2006 GEN MED:

31.

ANS: C: TRIGEMINAL NERVE

Ref: net sources

Exp:

Afferent fibres of cornea pass through trigeminal nerve while efferent fibres come by facial nerve.

Additional info:

Corneal reflex

The corneal reflex, also known as the blink reflex, is an involuntary blinking of the eyelids elicited by stimulation of the cornea (such as by touching or by a foreign body), or bright light, though could result from any peripheral stimulus.

Stimulation should elicit both a direct and consensual response (response of the opposite eye). The reflex consumes a rapid rate of 0.1 second.

The evolutionary purpose of this reflex is to protect the eyesfrom foreign bodies and bright lights (the latter known as the optical reflex)

The blink reflex also occurs when sounds greater than 40-60 dB are made.

The reflex is mediated by:

the nasociliary branch of the ophthalmic branch (V1) of the 5th cranial nerve (trigeminal nerve) sensing the stimulus on the cornea, lid, or conjunctiva (i.e. it is the afferent).

the temporal and zygomatic branches of the 7th cranial nerve (Facial nerve) initiating the motor response (i.e. it is the efferent).

Mediated by centre in the pons of brainstem.

Use of contact lenses may diminish or abolish the testing of this reflex.

The optical reflex, on the other hand, is slower and is mediated by the visual cortex, which resides in the occipital lobe of the brain.

The reflex is absent in infants under 9 months.

The examination of the corneal reflex is a part of some neurological exams, particularly when evaluating coma.

Damage to the ophthalmic branch (V1) of the 5th cranial nerve results in absent corneal reflex when the affected eye is stimulated.

An absent corneal reflex can be due to sensory loss in Vi (e.g. neuropathy or ganglionpathy), weakness or paralysis of the facial muscles (myopathy) or facial nerve (facial palsy, for example Bell's palsy) or brain stem disease. For a myopathy to cause a loss of the blink reflex the weakness has to be very severe, for example a chronic

progressive external ophthalmoplegia

Pathway of corneal reflex:

stimulus short ciliary nerves ciliary ganglion

nasociliary nerve

trigeminal ganglion opthalmic nerve

main sensory nuclues reticular formation

B/L facial nuclei

B/L facial nerves

Closure of eye lids/ contraction of palpebral muscles/blinking

32.

Ans: a: inadequate dietary intake.

REF: HARRISON 17/e – pg 325

Exp: folic acid deficiency results from either inadequate dietary intake or increased metabolic demand.among the options provided A is the choice of answer.

Additional info:

Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to body tissues.

Megaloblastic anemia is of 2 types.

1. Cobalamine / vit B12 deficiency: most common cause is malabsorption.the dietary intake is more than adequate for body’ s requirement except in vegetarians and breast fed infants. Thus its most commonly due to malabsorption.

2. Folate/ folic acid deficiency: folic acid deficiency results from either inadequate dietary intake or increased metabolic demand.The dietary intake is marginal and body stores of folate is also very low hence folic acid deficiency arise when there is sudden decrease of dietary intake.

Folate is a type of B vitamin. It is also called folic acid. Folate-deficiency anemia is a decrease in red blood cells (anemia) due to a lack of folate.

Folate  is needed for red blood cells for formation and maturation.  folate is present in green leafy vegetables and liver. However, our body does not store folate in large amounts. So, we need to eat plenty of folate-rich foods to maintain normal levels of this vitamin. 

In folate-deficiency anemia, the red  blood cells are abnormally large. Such cells are called megalocytes. They are also called megaloblasts. They are seen in the bone marrow. This is why this anemia is also called megaloblastic anemia.

Causes :

Inadequate folic acid in our diet Hemolytic anemia Long-term alcoholism Use of certain medications (such as phenytoin [Dilantin], methotrexate,

sulfasalazine, triamterene, pyrimethamine, trimethoprim-sulfamethoxazole, and barbiturates)

Risk factors:

Alcoholism Eating overcooked food Poor diet (often seen in the poor, the elderly, and people who do not eat

fresh fruits or vegetables) Pregnancy

C/F:

Fatigue Headache Pallor Sore mouth and tongue

Diagnosis;

. Tests done include:

Complete blood count (CBC) Red blood cell folate level

Rarely, a bone marrow examination may be done.

Treatment

The goal is to identify and treat the cause of the folate deficiency.

You may receive folic acid supplements, taken by mouth or given through a vein. folic acid 1 mg PO qd (5 mg qd) for those with malabsorption.

Diet changes can help boost folate level. Eat more green, leafy vegetables and citrus fruits.

Its recommend that women should take 400 micrograms (mcg) of folic acid supplements every day in the first trimester.

Outlook (Prognosis)

Anemia usually responds well to treatment within 2 months.

Possible Complications

Symptoms of anemia can cause discomfort. In pregnant women, folate deficiency has been associated with neural tube or spinal defects (such as spina bifida) in the infant.

Other, more severe complications may include:

Increased pigmentation Infertility Worsening of heart disease or heart failure.

33.

Ans:c: decreased fibrinogen levels

Ref: harrison 17/ e –pg 1118.

Exp: increased fibrinogen levels are associated with increased risk of atherosclerosis and not decreased levels of fibrinogen. Fibrinogen levels co relate with the coronary risk and are independent of lipoprotein profile regarding coronary risk. Elevated levels of fibrinogen promote thrombotic diathesis.

Additional info: Cardiovascular disease is the leading cause of death world wide; preventionis targeted at modifiable atherosclerosis risk factors

Identification and control of these attributes reduce subsequent cardiovascular event rates.

risk factors:

table 213- 1 in harrison 17/e – pg 1118

ESTABLISHED RISK FACTORS

Cigarette Smoking Cigarette smoking increases the incidence of, and mortalityassociated with, coronary heart disease (CHD).

Observational studies showthat smoking cessation reduces excess risk of coronary events within months; after 3–5 years, the risk falls to that of individuals who never smoked.

Patientsshould be asked regularly about tobacco use, followed by counseling and, asneeded, antismoking pharmacologic therapy to assist cessation.

Lipid Disorders :Both elevated LDL and low HDL cholesterolare associated with cardiovascular events.

Each 1-mg/dL increase in serum LDL correlates with a 2–3 % rise in CHD risk; each 1-mg/dL decrease in HDL heightens risk by 3–4%. ATP III guidelines advise a fasting lipid profile [total cholesterol, triglycerides, HDL, LDL (calculated or directly measured)] in all adults,repeated every 5 years.

Recommended dietary and/or pharmacologic approach depends on presence or risk of coronary artery disease (CAD) and the LDL level(Table 213-2);( pg 1119- harrisson 17/e)

treatment should be most aggressive in patients with established CAD and in those with “equivalent risk” (e.g., presence of peripheral arterial disease or diabetes mellitus). Drug therapy is indicated when LDL level exceeds goal in Table 213-2 by 30 mg/dL (0.8 mmol/L).

If elevated triglyceride level [>200 mg/dL (> 2.6 mmol/L)] persists after control of LDL, secondary goal is to achieve non-HDL level (calculated as total cholesterol minus HDL) ≤30 mg/dL (0.8 mmol/L) above the target values listed in Table 213-2.

In patients with isolated low HDL, encourage beneficial lifestyle measures: smoking cessation, weight loss, and increased physical activity. Consider addition of fibric acid derivative or niacin to raise HDL in patients with established CAD.

Hypertension :Systolic or diastolic bp > “optimal” level of115/75 mmHg is associated with increased risk of cardiovascular disease;

Each augmentation of 20 mmHg systolic, or 10 mmHg diastolic, above this value doubles\ the risk.

Treatment of elevated blood pressure reduces the rate of stroke,congestive heart failure, and CHD events, with general goal of bp < 140/90mmHg or <130/80 in patients with diabetes or chronic kidney disease.

Cardiovascular event rates in elderly patients with isolated systolic hypertension (systolic > 160 but diastolic < 90) are also reduced by antihypertensive therapy.

Patients with “prehypertension” (systolic bp 120–139 mmHg or diastolic bp 80–89 mmHg) should receive counseling about beneficial lifestyle modifications such as those listed below (e.g., low-fat diet replete with vegetables and fruit, weightloss if overweight, increased physical activity, reduction of excessive alcoholconsumption).

Diabetes Mellitus/Insulin Resistance/Metabolic Syndrome

Patients with diabetes most often succumb to cardiovascular disease.

LDL levels are typically near average in diabetic pts, but LDL particles are smaller,denser, and more atherogenic;

low HDL and elevated triglyceride levels are common.

Tight control of serum glucose reduces microvascular diabetic complications(retinopathy, renal disease), but a decrease in macrovascular events(CAD, stroke) has not been definitively shown.

Conversely, successful management of associated risk factors in diabetics (e.g., dyslipidemia and hypertension) does reduce cardiovascular events and should be vigorously pursued.

As needed, antilipidemic (especially statin) therapy should be used to lower LDL to <100 mg/dL in diabetics, even if patient has no symptoms of CAD.

Individuals without overt diabetes but who have “metabolic syndrome”(constellation of insulin resistance, central obesity, hypertension, hypertriglyceridemia,low HDL are also at high risk of cardiovascular events.

Dietary counseling, weight loss, and increased physical activity are importantin reducing the prevalence of this syndrome.

Waist hip ratio:This refer to characteristic male distribution of adipose tissue i.e excess of fat in the abdomen compared to that in hips. A elevated waist/ hip ratio have been associated with symptomatic cardiovascular disease and cerebro vascular disease in both men and women

Male Gender/Postmenopausal State

Coronary risk is greater in men compared to that of premenopausal women of same age, but female risk accelerates after menopause.

Estrogen-replacement therapy lowers LDL and raises HDL in postmenopausal women and in observational studies has been associated with reduced coronary events.

However, prospective clinical trials do not support such a benefit and hormone-replacement therapy should not be prescribed for the purpose of cardiovascular risk reduction, especially in older women.

EMERGING RISK FACTORSMay be assessed selectively in patients without above traditional risk factorswho have premature vascular disease or strong family history of premature vasculardisease.

.Homocysteine

There is a graded correlation between serum homocysteine levelsand risk of cardiovascular events and stroke.

Supplemental folic acid and other B vitamins lower serum levels, but prospective clinical trials have not shown that such therapy reduces cardiac events.

Inflammation

Inflammatory serum markers, such as high-sensitivity C-reactive protein (CRP), correlate with the risk of coronary events. CRP prospectively predicts risk of MI and outcomes after acute coronary syndromes; its usefulness and role in prevention as an independent risk factor is currently being defined.

Potential benefits of assessing other emerging risk factors [e.g., lipoprotein(a), fibrinogen, infections by Chlamydia or CMV] remain unproven and controversial.

PREVENTION

Antithrombotic Therapy in Primary Prevention Thrombosis at the site of disruptedatherosclerotic plaque is the most common cause of acute coronary events.

In primary prevention trials, chronic low-dose aspirin therapy has reduced the risk of a first MI in men and the risk of stroke in women.

The AmericanHeart Association recommends aspirin (75–160 mg daily) for men and women who are at high cardiovascular risk, for men with ≥10% 10-year risk, or women with ≥20% 10-year risk).

Lifestyle Modifications

Encourage beneficial exercise habits (> 30 min moderate intensity physical activity daily)

sensible diet (low in saturated and trans fat; 2–3 servings of fish/week to ensure adequate intake of omega-3 fatty acids; balance caloric consumption with energy expenditure).

Advise moderation in ethanol intake (no more than 1–2 drinks/day).

34.

Ans:A : flourosis Ref: harrison 17/e – pg 966

Exp:flourosis is associated with osteosclerosis and not osteoporosis. Hypogonadism, hyperparathyroidism are all known causes for osteoporosis. Hence A is the choice of answer.

Additional info:

Osteoporosis is defined as a reduction in bone mass (or density) or the presenceof fragility fracture.

It is defined operationally as a bone density that falls 2.5 SD below the mean for a young normal individual (a T-score of <–2.5). Those with a T-score of <1.0 have low bone density and are at increased risk for osteoporosis.

The most common sites for osteoporosis-related fractures are the vertebrae,hip, and distal radius.

Etiology Low bone density may result from low peak bone mass or increasedbone loss.

Risk factors for an osteoporotic fracture are listed in Table 186-1 and diseases associated with osteoporosis are listed in Table 186-2.( note- tables in harrison 17/e – pg 966, 967

Certain drugs, - causing incresed risk for osteoporosis

glucocorticoids, cyclosporine, cytotoxic drugs, anticonvulsants,aluminum, and heparin.

Clinical Features

Pts with multiple vertebral crush fractures may have height loss, kyphosis, and secondary pain from altered biomechanics of the back.

Thoracic fractures can be associated with restrictive lung disease, whereas lumbarfractures are sometimes associated with abdominsion leading to sciatica.

Diagnosis

Dual-energy x-ray absorptiometry has become the standard for measuring bone density.

The U.S. Preventive Health Services Task Force recommends that women aged 65 and older be screened routinely for osteoporosis, and at age 60 for women with increased risk.

Ageneral laboratory evaluation includes complete blood count, serum and 24-hurine calcium, 25(OH)D level, and renal and hepatic function tests.

Further testing is based on clinical suspicion and may include thyroid-stimulating hormone (TSH), urinary free cortisol, parathyroid hormone (PTH), serum and urine electrophoresis, and testosterone levels (in men).

Transglutaminase Ab testing may identify asymptomatic celiac disease.

Markers of bone resorption (e.g., urinecross-linked N-telopeptide) may be helpful in detecting an early response to antiresorptive therapy if measured prior to and 4–6 months after initiating therapy.

Treatment

involves the management of acute fractures,

modifying risk factors,

and treating any underlying disorders that lead to reduced bone mass.

Treatment decisions are based on an individual’s risk factors, but active treatment isgenerally recommended if the T-score is ≤2.5.

Oral calcium (1–1.5 g/d of elemental calcium in divided doses), vitamin D (400–800 IU/d), exercise, and smoking cessation should be initiated in all patients with osteoporosis.

Bisphosphonates (alendronate, 70 mg PO weekly; risedronate, 35 mg PO weekly;ibandronate, 150 mg PO monthly or 3 mg IV every 3 mo; zoledronic acid, 5 mg IV annually) augment bone density and decrease fracture rates.

Oral bisphosphonates are poorly absorbed and should be taken in the morning on anempty stomach with 0.25 L (8 oz) of tap water.

Estrogen decreases the rate of bone reabsorption, but therapy should be considered carefully in the context of increased risks of cardiovascular disease and breast cancer.

Raloxifene (60 mg/ d PO), a selective estrogen receptor modulator, increases bone density and decreases total and LDL cholesterol without stimulating endometrial hyperplasia, though it may precipitate hot flashes.

PTH(1-34) induces bone formation and may be administered as a daily injection for a maximum of 2 years.

35.

Ans: D : SLE

Ref: harrison 17/e – pg 885

Exp: SLE is a non erosive arthritis whereas others are all erosive arthritis.Hence the choice of answer.

Additional info:

SLE:

Definition and Pathogenesis Disease of unknown etiology in which tissues and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes.

Genetic, environmental, and sex hormonal factors are likely of pathogenic importance.

T and B cell hyperactivity, production of autoantibodies with specificity for nuclear antigenic determinants, and abnormalities of T cell function occur.

Clinical Manifestations 90% of pts are women, usually of child-bearing age; more common in blacks than whites

. Course of disease is often characterized by periods of exacerbation and relative quiescence.

May involve virtually any organ system and have a wide range of disease severity.

Common features include:• Constitutional—fatigue, fever, malaise, weight loss• Cutaneous—rashes (especially malar “butterfly” rash), photosensitivity,vasculitis, alopecia, oral ulcers• Arthritis—inflammatory, symmetric, nonerosive

• Hematologic—anemia (may be hemolytic), neutropenia, thrombocytopenia,lymphadenopathy, splenomegaly, venous or arterial thrombosis• Cardiopulmonary—pleuritis, pericarditis, myocarditis, endocarditis• Nephritis—classification is primarily histologic (see Table 313-2, p. 2077,in HPIM-17)• GI—peritonitis, vasculitis• Neurologic—organic brain syndromes, seizures, psychosis, cerebritis

Drug-Induced Lupus A clinical and immunologic picture similar to spontaneous SLE may be induced by drugs; in particular: procainamide, hydralazine, isoniazid, chlorpromazine, methyldopa, minocycline, anti-TNF agents.

Features are predominantly constitutional, joint, and pleuropericardial;

CNS and renal disease are rare.

All pts have antinuclear antibodies (ANA); antihistone antibodies may be present,but antibodies to dsDNA and hypocomplementemia are uncommon.

Most pts improve following withdrawal of offending drug.

Evaluation

• Hx and physical exam

• Presence of ANA is a cardinal feature, but a (+) ANA is not specific for SLE.

Laboratory assessment should include: CBC, ESR, ANA and ANAsubtypes (antibodies to dsDNA, ssDNA, Sm, Ro, La, histone), complementlevels (C3, C4, CH50), serum immunoglobulins, VDRL, PT, PTT, anticardiolipinantibody, lupus anticoagulant, UA.

• Appropriate radiographic studies

• ECG• Consideration of renal biopsy if evidence of glomerulonephritis

Diagnosis Made in the presence of four or more published criteria (Table 313-3,p. 2077, in HPIM-17).

Treatment:

Choice of therapy is based on type and severity of disease manifestations.

Goals are to control acute, severe flares and to develop maintenance strategieswhere symptoms are suppressed to an acceptable level.

Treatment choices depend on (1) whether disease is life-threatening or likely to cause organ damage; (2) whether manifestations are reversible; and (3) the best approach to prevent complications of disease and treatment

CONSERVATIVE THERAPIES FOR NON-LIFE-THREATENING DISEASE• NSAIDs (e.g., ibuprofen 400–800 mg three to four times a day). Must consider renal, GI, and cardiovascular complications.

• Antimalarials (hydroxychloroquine 400 mg/d)—may improve constitutional,cutaneous, articular manifestations

. Ophthalmologic evaluation required before and during Rx to rule out ocular toxicity.

TREATMENTS FOR LIFE-THREATENING SLE

• Systemic glucocorticoids.

• Cytotoxic/immunosuppressive agents—added to glucocorticoids to treatserious SLE.1. Cyclophosphamide—administered as IV pulse 7–25 mg/kg every 4 weeks. Daily oral dosing 1.5–3.0 mg/kg per day can also be used but has a greater risk of urinary bladder toxicity.

2. Mycophenolate mofetil—2–3g/d; efficacy data limited to nephritis.

3. Azathioprine—may be effective but is slower in inducing therapeutic response.

• Anticoagulation—may be indicated in pts with thrombotic complications.

36

Ans: A: lytic bone lesions

Ref: harrison 17/e pg 361

Exp: multiple myeloma is now widely defined in accordance with the durie and salmon Diagnostic criteria. The diagnostic criteria is divided into major and minor criteria. Lytic bone lesions constitute minor criteria and all other options are part of the major criteria Hence the choice of answer.

Additional info:

Multiple myeloma:

A malignant proliferation of plasma cells in the bone marrow (notably not in lymph nodes).

Causes: Disease manifestations result from tumor expansion, local and remote actions of tumor products, and the host response to the tumor.

Clinical features:

About 70% of pts have bone pain, usually involving the back and ribs, precipitated by movement.

Bone lesions are multiple, lytic, and rarely accompanied by an osteoblastic response.Thus, bone scans are less useful than radiographs.

The production of osteoclast-activating cytokines by tumor cells leads to substantial calcium mobilization, hypercalcemia, and symptoms related to it.

Decreased synthesis and increased catabolism of normal immunoglobulins leads to hypogammaglobulinemia, and a poorly defined tumor product inhibits granulocyte migration.These changes create a susceptibility to bacterial infections, especially thepneumococcus, Klebsiella pneumoniae, and Staphylococcus aureus affectingthe lung and Escherichia coli and other gram-negative pathogens affecting theurinary tract.

Infections affect at least 75% of pts at some time in their course.

Renal failure may affect 25% of pts; its pathogenesis is multifactorial—hypercalcemia,infection, toxic effects of light chains, urate nephropathy, dehydration. Neurologic symptoms may result from hyperviscosity, cryoglobulins, andrarely amyloid deposition in nerves.

Anemia occurs in 80% related to myelophthisis and inhibition of erythropoiesis by tumor products

Clotting abnormalities may produce bleeding.

Oral manifestations:

Involvement of jaws is frequent especially mandibular molar area.

Jaw involvement shows pain , swelling, expansion of the jaws, numbness and mobility of the teeth.

extension of the disease to various other sites like lymph nodes, skin and viscera is seen.

Lab features:

Reversal of A:G ratio

Bence jones proteins are present in the urine samples.these are unusual proteins which coagulate when heated 40-60 C and disappears when boiled and reappears when cooled.(Bence jones protein are present in polycythemia and leukemia also).

Monoclonal hypergammaglobulinemia –IgG common followed by IgA.

Increased ESR

Increased alkaline phosphate.

Diagnosis

Marrow plasmacytosis >10%, lytic bone lesions, and a serum and/orurine M component are the classic triad.

Monoclonal gammopathy of uncertain significance (MGUS) is much more common than myeloma, affecting about 6% of people over age 70; In myeloma, serum levels of paraprotein, creatinine, and 2-microglobulin levels predict survival.

Durie and salmons major and minor criteria is used to diagnose multiple myeloma.

Major Diagnostic CriteriaPlasmacytoma on tissue biopsy

Bone marrow plasmacytosis of > 30%

M Protein: IgG > 3.5 g/L; IgA > 2.0 g/L

Urinary kappa or lambda chain excretion of > 1g / 24 hours in absence of amyloidosis

Minor Diagnostic CriteriaMarrow plasmacytosis of 10-30%

Lytic bone lesions

Evidence of a monoclonal protein but lessor amounts than above

Hypoglobulinemia of normal proteins: IgM < 500 mg/L, IgA < 1 g/L or IgG < 6g/L

The diagnosis of multiple myeloma requires minimum of 1 major and 1 minor criteria or 3 minor criteria as listed in the table above. Once the diagnostic criteria are met durie and salmon clinical staging is done.

Staging (Table 71-4)- harrison 17/ e –pg 362

About 10% of pts have very slowly progressive disease and do not require treatment until the paraprotein levels rise above 50 g/L or progressive bone disease occurs.

Pts with solitary plasmacytoma and extramedullary plasmacytoma are usually cured with localized radiation therapy.

Supportive care includes early treatment of infections; control of hypercalcemia with glucocorticoids, hydration, and natriuresis; chronic administration of bisphosphonatesto antagonize skeletal destruction; and prophylaxis against urate nephropathy and dehydration.

Therapy aimed at the tumor is usually palliative.

Initial therapy is usually one of several approaches, based on whether the pt is a candidate for high-dose therapy and autologous stem cell transplant.

Transplant-eligible (avoid alkylating agents): thalidomide, 400 mg/d PO or 200 mg qhs, plus dexamethasone, 40 mg/d on days 1–4 each month, with or without chemotherapy such as liposomal doxorubicin; addition of bortezomib may be even more effective.

Transplant-ineligible: melphalan, 8 mg/m2 orally for 4–7 days every 4–6 weeks, plus prednisone. About 60% of pts have significant symptomatic improvement plus a 75% decline in the M component. Bortezomib also appears to improve response rates to melphalan.

Experimental approaches using sequential high-dose pulses of melphalan plus two successive autologous stem cell transplants have produced complete responses in about 50% of pts <65 years.

Long-term follow-up is required to see whether survival is enhanced. Palliatively treated pts generally follow a chronic course for 2–5 years, followed by an acceleration characterized by organ infiltration with myeloma cells and marrow failure.

More aggressive treatment may produce medianmedian survival of 6 years. New approaches to salvage treatment include bortezomib, 1.3 mg/m2 on days 1, 4, 8,and 11 every 3 weeks, often used with dexamethasone, vincristine, and/orliposomal doxorubicin. Lenalidomide is also active.