistance, obesity (not a normal aging change) likely plays a more important role.







END OF ANNOTATED EXAMINATION




MULTIPLE CHOICE EXAMINATION ASSESSING CLINICAL GERIATRICS & UNDERLYING SCIENCE Circle Correct Answers and Submit as Directed

1. Pulmonary function tests were ordered on an 85 year old patient. When reviewing the report, which of the following factors would you expect to decline compared to a healthy normal 25 year old man of the same size? A) A-a gradient B) PCO2 C) Residual volume D) Total lung capacity E) Vital capacity

ANSWER: E) Vital capacityPulmonary function changes as a result of aging. The pCO2 is unchanged; the main effect on gas exchange is declining pO2 and an increase in the A-a gradient. These changes can be accelerated by smoking, but are also seen among non-smoking patients. Total lung capacity is unchanged with aging. With aging, mechanical changes of lung function are associated with some air trapping and a rise in residual volume resulting in a decline in the vital capacity with aging.



2. What is the underlying science that best explains these age-related pulmonary changes? A) Altered immunity B) Connective tissue changes C) Growth hormone decline D) Osteoporosis of the ribs E) Smoking

ANSWER: B) Connective tissue changesANNOTATIONS: An important underlying mechanism involves changes in the connective tissue

(collagen cross linking, elastin degeneration) affecting the pulmonary parenchyma as well as the chest wall. Bone loss of the ribs is not the important chest wall connective tissue change that affects pulmonary function (kyphoscoliosis, calcification of costal cartilages play a larger role). Sarcopenia of the diaphragm also plays a role. These changes can be accelerated by smoking, but are not all due to smoking and are seen among non-smoking subjects. Although there is growth hormone decline with aging and altered immunity, these would not explain the pulmonary changes.

TOPIC: Normal agingMedical College of Wisconsin – September 12, 2013 19 | P a g e




THEMES: Connective tissue changes REFERENCE: Pisani M, Ely EW. Respiratory Diseases and Disorders. In: Pacala JT, Sullivan GM.


3. You are caring for a geriatric woman with urinary incontinence who is sexually active. A pelvic exam was done to better understand her incontinence. The examination reveals thin vaginal mucosa with decreased rugae and reduced vaginal secretions.

The most likely explanation for these findings is: E) Age-related connective tissue changes F) Estrogen decrease G) Impact of urinary leakage on surrounding vaginal mucosae H) Sexual activity

ANSWER: B) Estrogen decrease

ANNOTATIONS: The decline in estrogen influences target tissue (such as the vaginal mucosae) resulting in the atrophic changes seen in this patient. This anatomic change is not solely age related as estrogen hormone replacement can restore tissues to their prior status. Sexual activity should not result in tissue atrophy. Urinary leakage is a condition not uncommonly seen with aging and can lead to vaginal tissue changes, but these changes would more likely be inflammatory and not simply atrophy.


Press; 2003.

4. The underlying science that best explains the pelvic findings is: F) Autoimmunity associated with aging G) Cellular senescence H) Loss of cellular structural integrity I) Neurodegenerative central pituitary failure J) Neurodegenerative hypothalamic failure

ANSWER: B) Cellular senescenceANNOTATIONS: Menopause is a classic example of aging changes. The primary etiology of

menopause problem is cellular senescence with ovarian failure and the loss of follicles that are able to develop and result in ovulation. This follicular loss results in the loss of steroid hormones. The hypothalamus and pituitary do not primarily drive ovarian loss and pituitary hormones, in fact, luteinizing (LH) and follicular





stimulating hormone (FSH) are both initially elevated in response to ovarian failure. Chronic inflammatory changes in the ovary are not considered to be the cause of this follicular loss. Cellular structural integrity is not the cause of ovarian failure.


Press; 2003.

5. An 88 year old patient comes to your clinic with a chief complaint of memory loss, which has been gradual and progressive over the past two years. More recently, the patient notices difficulty with finding the “right” words and has more difficulty managing work at home. The patient’s spouse mentions that the patient has had some problems with getting lost while driving, has made some errors in balancing the checkbook and has lost interest in some of the activities that used to be enjoyed. Clinically the patient seems to have a flat affect. Given this history, the most likely etiology of the patient’s symptoms is:

F) Age-related memory loss G) Alzheimer’s dementia H) Delirium I) Mild cognitive impairment J) Vascular dementia

ANSWER: B) Alzheimer’s dementiaANNOTATIONS: This patient has symptoms of Alzheimer’s Dementia. This includes cognitive

impairment in memory and other areas of cognitive functioning that impair normal home, work, or social functioning. These cognitive and resulting functional changes occur slowly over time. Age-related memory loss is described by mild changes or occasional impairment in word finding, recall, or information retrieval. Delirium is distinguished from dementia in part, by its onset and course. Dementia’s gradual onset and general constancy differs from the medical condition of delirium, which is an acute, potentially reversible, decline in cognition and function as a response to a medical or systemic illness or event. Mild cognitive impairment is a decrease in some areas of memory, such as new task learning or difficulty making new memories. This loss is mild, and, unlike dementia, does not contribute to functional decline and loss. Vascular dementias are the second most common cause of dementia, causing cognitive loss through direct injury to cognitive portions of the brain. Vascular dementia may present in a “step-wise” manner, with periods of abrupt cognitive decline, then stabilization, and further abrupt decline over time.

TOPIC: Genetics – basic science principles of agingTHEMES: Post-mitotic tissue predilection for age changes





REFERENCE: Budson AE, Solomon PR. New criteria for Alzheimer’s disease and mild cognitive impairment: implications for the practicing clinician. Neurologist. 2012;18(6):356-363.

6. The underlying science that explains the cognitive complaints and decreased function is that there are genetic mutations leading to:

F) Decreased blood perfusion to neuronal cells in the brain G) Decreased serotonin levels in the brain with aging H) Increased amyloid proteins I) Increased acetylcholine in the brain J) Increased oxidation, free radicals, and neuronal cell damage

ANSWER: C) Increased amyloid proteinsANNOTATIONS: Genetic mutations leading to Increased amyloid proteins is the underlying etiology

of the patient’s dementia. The aging brain develops amyloid plaques and neurofibrillary tangles, and undergoes both synaptic and neuronal loss. Plaques can develop extracellularly throughout the nervous system, and is thought to induce cell death by the development of free radicals and inflammatory products. Neurofibrillary tangles develop from tau proteins, and deposit within neuronal cells. When tangles developing within the hippocampal, medial temporal, parietotemporal and frontal cortices reach a critical point, they can lead to neuronal cell death and impair cognitive and brain function. This constitutes the most common form of dementia, with prevalence increasing with age. While periods of decreased blood perfusion to neurons in the brain may result in cognitive loss from stroke (vascular dementia), this etiology of dementia is not due to clear genetic mutations. Serotonin is a neurotransmitter in the brain that is associated with depression. Acetylcholine levels in the brain do not increase with genetic mutations, and may, in patients with increased amyloid and tau proteins decrease as a result of neuronal cell death. Increased oxidation, free radicals and neuronal cell damage are occurring in the process of Alzheimer’s dementia, but this is not a direct result of a genetic mutation.



7. A 70 year old presents to clinic for routine follow-up and an annual physical exam. The patient has a history of hypertension, hypercholesterolemia, and coronary artery disease. The patient is a retired farm hand,





having worked on several large ranches in Texas, New Mexico, and Arizona. On exam, the patient has moderately pigmented, very wrinkled skin.

Also notable is a small scaly red plaque lesion on the helix of the right ear, and several small lesions on the scalp where the hair is thinning. There is a history of extensive sun exposure, but rarely of blistering burns. The most likely lesion is:

ANSWER: B) Squamous cell cancer ANNOTATIONS: This lesion is most characteristic of a squamous cell skin cancer. Squamous cell

cancer is the second most common type of skin cancer, mainly caused by lifetime of cumulative UV exposure. Seven hundred thousand squamous cell cancers are diagnosed annually, with approximately 2500 annual deaths. It is characterized by red, elevated scaly patches often with a central depression. A melanoma skin cancer is characterized as a dark lesion, potentially multicolored, with variation in color and roughness of lesion borders. Seborrheic keratosis is a non-malignant skin lesion which is frequently confused with melanoma in appearance. It darkens in appearance over time, appears rough in texture and “stuck on” in appearance. Tophus is a lesion which may be seen in cartilaginous areas of the body and is associated with gout.



8. The underlying science that best explains the pathology of this skin lesion is: F) Thymidine dimer damage in the p53 tumor suppressor gene preventing repair of mutated

keratinocytes G) Damage to melanocyte tumor suppressor gene p16 H) Mutation to gene CDKN2A on 9p21 resulting in melanocyte suppressor damage to p16 and p14ARF I) Autosomal dominant mutation to the PTEN tumor suppressor gene J) Purine nucleotide metabolism end-product deposition in joints and soft tissues

ANSWER: B) Thymidine dimer damage in the p53 tumor suppressor gene preventing repair



F) Melanoma G) Squamous cell cancer H) Seborrheic keratosis I) Psoriasis J) Tophus



of mutated keratinocytes ANNOTATIONS: The underlying pathophysiology of squamous cell cancer is thought to be

thymidine dimer damage at the p53 tumor suppressor gene, which then prevents the genetic repair of UV damaged keratinocytes. The melanocyte tumor suppressor gene p16 has been implicated in melanoma formation. CDKN2A on 9p21 is a tumor suppressor gene that is associated with a number of tumors, including melanoma. PTEN is a tumor suppressor gene linked to glioblastoma, endometrial cancer, and prostate cancers.. Purine nucleotide end-products are associated with gout, which can form tophi.



9. A patient is interested in maximal longevity. She asks you for the current best evidence in animal studies that supports increasing the life span. Which of the following factors has the best data to support its efficacy to increase mammalian life span?

F) Acetylcholinesterase -Inhibitors G) Caloric restriction H) Exercise I) HMG-CoA reductase inhibitors J) Stress reduction

ANSWER: B) Caloric restriction ANNOTATIONS: Caloric restriction has the best experimental evidence in animals to support

increasing life span. The other measures (ACE inhibitors, exercise, HMG-CoA redutase inhibitors) may contribute to increased life expectancy but do not explain maximal longevity associated with caloric restriction.

TOPIC: TOR-Target of Rapamycin-signaling conserves cellular energy (beneficial to aging)THEMES: Cellular replication and control of mitotic processesREFERENCE: . Kapahi P, Vijg J. Aging — Lost in Translation? N Engl J Med. 2009;361:2669-2670

10. Drawing upon your basic science knowledge, which of the following genetic pathways is felt to modulate longevity?

E) Hedgehog pathway F) Rapamycin (now known as sirolimus)(TOR) pathway G) Ras-regulated signal pathway H) Transforming growth factor ß (TGF ß) Pathway

ANSWER: B) Rapamycin (now known as sirolimus)(TOR) pathway





ANNOTATIONS: On the molecular level, caloric restriction inhibits the TOR pathway. A downstream target of the TOR pathway is ribosomal protein S6 kinase. Deletion of this kinase gene leads to an increased life span. Inhibition of TOR has a similar effect. The other pathways listed do not explain longevity associated with caloric restriction.

TOPIC: TOR-Target of Rapamycin-signaling conserves cellular energy (beneficial to aging)THEMES: Cellular replication and control of mitotic processesREFERENCE: Kapahi P, Vijg J. Aging — Lost in Translation? N Engl J Med. 2009;361:2669-2670

11. Mrs. Golden is an 85 year old woman who presents to your clinic with excruciating, new onset mid-back pain that is constant and non-radiating. She states she fell on the ice yesterday while walking her dog. Her pain has not decreased with acetaminophen and ibuprofen. What would be the next step you would take with this patient?

F) Obtain calcium and 25(OH) D levels G) Order DEXA scan H) Order bed rest and increase ibuprofen dosage I) Obtain physical therapy consultation J) Order radiograph of the thoracic vertebrae

ANSWER: E) Order radiograph of the thoracic vertebrae ANNOTATIONS: The best next step in the evaluation of this patient with osteoporosis risk factors

and unremitting pain after a fall is to image the area of pain, specifically the back. A result of a vertebral fracture will give the etiology of the pain and will guide treatment decisions. Calcium and 25 (OH) D levels may indicate an underlying etiology for possible osteoporosis or low bone mass, and should be done as a secondary step in overall bone health and osteoporosis prevention and treatment. A DEXA scan is used to further quantify, radiographically, bone mass. It may be helpful in understanding bone health, but will not diagnose the cause of the back pain. Bed rest can increase symptoms and risks associated with immobility, and ibuprofen may lead to renal and gastric side effects. Physical therapy will likely be of benefit, but the first step is diagnostic with a radiograph of the thoracic vertebrae



12. The underlying science that explains the etiology of the patient’s pain is: F) A homeostatic imbalance between osteoclastic and osteoblastic activity G) A physiological decrease in parathyroid hormone secretion with aging H) Connective tissue cross-linking of collagen decreases with aging





I) Horizontal trabeculae of trabecular bone of vertebrae are lost with aging J) Insulin-like growth factor-1 (IGF-1) over activity

ANSWER: A) A homeostatic imbalance between osteoclastic and osteoblasticANNOTATIONS: Osteoporosis is caused by a homeostatic imbalance between osteoclastic and

osteoblastic activity. Risk factors for osteoporosis include being female, thin, small framed, family history, post-menopausal estrogen deficiency, low testosterone [in males], Asian or Caucasian, and old. Secondary conditions like parathyroidism can induce bone resorption, typically this is seen with low parathyroid states and is not a part of normal aging. Collagen cross-linking does not decrease with aging. Growth hormone and IGF-a overactivity are associated with acromegaly and not osteoporosis.



13. A 75 year old is evaluated for a 2 year history of progressive pain in the left knee that worsens with activity and decreases with rest. It is worst along the medial aspects of the joints, but does not lock or give way. There is neither swelling nor any morning stiffness. On exam, there is a no evidence for an effusion, but passive range of motion is painful for flexion and extension. Plain radiography and lab work (including CRP, ESR, and CBC) are normal. Which of the following is the most appropriate next step in management?

F) Arthrocentesis G) MRI of the knee H) Physical therapy I) Rheumatoid Factor J) Uric acid level

ANSWER: C) Physical TherapyANNOTATIONS: In a patient with pain in a load bearing joint without evidence for infection,

effusion, or severe inflammation, the most prudent course of action is physical therapy. Arthrocentesis would not be considered a first line treatment for pain in a joint, especially a joint without an effusion noted on clinical exam. An MRI is unlikely in this situation to provide actionable information beyond the clinical exam, and is an expensive first step. Without symptoms of rheumatoid arthritis or active gout, laboratory studies for rheumatoid factor, and uric acid levels are not warranted and will be of low clinical yield diagnostically.







14. The underlying basic science that explains the patient’s clinical problem is: E) Defective repair, inflammatory infiltrates and synovitis, and cytokine mediated cartilage degradation F) HLA-DRB1*0401 and *0404 histocompatibility loci on synovial macrophages acting as antigen

presenting cells G) Immune-complex mediated deposition and tissue destruction H) Purine nucleotide metabolism end-product deposition in joints and soft tissues

ANSWER: A) Defective repair, inflammatory infiltrates and synovitis, and cytokine mediated cartilage degradation

ANNOTATIONS: The mechanisms for arthritic pain in a joint are inflammatory infiltrates and synovitis with cytokine medicated cartilage degradation and defective repair. . HLA-DRB1*0401 and *0404 histocompatibility loci are related to genetic risks of developing rheumatoid arthritis and are not associated with osteoarthritis. Immune complex mediated deposition and tissue destruction is a hallmark of immune mediated or reactive arthritis Purine nucleotide metabolism end-product deposition in joints and soft tissues is the pathophysiology of gout and does not explain the patient’s condition.



15. An 85 year old woman is admitted to your ward service. She has isolated systolic hypertension. Her carotid pulse upstroke is bounding. Which of the following aging changes accounts for these findings?

F) Adrenal Medullary Catecholamines G) Arteriosclerosis H) Atherosclerosis I) Cardiac Output J) Renal Function

ANSWER: B) ArteriosclerosisANNOTATIONS: Arteriosclerosis is the process by which blood vessels stiffen due to deterioration

of the elastin and collagen in the media of the vessel wall associated with calcium deposition over time. Atherosclerosis is a disease of the intima and is responsible for vessel occlusion; it would not cause the changes in the pulse contour described





in this case nor the blood pressure findings. Cardiac output overall does not change substantially with aging alone, although is frequently decreased, and occasionally increased, as a result of disease processes. Age related changes in renal function would not be expected to change arterial pulse contour.

TOPIC: Arterial aging - w/age the arterial walls stiffen. Eventually, the transmission of flow pulsations downstream to organs (brain and kidney’s first). Elastin comprises 90% of arterial fibers.



16. The underlying science that best explains these blood pressure and blood vessel findings is: F) Neural aging G) Connective tissue changes of the vessel media H) Blood vessel intimal plaque formation I) Renal-hormonal changes associated with aging J) Catecholamine depletion with aging

ANSWER: B) Connective tissue changes of the vessel media ANNOTATIONS: Arteriosclerosis is the process by which blood vessels stiffen with aging due to

deterioration of the elastin and collagen in the media of the vessel wall associated with calcium deposition. These changes can cause vessel rigidity and can contribute to systolic blood pressure increase and an increased upstroke when palpating the pulse. With aging, renin typically declines as a result of renal aging changes. Renal aging will not explain the findings. Beta receptors are blunted as a function of age. Catecholamine levels are maintained and do not explain these findings.

TOPIC: FIBERS. Arterial aging - w/age the arterial walls stiffen. Eventually, the transmission of flow pulsations downstream to organs (brain and kidney’s first). Elastin comprises 90% of arterial



17. A 70 year old man wishes to conceive a child with his 37 year old wife. This would be their third child, the other two being healthy. Both parents are healthy with no diagnosed medical conditions. The wife continues to have normal menses. Despite a 12 month course of fertility drugs, the couple is unable to conceive.





What is the most likely male factor preventing conception? E) Benign prostatic hyperplasia F) Chronic UTIs G) Diminished sperm concentration in the ejaculate H) Diminished sperm viability

ANSWER: D) Diminished sperm viability ANNOTATIONS: An estimated 15% of couples are infertile, of which 20-40% is related to male

infertility problems. Male infertility can be broadly divided into abnormal sperm production, sperm function, and obstruction to outflow. Of these, diminished sperm viability is the most common cause, as androgens are central in both cell division and in seminal fluid production. Other common medical causes include varicocele, infections (gonorrhea, chlamydia, prostatitis, or mumps orchitis), retrograde ejaculations (from diabetes, spinal injury, meds, surgical changes), auto-antibodies to sperm, tumors, undescended testes, hormone imbalances, sperm duct defects, chromosomal abnormalities, erectile dysfunction, celiac disease, and certain medications .Environmental causes include chronic overheating of the testicles, radiation exposure, lead and other heavy metals as well as benzene, toluene and other organic industrial chemicals. Lifestyle causes include illicit drug use, alcohol, tobacco, stress, prolonged bicycling or horseback riding, and obesity.



18. The science underlying the patient’s infertility is: F) Age-related degeneration of the Leydig and Sertoli cells G) Age-related impairment in production of seminal fluid H) Epididymal amyloid deposition preventing mature sperm transport I) Germ cell degeneration and loss during meiosis and mitosis J) Impaired inflammatory response in bladder mucosa

ANSWER: D) Germ cell degeneration and loss during meiosis and mitosisANNOTATIONS: Androgens are central in both cell divisions and in seminal fluid production, and

would cause germ cell degeneration and loss in both meiosis and mitosis. This is the most likely cause of infertility of the choices offered. While age related changes in seminal fluid and in Sertoli cells (that help mature spermatozoa) and Leidig cells (which release androgens) would impact spermatogenesis, it would not impact fertility as directly as germ cell degeneration. The bladder mucosa is part





of the urologic system but does not impact the reproductive system in this way.TOPIC: Telomeres – role of telomere shortening in infertilityTHEMES: Post mitotic tissue, age changes.REFERENCE: Wiener-Magnazi, Auslender R, Dirnfeld M. Advanced paternal age and


19. A 90 year old with a history of dementia was brought to the emergency department after a fall at home, and was noted to be confused and agitated by the daughter. The patient was recently started on risperidone as an outpatient. The patient complains of cough, rhinorrhea and myalgias. EMR indicates all immunizations are current. Patient’s vitals showed temp 102.5F, RR 24, HR 90, ox sat 96% on RA. Cardiac and abdominal examinations were unremarkable, pulmonary exam showed bilateral wheezes. Pertinent Lab values showed: Na 132, WBC 14.0. CXR was negative. UA showed positive nitrates, 0-5 WBC, hyaline casts and moderate bacteria. What is the most likely ROOT CAUSE of the patient’s change in condition?

F) Delirium G) Hyponatremia H) Influenza I) Neuroleptic malignant syndrome J) Urinary tract infection

ANSWER: C) InfluenzaANNOTATIONS: While this patient is presenting with delirium (an acute change in cognitive

function and attention), this is a syndrome and does not represent the root cause of her clinical complaints and findings. Of the listed choices, influenza is the only choice that would meet the symptoms of an upper respiratory infection, fevers, and cough. Although she was vaccinated, immunosenescent changes in vaccine response commonly decrease the protective effects of influenza vaccines, and this patient has the typical clinical presentation of influenza. The patient’s hyponatremia is not severe, and is unlikely to be at a level to cause her clinical condition. There is no evidence for a urinary tract infection on testing, and she has no evidence of neuroleptic malignant syndrome given her respiratory complaints.




20. The underlying science that explains the change in the patient’s condition is:





F) Age related increase in AVP release G) CNS neuroendocrine changes with aging H) Decreased cytotoxic T lymphocyte activity I) Drug related side effect J) Increased proliferative capacity of lymphocytes in response to antigens

ANSWER: C) Decreased cytotoxic T lymphocyte activity ANNOTATIONS: Decreased cytotoxic T lymphocyte activity is the most likely cause of the patient’s

symptoms. Common changes in the immune system with aging include slower immune response to infection and vaccination, impaired healing, tumor and malignancy management, and increased risks of autoimmune disorders. Immunosenescence manifests through changes in antigen presentation, decreased specific antibody responses, and altered cytokine functions. Changes to T and B cells see both rises in pro-inflammatory cytokines and autoimmune antibodies, and decreases in T and B cell activity and function. There is also a decrease in neutrophil, macrophage, NK, and dendritic cells. Studies have demonstrated up to a 50% decline in antibody response to vaccines in persons over the age of 65. The end result is increased susceptibility to infection, and decreased vaccination efficacy. AVP would have more impact on sodium and water balance and does not affect the immune system directly in this way. CNS neuroendocrine changes with aging, while perhaps contributing to the patient’s underlying cognitive loss and predisposing the patient to delirium, are not the acute etiology behind the patient’s current presentation. Risperidone may contribute to the patient’s cognitive decline and agitation but would not explain her pulmonary disease and fever.




21. A 79 year old woman presents to the clinic with a chief complaint of back pain. The pain has been present for the past four months. On ROS the patient is found to have a 20 lb unintentional weight loss. Physical examination shows some point tenderness over the spine where here pain is. Lab studies reveal a hematocrit of 30. What is the next step in the patient’s management?

F) Bone marrow biopsy G) CT of the spine with contrast





H) Parathyroid level I) Radionuclide bone scan J) SPEP/UPEP (Serum & Urine Protein Electrophoresis)

ANSWER: E) SPEP/UPEP (Serum & Urine Protein Electrophoresis) ANNOTATIONS: The patient’s medical presentation is most consistent with a disease of multiple

myeloma. Multiple myeloma is the second most common hematologic malignancy after non-Hodgkin’s lymphoma. The most common symptoms of multiple myeloma include bone pain, often in the spine and ribs, infection (related to impaired immune response; often a pneumonia), renal failure (due to nephrotoxic effects of light chains within the kidneys), anemia (usually a normocytic and normochromic anemia), and neurological symptoms (fatigue, confusion, headache, weakness).

Initial evaluation is usually serum and urine electrophoresis looking for paraproteins (for example, Bence-Jones proteins in the urine). The most common serum paraprotein is IgG, followed by IgA and IgM. This first step is ideal in that it begins with relatively non-invasive and less expensive diagnostic tests. A bone marrow biopsy is helpful and can be diagnostic, but is also invasive and not a first line test. A CT of the spine may demonstrate lytic lesions that would raise suspicion for multiple myeloma, but would not be diagnostic of it. A parathyroid level is non-diagnostic for multiple myeloma. Skeletal surveys and radionucleotide bone scans are helpful to identify abnormalities in the bone but are usually non-specific and need to be combined with the electrophoresis data to be more diagnostic of multiple myeloma.



22. One underlying basic science theory that may explain the clinical findings in this case is: E) Continuously mitotic cells are more prone to oncogenic transformation F) Increased tumor growth due to a decline in humoral immune function G) Oxidative damage to cell membranes occurs over time H) Tumor suppressor genes are auto-regulated in elderly patients

ANSWER: B) Continuously mitotic cells are more prone to oncogenic transformation ANNOTATIONS: The basic science underlying multiple myeloma, and many cancers in general, is

that continuously mitotic cells are more prone to genetic injury and oncogenic transformation than those cells that are less frequently mitotic. While the other three answer choices are related to cancer development, they are not the primary





basic science underlying the oncogenic transformation of healthy cells into the oncogenic cells of multiple myeloma



23. A 70 year old is brought into the Emergency Department at midnight following a motor vehicle crash on the way home from a restaurant. The patient has a history of diabetes, hypertension, and hyperlipidemia. The patient often has vision problems at night, with seeing halos around lights, and visual acuity is a bit “hazier” lately. The patient has recently started limiting night driving, wears glasses, and was wearing them at the time of the incident. On exam there are no visual field deficits. The most likely visual impairment contributing to the accident is:

E) Age-related macular degeneration F) Diabetic retinopathy G) Cataract formation H) Glaucoma

ANSWER: C) Cataract formation ANNOTATIONS: Cataracts are a formed by a chronic opacification of the lens of the eye, leading to

decreased visual acuity. The visual changes are caused by spatial density fluctuations, scattering and absorption of light, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment. The result is a gradual decrease of visual acuity, clouding of vision resulting in glare and nighttime/ low light transmission through the eye. The causes include age (most common cause), ultraviolet radiation exposure, especially uv-B, trauma, cigarette smoking, medications, and certain diseases. There are genetic conditions that are associated with cataract formation, notably Down’s and Turner’s syndromes, and trisomy 18. Macular degeneration is a loss of central vision due to damage of the macular portion of the retina. Diabetic retinopathy is damage to the retinal caused by systemic (including the eye) vascular disease and may present with blurred vision. Glaucoma describes an ocular disorder with increased intraocular pressure, which may clinically present as a loss of peripheral vision with remaining, “tunnel vision”.



24. The underlying science that explains the visual impairment is:





E) Drusen deposition, geographic atrophy, serous detachment of the retinal pigment epithelium, and neovascularization

F) Gradual changes in retinal microvasculature leading to retinal nonperfusion, increased vascular permeability, and uncontrolled neovascularization

G) Age-related spatial density fluctuations, light scattering and absorption, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment

H) Intraocular pressure causing blockade of the lamina cribrisa of axonal protein transport, causing neuronal retinal ganglion cell death by trophic insufficiency

ANSWER: C) Age-related spatial density fluctuations, light scattering and absorption, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment

ANNOTATIONS: The underlying science of cataract formation is age-related spatial density fluctuations, light scattering and absorption, formation of opaque lens fibers, fibrous metaplasia, epithelial opacification, and accumulation of pigment. Age related macular degeneration is a leading cause of blindness that affects the macula faster than the peripheral retina. It is related to drusen deposition, geographic atrophy, and serous detachment of the retinal pigment epithelium as well as neovascularization. Diabetic retinopathy is caused by microvascular retinal changes that lead to non-perfusion and increased vascular permeability; this can cause a hypoxic or anoxic state within the retina, which in turn stimulates uncontrolled neovascularization. Glaucoma causes gradual vision loss often beginning in the periphery and causing tunnel vision. It is related to increased intraocular pressure causing blockage of the lamina cribrisa and impairing axonal protein transport and causing neuronal retinal ganglion cell death by trophic insufficiency.



25. An 88 year old patient is under your care in the hospital. The patient develops delirium and is found to have a serum glucose level of 750 mg/dl. There was no prior history of diabetes. The patient had received a glucose infusion post operatively. Which of the following age-related changes most likely contributed to the patient’s risk of developing hyperglycemia?

F) Accelerated glycogenolysis G) Growth hormone excess H) Hypercortisolism I) Insulin resistance J) Pancreatic endocrine failure





ANSWER: D) Insulin resistance ANNOTATIONS: Diabetes is a major health problem and has an increased prevalence in later life.

Type 2 diabetes can result in patients developing very high blood glucose levels. The fundamental problem is insulin resistance which can be traced to cellular changes beyond the insulin receptor. Patients may be asymptomatic at baseline but the stress of illness and hospitalization, as well as the challenge of IV glucose and some medications (e.g., glucocorticoids) or infection, may result in an increase in serum glucose levels. Growth hormone excess and hypercortisolism are not endocrinological changes of normal aging. Additionally, a decrease or lack of insulin from pancreatic endocrine dysfunction is not typically seen with aging alone.



26. While the basic science underlying body composition is not yet clear, which of the following changes in body composition contributes to glucose intolerance with aging?

F) Increased cross linking of connective tissue G) Increased hepatic size accelerating insulin breakdown H) Increased lipofuscin deposition in the pancreas I) Reduced lean body mass J) Reduced renal mass with altered glucagon excretion

ANSWER: D) Reduced lean body mass ANNOTATIONS: With age there are important changes in body composition. There is loss of lean

mass which can result in sacropenia. There is also a loss of body water and cell solid. Body potassium, an indirect marker of lean body mass, also declines with age. Body fat increases as a function of age. Although these body composition changes are important contributors to relative insulin resistance, obesity (not a normal aging change) likely plays a more important role.






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