Medicine: Prep Manual for Undergraduates

2015·75.67 MB·English

by  K. George Mathew

Contents
Preface to the Fifth Edition vii
Preface to the First Edition ix
Chapter 1 Diseases of Blood 1
Chapter 2 Diseases of the Respiratory System 116
Chapter 3 Immunological Factors in Disease 265
Chapter 4 Diseases of the Skin 297
Chapter 5 Diseases of the Nervous System 316
Chapter 6 Diseases of the Liver and Biliary System 421
Chapter 7 Diseases of the Cardiovascular System 487
Chapter 8 Diseases of the Gastrointestinal System 663
Chapter 9 Diseases of the Connective Tissues and Joints 717
Chapter 10 Acute Poisoning and Environmental Emergencies 753
Chapter 11 Nutritional Factors in Disease 775
Chapter 12 Psychiatry 791
Chapter 13 Oncology 806
Chapter 14 Genetics and Diseases 814
Chapter 15 Disturbances in Water, Electrolyte and Acid-Base Balance 825
Chapter 16 Diseases of the Kidneys and Genitourinary System 840
Chapter 17 Diseases Due to Infections 867
Chapter 18 Endocrine and Metabolic Diseases 935
Index 997
xi
Chapter 1
Diseases of Blood
Q. Give a brief account of erythropoietin (EPO), recombinant human erythropoietin (rHuEPO) and
darbepoietin alpha.
Q. What are the ectopic sources of erythropoietin?
• Erythropoietin (EPO) is a glycoprotein having a molecular weight of 36,000 Dalton. It is primarily produced by the
juxtatubular interstitial cells of the renal cortex. In foetus, liver is the primary site of production of EPO.
• Hypoxia is the most potent stimulus for EPO production. Kidneys respond to hypoxia by increased production of EPO.
Another important stimulant is the presence of anaemia.
• EPO stimulates erythropoiesis by acting on the erythropoietic stem cells, stimulating increased proliferation. It may also
protect neuronal cells from noxious stimuli.
Hypoxia Reduction in hypoxia
Erythropoietin �---- Erythropoiesis i
Ectopic Sources of EPO
• Polycystic kidneys.
• Cerebellar haemangioblastoma.
• Uterine fibroma.
• Renal carcinoma.
• Hepatoma.
• Phaeochromocytoma.
Recombinant Human Erythropoietin (rHuEPO)
has the same biological effects as endogenous erythropoietin.
• It
• Available as erythropoietin-a and erythropoietin-[3.
• Recommended in the treatment of anaemia associated with chronic renal failure. (Patients with normal or low iron
stores need concomitant administration of iron to achieve an optimal erythropoietic response).
• Other possible indications include anaemia of chronic inflammation and anaemia (haemoglobin <10 g/dL) in patients
with cancer given chemotherapy without curative intent. It is not indicated in patients with cancer who are not being
treated with chemotherapy.
• Also useful for treating zidovudine-induced anaemia in HIV patients, and for the treatment of anaemic patients
(haemoglobin > 10 to � 13 g/dL) who are at high risk for peri-operative blood loss from elective, non-cardiac,
non-vascular surgery to reduce the need for allogeneic blood transfusions.
• Side effects include hypertension, bleeding, increased risk of thrombosis, headache, arthralgia, nausea, oedema, diarrhoea
and progression of cancers.
Darbepoetin Alpha
• An erythropoiesis stimulating protein similar to EPO.
• Produced in Chinese hamster ovary cells by recombinant DNA technology.
2 Medicine: Prep Manual for Undergraduates
• Half-life approximately three times rHuEPO and hence needs to be given less frequently.
• Side-effect profile and therapeutic value similar to rHuEPO; not approved for zidovudine-induced anaemia and for
peri-operative blood loss.
Q. Discuss briefly about haematopoietic growth factors.
• Haematopoietic growth factors (HGFs) act at different stages of haematopoietic cell differentiation.
• Some HGFs such as interleukin (IL)-1, IL-3, IL-6 exert their primary effects early in stem cell differentiation and are
therefore important for the differentiation of multiple blood lineages.
• Others such as EPO, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating
factor( GM-CSF) and thrombopoietin (TPO) exert their effects later in the differentiation cascade, and their effects are
more lineage specific. Their recombinant forms are available for therapeutic use.
Erythropoietin
• Discussed above.
G-CSF
• Promotes the survival, stimulates the proliferation of neutrophil progenitors and promotes their differentiation into
mature neutrophils. In addition, it causes premature release of neutrophils from the bone marrow and enhances their
phagocytic function.
• Normally it is produced by endothelial cells, fibroblasts and macrophages.
• Dose is 5 µg/kg daily as subcutaneous injection. Its pegylated form has a long duration of action and requires to be
given as a one-time dose of 6 mg subcutaneously for each cycle of chemotherapy.
• Recommended for primary prophylaxis (to reduce chances of febrile neutropenia following chemotherapy) only
if the risk of febrile neutropenia is high (>20%) as determined by disease characteristics and myelotoxicity of
drugs used. For patients receiving chemotherapeutic regimens who have an intermediate risk of febrile neutrope­
nia (10 to2 0%), age >65 years, coexisting illnesses and poor performance status, prophylactic use of G-CSF is
indicated.
• Recommended for primary prophylaxis after autologous stem cell transplantation. However, not recommended after
allogeneic stem-cell transplantation because of increased risks of severe graft-versus-host disease and transplantation­
related death.
• Also recommended for secondary prophylaxis in patients with solid tumours with a previous history of febrile neutro­
penia who require high-dose chemotherapy and any dose reduction may compromise treatment outcome (e.g., patients
with estrogen-receptor-negative breast cancer or non-Hodgkin's lymphoma). If further infections in the next treatment
cycle are considered life threatening, G-CSF may be used.
• It is not routinely recommended in all patients with neutropenia and fever. However, it may be administered in patients
who have high risk of infection-related complications, prolonged(> 10 days) and severe neutropenia ( < 100/µL), hypo­
tension, multiorgan dysfunction or invasive fungal infection.
• It is not recommended in neutropenic patients who are afebrile.
• Both G-CSF and GM-CSF have been used successfully in mobilising stem cells from bone marrow for stem cell
transplantation.
• The use of G-CSF in patients undergoing chemotherapy for breast carcinoma may predispose the patient to acute
myeloid leukaemia or myelodysplastic syndrome. However, the benefit of using growth factors outweighs possible
risks.
• Adverse effects include fever, and bone and joint pains.
GM-CSF
• It causes an increase in neutrophil, eosinophil, macrophage and sometimes lymphocyte counts.
• Usually administered as a daily subcutaneous injection of250 µg/m2.
• Both G-CSF and GM-CSF appear to have similar efficacy in the indications given above.
ChapIt1e D ri seoafBs leoso3 d
TPO
• Iitts h meo spto tceyntto pkrionmeo ptrionlgi faenrmdaa ttiuoronafm t eigoank arIyaotlc psyroti etmshe.pes l atteolets
aggreignra etsep osnusbet htrole esvohefotll hsdr omcboilnla,an gaded ne nodspiih noesp (hAaDtPe) .
• Normaplrloyd buycl eidvs ekre,lm eutsacalln ekdsi dneys.
• Inc anpcaetri reenctesci hveimnogt hihetar bsae pesynh, o tworn e dtuhcdeeu raotfpi oosnt -chetmhortohrnebroacpyy­
topetnhioaut,gh hei rnseo i ncriensau srev ival.
• Howevmearnp,ya tipernotdsau nctei baogdaiiTenPssO at n tdh easnet ibaoldsciore oss sw-irtaehnan dce tu tralize
endogetnhoruosm botpopo rioedatup icaner adtohxriocmablo cytopenia.
• TwToP O-reacgeopntfioorsrret fsr aIcTptPao triyee lnttrso:m abnordpo amgi plostim
Q. Define eosinophilia. What are the common causes of eosinophilia?
• Eosinoipashn ai blsioealo ustien coopuehnxitcl e e5d0i0n/Cgµo Lm.m cona uosfee oss inoaprthehifo ell ilao wing:
•
Helminthic infestations • Drugs • Collagen vascular diseases
• Loeffler's syndrome • Sulphonamides • Rheumatoid arthritis
• Tropical eosinophilia • Aspirin • Churg-Strauss syndrome
• Allergic conditions • Nitrofurantoin • Malignancies
• Hodgkliynm'psh oma
• Hay fever • Penicillins
• Asthma (including allergic • Cephalosporins • Chronic myeloid
bronchopulmonary asper­ • Allopurinol leukaemia
gillosis) • Carbamazepine • Solid organ cancers
• Serum sickness • Eosinophilic leukaemia
• Idiopathic hypereosinophilic
syndrome
Q. Discuss the abnormalities that can be seen on a peripheral blood smear examination.
Anisocytosis
• Variaitnti hsoein ozsfre e bdl ocoedl ls.
• Seeinin r doenfi caineanetmm eigaa,l oabnlaaesmmtoiidace, or rsa etvete hrael aspsotesrmtai nas,afu nssdii odne roblastic
anaemia.
Poikilocytosis
• Variaitntih soehn asop fre e bdl ood cells.
• Seeinni rdoenfi caineanettm hiaal,a sasnasdei mdiear oabnlaaesmtiiac.
Microcytosis
• Rebdl ocoedls lmsa ltlhetarhn e ir snio(z<r e7m 5fLa )l.
• Seeinni rdoenf iacniaeentmthi aal,a sasnasdei mdiear oblastic anaemia.
Macrocytosis
• Rebdl ocoedll lasrt ghea1rn0 fL 0.
• Seeinnv itaBm12 ainnfod l iacc diedfi ciency.
Hypochromia
• Recde lhlasv lionwghe are mogalsjo ubdigbneyt d h eaiprp eaurnadnmecirec rosTcheco epnypt.ra alillms oo rrt eh an
one-tthhdeii radm oefrt eecdre ll.
• Seeinni rdoenfi caineanettm hiaal,a sasnasdei mdiear oblastic anaemia.
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Polychromasia
• Rebdl ocoedls lhsoc wo lvoaurri asboiml(eiu tsyut;ahm leal jyo rariuets yur)ae cldo lwohri,ol teh aerrbesl uish.
• Assocwiiarttehet di culocytosis.
BasopShtiilpipcol rPi unngc tBaatseo philia
• Presoefsn ccaet dteeerbpel dud eo itnst hcey topolfra esbdml ocoedlw listR ho manoswtsakiyTn hienrsgee.p resent
altreirbeods omes.
• Seeinnp a tholodgaimcayagoleuldrny eg cd e lls.
• Alssoe ienns evaenraee 13m-itah,a lascsharemolineaipa coda i nsdo ning.
TargCeetl ls
• Flraetcd e lwlistac h e nmtarsaoslfh aemog(ldoebanirsnees a u)r,r obuynar d ieondfpg a l(lpoaarlr eea an)ad no uter
rionfhg a emog(ldoebanirsnee a ).
• Seeinnc hrolniivdcei rs ehayspeoss,p alnehdna iesmmo globinopathies.
Howell-BJoodlileys
• Theasree reomfnn uacnlmteasat rel reiifanttl h e er ytharfottcehynretu ec lieesux st rTuhdeeaydrn .eo rmraelmloyv ed
byt hsep leen.
• Appeaassr o lirtoaumrnyad s rse,l atliavrwegilety hh aienm oglopboirntoiifrzo eebndd l ocoedlo lnW; r igshtta'isn ,
appdeaarbrkl ourep urple.
• Seeinnn on-funocrat bisosenpniltnae gne mdne galoabnlaaesmtiiacs .
HeinBzo'dsi (eEsh rlBiocdhi'ess )
• Formfreodmd enataugrgerdeh gaaetmeodg lobin.
• As ubmembsrmaanrlooluu msna dsi snr ecde lsleseo nns uprasvtiantioasntle; e wni rtho utsitnaeifilnlyem d.
• Seeinnt halashsaaeemmoiilangy, ls uicso se-6d-ephhyodsrpo(hgGae6tnPedaD es)fie c iaesnpclyae,nnc dih ar olniivce r
disease.
AcanthoocrSy ptueCrse lls
• Rebdl ocoedls lhso wiirnrge sgpuilcaurl es.
• Seeinna betalipopardovtaenlicinvedaedier sm eaianashd,ey ,p osplenism.
BurCre lls
• Rebdl ocoedls lhso wrienggu larslpyi cpullaecse.d
• Seeinnu raeamnipdao ,s t transfusion.
Schistocytes
• Theasrefre a gmernetcdee dl( lwsic tehn ptarlaollfo tmrei ns sainndg s)ae reienni ntravhaasecmuollayrs is.
Spherocytes
• Theasrese m adleln,sp ealcykr eecdde lwlislt ohos fcs e nptarlaallno odrc ciunhr e redsipthaerryoa cnyidtm omsuinso ­
haemoalnyateimci as.
Microspherocytes
• Rebdl ocoedla lrbseo htyh percahnrsdoi mginci firceadnuitcnsle iydaz nedd i ameotceciurlnr;o nwu mbienpra st ients
witah sphehraoecmyotalinycat eiTmcypi iac.oa fbl u masn odfm icroanghiaoepmaotalhnyiatcei mci a.
ChapIt1e D ri seoafBs leoso5 d
Q. Describe various blood indices used in patients with anaemia.
• Mean corpuscular volume (MCV)
Haematocrit x1 0/RBC count X 106 (normal range 90 ± 8 fl; fl stands for femtolitres)
• Mean corpuscular haemoglobin (MCH)
Haemoglobin (g/dl) X10/RBC count x1 06 (normal range 30 ± 3 pg)
• Mean corpuscular haemoglobin concentration (MCHC)
Haemoglobin (g/dl) X 10/haematocrit (normal range 33 ± 2%)
• Red blood cell count
Males 4.5-5.5 X 106/mm3 Females 4-4.5 x 106/mm3
;
• Reticulocyte count
Expressed as percent of red blood cell count (normal < 2.5%)
• Corrected reticulocyte count (to adjust for severity of anaemia)
Expressed as % reticulocyte count xo bserved haematocrit/normal haematocrit
• Reticulocyte index
Expressed as% reticulocyte count x observed haematocrit/normal haematocrit x 1/2 (multiplication by
1/2 is to account for premature release of reticulocytes from bone marrow in anaemia)
• Red cell distribution width (ROW)
(Standard deviation of red cell volume + mean cell volume) X 100 (normal 11-16) (an index of variation
in cell volume within the red cell population)
Increased in iron-deficiency anaemia and megaloblastic anaemia
Normal in thalassaemias, anaemia of chronic disease and bone marrow aplasia
Q. Discuss the aetiology, classification, clinical features and general management of anaemia.
Definition
• Anaeimdsie afi naesasd t aitnwe h itchhbe l ohoade moglleovibebsile n l own otrhmreaa lnfo grte h pea tiaegnsete,'x s
anadl tiotfru edsei dence.
• Normaadluh late moglleovlbeiiblene s t w1e3e-ng1 /6di Lnm alaens1d 1 .5-g1/5di.Lnf0 e males.
Classification
• Anaemciabanesc lasisnit fwwioae yds :
1.Basoentd h cea uosfae n aemia.
2.Basoentd h meo rphoolfro ecgdey l ls.
Based on the cause of anaemia Based on the morphology of red cells
• Blood loss, which may be acute or chronic • Normocytic
• Acute (large volume over short period) • Microcytic
• Chronic (small volume over long period) • Macrocytic
• Inadequate production of normal red cells
• Excessive destruction of red cells
Aetiology
Due to blood loss
• Acute blood loss Trauma, post-partum bleeding
• Chronic blood loss Hook worms, bleeding peptic ulcer, haemorrhoids, excessive menstrual loss
6 MediciPnree:Mp a nuaflo Urn dergraduates
Duet oi nadeqpuraotdeu cotfni oornm al
recde lls
• Deficiency Irovni,t aBm1i2,nf olate
• Toxifca ctors Chroniincf lammaantdio nrfye cdtiisveear seensfa,al i lure,
hepaftaiicl durruelg,es a dtiona gpl aasntaiecm ia
• Endroicndee ficiencyHypothyrohiydpiosamd,r enraeldiuscEmeP,dOd uet or enfaali lure,
hypogonahdyipsomp,i tuitarism
• Marroiwn vasion Leukaemfiiabsr,os seicso,n dcaarryc inoma
• Marrofwa ilure Hypoplastic, aplastic anaemia
• MaldevelopmentSiderobalnaasetmhiiacae ,m oglobinloipskaietc hkiledesi sceeaalnslde
thalassnaeeompilaasds,it siocro dfee rryst hropoiesis
Duet oe xcesdseisvter uocfrt eicdoe nl ls
(Haemolytic anaemias)
• Genetdiics orders Redc elmle mbrahnaee,m oglooreb nizny me abnormalities
• Acquidriesdo rders Immunteo,x miecc, hanaincdia nlf ecctaiuosuess
ClinFiecaatlu res
Symptoms
• Fatilgauses,id tyusdpenp,oa elap,i tation.
• Dizzihneeasdsas,cy hnec,to ipnen,vi etrutsi,g o.
• Irritsalbedieilpsi ttuyr,lb aaocnfckc o ensc,e ntration.
• Throbibhni enaagdn e da rpsa,r aesitnfh iensagientardo s e s.
• Anoreixnidai,g neasutsibeoonawd,,ei ls turbances.
• Angiinnat,e rcmliatutdeintctra atnicsoeinre,eni btsr cahla emia.
• Symptoofcm asr dfiaaicl ure.
• Amenorprohloyemae,n orrhoea.
Signs
• Palolfso krip na,lo mrsma,ul c omuesm brnaanbieel,da snp da lpceobnrjauln Tchtpeia vlarncear.re abseecsoa mspea le
ast hseu rrousnkdwiihnne tgnhh ea emogilbsoe bli7ogn w/ dL.
• Tachycawriddpieua lp,sr ee ssure.
• Oedema.
• Cervviecnaohluu smh ,y perdpyrneacmoircd ium.
• Ejecstyisotmnou lrimbcue rhs,et a orvdte hrpe u lmoanraeray.
• Carddiialca taanltdai tsoeinrg o nfcs a rdfaiialcu re.
SigSnusg gesat iSnpge cAieftiico loofAg nya emia
• Jaundice Haemolayntaiecm cihar,o hneipca tmietgiasl,o balnaasetmiica
• Angulcahre ilitis Iron-defaincaieemnicay
• Glossitis Iron-defaincaieemnviciayt, a Bmidne ficifeonlcdayet,fe i ciency
12
• Splenomegaly Malarcihar,o nic haaenmaoelmyaitcaiu,cit nef eclteiuokna,e mia,
lymphopmoar,th aylp ertevnistiaoBmni dne ficiency
12
• Fronbtoasls ing Chronhiace molayntaiecm ia
• Neurolocghiacnag(led se mentViiat,amBidne ficiency
12
ataxia)
I
Chapter 1 Diseases of Blood 7
Approach to Diagnosis of Cause of Anaemia
Anaemia I
yes
Reticulocyte count i bilirubin, J, haptoglobin, i LDH ,.___ _, Haemolytic anaemia
No
Normal or low
Acute blood loss
Check MCV,
peripheral smear
Normocytic Macrocytic
Check B12 and folate
Pancytopenia
Normal ferritin
yes No
Hb electrophoresis Normal
Aplastic anaemia Creatinine
Myelophthisic anaemia
Leukaemia TSH Folate/B12
deficiency I
Normal
Thalassaemia ACD
Siderblastic anaemia TSH Anaemia of CKD
(Bone morrow
to differentiate)
Normal High Hypothyroidism
Serum electrophoresis
Liver disease Use of drugs I
Normal 'M'-spike
yes No
Multiple myeloma
(confirm by MDS
bone morrow) f ?drug-induced! (confirm by
bone morrow)
MCV = mean corpuscular volume; AIHA = Autoimmune haemolytic anaemia; IDA= Iron deficiency anaemia;
ACD = Anaemia of chronic disease; TSH= Thyroid stimulating hormone; CKD = Chronic kidney disease;
LFT = Liver function tests; MDS = Myelodysplastic syndrome
8 Medicine: Prep Manual for Undergraduates
General Management
• Blood transfusion.
• In significantly symptomatic and severely anaemic patients.
• Packed cells are preferred.
• Care has to be taken to avoid circulatory overloading, especially in elderly patients. Intravenous frusemide 20 mg
may be given prior to transfusion.
• Prompt treatment of infections and cardiac failure.
Q. Give a brief description about the anaemias due to blood loss.
• Anaemias due to blood loss could be acute (large volume over short period) or chronic (small volume over long period).
Anaemias Due to Acute Blood Loss
• A healthy adult can lose about 500 rnL of whole blood without any ill effect, e.g. blood donation. When more is lost,
compensatory mechanisms come into operation. The blood flow to skin and skeletal muscle is reduced, conserving
the blood flow to vital organs like brain, kidney and heart. With continued blood loss, these compensatory mecha­
nisms fail.
Clinical Features
• In the initial stages, pulse rate rises and blood pressure is maintained. Patient is pale, cold and sweating.
• If bleeding gets arrested, production of plasma replenishes the volume loss, resulting in dilution of remaining red
cells. Anaemia appears in 24-36 hours. This anaemia gets corrected in a few weeks, provided body iron stores are not
depleted.
• If bleeding continues, compensatory mechanisms fail and hypovolaemic shock ensues, which may result in death.
Earliest signs to look for in a patient with suspected blood loss (especially internal bleeding) are postural
hypotension and tachycardia.
Investigations
• Haemoglobin and haematocrit are normal in early stages (before haemodilution).
• Anaemia (haemoglobin and haematocrit drop) develops in 24-36 hours due to haemodilution.
• A transient leucoerythroblastic blood picture may be seen in very early stages.
• Reticulocytosis occurs at a later stage.
Treatment
• If symptomatic replace the blood loss by transfusion of whole blood or packed cells.
Anaemia of Chronic Blood Loss
• Compensatory mechanisms replenish the plasma volume and red cell loss. But, if the blood loss continues, body iron
stores are depleted and anaemia due to iron deficiency appears.
Q. Discuss the aetiology, clinical manifestations, diagnosis and management of iron deficiency anaemia.
Q. Write a short note on Plummer-Vinson syndrome (sideropenic dysphagia; Patterson-Kelly
syndrome).
• Iron deficiency is the most common cause of anaemia.
• Daily iron requirement is 10-15 mg, of which nearly 10% is absorbed in males and 15% in females.
• Children who consume large amounts of cow milk are particularly prone to iron deficiency:
• Cow's milk iron poorly absorbed
• Calcium present in milk inhibits iron absorption
• Cow's milk may cause protein allergy with GI bleeding (occult or gross).