Medicine

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 Index
Sl.No. Chapter Pg.No.
1. Cardiovascular disease 09
2. Respiratory disease 47
3. GIT and Hepatobiliary system 79
4. Hematology 106
5. Nephrology and Urology 119
6. Endocrinology including DM 136
7. Rheumatology and connective tissue disorders 154
8. Infectious diseases including STD and HIV 175
9. Neurology 192
 9

Cardiovascular Diseases
Heart failure
Abnormality of cardiac structure and/or function resulting in clinical symptoms
(e.g., dyspnea, fatigue) and signs (e.g., edema, rales), hospitalizations, poor
quality of life, and shortened survival.
Mechanisms of heart failure

Reduced ventricular MI (segmental dysfunction)

contractility Myocarditis/cardiomyopathy (global dysfunction)

Ventricular outflow Hypertension, aortic stenosis (left heart failure)

obstruction Pulmonary hypertension, pulmonary valve stenosis
(pressure overload) (right heart failure)

Ventricular inflow Mitral stenosis, tricuspid stenosis

obstruction
Ventricular volume Ventricular septal defect, Right ventricular volume
overload overload (e.g. atrial septal defect) Increased
metabolic demand (high output)

Arrhythmia Atrial fibrillation

Tachycardia cardiomyopathy Complete heart block
Diastolic dysfunction Constrictive pericarditis, Restrictive cardiomyopathy
Left ventricular hypertrophy
fibrosis Cardiac tamponade
Acute Precipitating Factors
(7) Pulmonary embolism,
(1) Excessive Na+ intake,
(8) Anemia,
(2) Noncompliance with heart failure
(9) Thyrotoxicosis,
medications,
(10) Pregnancy,
(3) Acute MI (may be silent),
(11) Acute myocarditis or infective
(4) Exacerbation of hypertension,
endocarditis,
(5) Acute arrhythmias,
(12) Certain drugs (e.g., nonsteroidal
(6) Infections and/or fever,
anti-inflammatory agents, verapamil).
 10
Clinical features of left and right heart failure.

Investigations
CXR may reveal cardiomegaly, pulmonary vascular redistribution, interstitial
edema, pleural effusions.
Prominence of
Reticular shadowing upper lobe Enlarged
of alveolar oedema blood vessels hilar vessels

Enlargement of lung base showing

septal or ‘Kerley B’ lines (arrow)

Septal or ‘Kerley B’ lines Enlarged cardiac silhouette; usually

with coexisting chronic heart failure
Chest X-ray of a patient with pulmonary oedema.
 11
Serum urea, creatinine and electrolytes, haemoglobin, thyroid function, ECG
Left ventricular systolic and diastolic dysfunction can be assessed by
echocardiography with Doppler, and EF calculated or estimated.
Brain natriuretic peptide (BNP) is elevated in heart failure and is a
marker of risk
TREATMENT
Transplant/ ventricular
assist device evaluation

Hydralazine plus an oral nitrate instead in pts who develop

hyperkalemia or renal insufficiency on ACE inhibitor.
Digoxin if symptomatic with spironolactone
Cardiac resynchronization if QRS > 150 mSec

Diuretics
Order of therapy

Beta blockers with EF < 40% once euvolemic

Spironolactone if EF < 30% with stable renal function & potassium
Defibrillator for EF < 30%

ACE inhibitor
Angiotensin receptor blockers (ARBs) if pt is intolerant of ACE inhibitor

NYHA NYHA NYHA NYHA

Class I Class II Class III Class IV
No limitation Slight limitation Marked limitation Unable to undertake
during ordinary during ordinary of normal physical activity without
activity activity activities without symptoms; symptoms
symptoms at rest maybe present at rest

related CLINICAL question

Q. A 62 yr old man with hypertension and non ischemic cardiomyopathy comes for follow
up after recent hospital discharge for acute decompensated heart failure. The patient
becomes short of breath after walking 1 block or climbing a flight of stairs but does not
have Orthopnea, cough, or hemoptysis. Current medications include metoprolol succinct,
lisinopril, furosemide , spironolactone and hydralazine. Echocardiogram performed during
hospital admission shows left ventricular ejection fraction of 30% , mild mitral
regurgitation and moderate pulmonary hypertension. Blood pressure is 133/72 mmHg,
pulse is 80/min. Jugular venous pressure is estimated at 8cm H O. Lungs are clear on
auscultation and third heart sound is heard at apex. There is trace peripheral edema. The
patient’s serum creatinine is 1.2 mg/dL and serum potassium is 5.0 mEq/L. What is the
best medication to add to this patient’s regimen.
 12

Clinical formula

Reduced ventricular Left: Raised JVP, Chest X-ray, ACE inhibitor, ARBs
contractility, Pulmonary oedema, BNP elevated, Diuretics, Beta
Ventricular outflow Cardiomegaly, Serum urea, blockers,
obstruction, Pleural effusion, creatinine and Spironolactone
Heart Ventricular inflow electrolytes,
Pitting oedema Hydralazine plus an
failure obstruction, Right: Raised JVP, haemoglobin, oral nitrate, Digoxin,
Ventricular volume hepatomegaly, thyroid Transplant/
overload, Arrhythmia ascites, Pitting function, ECG , ventricular assist
Diastolic dysfunction oedema echo, Doppler device evaluation

Syncope
Transient, self-limited loss of consciousness due to acute global impairment of
cerebral blood flow.
• cardiac syncope due to mechanical cardiac dysfunction or arrhythmia
• neurocardiogenic syncope, in which an abnormal autonomic reflex
causes bradycardia and/or hypotension
• postural hypotension, in which physiological peripheral vasoconstriction
on standing is impaired, lead to hypotension.

Vasovagal syncope
Triggered by a reduction in venous return due to prolonged standing,
excessive heat or a large meal.
Mediated by the Bezold–Jarisch reflex
Head-up tilt-table testing is a provocation test used to establish the diagnosis,
A positive test is characterised by bradycardia (cardio-inhibitory response) and/or
hypotension (vasodepressor response) associated with typical symptoms.
 13

Prolonged standing/ Stress/ Strong emotion

l
Excessive peripheral venous pooling

Venous return

Reduced ventricular filling

Vigorous contraction of relatively under-filled ventricles
Stimulates ventricular mechanoreceptors

Afferent impulses to dorsal nucleus of the vagus (brainstem)

Parasympathetic (vagal) activation and sympathetic withdrawal

Bradycardia and Vasodilatation

SYNCOpe
Treatment
Lifestyle modification
Salt supplementation and avoiding prolonged standing, dehydration or missing meals
Medical treatment
Fludrocortisone - causes sodium and water retention and expands plasma volume
Disopyramide - a vagolytic agent
Midodrine - a vasoconstrictor α-adrenoceptor agonist
Beta-blockers - inhibit the initial sympathetic activation

related CLINICAL question

Q. A 60-year-old man is brought to the casualty after sudden passing out at home.
According to his wife, he was unconscious for 1-2 minutes and displayed several
muscle jerks while unconscious. Medical history includes hypertension and
hyperlipidemia. The patient had a myocardial infarction 6 months ago and spent 5
days in the hospital. He now appears comfortable and has no symptoms. Blood
pressure is 130/85 mm Hg and pulse is 80/min with frequent ectopic beats. Physical
examination reveals a 2/6 holosystolic apical murmur radiating to the axilla. What is
the probable diagnosis?
 14

Clinical formula
Cardiac syncope:
Palpitations, chestpain, Blood sugar, Salt supplementation
breathlessness sodium and urea, and avoiding prolonged
Neurocardiogenic syncope: ecg, Echo standing, dehydration
Syncope Nausea, sweating, Holter monitoring, or missing meals,
lightheaded Carotid sinus Fludrocortisone
Postural hypotension, massage Disopyramide
Confusion, hyperexcitability, Tilt-table test Midodrine
olfactory hallucinations, aura CT head B blocker

acute coronary syndrome (ACS)

ACS represents clinically acute myocardial ischaemia and comprises:

1. Unstable angina (UA)
2. NonST elevated myocardial infarction (NSTEMI)
3. ST elevated myocardial infarction (STEMI)

Clinical Features
(1) new onset of severe angina,
(2) angina at rest or with minimal activity,
(3) recent increase in frequency and intensity of chronic angina.

Stable angina Acute coronary syndrome

Pathophysiology

Clinical
features

Risk
assessment
 15

NonST elevated myocardial infarction (NSTEMI)

Pathogenesis
In unstable angina, myocardial ischaemia results from a primary decrease in
oxygen delivery rather than in increase in myocardial oxygen demand
Diagnostic criteria of unstable angina
• Angina on effort of recent onset (one month).
• Angina of effort with increasing frequency and duration and provoked by less
than usual stimuli (accelerated or crescendo angina).
• Prolonged (>20 min) anginal pain at rest
• Angina in early (<1 month) post-infarction period.
• New onset (de novo) severe angina,
• Recent destabilization of previously stable angina with crescendo angina
• Post MI angina

NSTEMI
Unstable angina
Ischemic discomfort with at least one of three features:
1. Occurs at rest , usually lasting
2. Severe and of new onset
3. Occurs with a crescendo pattern
NSTEMI is Unstable angina with evidence of myocardial necrosis in elevated cardiac
biomarkers.
Pathophysiology
1. Plaque rupture or erosion with a superimposed nonocclusive thrombus
2. Dynamic obstruction (coronary spasm as in Prinzmetal’s variant angina)
3. Progressive mechanical obstruction
4. UA secondary to increased myocardial oxygen demand or decreased supply

ECG Changes Cardiac biomarkers

1. ST-segment depression 1. CK-MB
2. T-wave inversion 2. Troponin
cardiac troponin T: <0.1 ng/mL
cardiac troponin I: <0.03 ng/mL
 16

Evaluation and treatment of suspected acute coronary syndrome

TREATMENT OF Nstemi
1. ABAXIMAB
2. BETA BLOCKER- METOPROLOL FAILS
3. ENOXAPRIN
4. MORPHIN MNEMONIC DELAYED
5. O2 ABE MOAN PCI
6. ASPIRIN
7. NTG

Relative contraindications to thrombolytic therapy

(potential candidates for primary percutaneous coronary intervention)
• Active internal bleeding
• Previous subarachnoid or intracerebral haemorrhage
• Uncontrolled hypertension
• Recent surgery (within 1 mth)
• Recent trauma (including traumatic resuscitation)
• High probability of active peptic ulcer
• Pregnancy
 17

related CLINICAL question

Q. A 62-year-old man comes to the casualty due to chest pain. The patient had
occasional episodes of chest heaviness yesterday. Two hours ago, he had burning
midline chest pain that lasted 30 minutes. The patient took aspirin on the way to
the hospital; he currently has no chest pain or other issues. Medical history is
significant for diet-controlled type 2 diabetes mellitus. The patient is an ex-
smoker with a 20-pack-year smoking history. Blood pressure is 135/80 mm Hg,
and pulse is 82/min and regular. Oxygen saturation is 95% on room air. BMI is 32
kg/m2. ECG shows normal sinus rhythm with T-wave inversions in leads aVF and III.
Cardiac troponin I level is 2.1 ng/mL (normal: <0.01 ng/mL). What is the probable
diagnosis?

ST-Segment Elevation Myocardial Infarction

Myocardial infarction is myocardial necrosis occurring as a result of a critical
imbalance between coronary blood supply and myocardial demand.
It is usually due to the formation of an occlusive thrombus at the site of rupture of
an atheromatous plaque in a coronary artery.
ST-segment is persistently elevated in STEMI.

Clinical Features
Symptoms
● Pain: like that of angina but more severe and prolonged.
● Breathlessness.
● Vomiting:due to vagal stimulation, particularly in inferior MI.
● Syncope or sudden death due to arrhythmia.
● MI may occasionally be painless, especially in diabetic or elderly patients.
Signs
• Mild fever • Diffuse apical impulse
• Pallor, sweating • Soft first heart sound
• Tachycardia or bradycardia • Third heart sound
• Arrhythmias • Pericardial friction rub
• Narrow pulse pressure • Systolic murmur due to mitral regurgitation or
• Raised JVP uncommonly due to VSD
• Basal crepitations
 18

Changes in plasma cardiac biomarker concentrations

after myocardial infarction.

Creatine kinase (CK) and troponin I

(Tn I) are the first to rise, followed by
aspartate aminotransferase (AST)
and then lactate (hydroxybutyrate)
dehydrogenase (LDH). In patients
treated with reperfusion therapy, a
rapid rise in plasma creatine kinase
(curve CK (R)) occurs, due to a
washout effect.

Marker Onset Peak Duration

CK-MB 3–6 hours 18–24 hours 36–72 hours
Troponins 4–10 hours 18–24 hours 8–14 days
Myoglobin 1–4 hours 6–7 hours 24 hours

Troponins
Specific markers for myocardial infarction
3 Types
1. Troponin C (calcium binding subunit)
2. Troponin I (actomyosin ATPase inhibitory subunit)
3. Troponin T (tropomyosin binding subunit).
not increased in muscle injury unlike CK
Normal values
cardiac troponin T: <0.1 ng/mL
cardiac troponin I: <0.03 ng/mL
 19
Electrocardiogram

The serial evolution of ECG changes in full-thickness myocardial

infarction.
A Normal ECG complex.
B (Minutes) Acute ST elevation.
C (Hours) Progressive loss of the R wave, developing Q wave, resolution of the ST elevation and terminal T-wave
inversion.
D (Days) Deep Q wave and T-wave inversion.
E (Weeks or months) Old or established infarct pattern; the Q wave tends to persist but the T-wave changes
become less marked.

12-lead ECG showing acute inferior wall myocardial infarction

Area of infarct Leads showing abnormal Q waves

Diaphragmatic II, III, aVF
Antero-lateral I, aVL, V5, V6
Antero-septal V1, V2, V3, V4
True posterior Tall R in V1, V2
Right ventricular Tall R in V3R, V4R
 20

Laboratory Investigations
• Leucocytosis with a peak on 1st day.
• Raised ESR that may remain so for days.
• Elevated C-reactive protein.
• Chest radiography.
• Heart size is usually normal. Enlargement of cardiac shadow may indicate
previous myocardial damage or pericardial effusion.
• Evidence of pulmonary oedema.
• Radionuclide scanning shows the site of necrosis and the extent of impairment of
ventricular function.
• Echocardiography for regional wall motion abnormality and ejection fraction.

Management of Acute Myocardial Infarction

Initial treatment
• Attach a cardiac monitor
• Secure an intravenous line
• Administer oxygen if oxygen saturation <94%
• Administer sublingual nitrate (if not taken by the patient and pain is present)
• If no relief, give intravenous morphine 3-5 mg along with an antiemetic.
May repeat it 5-10 minutes after the first dose
• Give aspirin 150 mg to be chewed
• Give clopidogrel 300-600 mg orally (unless coronary artery bypass surgery is
contemplated)
Confirm diagnosis
• ECG
• If available, troponin T or I and CK-MB
Specific therapy
• Thrombolysis or percutaneous coronary interventions
• B-blockers unless contraindicated
• Treat complications (arrhythmias, congestive failure and shock)
• Admit in intensive coronary unit
 21

related CLINICAL question

Q. A 68-year-old woman comes to the casualty due to sudden-onset chest pain
associated with 2 episodes of vomiting.Medical history includes hypertension and
chronic obstructive pulmonary disease. The patient smoked a pack of cigarettes per
day for 30 years and quit 5 years ago. Blood pressure is 80/50 mm Hg, pulse is 60/min,
and respirations are 14/min. Examination shows diaphoresis and elevated jugular
venous pressure. Heart sounds are normal. A grade 2/6 lower left parasternal systolic
murmur is heard and increases with inspiration but does not radiate. ECG reveals 2-mm
ST-segment elevation in leads II, III and aVF and 1-mm ST-segment depression in leads
I and aVL. What is the probable diagnosis?
Clinical formula
STEMI NSTEMI STEMI: ST 1. ABAXIMAB
Arrhythmias, Pulmonary elevation,
2. BETA BLOCKER-
Narrow pulse oedema, New METOPROLOL
Progressive loss 3. ENOXAPRIN
acute pressure, Raised or worsening of the R wave,T-
coronary JVP, Diffuse apical MR murmur, 4. MORPHIN
wave inversion, 5. O2
syndrome impulse, Soft New/worsening Deep Q wave
S1,S3, Pericardial 6. ASPIRIN
rales,
(ACS) friction rub Hypotension, NSTEMI: ST-segment 7. NTG
depression, T-wave 8.Thrombolysis or
Systolic murmur, bradycardia or
inversions percutaneous
Basal crepitations tachycardia
CK-MB,TroponinT & I coronary interventions

Brugada syndrome

• It is characterised by ST segment elevation ( > 2 mm) in right pre-cordial leads (V I to

r

V3) followed by inverted T waves, incomplete or complete right bundle branch block, and
susceptibility to ventricular tachyarrhythmia (particularly poly morphic ventricular
tachycardia) and sudden cardiac death.
• Genetically transmitted as an autosomal dominant syndrome with incomplete
penetrance.
• Syncope due to tachyarrhythmia usually occurs during sleep or at rest.
• Typically presents in third or fourth decade.
• Similar ECG patterns are seen in anterior wall infarction, arrhythmogenic right
ventricular dysplasia, acute pericarditis, Duchenne muscular dystrophy, hypercalcaemia
and hyperkalaemia.
• Treatment involves implantable cardioverter defibrillator (ICD) in patients who have
experienced at least one attack of cardiac arrest. Quinidine may be used if ICD
implantation is not feasible. It can also be used along with ICD to reduce number of
shocks delivered by ICD.
 22

paroxysmal supraventricular tachycardia (PSVT)

Paroxysmal and recurrent, and has a rate of 140-220 beats/minute with 1: 1 conduction.
Usually results from re-entry of an atrial ectopic in the AV node (AV nodal re-entry
tachycardia-AVNRT).
Can also result from re-entry in the accessory pathways [AV re-entry tachycardia
(AVRT)].
Causes
• Idiopathic in majority.
• As for atrial ectopics – notably rheumatic and ischaemic heart disease.
• Digitalis intoxication.
• Preexcitation (WolffParkinsonWhite syndrome).
• Short PR interval with normal QRS complex (Lown GanongLevine syndrome).

Clinical features
• Local – Precordial discomfort or anginal pain. Disagreeable fluttering over
precordium. Fullness in neck. Pounding of vessels in head, arms, abdomen and leg.
• Psychic and reflex nervous symptoms – Anxiety, coldness, sweating, and
dizziness. Abdominal distension, nausea and vomiting. Polyuria at end of attack.
• Cardiovascular – If heart diseased or paroxysm prolonged –
(a) Symptoms due to cerebral ischaemia – Syncope or AdamsStokes syndrome.
(b) Cardiac failure especially when there is underlying heart disease or in children

Electrocardiogram
• The P wave is usually buried in the QRS complex or occurs slightly before or after
the QRS complex.
• The QRS complexes occur at regular intervals (there is constant RR cycle length
• Significant ST segment depression during tachycardia
Treatment
Vagal manoeuvres like carotid sinus massage, Valsalva manoeuvre and gag reflex are
useful - delay conduction in AV node in a patient with circuit tachycardia.
If vagal manoeuvres are unsuccessful, drug therapy is warranted. They prolong the
AV refractory period.
Synchronised cardioversion is performed if patient is hemodynamically compromised.
Long-term control can be achieved by radiofrequency ablation of the re-entrant
pathway.
 23

12-lead ECG atrioventricular nodal reentrant tachycardia (AVNRT)

related CLINICAL question

Q. A 25-year-old woman is evaluated for occasional episodes of palpitations. She
describes the episodes as a sudden, abrupt onset of fast and regular heartbeats that
feel like "her heart is racing in her chest." The episodes are commonly unprovoked
and are not related to exertion. During one episode, her blood pressure was recorded
as 100/60 mm Hg and her heart rate was 185/min and regular. Generally, she says,
cold-water immersion relieves her symptoms abruptly within several minutes. What is
the probable diagnosis?
 24

Clinical formula

Idiopathic, Angina, Disagreeable ECG: P wave is Vagal

Rheumatic and fluttering over precordium. usually buried in manoeuvres,
paroxysmal ischaemic heart Anxiety, coldness, the QRS complex Synchronised
supraventri disease, sweating, and dizziness. or occurs slightly cardioversion,
cular Digitalis intoxication, Abdominal distension, before or after the radiofrequency
tachycardia WolffParkinsonWhite nausea and vomiting. QRS complex. ablation of the
(PSVT) syndrome, Polyuria at end of attack, QRS : regular re-entrant
Lown GanongLevine Syncope or AdamsStokes intervals pathway.
syndrome, syndrome, Cardiac failure ST depression

digoxin toxicity
Action
• Increases myocardial contractility.
• Prolongs the refractory period of AV node, thereby slowing ventricular rate.
• Reflex vasodilatation from withdrawal of sympathetic constrictor activity in
patients with congestive heart failure.
Cardiac manifestations
Bradycardia
Multiple ventricular ectopics
Ventricular bigeminy
Paroxysmal atrial tachycardia with block
Ventricular tachycardia (VT)
Ventricular fibrillation
Conduction defects
Investigations
(a) ECG – Arrhythmias, changes of hyperkalaemia (in acute overdose):
ST-T wave changes; decreased QT interval.
(b) Serum K – Increased in acute overdose, decreased or normal in chronic overdose.
(c) Serum digoxin – High in acute overdose (>10 µg/litre if severe toxicity).

Management
• Stop digoxin, check urea, electrolytes and plasma digoxin concentration
• Correct hypokalaemia and dehydration
• Correct bradycardia using atropine or pacing
• Treat atrial tachycardia with J3-blockers
• Treat VT with lignocaine or amiodarone
• Antidigoxin antibodies rarely needed
 25

Wolff-Parkinson-White syndrome (WPW syndrome)

Cause
A strip of accessory conducting tissue allows electricity to bypass the AV
node and spread from atria to ventricles without delay.

(1) When ventricular activation occurs through the AV

node , the ECG is normal

(2) When it occurs through the accessory

pathway, a very short PR interval and a broad
QRS complex are seen.

In sinus rhythm, ventricular activation occurs by

both paths, causing the characteristic short PR and
slurring of the upstroke of the QRS complex (delta
wave).

Clinical features
This tract can act as a re-entry pathway and the patient may develop supraventricular
tachycardia.
Complications
Ventricular tachycardia,
Supraventricular tachycardia,
Ventricular fibrillation (VF)
Atrial fibrillation,
Death.

Treatment
Narrow complex tachycardia is treated in the same way as PSVT.
For broad-complex tachycardia,
Isopyramide, quinidine, flecainide, propafenone and amiodarone - increase the
refractory period and reduce the conduction rate through the bypass tract.
Radiofrequency ablation of the bypass tract can be done.
In patients with WPW syndrome and atrial fibrillation, cardioversion is the
treatment of choice.
Digoxin and verapamil shorten the refractory period of the accessory pathway
and must be avoided.
 26
related CLINICAL question
Q. A 34-year-old man comes to the casualty with palpitations for the past 4 hours. He
has no associated chest pain, shortness of breath, or dizziness. His medical history is
significant with 3 prior episodes of supraventricular tachycardia. The patient does not
use tobacco or illicit drugs and drinks alcohol only on social occasions. On examination,
his blood pressure is 120/80 mm Hg and pulse is irregularly irregular. ECG shows atrial
fibrillation with a rate of 160/min. What is the probable diagnosis?

Clinical formula
Accessory Isopyramide,
Supraventricular
conducting tissue Short PR and quinidine,
tachycardia, Atrial
allows electricity slurring of the flecainide,
fibrillation,
WPW to bypass the AV upstroke of propafenone and
syndrome Ventricular
node and spread the QRS amiodarone,
tachycardia,
from atria to complex Radiofrequency
Ventricular
ventricles without (delta wave). ablation,
fibrillation (VF)
delay. cardioversion

Atrioventricular block

Impaired conduction from atria to ventricles may be structural and permanent, or

reversible (e.g., autonomic, metabolic, drug-related)
First-degree AV block
Prolonged, constant PR interval (>0.20 s).
May be normal or secondary to increased vagal tone or drugs
(e.g., beta blocker, diltiazem, verapamil, digoxin);
Treatment not usually required.
Causes of first degree heart block
Acute rheumatic fever First-degree AV block
Inferior myocardial infarct
Myocarditis, e.g. diphtheritic
Degenerative myocardial disease
Drugs – Digitalis, β-blockers, calcium antagonists, emetine
Hyperkalaemia
Congenital heart disease (ASD)
Increased vagal tone (in normal individuals)
 27

First degree heart block. P-R interval almost 0.4 second

Second-degree AV block
Some atrial impulses fail to conduct to the ventricles, resulting in dropped beats.
Mobitz type I block (‘Wenckebach’s phenomenon’):
There is progressive lengthening of the PR intervals, culminating in a dropped
beat. The cycle then repeats itself.
It is sometimes observed at rest or during sleep in athletic young adults with
high vagal tone.
Mobitz type II block:
The PR interval of conducted impulses remains constant but some P waves are
not conducted.
It is usually caused by disease of the His–Purkinje system and carries a risk of
asystole.
Second-degree atrioventricular block (Mobitz type II).

The PR interval of conducted beats is normal but some P waves are not conducted. The
constant PR interval distinguishes this from Wenckebach’s phenomenon.

Stokes–Adams attacks
Episodes of ventricular asystole may complicate complete heart block, Mobitz type
II second-degree AV block and sinoatrial disease, resulting in recurrent syncope
 28

Third-degree (complete) AV block

Complete failure of conduction from atria to ventricles;
Atria and ventricles depolarize independently.
May occur with MI, digitalis toxicity, or degenerative conduction system disease.
Permanent pacemaker is usually indicated, except when reversible (e.g., drug-
related or appears only transiently in MI without associated bundle branch block).

There is complete dissociation of atrial and ventricular complexes. The

atrial rate is 80/min and the ventricular rate is 38/min.

Causes of third degree heart block

 29

related CLINICAL question

Q. A 45-year-old man comes to the opd after experiencing left-sided chest pain
for a day. The pain is nonradiating and constant and increases with movement of
the left hand. The patient has had no nausea, dyspnea, diaphoresis,
lightheadedness, or syncope. He has a 25-pack-year smoking history. Vital signs
are within normal limits. On examination, the pain is reproduced with palpation
of the left-sided chest wall muscles. ECG reveals no significant ST-segment or
T-wave abnormalities. What is the probable diagnosis?

Clinical formula

Causes of Complete Regular and slow ECG: Constant P-P and IV atropine, IV
Heart Block pulse (30-40/ R-R intervals but with infusion of B-
Lenegre's disease minute) Varying complete AV adrenergic agonists
Lev's disease intensity of S1, dissociation, i.e. the with dopamine,
AV Myocardial ischaemia High volume atria and ventricles beat epinephrine or
block or infarction pulse, Stokes- independently and there transcutaneous
lntracardiac surgery Adams attacks, is no relation between pacing, immediate
Digitalis intoxication Irregular cannon the P waves and the insertion of
Infective endocarditis waves on JVP QRS complexes. pacemaker.

Bundle branch block

Interruption of the right or left branch of the bundle of His delays activation of the
corresponding ventricle, broadens the QRS complex (≥ 0.12 sec) and produces
characteristic alterations in QRS morphology
Right bundle branch block.
Causes Diagnosis
Physiological Wide splitting of S2
IHD ECG: Wide QRS,
Cong. heart disease e.g. ASD S wave in lead I,
Cardiomyopathy R in V1
RV hypertrophy or strain e.g. pulmonary embolism
Left bundle branch block
Causes
• Coronary artery disease Diagnosis
• Aortic valve disease Reversed splitting of S2
• Hypertension ECG: Broad and. slurred QRS complexes,
• Cardiomyopathy qs wave in V1
 30

Right bundle branch block Left bundle branch block

Note the wide QRS complexes with ‘M’-shaped Note the wide QRS complexes with the loss of the Q
configuration in leads V1 and V2 and a wide S wave or septal vector in lead I and ‘M’-shaped QRS
wave in lead I. complexes in V5 and V6.

12-lead ECG showing right bundle branch block (RBBB)

 31

12-lead ECG showing left bundle branch block (LBBB)

aortic regurgitation
Due to disease of the aortic valve cusps or dilatation of the aortic root .
The LV dilates and hypertrophies to compensate for the regurgitation.
Stroke volume of the LV may eventually be doubled or trebled, and the
major arteries are then conspicuously pulsatile.
As the disease progresses, left ventricular diastolic pressure rises and
breathlessness develops.
Causes of aortic regurgitation
 32

Clinical features of aortic regurgitation

Symptoms
Mild to moderate aortic regurgitation
• Often asymptomatic
• Awareness of heart beat, ‘palpitations’
Severe aortic regurgitation
• Breathlessness
• Angina
Signs
Pulses
• Large-volume or ‘collapsing’ pulse
• Low diastolic and increased pulse pressure
• Bounding peripheral pulses
• Capillary pulsation in nail beds: Quincke’s sign
• Femoral bruit (‘pistol shot’): Duroziez’s sign
• Head nodding with pulse: de Musset’s sign
Murmurs
• Early diastolic murmur
• Systolic murmur (increased stroke volume)
• Austin Flint murmur (soft mid-diastolic)
Other signs
• Displaced, heaving apex beat (volume overload)
• Pre-systolic impulse
• Fourth heart sound
• Crepitations (pulmonary venous congestion)
Peripheral Signs of Aortic Regurgitation
• Collapsing pulse Best appreciated on the radial artery when the arm
(water hammer pulse) is elevated. This is characterised by a rapid
upstroke, rapid down stroke and a high volume

• Corrigan's pulse A jerky carotid pulse characterised by full expansion

followed by quick collapse

• Pulsus bisferiens Results from a low diastolic pressure from aortic run-off
and high systolic pressure from increased stroke volume
 33

• Hill's sign Popliteal cuff systolic pressure exceeding brachial cuff

systolic pressure by more than 20 mmHg
• A difference of 20-39 mmHg indicates mild AR
• A difference of 40-59 mmHg indicates moderate AR
• A difference of 60 mmHg or more indicates severe AR
• Corrigan's neck sign Prominent carotid pulsations visible in the neck

• De-Musset's sign Anteroposterior motion of the head (head nodding)

synchronous with cardiac cycle
• Landolfi's sign Alternating dilatation and constriction of pupil synchronous
with cardiac cycle
• Muller's sign Pulsations of the uvula

• Lighthouse sign Capillary pulsations on the forehead and face resulting

in alternate blanching and flushing
• Quincke's sign Alternate paling and flushing of lightly compressed nail bed
or mucous membrane of mouth
• Rosenbach's sign Pulsations of the liver

• Gerhardt's sign Pulsations of an enlarged spleen

• Pistol-shot Booming sound synchronous with systole heard over the

femorals femoral arteries
• Traube's sign Booming systolic and diastolic sounds heard over the
femoral artery
• Duroziez sign A systolic murmur heard over the femoral artery when it is
compressed proximally and a diastolic murmur when it is
compressed distally
• Mayne sign More than a 15-mmHg decrease in diastolic blood pressure with
arm elevation from the value obtained with the arm in the
standard position
• Becker sign Accentuated retinal artery pulsations
 34

Investigations
• ECG – Left ventricular hypertrophy, with diastolic overload pattern in severe AR.
• Chest X-ray – Enlargement of the left ventricle, with ‘duckback’ shape of left border.
Ascending aorta shows uniform enlargement.
• Echocardiography – is vital for examining aortic valve, determining size of aortic root
and assessing LV func tion. Aetiology of AR can thus be established. Severity of
regurgitation can be established from Colour Doppler study
Cardiac catheterisation and aortography: in assessing the severity of regurgitation,
aortic dilatation and the presence of coexisting coronary artery disease.
• Blood tests – Treponemal serology and determination of inflammatory indices in
patients with aortic wall disease.

Early decrescendo murmur of AR

Dilated left ventricle and prominent aorta due to

chronic aortic regurgitation

Treatment
Treatment of the underlying cause
Rheumatic fever prophylaxis
Medical treatment of cardiac failure with digoxin, diuretics, salt restriction and fluid
restriction
Afterload reduction therapy
• Isosorbide dinitrate 20-40 mg 6 hourly
• Hydralazine 50 mg 6 hourly
• Captopril 25-50 mg 8 hourly or enalapril 5-10 mg twice daily
 35

Asymptomatic patients with normal left ventricular (LY) size and systolic
function do not require surgery but should be monitored carefully for
development of symptoms, LY dysfunction or progressive LY dilatation.
Surgical therapy is required in symptomatic patients or those with LY ejection
fraction <50% or end-systolic LV diameter >55 mm (even if asymptomatic). It
involves aortic valve replacement (open or TAYI).

related CLINICAL question

Q. A 32-year-old man comes to the opd due to occasional palpitations. The
patient's medical history is unremarkable, and he considers himself healthy. His
maternal uncle died suddenly at age 40, and a cousin underwent heart surgery at a
young age. The examiner asks the patient to sit upright, lean forward, and hold his
breath in full expiration as the stethoscope diaphragm is placed at the left sternal
border and firm pressure is applied. There is a decrescendo early diastolic
murmur. What is the probable diagnosis?

Clinical formula

Collapsing’ pulse, ECG – Left ventricular Rheumatic fever

increased pulse pressure, hypertrophy prophylaxis
Bounding peripheral pulses, X-ray –‘duckback’ shape digoxin, diuretics, salt
Quincke’s sign, Duroziez’s of left border. restriction and fluid
aortic sign, de Musset’s sign, Echo – size of aortic root restriction, Isosorbide
regurgitation Cardiac catheterisation, dinitrate, Hydralazine,
Early diastolic murmur,
Systolic murmur, Austin Flint aortography Captopril or enalapril
murmur, Early decrescendo Treponemal serolog, Aortic valve replacement
murmur of AR inflammatory indices (open or TAYI).

aortic dissection
• Aortic dissection is caused by a tear of the intima. The dissection usually
propagates distally, but may also propagate proximally. The dissection usually
results in aortic dilatation, resulting in dissecting aneurysm of aorta.
• Afflicts males more than females in their fifth and sixth decades.
Conditions associated
• Hypertension (in majority)
• Cystic medial degeneration
• Marfan’s syndrome
• Ehlers-Danlos syndrome
• Previous surgery: Coronary bypass, replacement of aortic valve
• Pregnancy (usually third trimester)
 36

Stanford classification DeBakey classification

• Type A-dissection involving the • Type I-involves ascending to descending aorta

ascending aorta independent of site of • Type II-limited to ascending or arch of aorta
tear and distal extension • Type III-involves descending aorta only
• Type B-dissection limited to
descending aorta

Classification of aortic dissections.

Stanford classification:
Top panels illustrate type A dissections that involve the ascending aorta
independent of site of tear and distal extension;
Type B dissections (bottom panels) involve transverse and/or descending
aorta without involvement of the ascending aorta.
DeBakey classification:
Type I dissection involves ascending to descending aorta (top left);
type II dissection is limited to ascending or transverse aorta, without
descending aorta (top center + top right);
type III dissection involves descending aorta only (bottom left).
 37
Clinical features
Symptoms
Sudden onset of severe anterior or posterior chest pain, with “ripping” quality;
maximal pain may travel if dissection propagates.
Additional symptoms relate to obstruction of aortic branches (stroke, MI),
dyspnea (acute aortic regurgitation), or symptoms of low cardiac output due to
cardiac tamponade (dissection into pericardial sac).
Signs
Sinus tachycardia common; if cardiac tamponade develops, hypotension, pulsus
paradoxus, and pericardial rub appear.
Asymmetry of carotid or brachial pulses, aortic regurgitation, and neurologic
abnormalities associated with interruption of carotid artery flow are possible
findings.
Investigations
The CXR may show broadening of the upper mediastinum and distortion of the aortic
‘knuckle’.
Transthoracic echocardiography can only image the first 3–4 cm of the ascending
aorta but transoesophageal echocardiography, CT and MRI are all very useful.
Spiral CT scan is the modality of choice for diagnosis.

Treatment
Type A dissection is preferably treated by emergency surgical correction.
Type B dissection that is stable and uncomplicated is preferably treated by
medical measures
Medical therapy is aimed at reducing cardiac contractility and systemic arterial
pressure to 100-120 mrnHg systolic.

Endoluminal repair with fenestration of the intimal flap or insertion of a

stent-graft may be effective.
 38

related CLINICAL question

Q.A 69-year-old man is brought to the casualty due to severe chest pain that started
suddenly, approximately 3 hours ago. He describes the pain as sharp and the "worst pain
in my life." He feels the pain anteriorly as well as in his neck and between the shoulder
blades. On physical examination he appears very uncomfortable. There is an early
diastolic decrescendo murmur at the right upper sternal border. ECG shows sinus
tachycardia with nonspecific ST-segment and T-wave changes. Chest x-ray reveals
widening of the superior mediastinum. What is the probable diagnosis?

Clinical formula
CXR: broadening of the Medical therapy is
Chest pain, with “ripping” upper mediastinum and aimed at reducing
quality; dyspnea Sinus distortion of the aortic cardiac contractility
tachycardia hypotension, ‘knuckle’. and systemic arterial
aortic pulsus paradoxus, and > Transthoracic >
dissection pressure.
pericardial rub appear. echocardiography. Endoluminal repair
Asymmetry of carotid or Spiral CT scan is the with fenestration of the
brachial pulses, aortic modality of choice for intimal flap or insertion
regurgitation, diagnosis. of a stent-graft.

Acute rheumatic fever

Rheumatic fever is an inflammatory disease occurring as a delayed sequel to

pharyngeal infection with group A streptococci.
It primarily involves the heart, joints, central nervous system, skin and
subcutaneous tissues.
Acute rheumatic fever is characterised by exudative and proliferative inflammatory
lesions of the connective tissues.
It mainly involves the heart, joints and subcutaneous tissues.

Cardinal Features of Acute Rheumatic Carditis

• Murmurs
• Apical systolic murmur
• Apical mid-di.astolic murmur (Carey-Coombs murmur)
• Basal diastolic murmur
• Pericarditis
• Cardiomegaly
• Congestive heart failure
 39

Jones criteria for the diagnosis of rheumatic fever

Investigations in acute rheumatic fever

Raised WCC, ESR and CRP indicate systemic inflammation and are useful for
monitoring progress of the disease.
ECG (AV block, pericarditis) and echocardiography (cardiac dilatation, valve
abnormalities) may reveal evidence of carditis.
 40

Management
Penicillin is given to eliminate any residual streptococcal infection.
Bed rest lessens joint pain and reduces cardiac workload.
Cardiac failure should be treated as necessary.
High-dose aspirin (60–100 mg/ kg up to 8 g per day) usually relieves the
symptoms of arthritis and a response within 24 hrs helps to confirm the diagnosis.
Prednisolone 1–2 mg/kg produces more rapid symptomatic relief and is indicated
for carditis or severe arthritis, until the ESR returns to normal.
Patients are susceptible to further attacks of rheumatic fever if subsequent
streptococcal infection occurs, and long-term prophylaxis with penicillin should be
given, usually until the age of 21.

Infective Endocarditis
• Infective endocarditis is due to microbial infection of the heart valve or the lining
of cardiac chamber (endothelium).
Acute bacterial endocarditis (ABE) is caused by virulent organisms and runs its
course over days to weeks.
Subacute bacterial endocarditis (SBE) is caused by organisms of low virulence
and runs its course over weeks or months.

Subacute endocarditis Acute endocarditis Post-operative endocarditis

• Viridans streptococci: • Staphylococcus aureus • Staphylococcus albus
• S. sanguis • Pseudomonas • Candida
• S. mitis • Candida • Aspergillus
• Streptococcus milleri • Streptococcus pneumoniae • All organisms causing
• Streptococcus bovis • Neisseria gonorrhoeae acute and subacute
• Enteroccocus faecalis endocarditis
• Staphylococcus aureus
• HACEK group*

Haemophilus,
Aggregatibacter (formerly Actinobacillus),
Cardiobacterium, HACEK group
Eikenella
Kingella
 41
THE MODIFIED DUKE CRITERIA FOR THE CLINICAL DIAGNOSIS
OF INFECTIVE ENDOCARDITIS

Definite endocarditis:
Two major, or one major and three minor, or five minor
Possible endocarditis:
One major and one minor, or three minor
 42

Conjunctival petechiae splinter haemorrhages

Clubbing Osler's nodes

Janeway lesions Roth's spots

Osler’s nodes – Tender, peasized nodules on pads of fingers and toes. Often
pale in the centre. May occur in crops. Fade after few days usually without breaking
down or leaving any residue. Either due to minute emboli in superficial terminal
vessels or due to vasculitis.
Janeway lesions – Large nontender macules on palms and soles, it is vascular
phenomenon due to septic embolization.
Roth's spots-circular retinal haemorrhages with white central spots
 43
Investigations
Diagnosis: based on the modified Duke criteria .
Blood culture: the crucial investigation because it may identify the infection and
guide antibiotic therapy;
Echo- cardiography: allows detection of vegetations and abscess formation, as well
as assessment of valve damage.
Transoesophageal echo > transthoracic echo particularly for patients with
prosthetic heart valves.
A normochromic, normocytic anaemia and elevated WCC, ESR and CRP: common.
CRP is superior to ESR for monitoring progress.
Microscopic haematuria: usually present.
ECG: may show the development of AV block
Management
Any source of infection (e.g. dental abscess) should be removed as soon as
possible.
Empirical antibiotic therapy is with flucloxacillin and gentamicin if the
presentation is acute, or with benzylpenicillin and gentamicin if it is subacute or
indolent.
Subsequent antibiotic treatment is guided by culture results and is usually
continued for at least 4 wks.
Indications for surgery (debridement of infected material, valve replacement)
include heart failure, abscess formation, failure of antibiotic therapy and large
vegetations on left-sided heart valves (high risk of systemic emboli).

related CLINICAL question

Q. A 38-year-old woman is brought to the casualty due to an episode of
syncope. The patient has felt weak and has not eaten well over the last 2
weeks. As a result, she believes she is "dehydrated." Temperature is 38.2 C
(100.8 F), blood pressure is 112/58 mm Hg, and pulse is 49/min and regular.
The oral mucosa is dry and dentition is poor. An early diastolic murmur is
heard at the left sternal border at full expiration. ECG reveals sinus rhythm
with a 2:1 second-degree atrioventricular block. What is the diagnosis?
 44

Clinical formula

Conjunctival Empirical antibiotic

Modified Duke criteria . therapy with
Streptococci petechiae Blood culture
aureus, splinter flucloxacillin
Echo: vegetations and gentamicin,
Infective Staphylococc haemorrhages abscess formation,
Endocarditis us albus, Clubbing benzylpenicillin,
anaemia and elevated gentamicin.
Candida, Osler's nodes WCC, ESR, CRP
HACEK group Janeway lesions Surgery- debridement
Microscopic haematuria of infected material,
Roth's spots ECG: AV block valve replacement

MITRAL STENOSIS (MS)

Rheumatic fever is the most common cause of mitral stenosis.
Causes

Mitral stenosis
Left atrial pressure Left atrial dilatation

Pulmonary venous Atrial fibrillation Stasis of blood

hypertension

Pulmonary arterial hypertension Thrombus formation

(pulmonary hypertension)
Systemic embolism
Right ventricular hypertrophy

Right ventricular dilatation Right ventricular failure

Functional tricuspid regurgitation

 45
Investigations
● ECG: may show bifid P waves (P mitrale) due to left atrial hypertrophy,orAF.
● CXR:may show an enlarged left atrium and features of pulmonary congestion.
● Doppler echocardiography: provides the definitive evaluation of mitral stenosis,
allowing estimation of valve area, pressure gradient across the valve and pulmonary
artery pressure.
Complications
• Atrial fibrillation • Winter bronchitis
• Pulmonary hypertension • Dysphagia due to oesophageal
• Right ventricular failure compression by the left atrium
• Systemic thromboembolism • Ortner's syndrome
• Haemoptysis • Infective endocarditis (very rare)

Management
Medical management consists of diuretics for pulmonary congestion, with
anticoagulants and rate-limiting agents in the presence of AF.
For persistent symptoms or pulmonary hypertension, balloon valvuloplasty is the
treatment of choice, although valvotomy is an alternative.
Valve replacement is indicated for severe reflux or rigid, calcified valves.

related CLINICAL question

Q. A 37-year-old woman comes to the casualty due to left-sided weakness that
started several hours ago. She has had no fever, headache, or vision changes. Over
the past 6 months, the patient has had progressive exertional dyspnea, nocturnal
cough, and occasional hemoptysis. She also has had frequent episodes of
palpitations and an irregular heartbeat. On neurologic examination, left-sided
hemiparesis is present. What is the most likely diagnosis?

Clinical formula
Rheumatic fever, Dyspnoea, ECG: bifid P Diuretics for
Congenital mitral Orthopnoea and waves pulmonary
stenosis Paroxysmal Nocturnal (P mitrale) congestion, with
Coxsackie B virus, Dyspnoea, Pulmonary CXR: anticoagulants and
MITRAL SLE
STENOSIS Oedema,Haemoptysis, enlarged left rate-limiting agents in
Atrial myxoma, bronchitis, Symptoms atrium and the presence of AF.
(MS) Gout of right ventricular features of hypertension, balloon
Infective failure like peripheral pulmonary valvuloplasty is the
endocarditis, oedema, right congestion. treatment of choice,
Rheumatoid hypochondriac pain. Doppler valvotomy
arthritis echo Valve replacement
 46
Kerley’s A line
These are thin, non-branching
lines radiating from the hilum,
may be 2–6 cm in length, found in
the mid- and upper zones of the
lung fields.
These lines are due to the thick
interlobar septa, much thinner
than the adjacent blood vessels,
which do not reach the lung edge

Kerley’s B line
These are transverse lines at the lung
base, perpendicular to the pleura,
usually 1–2 cm in length, seen laterally
in the lower zone, reach up to the lung
edge (blood vessel do not reach the lung
edge).
Kerley’s B line is due to the thickening
of the interlobar septa caused by
oedema
Causes of Kerley’s line :-
• Pulmonary oedema (usually B type).
• Mitral valvular disease.
• Pneumoconiosis.
• Lymphangitis carcinomatosa.
• Sarcoidosis.
• Fibrosing alveolitis.
• Alveolar cell carcinoma.
• Lymphangiectasia.
• Idiopathic.
 47

Respiratory Disease
Pulmonary Function Tests

Inspiratory The maximum amount of air that can be

Reserve inhaled after a normal tidal volume
Volume inspiration (3000ml)
Vital Inspiratory
Capacity Capacity
Tidal Volume of air inspired or expired during
Volume normal quiet breathing (500ml)
Total
Lung
Capacity Maximum amount of air that can be exhaled
Expiratory
Reserve over normal tidal volume when person expires
FunctionAl Volume forcefully (1100ml)
Residual
Capacity Volume of air remaining in the lungs at the
Residual Residual
Volume Volume end of maximum expiration.(1200 ml)

Spirogram of a slow vital capacity maneuver demonstrating various lung volumes.

Lung capacities
Inspiration capacity= TV + IRV
Functional residual capacity = ERV + RV
Vital capacity = TV+ IRV+ ERV
Total lung capacity = VC+ RV
 48

Volume-time curve Flow volume curves

The FEV1 depends on good effort in healthy Tracing (a triangular shaped envelop) obtained when a
individuals, because the rate at which the lungs empty maximal forced expiration is followed immediately by a
is determined by the elastic recoil of the lungs and the forceful maximal inspiration. It is the recording, during
positive thoracic pressure applied round them by the spirometry, of expiratory flow plotted against volume.
expiratory muscles.
 49

related CLINICAL question

Q. A 62-year-old man comes to the opd due to a year of progressive exertional dyspnea
and dry cough. The patient has a history of gastroesophageal reflux and osteoarthritis.
He has smoked a pack of cigarettes daily for 40 years.The patient worked as a carpenter
for 20 years. Chest x-ray reveals pleural calcifications. Pulmonary function studies are
as follows.
FEV1 decreased. FVC decreased. FEV1/FVC ratio. normal
Diffusion capacity of the lung for carbon monoxide decreased
What is the most likely cause of this patient's symptoms?

Clinical formula

Inspiration capacity= Reduced diffusion capacity Elevated diffusion

TV + IRV Interstitial lung diseases capacity
Functional residual Sarcoidosis Severe obesity
Pulmonary capacity = ERV + RV Asthma
Function Emphysema
Vital capacity = Smokers Polycythemia
Tests Pulmonary haemorrhage
TV+ IRV+ ERV Anaemia
Total lung capacity = Pulmonary vascular diseases Left-to-right intracardiac
VC+ RV shunting

acute respiratory distress syndrome

ARDS describes the acute, diffuse pulmonary inflammatory response to either
direct (via airway or chest trauma) or indirect blood-borne insults from
extrapulmonary pathology.
It is characterised by:
● Neutrophil sequestration in pulmonary capillaries.
● Increased capillary permeability.
● Protein-rich pulmonary oedema.
Clinical Features
• About 50% patients who develop ARDS do so within 24 hours of the inciting event.
• The earliest sign is tachypnoea, shortly followed by dyspnoea. A few fine
inspiratory crepitations may be audible.
• With progression, the patient becomes cyanotic, more dyspnoeic and tachypnoeic.
Crepitations are more prominent and heard throughout both lung fields, especially
over basal areas. Tubular breath sounds may be heard.
• With further progression, hypotension and worsening of blood gas abnormalities
lead to death.
 50

Decreased arterial PaO2/FiO2 ratio

a)mild ARDS: 201-300 mmHg (≤39.9 kPa)

b)moderate ARDS: 101-200 mmHg (≤26.6 kPa)
c)severe ARDS: ≤100 mmHg (≤13.3 kPa)

Investigations
Plain radiograph
- 12-24 hours :
Chest x-ray features usually develop 12-24 hours after initial lung insult as result
of proteinaceous interstitial edema
- <1 week
Within one week, alveolar pulmonary edema (hyaline membrane) occurs due to type
1 pneumocyte damage.
- In contrast to cardiogenic pulmonary edema, which clears in response to diuretic
therapy, ARDS persists for days to weeks.
- The initial radiographic findings of ARDS clear, the underlying lung appears to
have a reticular pattern secondary to type 2 pneumocyte proliferation and fibrosis

(a) Early changes show bilateral infiltrates (b) Bilateral white-out

ABG analysis
• In the early stages, the only abnormality is mild hypoxaemia (low Pa02). As the
disease progresses, hypoxaemia worsens and hypercapnia appears.
• In the late stages, there occurs severe hypoxaemia (low Pa02) and severe
hypercapnia (high PaC02).
 51
Management

Algorithm for the initial management of

acute respiratory distress syn- drome
(ARDS). Clinical trials have provided
evidence-based therapeutic goals for a
stepwise approach to the early
mechanical ventilation, oxygenation,
and correction of acidosis and diuresis of
critically ill pts with ARDS. FIO2, inspired
O2 percentage; MAP, mean arterial
pressure; PBW, predicted body weight;
PEEP, positive end- expiratory pressure;
RR, respiratory rate; SpO2, arterial
oxyhemoglobin saturation measured by
pulse oximetry.

related CLINICAL question

Q. A 38-year-old man comes to the casualty with high-grade fever, shaking chills,
productive cough, and shortness of breath. He has had 2 hospital admissions for
alcohol-withdrawal seizures in the past year but continues to drink alcohol every day.
The patient has no other medical problems and takes no medications. Temperature is
39.7 C (103.5 F), blood pressure is 100/70 mm Hg, pulse is 110/min, and respirations
are 20/min. Skin and mucous membranes are dry. Physical examination reveals
crackles and bronchial breath sounds in the right lower lung field. Cardiac examination
is unremarkable. Chest x-ray reveals right lower lobe consolidation. The patient is
prescribed intravenous antibiotics. Twelve hours later, he develops significant
shortness of breath. Respirations are 38/min. Oxygen saturation is 80% on a
nonrebreather mask. What is the probable diagnosis?

Clinical formula
Tachypnoea, shortly followed by Chest X-ray :diffuse,
dyspnoea, cyanotic. Crepitations extensive bilateral Initiate volume/
acute are more prominent and heard interstitial and alveolar pressure limited
respiratory throughout both lung fields, infiltrates appear ventilation
distress especially over basal areas. ("fluffy" or "soft" Oxygenate
syndrome Tubular breath sounds may be shadowing). Minimise acidosis
heard, hypotension and Mild hypoxaemia (low Diuretics
worsening of blood gas Pa02), hypercapnia
abnormalities lead to death.
 52

Bronchial Asthma

Bronchial asthma is a heterogeneous disease, usually characterised by chronic

inflammatory disease of the airways.
It is defined by history of dyspnoea, cough, chest tightness and wheezing, that vary over
time and in intensity, together with variable expiratory airflow limitation.
It results from narrowing of the airways produced by a combination of muscle spasm,
mucosal oedema and viscid bronchial secretion.
The airflow limitation is generally reversible spontaneously or with treatment.
Extrinsic asthma – applies to those who produce exces- sive IgE in
response to allergens (atopic).
Intrinsic asthma – refers to those cases in whom exces- sive IgE
production cannot be demonstrated (non- atopic).
 53
Immediate assessment of acute severe asthma
Acute severe asthma
• PEF 33–50% predicted (<200 L/min)
• Inability to complete sentences in 1 breath
• Heart rate ≥110/min
• Respiratory rate ≥25/min
Life-threatening features
• PEF <33% predicted (<100 L/min)
• SpO2 <92% or PaO2 <8 kPa (60 mmHg) • Normal or raised PaCO2
• Silent chest/feeble respiratory effort
• Cyanosis
• Hypotension
• Exhaustion
• Confusion
• Coma
• Bradycardia or arrhythmias
Near-fatal asthma
• ↑PaCO2 and/or requiring mechanical ventilation with raised inflation pressures

Investigations
1. Chest radiograph may be normal, or show signs of segmental or lobar collapse.
2. Full blood count – Eosinophilia.
3. Sputum – Eosinophils, Charcot-Leyden crystals and at times Curschmann’s spirals may
appear purulent (due to eosinophilic leucocytes) in absence of infection.
4. Skin tests – may confirm allergens suggested by history.
5. Lung function test – Spirometry shows reduction in FEV1, FEV1/FVC ratio and peak
expiratory flow (PEF). Reversibility, which is one of characteristic feature of asthma, is
shown by >12% or 200 ml increase in FEV1 15 minutes after inhaled short acting β2
agonist or 2–4 weeks trial of oral corticosteroids.
6. Provocation (challenge) tests – Exercise challenge tests useful in young adults and can
be used to confirm diagnosis of asthma, since fall in FEV1 or PEFR occurs after 5–7
minutes of vigorous exercise in most patients with asthma.
7. IgE and IgE specific test – Elevation of total serum IgE supports diagnosis of atopy, and
measurement of frac- tions of IgE specific to one allergen, radioallergosorb- ent test
(RAST) can be useful in some patients in whom a specific allergy is suspected.
 54

Management

Stepwise approach to asthma

therapy according to the severity
of asthma and ability to control
symptoms. ICS, inhaled
corticosteroid; LABA, long- acting
β2 agonists; OCS, oral
corticosteroid.
 55

related CLINICAL question

Q. A 32-year-old woman comes to the casualty with progressive difficulty
breathing over the past few days. The patient has nasal congestion, dry
cough, and wheezing but no fever, chills, recent travel, or sick contacts.
Medical history is significant for eczema and a family history of asthma.
Temperature is 37 C (98.6 F), blood pressure is 138/78 mm Hg, pulse is 114/
min, and respirations are 28/min. Oxygen saturation is 95% on room air.
Nasal congestion is noted on examination. The ears and throat are normal,
and heart sounds are normal without murmurs. The patient has mild
scattered wheezing but does not appear to be in respiratory distress. What is
the probable diagnosis?

Clinical formula
Dry irritant cough may precede X-ray hyperinflated lungs
or accompany attacks of Direct challenge tests: 1. B-adrenoreceptor
wheezy breathlessness, Histamine or methacholine agonists.
Anxiety, cyanosis, perspiration provocation test 2. Methylxanthines.
Bronchial and cold extremities. ABG analysis: hypoxaemia 3. Corticosteroids.
Asthma In auscultation, Inspiration and hypocarbia 4. Chromones.
short and high pitched, Skin hypersensitivity tests: 5. Anticholinergics.
expiration prolonged, plenty of wheal and flare reaction 6. Leucotriene inhibitors.
wheeze. Crackles heard at the eosinophilia. 7. Miscellaneousagents.
bases towards the end of an • Elevated serum IgE levels.
attack.

LUNG ABSCESS
Lung abscess is defined as necrotic area of lung parenchyma containing purulent material.
Lung abscess can have two modes of presentations: acute (<l month of
symptoms) and chronic (>l month of symptoms).

• Primary lung abscesses usually arise from aspiration in the absence of an

underlying pulmonary or systemic condition, are often polymicrobial (primarily
including anaerobic organisms and microaerophilic streptococci), and occur
preferentially in dependent segments (posterior upper and superior lower lobes)
of the right lung.
• Secondary lung abscesses arise in the setting of an underlying condition
(e.g., a postobstructive process, an immunocompromising condition) and can be
due to a number of different organisms, among which P. aeruginosa and other
gram- negative rods are most common.
 56

Clinical features
• General examination reveals anaemia, fever, finger clubbing, halitosis and
oronasal sepsis.
• Respiratory system examination may be normal in the early stages. Later, frank
signs of consolidation like dullness on percussion, increased vocal fremitus and
vocal resonance, bronchial breathing, crepitations and pleural rub appear. Once the
abscess cavity opens into a bronchus, signs of cavitation like cavernous or
amphoric bronchial breathing and coarse post-tussive crepitations appear.

Investigations
• Anaemia, leucocytosis and raised ESR.
• Sputum studies should include Gram's stain, Ziehl-Neelsen staining for acid fast
bacilli, aerobic and anaerobic cultures and their sensitivity and cytological
examination for malignant cells.
• Chest radiograph often shows radiolucency in an opaque area of consolidation.
The wall or the border of the cavity completely surrounds the lucent area and an
air-fluid level may be seen.
• Bronchoscopy is indicated to exclude malignancy, obtain specimens for studies
and for removal of secretions.
• CT scan of thorax can detect lung abscess with certainty.

CECT chest axial view showing right middle

lobe atelectasis with lung abscess

X-ray chest showing a thick walled abscess

cavity with air fluid level in left lower lobe
 57
Complications
• Haemoptysis • Residual fibrosis and bronchiectasis
• Amyloidosis • Metastatic cerebral abscess
• Pleural effusion, empyema
• Aspergilloma
• Pneumothorax, pyopneumothorax and bronchopleural fistula
Treatment
• For primary lung abscesses, the recommended regimens are clindamycin (600 mg
IV tid) or an IV-administered β-lactam/β-lactamase combination. After clinical
improvement, the pt can be transitioned to an oral regimen (clindamycin, 300 mg
qid; or amoxicillin/clavulanate).
• In secondary lung abscesses, antibiotic coverage should be directed at the
identified pathogen.
• Continuation of oral treatment is recommended until imaging shows that the lung
abscess has cleared or regressed to a small scar.
• Pts who continue to have fever ≥7 days after antibiotic initiation and whose
additional diagnostic studies fail to identify an another treatable pathogen may
require surgical resection or percutaneous drainage of the abscess.

related CLINICAL question

Q. A 72-year-old man is brought to the opd due to 4 weeks of worsening productive
cough of abundant yellow sputum. The patient has also had malaise and night sweats
and has lost 3 kg during this period. The patient has a history of hypertension and
Parkinson disease. On examination, the patient appears frail with resting tremor of
both hands. Lung auscultation reveals scattered rhonchi but no wheezing. Heart
sounds are normal.Chest x-ray reveals a density with cavitation in the right lower
lobe. What is the probable diagnosis?

Clinical formula
Anaemia, fever, finger Anaemia, leucocytosis and Clindamycin or β-
clubbing, halitosis and raised ESR, Gram's stain, lactam/β-lactamase
oronasal sepsis, Ziehl-Neelsen staining for combination, In
LUNG dullness on percussion, acid fast bacilli, secondary lung
ABSCESS increased vocal fremitus often shows radiolucency in abscesses, antibiotic
and vocal resonance, an opaque area of coverage should be
bronchial breathing, consolidation, Bronchoscopy, directed at the identified
crepitations and pleural CT scan of thorax pathogen,
rub appear.
 58

Bronchiectasis
Bronchiectasis is defined as an irreversible abnormal dilatation of the bronchial tree.
ETIOLOGY
Impaired host defenses
- Cystic fibrosis (CF) (MCC in children)
- Primary ciliary dyskinesia, Kartagener syndrome, Young syndrome
- Primary immunodeficiency disorder, common variable
- Immunodeficiency: hypogammaglobulinemia, chronic granulomatous disease
- HIV/AIDS
obstruction
- Severe obstructive lung disease: asthma or COPD
- Neoplasm,bronchial carcinoid, bronchogenic carcinoma -Inhaled foreign bodies
postinfective (most common known non-CF cause in adults)
- Bacterial pneumonia and bronchitis, S. aureus, H. influenzae, B. pertussis
- Mycobacterial infection, e.g. tuberculosis, Mycobacterium avium-intracellulare
complex
allergic and autoimmune
- Allergic bronchopulmonary aspergillosis (ABPA)
- Connective tissue disease, e.g. rheumatoid arthritis,Sjögren syndrome,
systemic lupus erythematosus (SLE)
Congenital
- Alpha-1-antitrypsin deficiency

Clinical features
- Recurrent chest infections
- Productive cough more than 8 weeks
Cough is chronic and worse in the mornings. It is brought about by postural changes.
- Production of copious amounts of sputum
Sputum is characteristically copious, purulent and foul-smelling due to anaerobic
infections. Sputum production varies with posture and is maximum in the first 2 hours
after waking up.
- Hemoptysis.
Haemoptysis is due to rupture of the thin-walled vessels on the walls of dilated bronchi.
It is often recurrent and may
vary from slight blood-streaked sputum to massive fatal bleeding.
 59
Investigations
X-rays CT and HRCT :
- Tram-track opacities -> cylindrical - Demonstrate the airways
bronchiectasis, -Able to a greater or lesser degree to
- Air-fluid levels may be seen in cystic - distinguish some of the various
bronchiectasis. underlying causes.
- Increase in bronchovascular markings. -Signet ring appearance is seen in
bronchiectasis.

Chest radiograph (A) reveals ill-defined perihilar linear opacities and “tram-track” lesions in
bilateral lung fields. Computed tomography shows cylindrical bronchiectasis in right upper
and middle lobes with mucous plugging at places (B). Cystic bronchiectasis is present in left
upper lobe (C)

TREATMENT
• Acute exacerbations should be treated with a 7- to 10-day course of antibiotics
targeting the causative or presumptive pathogen; H. influenzae and P. aeruginosa
are isolated commonly.
• Hydration and mucolytic administration, aerosolization of bronchodilators and
hyperosmolar agents (e.g., hypertonic saline), and chest physiotherapy can be used
to enhance secretion clearance.
• For pts with ≥3 recurrences per year, suppressive antibiotic treatment to mini-
mize the microbial load and reduce the frequency of exacerbations has been
proposed.
• In select cases, surgery (including lung transplantation) should be considered.
 60

related CLINICAL question

Q. A 24-year-old man comes to the opd due to worsening productive cough with
tenacious sputum, fever, and shortness of breath for a week. Today, he noticed blood
streaks in the sputum. He also has decreased exercise tolerance, fatigue, and weight
loss. Temperature is 38.9 C (102 F), blood pressure is 130/80 mm Hg, pulse is 102/min,
and respirations are 20/min. Examination reveals crackles in both upper lung fields,
and heart sounds are normal without murmurs. Digital clubbing is present. Leukocyte
count is 15,000/mm3. Chest x-ray reveals a right upper lobe infiltrate, and a sputum
culture grew Pseudomonas aeruginosa. What is the probable diagnosis?

Clinical formula

Recurrent chest Antibiotics, Hydration

infections,Cough is CXray: Tram-track and mucolytic
chronic and worse in the opacities(cylindrical) Air-fluid administration,
Bronchiec mornings. It is brought levels (cystic), Increase in aerosolization of
tasis about by postural bronchovascular markings. bronchodilators and
changes, Production of CT: -Signet ring appearance hyperosmolar agents,
copious amounts of is seen in bronchiectasis. and chest
sputum, Hemoptysis physiotherapy

Pneumonia
Pneumonia is defined as inflammation with exudative solidification of the lung
parenchyma, generally acute.

Pathological Stages
• Stage of congestion-just congestion of the vessels without alveolar
exudation; fine crepitations may be heard
• Stage of red hepatisation-intra-alveolar exudation especially with
RBCs; tubular bronchial breathing heard
• Stage of grey hepatisation-the exudation is of mainly WBCs with
minimal RBCs; tubular bronchial breathing heard
• Stage of resolution-the exudate is absorbed or removed by macrophages
& proteolytic enzymes; coarse crepitations heard
 61
Causes

CLINICAL FEATURES
Symptoms: Onset often sudden although sometimes it follows a minor respiratory
infection of a few days dura- tion.
1. General symptoms of infection – Malaise, fever, rigors, and night sweats,
vomiting; in the elderly confusion and disorientation.
2. Pulmonary symptoms – Dyspnoea, cough, and sputum which is often blood-
stained or rusty and difficult to expectorate.
3. Pleural symptoms – Pain aggravated by cough, deep breath or movement, usually
localised to site of inflam- mation.
 62
Investigations

In lobar pneumonia, CXR reveals a

homogeneous opacity localised to the
Lobar pneumonia of the right middle lobe affected lobe or segment

Treatment
 63

Hospital CURB-65. *Defined as an

abbreviated mental test score ≤8,
or new disorientation in person,
place or time. (A urea of 7 mmol/L
≅ 20 mg/dL.)

related CLINICAL question

Q. A 68-year-old man is brought to the casualty with h/o 3 days of fever and
cough productive of yellow sputum. He has a history of coronary artery disease
and has smoked a pack of cigarettes daily for 40 years. Temperature is 39.4 C
(103 F), blood pressure is 110/70 mm Hg, pulse is 110/min, and respirations are
24/min. Pulse oximetry is 92% on room air. Chest auscultation reveals crackles
and reduced breath sounds over the right lower chest. Chest x-ray reveals
alveolar infiltrates in the right lower lobe. What is the probable diagnosis?

Clinical formula

Sudden onset of rigors Check the airway,

followed by fever, pleuritic Leucocytosis, Blood culture,
Microscopic examination breathing and
chest pain, cough productive circulation.
of purulent sputum and should include Gram staining
and Ziehl-Neelsen staining. Treat shock with
haemoptysis. intravenous fluids.
Pneumonia Patients with atypical Pneumococcal antigens can
be detected in the serum or Correct hypoxia with
pneumonia: dry cough, oxygen inhalation,
myalgias, arthralgias, urine in pneumococ cal
pneumonia,Chest radiograph Treatment of pleuritic
prominent headache, mental pain with analgesics
confusion, abdominal pain is essential for the
confirmation of diagnosis like paracetamol or
and diarrhoea. Haemoptysis codeine.
 64

Interstitial lung disease

Interstitial lung disease (ILD) spectrum of conditions included is broad, ranging
from occasional self-limited inflammatory processes to severe debilitating
fibrosis of the lungs.
Classification

Smoking related ild

i. Respiratory Bronchiolitis with interstitial lung disease ( RB-ILD )
ii. Desquamative Interstitial Pneumonia ( DIP )
iii. Pulmonary Langerhans Cell Histiocytosis ( PLCH )
These diseases are result of active or prior tobacco smoke exposure.
DIP has also known to occur in children with Familial Pulmonary Fibrosis (FPF)
Clinical manifestation
Predominantly occurs in active and cases of heavy smokers.
Occurs b/w 40 - 50yrs of age
Dysnea
Cough
Wheezing
 65

Investigation
RB-ILD DIP
Central bronchial wall Diffuse (or patchy ) B/L symmetric
thickening,peripheral bronchial wall ground glass opacities tend to be
thickening,centrilobular nodules and even more prominent.
ground glasss opacities.
Honey combing if present indicates
worse prognosis.

Treatment
Discontinue smoking
Immunosuppressive agents ( Prednisone )
Cytotoxic agents ( Azathioprine and Cyclophosphamide)
Bronchodilators can also be used

related CLINICAL question

Q. A 65-year-old woman is brought to the physician due to 6 months of dry cough and
worsening dyspnea. Her dyspnea has progressed so that she is now able to walk only a
few steps. She has no fever, chest pain, or hemoptysis. Her only medication is
hydrochlorothiazide for hypertension. The patient is a retired schoolteacher and does
not use tobacco or alcohol. Temperature is 37.2 C (99 F), blood pressure is 140/86 mm
Hg, pulse is 84/min, and respirations are 18/min. Chest examination shows dry, late
inspiratory crackles and digital clubbing. There is no peripheral edema. Serology is
negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies. Chest x-
ray shows diffuse reticular opacities. What is the probable diagnosis?
 66

Clinical formula
RB-ILD Discontinue
Predominantly occurs in bronchial wall smoking
active and cases of thickening,centrilobular Immunosuppressiv
heavy smokers. nodules and ground glasss e agents
Interstitial Occurs b/w 40 - 50yrs of opacities, Honey combing
lung disease ( Prednisone )
age DIP Cytotoxic agents
Dysnea Diffuse (or patchy ) B/L ( Azathioprine and
Cough symmetric ground glass Cyclophosphamide
Wheezing opacities Bronchodilator

Occupational lung disease

ASBESTOSIS
Asbestosis refers to development of diffuse interstitial fibrosis secondary to
asbestos fiber inhalation.

-Subpleural reticulations
- Subpleural plaques and
- Sub pleural calcifications

Chest radiograph
- irregular opacities with a fine reticular pattern
- evidence of asbestos exposure such as calcified or noncalcified pleural plaques
may be evident.
- Pleural effusions and pleural plaques are common manifestations
 67

(A) HRCT features of early asbestosis include subpleural (B) In more advanced disease, a coarse reticular
lines (arrowheads) and fine reticulation (arrows). These pattern with honeycombing, often
subtle abnormalities persisted on prone sections. indistinguishable from usual interstitial pneumonia
on HRCT, is seen. Note the calcified pleural plaques
in both examples.
SILICOSIS
- Silicosis is a fibrotic pneumoconiosis caused by the inhalation of fine particles of
crystalline silicon dioxide (silica).
Characterised by pulmonary oedema, interstitial inflammation and accumulation
of proteinaceous fluid rich in surfac tant within the alveoli.
Multiple small nodules with ground glass densities
Thickened interlobular and intralobular septa with CRAZY PAVING pattern
polygonal shape

Radiographic findings on chest x-ray

- Bilateral consolidation and/or
ground-glass opacities
- which tend to appear in perihilar
regions.

Silicosis. There is bilateral hilar adenopathy and

many of the nodes are calcified, some of them
demonstrating ‘eggshell’ calcification
 68
Coal workers’ pneumoconiosis (CWP)
Coal dust inhalation
CWP is subdivided into two:
1. SimpleCWP
2. Progressive massive fibrosis (PMF).

Caplan’s syndrome. (A) Coal worker with rheumatoid arthritis. Multiple rounded
opacities are present (some are calcified). (B) There is a left-sided cavitating
pulmonary nodule (arrows) on a background of pneumoconiosis.

Progressive massive fibrosis (PMF).

Commonly seen in silicosis than in CWP and is due to the coalescence of larger
nodules, leading to mass-like opacities
Clinically characterised by cough with blackish expectoration (melanoptysis) and
progressive breathlessness.

Progressive massive fibrosis in coal workers’

pneumoconiosis. Mass- like opacities are seen bilaterally
Progressive massive fibrosis. Large confluent masses
in the upper lobes in association with multiple small
have formed. Cavitation is evident on the left
nodules and calcified mediastinal lymphadenopathy
 69

related CLINICAL question

A 56-year-old man comes to the opd due to progressively worsening exertional
dyspnea over the last 4 months. The patient works for a home insulation and
plumbing company. Medications include hydrochlorothiazide and amlodipine for blood
pressure control. Temperature is 36.8 C (98.2 F), blood pressure is 130/78 mm Hg,
pulse is 76/min, and respirations are 15/min. Examination shows digital clubbing and
fine bibasilar end-inspiratory crackles. Jugular venous pressure is 2 cm H2O above
the sternal angle. There is no peripheral edema. What is the probable diagnosis?

Clinical formula

Cough,progressive CXray:small (1–3 mm) nodules , Controlling the dust at source.,

loss of exercise diffuse infiltrates,HRCT – patchy Rest and warmth, positive
tolerance due to ground-glass shadowing, ill- pressure oxygen with if
defined nodules, fibrosis and necessary mechanical ventilatory
Occupational breathlessness irregular opacities.Lung function assistance, correction of
lung disease with or without
accompanying tests – Restrictive lung function haemoconcentration in some
cough, inspiratory with reduced gas transfer.Serum cases, broad spectrum
crackles and Precipitins: Assaying for antibiotics if signs of infection,
squeak precipitating IgG anti- bodies corticosteroids

PLEURAL EFFUSION
Pleural effusions are abnormal accumulations of fluid within the pleural space.

Transudate: the rate of pleural fluid accumulation exceeds

resorption, leading to a plasma ultrafiltrate
- Cardiac failure -Dressler syndrome
- Nephrotic syndrome - Trauma
- Cirrhosis - Asbestos exposure
- Yellow nail syndrome

Exudate: increased pleural permeability leads to the accumulation

of proteinaceous pleural fluid -mesothelioma
-bronchial carcinoma -rheumatoid arthritis
-secondary (metastatic) malignancy -systemic lupus erythematosus
-pulmonary embolism and infarction (SLE)
-pleural effusions in pulmonary embolism
-pneumonia
-tuberculosis
 70

Left-sided Pleural Effusion etiology :- Bilateral Exudative Pleural Effusion

• Pancreatitis • Pulmonary embolism
• Pericarditis • Lymphoma
• Aortic dissection • Metastasis
• Esophageal rupture • RA, SLE
If pleural effusion is with air (shows air • Postcardiac injury syndrome
fluid level)- Hydropneumothorax • Myxoedema
On supine X-ray → veil like haziness
with preserved vascular markings Right-sided Pleural Effusion etiology:-
USG: • Liver abscess
• Transudate- echo free • Ascites
• Exudative- echoes (change shape • Heart failure
with breathing)
(Solid lesion does not change shape) Criteria for exudative type of pleural effusion:
MRI: At Least Anyone of following
• Limited role- Triple echo pulse 1) Pleural fluid protein/serum protein more
sequence can differentiate exudative than 0.5
from transudative 2) Pleural fluid LDH/serum LDH more than 0.6
Chylous effusion → high signal on 3) Pleural fluid LDH more than two third the
T1W (normally fluid low on T1W) upper limit for serum LDH.

Empyema
(Split pleura sign)

Infective effusions/empyema shows enhancing visceral

and parietal pleura giving split pleura sign
Bilateral pleural effusions. Erect CXR. The pleural
effusion obscures the diaphragm and both
costophrenic angles. It has a curvilinear upper margin
concave to lung and is higher laterally than medially.
 71
Management

Approach to the diagnosis

of pleural effusions. PE,
pulmonary embo- lism; PF,
pleural fluid; TB,
tuberculosis.

related CLINICAL question

Q. A 52-year-old woman comes to the opd with worsening
shortness of breath over the last 2 weeks. Her symptoms
are particularly worse at night. She was diagnosed with
breast cancer 2 years ago and had a left complete
mastectomy. Chest x-ray is shown in the image. What is
the probable diagnosis?
 72
Clinical formula
ESR may be raised. Therapeutic aspiration
Dry cough, fever Tuberculin skin test is Insertion of chest tube
and pleuritic chest positive if rapid reaccumulation
pain, Progressive Sputum positive for acid-fast of fluid occurs.
PLEURAL breathlessness bacilli Pleurodesis for
EFFUSION weight loss and Erect CXR. The pleural malignant effusion
easy fatigability, effusion obscures the using bleomycin or talc
Pleural friction rub diaphragm and both powder.
costophrenic angles.

Chronic Obstructive Pulmonary Disease

COPD is defined by the Global Initiative for Obstructive Lung Disease (GOLD) as a
disease characterized by air- flow limitation that is not fully reversible.
The airflow limitation is usually both progressive and associated with an abnormal
inflammatory response of the lungs to noxious particles or gases.
GOLD SPIROMETRIC GRADING CRITERIA FOR COPD SEVERITY

Clinical features
 73

Emphysema
Component of COPD characterised by abnormal permanent enlargement of the
airspaces distal to the terminal bronchioles.
It is caused by a combination of mechanical obstruction in the small airways from
inflammation and later scarring, and loss of elastic recoil of the lungs which makes
these airways more likely to collapse during expiration.

• Four types
–Paraseptal
–Centrilobular (MC)
–Panacinar/panlobular
–Irregular/paracicatricial

Lungs are hyperexpanded

with flattened
hemidiaphragms and
increased retrosternal
airspace. No focal
consolidation. Normal
cardiomediastinal contour

- Hyperinflation - Sternal bowing

- Flattened hemidiaphragm the most - Increased and usually irregular
reliable sign radiolucency of the lungs
- Increased retrosternal airspace - Increased anteroposterior diameter of
- Widely spaced ribs the chest
 74

related CLINICAL question

Q. A 45-year-old man presents with two days of bilateral hand pain that is most
severe in his wrists. Physical examination reveals bilateral wrist tenderness,
thickening of the distal fingers, and convex nail beds. There is nicotine staining
of the right index and middle fingers. He states that he has been smoking 2 packs
of cigarettes a day for the past 25 years. Chest examination reveals decreased
breath sounds and a prolonged expiratory phase. What is the probable diagnosis?

Clinical formula

‘Pink puffers’: thin and - Hyperinflation Smoking cessation

Smoking breathless, and - Flattened Antibiotics
Chronic Occupational maintain a normal hemidiaphragm Bronchodilators:
Obstructi exposure PaCO2. - Increased Nebulised short‐
ve Atmospheric ‘Blue bloaters’: develop retrosternal airspace
Pulmonary acting β2agonists
pollution hypercapnia, oedema - Widely spaced ribs and anti
Disease Alpha-1-antitrypsin - Sternal bowing
and secondary cholinergics
deficiency polycythaemia. - Increased AP Corticosteroids
diameter

PNEUMOTHORAX
- Presence of air in the pleural space.
- When this collection of gas is constantly enlarging with resulting compression of
mediastinal structures, it can be life-threatening and is known as a TENSION
PNEUMOTHORAX

a)Primary spontaneous: b)Secondary spontaneous:

- Marfan syndrome - Bullae
- Ehlers-Danlos syndrome - Emphysema
- Alpha-1-antitrypsin deficiency
c)Iatrogenic/Traumatic
- Homocystinuria

Plain radiograph
- Visible visceral pleural edge is seen as a very thin, sharp white line
- No lung markings are seen peripheral to this line
- Peripheral space is radiolucent compared to the adjacent lung
- Lung may completely collapse
- Mediastinum should not shift away from the pneumothorax unless a tension
pneumothorax is present.
- Subcutaneous emphysema and pneumomediastinum may also be present.
 75

‘Double diaphragm’ sign

Tension pneumothorax Supine pneumothorax
CXR Absent lung markings on the affected side Air in the right hemithorax displaces both the dome
Moderate or gross mediastinal displacement (white arrow) and the anterior costophrenic angle in this
away from the side of the pneumothorax patient with a large, right-sided pneumothorax. There is
Eversion of the diaphragm also a deep sulcus sign present (red arrow).
Management of spontaneous pneumothorax.

(1) Immediate decompression is

required prior to insertion of an
intercostal drain.
(2) Aspirate in the 2nd intercostal
space anteriorly in the mid-clavicular
line; discontinue if resistance is felt,
the patient coughs excessively, or > 2.5
L are aspirated.
(3) All patients should be told to
attend again immediately in the event
of noticeable deterioration.
 76

related CLINICAL question

Q. A 51-year-old man develops. ARDS while hospitalized for acute pancreatitis. On his
third day in ICU, the patient is sedated, intubated, and ventilated with a positive end-
expiratory pressure of 15 cm water and fraction of inspired oxygen of 0.6 (60%). His
pulse acutely increases from 100 to 140/min, systolic blood pressure drops from 120 to
90 mm Hg, and central venous pressure increases from 10 to 15 cm water. On chest
auscultation, breath sounds are absent on the left side. Which of the following is the
most likely explanation for the sudden deterioration of this patient?
Clinical formula
X-ray: Mediastinal shift to the Immediate
Sudden onset unilateral
opposite side,Sharply defined edge decompression ,
pleuritic chest pain or
of the deflated lung, Intercostal drains should
breathlessness,
Complete translucency and be inserted in the 4th,
decreased or absent
PNEUMOTHORAX breath sounds and a absence of bronchovascular 5th or 6th inter costal
markings,Presence or absence of space in the midaxillary
resonant percussion
a complicating pleural line, following blunt
note,raised intrapleural
effusion,Presence or absence of dissection through to the
pressure, cardiovascular
underlying lung lesion parietal pleura
compromise.
(‘Seldinger’ technique)

Pulmonary embolism
- Embolic occlusion of the pulmonary arterial system.
- MC result from thrombotic occlusion,
and therefore called as Pulmonary thromboembolism
PATIENTS history
- Recent immobilization
- Surgery
- Active malignancy
- Hormone usage
- Previous episode of Thromboembolism saddle embolism is seen.

Physical examination
- Clinical signs of DVT
- Asymmetric pitting edema of lower limbs
- Prominent superficial collateral vessels
- Tenderness to palpation along the deep venous system
- Tachycardia
- Dyspnea
- Pleuritic chest pain
- Hemoptysis
 77

Radiological findings
- Normal in 30% of patients
- Westermark’s sign (area of focal peripheral oligemia)
- Knuckle sign/Palla’s sign : an enlarged right descending pulmonary artery
- Hampton’s hump : peripheral wedge shaped opacity with convexity toward hilum
- Melting sign : infarct showing rapid clearing contrary to pneumonic consolidation
(melts like snow)
- Fleischner’s sign : elevated hemidiaphragm
Initial Screening :- D-Dimers (High negative predictive value to exclude PTE)
Gold standard :- Pulmonary angiography/ arteriogram

(A) Chest radiograph of a patient presenting (B) CT pulmonary angiography shows thrombi
with sudden onset shortness of breath. The in right and left main pulmonary arteries.
right lower zone shows an ill-defined opacity in Infarction is seen in right lower lobe (arrow)
the periphery of lung (arrow);

Wells criteria
Risk stratification score and clinical decision rule to estimate the probability
for acute pulmonary embolism (PE)
- Clinical signs and symptoms of DVT = 3
- An alternative diagnosis is less likely than PE = 3
- Heart rate more than 100 = 1.5
- Immobilization for 3 or more consecutive days or surgery in the previous 4 weeks = 1.5
- Previous objectively diagnosed PE or DVT = 1.5
- Hemoptysis = 1
- Malignancy (on treatment, treatment in last 6 months or palliative) = 1
a)0-1: low risk b)2-6: moderate risk c)>6: high risk
 78
Investigation and management

related CLINICAL question

Q. A 46-year-old truck driver
comes to the casualty with chest
pain and shortness of breath over
the last 10 hours. The pain is sharp
and does not radiate. He says that
taking shallow breaths helps to avoid
the pain. The patient takes over-
the-counter antacids for frequent
heartburn. He has a 25-pack-year
smoking history. His temperature
is 36.7 C (98 F), blood pressure is
110/70 mm Hg, pulse is 110/min,
and respirations are 31/min. The
patient's BMI is 29 kg/m2.
Electrocardiogram (ECG) shows
sinus tachycardia. What is the
probable diagnosis?

Clinical formula
Normal CXR Sufficient oxygen should be
Clinical signs of DVT, ECG: sinus tachycardia and given to all hypoxaemic patients
Asymmetric pitting edema anterior Twave inversion to restore SpO2 to > 90%.
of lower limbs, Prominent ABGs: Typically show a Subcutaneous low molecular
Pulmonary superficial collateral reduced PaO2 and a normal weight heparin (LMWH) should
embolism vessels, or low PaCO2, be administered for at least 5
Tachycardia, Dyspnea, Ddimer, Ventilation/perfusion days and anticoagulation
Pleuritic chest pain, scanning, CTPA: This is now continued using oral
Hemoptysis the firstline diagnostic test anticoagulants, usually warfarin.
Thrombolytic therapy,caval filters
 79

GIT and Hepatobiliary system

Gastro-oesophageal reflux disease
Gastro-oesophageal reflux disease (GORD) is caused by recurrent reflux of gastric
contents into the distal oesophagus.

Clinical Features
• Heartburn (pyrosis) is deeply placed burning pain behind the sternum radiating to the
throat. It occurs after meals, brought on by bending, lifting weight and straining.
Heartburn occurs on lying down in bed at night and is then relieved by sitting up.
• Regurgitation of gastric contents into the mouth (acid eructation) without associated
nausea or retching.
• Tracheal aspiration with coughing or laryngismus or aspiration pneumonia results from
regurgitated gastric contents in the mouth.
• Odynophagia-painful swallowing.
• Transient dysphagia to solids due to oesophageal spasm.
• Persistent dysphagia to solids due to strictures or development of oesophageal
carcinoma.
• Iron deficiency anaemia due to blood loss.
• Extraoesophageal symptoms include hoarseness, sore throat, sinusitis, otitis media,
chronic cough, laryngitis, non atopic asthma, recurrent aspiration and pulmonary
fibrosis.
 80
Barrett’s oesophagus

columnar lined oesophagus, CLO

This is a premalignant condition in which
the squamous lining of the lower
oesophagus is replaced by columnar
mucosa with areas of meta plasia. It
occurs in response to chronic reflux and
is seen in 10% of endoscopies for reflux.

Investigations
Endoscopy
• Oesophagitis can be visualised and confmned by biopsy.
• Strictures can be visualised.
• Barrett's mucosa can be confirmed by biopsy.
24-hr pH monitoring:
Intraluminal pH and symptoms are recorded during normal activities.
A pH of <4 for more than 6–7% of the study is diagnostic of reflux.
Barium swallow and meal can reveal a hiatus hernia.
Bernstein test is done in patients with high clinical suspicion but negative endoscopy.
Perfusion of acid into the lower oesophagus may reproduce the symptoms.

Treatment
Lifestyle advice should cover weight loss, avoidance of dietary triggers, elevation
of the bed head, avoidance of late meals and giving up smoking.
Antacids, alginates and H2receptor antagonists relieve symptoms without healing,
while PPIs also heal oesophagitis in the majority, and are the treatment of choice
for severe reflux disease.
Recurrence is common and some patients require lifelong treatment.
Longterm PPI treatment increases the risk of enteric infections and of H. pylori-
associated gastric mucosal atrophy.
Laparoscopic surgery is reserved for patients who fail to respond, are unwilling to
take longterm PPIs or have severe regurgitation.
 81

related CLINICAL question

Q. A 52-year-old man comes to the clinic due to frequent chest pain over the
last 6 weeks. The pain typically occurs at night and is described as retrosternal
and burning. The patient also has a history of chronic cough and occasional
hoarseness. Resting ECG reveals no significant abnormalities. The patient did
not experience chest pain during the stress test. What is the probable
diagnosis?

Clinical formula

Heartburn (pyrosis), Weight loss, avoidance of

Regurgitation, Tracheal dietary triggers, elevation
Gastro- Endoscopy of the bed head,
aspiration, Odynophagia,
oesophage 24-hr pH monitoring: avoidance of late meals
Transient dysphagia to
al reflux Barium swallow and meal and giving up smoking.
diseases solids, Iron deficiency
anaemia , hoarseness, Barium swallow and meal Antacids, alginates and
sore throat, sinusitis, otitis H2receptor antagonists
media Laparoscopic surgery

Dysphagia
 82
Schatzki ring
- Also called Schatzki-Gary ring
- Is symptomatically narrow esophageal
B-ring occurring in the distal esophagus
- Associated with a hiatus hernia.
- Intermittent dysphagia, especially to
solid food. (MC)
- A history of food impaction is also
very common

Zenker’s diverticulum
- also known as a pharyngeal pouch,
- Posterior outpouching of the hypopharynx,
just proximal to the upper esophageal
sphincter through a weakness in the muscle
layer called the Killian dehiscence.
- A Zenker diverticulum is a pulsion-
pseudodiverticulum and results from
herniation of mucosa and submucosa
through the Killian triangle (or Killian
dehiscence),
- A focal weakness in the hypopharynx at the normal cleavage plane
between the fibers of the two parts of the inferior pharyngeal
constrictor muscle - the cricopharyngeus and thyropharyngeus.

diffuse esophageal spasm

Cork screw appearence of esophagus
due to spastic contraction of circular muscle.
- Diffuse/distal esophageal spasm (DOS)
is a motility disorder of the esophagus.
~ Chest pain
~ Dysphagia are the primary complaints,
~ Regurgitation may also be a feature.
- On barium-Corkscrew or rosary bead esophagus
- Manometry is the gold-standard diagnostic test.
 83

Plummer-Vinson syndrome
(Patterson-Kelly syndrome)
A syndrome characterised by:
• Dysphagia to solids
• Iron deficiency
• Koilonychia
• Glossitis
• Dysphagia is due to a thin web in the postcricoid area.
The web is formed of degenerated epithelial cells.
• Usually seen in postmenopausal females.
• Increased risk for developing squamous cell carcinoma of upper gastrointestinal tract.
Investigations
• Haemoglobin and PCV low.
• Peripheral smear shows rnicrocytic hypochrornic anaemia.
• Serum iron is low and iron binding capacity is increased.
• Bone marrow iron stores are depleted.
• Barium swallow may show the web.
• Videofluoroscopy and endoscopy better than barium swallow.
Treatment
• Treatment of iron deficiency anaemia with iron may be effective in resolving dysphagia.
• Endoscopic dilatation.
• Follow-up endoscopy at periodic intervals to detect development of carcinoma.

related CLINICAL question

Q. A 50-year-old woman comes to the opd with history of intermittent, substernal
chest pain. she has difficulty swallowing both liquids and solids. The patient was
recently seen in the casualty due to sudden worsening of the pain; her evaluation
included a normal ECG, normal cardiac biomarkers, and a negative myocardial
perfusion scan. Which of the following is the most likely diagnosis?
A. Diffuse esophageal spasm
Clinical formula
Haemoglobin and PCV low,
Microcytic hypochrornic anaemia, Treatment of iron
Plummer- • Dysphagia to solids Serum iron is low and iron binding deficiency
Vinson • Iron deficiency capacity is increased, Bone marrow anaemia
syndrome • Koilonychia iron stores are depleted, Barium Endoscopic
• Glossitis swallow may show the web. dilatation.
Videofluoroscopy and endoscopy
 84
Achalasia
Dilation of esophagus and tapering of gastroesophageal junction and air fluid
level within oesophagus.
Achalasia (primary achalasia) is a failure
of organized esophageal peristalsis

Impaired relaxation of the lower esophageal sphincter,

Resulting in food stasis and often marked dilatation of the esophagus

Classification
It may be divided into three distinct types based on manometric patterns:
- Type I (classic) with minimal contractility in the esophageal body
- Type II with intermittent periods of pan-esophageal pressurisation
- Type III (spastic) with premature or spastic distal esophageal contractions
Clinical features
It usually develops slowly in middle age with intermittent dysphagia for solids,
which is eased by drinking, standing and moving around.
Heartburn is absent, but some patients experience severe chest pain due to
oesophageal spasm.
As dysphagia progresses, nocturnal pulmonary aspiration develops.
Achalasia predisposes to squamous carcinoma of the oesophagus.

Barium-filled oesophagus
showing distension above
(arrow head) the narrow
gastro-oesophageal junction
Note: The abrupt narrowing
Chest radiograph showing gross enlargement of the lower end of
of the oesophagus due to achalasia oesophagus (bird beak sign)
 85

Investigations
Endoscopy is essential to rule out carcinoma.
Barium swallow shows tapered narrowing of the lower oesophagus and a dilated,
aperistaltic and foodfilled oesophageal body.
Manometry confirms the nonrelaxing lower oesophageal sphincter and poor
contractility of the oesophageal body.
CXR may show widening of the mediastinum and features of aspiration.

Treatment
Endoscopic dilatation: Dilatation of the oesophageal sphincter using a
fluoroscopically positioned balloon improves symptoms . Endoscopic injection of
botulinum toxin into the sphincter induces remission but relapse is common.
Surgical myotomy: Performed either laparoscopically or as an open operation

related CLINICAL question

Q. A 62-year-old man comes to the opd due to difficulty swallowing both solids and
liquids. The patient's symptoms have progressively worsened over the last 3 months.
He also has occasional regurgitation of undigested food and a nighttime cough that
disturbs his sleep. Chest x-ray reveals a widened mediastinum, and barium studies
show a dilated esophagus with smooth tapering of the distal esophagus. What is the
probable diagnosis?

Clinical formula
Middle age with intermittent Endoscopy, Barium swallow:
dysphagia for solids, which is tapered narrowing of the lower Endoscopic
eased by drinking, standing oesophagus,Manometry : non‐ dilatation,
Achalasia and moving around. severe relaxing lower oesophageal Surgical
chest pain due to sphincter . CXR: widening of myotomy
oesophageal spasm,nocturnal the mediastinum
pulmonary aspiration

Peptic ulcer
Peptic ulcer refers to an ulcer in the lower oesophagus, stomach or duodenum,
in the jejunum after surgical anastomosis to stomach, and in the ileum adjacent
to a Meckel's diverticulum.
• Approximately 90% of peptic ulcers are caused by Helicobacter pylori infection
or nonsteroidal anti-inflammatory drug (NSAID) use.
● Recurrent episodes of epigastric pain in relation to meals.
● Occasionally, vomiting; persistent daily vomiting suggests gastric outlet obstruction.
 86
Causes

Pathogenesis
Antral inflammation leads to reduced
somatostatin production and, because
somatostatin has a negative feedback
effect on gastrin production, this results in
hypergastrinemia Gastrin acts on parietal
cells, resulting in high stimulated acid
production, increased duodenal acid load
and the formation of protective gastric
metaplasia in the duodenum,
Helicobacter pylori cannot colonize the
normal duodenum, but can colonize
gastric metaplasia, causing inflammation
and ulceration

Complications
• Upper gastrointestinal bleed
• Perforation
• Gastric outlet obstruction (with fluid and electrolyte imbalance)
• Gastric malignancy
• Pancreatitis (due to posterior penetration of ulcer)
 87
Factors Gastric ulcer Duodenal ulcer
• Age More than 40 years 20-50 years
• Sex Equal in both sexes More in males
• Course of the illness Less remittent More remittent
• Episodes of pain Relatively longer in duration Relatively shorter in duration
• Antacids Relief of pain not consistent Relief of pain prompt
• Food Provokes the pain Relieves the pain
• Heart burn Less common More common
• Night pains Less common More common
• Anorexia and nausea More common Less common

Barium study of gastric ulcer Barium study demonstrating duodenal ulcer

Investigations
• Double contrast barium meal may show the uker as a crater or as a deformed
duodenal cap.
• Endoscopy can visualise the ulcer. Typical location is duodenal bulb and lesser
curvature of stomach. A biopsy can be taken from a gastric ulcer to rule out
malignancy (10% of gastric ulcers are malignant) and H. pylori infection.
• Tests for H. pylori.
• Serum gastrin and gastric acid analysis in patients suspected to have Zollinger-
Ellison syndrome.
 88
Tests for H. pylori

Treatment

related CLINICAL question

Q. A 27-year-old man comes to the opd due to episodic abdominal pain. The pain is
in the epigastrium and is gnawing in quality. It wakes him up during the night and is
promptly relieved by a glass of water and a piece of bread. The patient has no
associated vomiting or diarrhea but has experienced occasional dark stools. Physical
examination shows mild epigastric discomfort on deep palpation. What is the
probable diagnosis?
 89

Clinical formula
Epigastric pain, burning in Double contrast Firstline therapy is a PPI,
character, Hunger pain, Pain barium meal, clarithromycin, amoxicillin or
relief by food,excessive Endoscopy ,Tests for metronidazole, H. pylori
Peptic salivation, heart bums, loss of
ulcer H. pylori.Serum eradication therapy, Cigarette
appetite and vomiting,Anorexia, gastrin and gastric smoking, aspirin and NSAIDs
nausea, fullness, bloating and acid analysis should be avoided.
dyspepsia.

Zollinger-Ellison syndrome.

It defines severe peptic ulcer disease secondary to unregulated gastrin release

from a non- B cell endocrine tumour (gastrinoma).
l

• Gastrinoma may be a part of multiple endocrine neoplasia(MEN) type I.

An autosomal dominant syndrome
Characterised by hyperplasia and/or multiple tumours in the parathyroid,
pancreas, duodenum, anterior pituitary,foregut-derived neuroendocrine tissue and
adrenocortical glands
Gastrin stimulates acid secretion through gastrin receptors on parietal cells by
inducing release of histamine from ECL cells. Hypergastrinemia is responsible for
the clinical manifestations of ZES.
Clinical features
(a) Peptic ulcers with atypical locations (second part of duodenum and post bulbar
(jejunum). Ulcers resistant to medical therapy, recurrence after acid-reducing
surgery. Ulcers presenting with complications (bleeding, perforation or obstruction).
(b) Oesophagus – Mild oesophagitis to frank ulceration and Barrett’s mucosa.
(c) Diarrhoea results from volume overload on small intestine, inactivation of
pancreatic enzymes by acid which also damages intestinal epithelial surface.
(d) Signs of hyperparathyroidism or hypophyseal or pancreatic tumour
(MEN 1 syndrome)
Investigations
Hypersecretion of acid under basal conditions, with little increase following
pentagastrin, may be confirmed by gastric aspiration.
Serum gastrin is grossly elevated (10 to 1000fold).
Tumour local isation is by EUS and radiolabelled somatostatin receptor scintigraphy.
 90
Treatment
(a) Omeprazole 60 mg/day in divided doses over 24 hours.
(b) Octreotide as adjuvant therapy if peptic symptoms difficult to control with PPI.
(c) Surgical resection of tumour.
(d) Chemotherapy for metastasis.

related CLINICAL question

Q. A 45-year-old man comes to the physician due to epigastric pain and diarrhea.
Past medical history is significant for peptic ulcer disease. He has a 20-pack-year
smoking history . Physical examination shows abdominal tenderness without rebound
or rigidity. Endoscopy shows prominent gastric folds, 3 duodenal ulcers, and upper
jejunal ulceration. What is the probable diagnosis?

Clinical formula
Gastrin stimulates Peptic ulcers, Hypersecretion of acid Omeprazole
acid secretion oesophagitis, ulceration, under basal conditions, Octreotide
Zollinger- through gastrin Diarrhoea, Signs of Serum gastrin is grossly Surgical
Ellison receptors on parietal hyperparathyroidism or elevated , EUS and resection,
syndrome. cells by inducing hypophyseal or radiolabelled Chemotherapy
release of histamine pancreatic tumour , somatostatin receptor
from ECL cells. (MEN 1 syndrome) scintigraphy.

Whipple's disease
• It is a chronic multisystem disease associated with malabsorption.
• It is caused by gram-positive bacteria, Tropheryma whippelii.
Pathogenesis
There are characteristic PAS positive macrophages in the small intestine and
other involved organs (including joints, lungs, central nervous system, heart and
eyes). These macrophages cause lymphatic blockade in the lamina propria of small
intestine causing malabsorption.
Clinical Features
• Eight times more common in males than in females.
• Symptoms are diarrhoea, chronic, migratory, non-destructive polyarthritis, weight loss
and abdominal pain. Steatorrboea is uncommon.
• Other features include migratory arthralgias, fever, ophthalmologic features and
neurologic features (dementia, nystagmus, myoclonus and ophtbalmoplegia in late stages).
• Signs include generalised lymphadenopathy, arthropathy, skin pigmentation, abdominal
distension and tenderness.
• Cardiac involvement leads to mitral and aortic regurgitation.
 91
Investigations
• Elevated erythrocyte sedimentation rate and C-reactive protein.
• Tests for malabsorption.
• Negative rheumatoid factor.
• Jejunal biopsy and biopsy of other involved tissues show plenty of PAS positive
macrophages that contain small bacilli.
• PCR tests for T. whipplii in saliva, stool or joint fluid.
Treatment
Trimethoprim-sulphamethoxazole (double strength tablet) should be given twice
a day for 1 year. Oral treatment should be preceded by a 2-week course of
parenteral therapy with ceftriaxone (2 g daily) or by meropenem.

related CLINICAL question

Q. A 50-year-old man comes to the opd due to diarrhea, abdominal pain and weight
loss. He has bulky, foul-smelling stools, abdominal distension and flatulence. He
also has arthralgias and a chronic cough. Physical examination shows generalized
lymphadenopathy, skin hyperpigmentation and a diastolic murmur in the aortic
area. Small bowel biopsy shows villous atrophy with numerous PAS-positive
materials in the lamina propria. What is the most likely diagnosis?

Clinical formula
Diarrhoea, chronic, migratory, non- Elevated ESR and CRP.
destructive polyarthritis, weight loss , Tests for malabsorption. Trimethoprim-
fever, ophthalmologic features and Negative rheumatoid factor. sulphamethoxaz
Whipple's neurologic features,generalised Jejunal biopsy : PAS ole, ceftriaxone
disease lymphadenopathy, skin pigmentation, positive macrophages that or meropenem.
abdominal distension and tenderness, contain small bacilli.
mitral and aortic regurgitation. PCR tests for T. whipplii

pseudomembranous colitis
- Yellowish green exudates
- Tough pseudomembrane is seen
- Common cause of antibiotic-associated diarrhea, and increasingly
encountered in sick hospitalized patients.
Clinical Features
- Diarrhea
- Fever
- Raised white cell count
- Abdominal pain with distension
 92

C. difficile produces two toxins (A and B) which have both cytotoxic and
enterotoxic effects on the bowel.
Clinical manifestation is thought to be predominantly due to toxin B.
Exudate composed of fibrin, white cells and cellular debris forms a
pseudomembrane on the mucosa of the colon, which is characteristic.

Investigations
Definitive diagnosis is made by isolating C. difficile toxin in the stool sample.

FINDINGS CT Findings include

- Bowel dilatation - Bowel wall thickening (most common)
- Mural thickening - Thumbprinting
- Thumbprinting - Accordion sign
- Untreated or fulminant cases: - Shaggy mucosal outline
Toxic Megacolon - Pericolic stranding
- Perforation
- Free intraperitoneal gas

Treatment
• Withdraw the offending drug.
• Oral or intravenous rehydration.
• Oral metronidazole 500 mg thrice daily for 10-14 days in mild to moderate cases.
• Oral vancomycin 125-500 mg 6 hourly for 14 days in severe cases.
• Oral vancomycin plus intravenous metronidazole in refractory cases.
• Intravenous vancomycin not effective.
• Oral probiotic therapy (use of live nonpathogenic bacteria to restabilise the gut
flora and provide colonisation resis tance against C. difficile) often used in
resistant or relapsed cases. Probiotics use organisms resistant to gastric acid.
Lactobacillus acidophilus and Saccharomyces boulardii produce proteases that
digest C. difficile toxins. However, clinical benefits not shown; may rarely produce
septicaemia.
• Antimotility drugs (loperarnide or diphenoxylate) should not be given as they can
precipitate toxic megacolon.
• Colectomy in severely ill, refractory patients.
 93

Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of
unknown etiology involving the gastrointestinal (GI) tract.
Pathogenesis of IBD involves activation of immune cells by unknown inciting agent
(microorganism, dietary component, bacterial or self-antigen) leading to release of
cytokines and inflammatory mediators.
 94

ULCERATIVE COLITIS (UC)

Ulcerative colitis is an inflammatory disease affecting mainly the large intestine,
characterised clinically by recurrent attacks of bloody diarrhoea and
pathologically by diffuse inflammation of colonic mucosa.

Clinical Features
Bloody diarrhea, mucus, fever, abdominal pain, tenesmus, weight loss;
spectrum of severity (majority of cases are mild, limited to rectosigmoid).
In severe cases, dehydration, anemia, hypokalemia, hypoalbuminemia.
Investigations
Sigmoidoscopy/colonoscopy: mucosal erythema, granularity, friability, exudate,
hemorrhage, ulcers, inflammatory polyps (pseudopolyps). Barium enema: loss of
haustrations, mucosal irregularity, ulcerations.
Crohn's disease
Crohn's disease is characterised by patchy and transmural inflammation, which
may affect any part of the gastrointestinal tract.
 95
Investigations
Sigmoidoscopy/colonoscopy, barium enema, upper GI and small-bowel series:
nodularity, rigidity, ulcers that may be deep or longitudinal, cobblestoning, skip
areas, strictures, fistulas. CT may show thickened, matted bowel loops or an abscess.

(A) Small bowel enema in Crohn's disease of terminal ileum

Barium enema showing marked contraction and
The lumen is narrowed and there is fissure ulceration (arrows);
shortening of the colon (pipe stem appearance)
(B) Combination of transmural thickening and spasm
due to long-standing ulcerative colitis
produces the classical ‘string sign’ in the terminal ileum

Treatment

Mild to Moderate Ulcerative Colitis Moderate to Severe Ulcerative Colitis

 96

✗ ✗

Mild to Moderate Crohn’s Disease

Moderate to Severe Crohn’s Disease Fistulizing Crohn’s Disease

related CLINICAL question
Q. A 25-year-old man comes to the casualty due to a 3-month history of abdominal
pain and diarrhea. Bowel movements occur 3 or 4 times a day, and he has occasionally
noticed blood in his stool. He was diagnosed with anterior uveitis 3 years ago Abdomen
is tender and bowel sounds are hyperactive. Laboratory results show anemia and an
elevated erythrocyte sedimentation rate. What is the probable diagnosis?

Clinical formula
Ulcerative colitis: Crohn’s Ulcerative: Aminosalicylates (e.g.
Gradual onset Bloody disease:Abdominal mesalazine, sulfasalazine,
Sigmoidoscopy
pain, Diarrhoea, olsalazine)
Inflammatory diarrhoea ,proctitis with
rectal bleeding and Obstructive
/colonoscopy,
Crohn’s: Budesonide, thiopurine
Bowel barium enema
constipation.Urgency symptoms, Mass in (azathioprine or mercap topurine)
Diseases right iliac fossa,
and crampy abdominal or methotrexate
discomfort before Acute ileitis , Rectal Topical corticosteroids, IV fluids
defecation. bleeding, Proctitis and enteral nutritional support
 97

chronic pancreatitis

Chronic pancreatitis represents the end result of a continuous, prolonged,

inflammatory and fibrosing process that affects the pancreas.
This results in
1) Irreversible morphologic changes and
2) Permanent endocrine and exocrine pancreatic dysfunction

Risk factors- TIGAR-O system

- T: toxic-metabolic (e.g. alcohol)
- I: idiopathic
Recent guidelines recommend that cystic fibrosis needs to
be ruled out in these patients before calling it idiopathic
- G: genetic
More commonly seen in the pediatric population
- A: autoimmune
- R: recurrent
- O: obstructive (e.g. choledocholithiasis, pancreatic head tumor)

Clinical Features
• Pain, acute or recurrent, continuous or intermittent.
May be referred to chest or back.
• Pain is often increased by alcohol or heavy meals.
• Features of local complications
(e.g. pseudocyst, obstruction of adjacent organs, or vascular thrombosis).
• Features of malabsorption-diarrhoea, steatorrhoea, weight Joss, features of
fat-soluble vitamin deficiency and vitamin B 12 deficiency (exocrine failure).
• Diabetes mellitus (endocrine failure).
• In late stages, mechanical obstruction of common bile duct can occur.
 98
Investigations in chronic pancreatitis

Imaging in chronic pancreatitis. CT scan

showing a grossly dilated and irregular duct
with a calcified stone (arrow A). Note the
calcification in the head of the gland (arrow B).

Treatment
Alcohol avoidance- crucial in halting disease progression and reducing pain, but
advice is frequently ignored
NSAIDs are valuable but the severe, unremitting pain often leads to
opiate use with risk of addiction.
Abstinent patients with severe chronic pain resistant to conservative measures
may respond to surgical or endoscopic treat ment of strictures, calculi and
pseudocysts or coeliac plexus neuroly sis. Patients without such correctable
abnormalities require total pancreatectomy.
Fat restriction and oral pancreatic enzyme supplements: These measures
are used to treat steatorrhoea. A PPI is added to optimise duodenal pH for
pancreatic enzyme activity.
 99
related CLINICAL question
Q. A 43-year-old man comes to the opd due to a 6-month history of intermittent
upper abdominal pain associated with nausea and weight loss . The patient describes
episodes of dull epigastric pain that are usually worse 15-30 minutes after meals and
last for a few hours. Pain is not relieved with antacids but improves when leaning
forward. He also has had occasional diarrhea.The patient consumes alcohol almost
daily. What is the probable diagnosis?

Clinical formula
Pain, acute or recurrent, USS, CT (may show Alcohol avoidance, NSAIDs,
continuous or atrophy, calcification surgical or endoscopic treat
chronic intermittent. or ductal dilatation), ment of strictures, Fat
pancreatitis increased by alcohol or AXR (may show restriction and oral
heavy meals,diarrhoea, calcification), MRCP, pancreatic enzyme
steatorrhoea, weight loss EUS supplements

Portal hypertension
Portal hypertension is defined as elevation of the hepatic venous pressure gradient to
>5 mmHg, which occurs as a consequence of cirrhosis.
It is caused by increased intrahepatic resistance to the passage of blood flow through
the liver due to cirrhosis together with increased splanchnic blood flow due to
vasodilatation within the splanchnic vascular bed.

Causes of generalized portal hypertension,

according to site of portal venous obstruction
 100

Causes of portal hypertension according

to site of vascular obstruction. *Most
common cause. Note that splenic vein
occlusion can also follow pancreatitis,
leading to gastric varices.

Clinical features
Abdominal wall veins are often prominent and rarely, they may form a caput medusae
around the umbilicus.
Murmurs—A venous hum may be heard over the collaterals radiating occasionally to
the precordium or over liver (Cruveilhier-Baumgarten syndrome). A thrill may be
felt at the site of maximum intensity.
Spleen—Enlarges progressively, the edge is firm. Massive if presinusoidal portal
obstruction, cirrhosis with hypersplenism, rarely tropical splenomegaly.
Liver—High pressures are more often associated with a small, fibrotic liver. A soft
liver suggests extrahepatic portal venous obstruction, a firm liver cirrhosis.
Ascites—Portal hypertension raises capillary filtration pressure and increases
quantity of ascitic fluid.
 101

Complications
Variceal bleeding: In cirrhotics risk of bleeding is related to:
Size of varices
Presence of red signs at endoscopy (red weal marks)
Degree of liver dysfunction
• Ascites
• Congestive gastropathy
• Hypersplenism
• Hepatic encephalopathy
• Kidney failure

Investigations
• Barium swallow usually shows varices as filling defects in the lower-third of
oesophagus ("bag of worms appearance").
• Upper gastrointestinal scopy.
• Most reliable method.
• Oesophageal varices are seen as blue rounded projections under submucosa.
• "Cherry red spots" indicate impending rupture.
Ultrasonography and Echo-Doppler ultrasonography should exclude an obvious
space-occupying lesion and establish patency of the portal and hepatic veins.
Portal venography demonstrates the site and often the cause of portal venous
obstruction and is performed prior to surgery. A typical ‘spider web’ appearance
on hepatic venography is diagnostic of Budd-Chiari syndrome.

Treatment
• Non-selective B-blockers (propranolol and nadolol) produce vasodilatation of both
splanchnic arterial bed and portal venous system along with reduced cardiac output.
• Nitrates (nitroglycerine and isosorbide dinitrate) reduce venous return and post-
sinusoidal resistance and are useful in combination with B-blockers in reducing risk of
variceal bleed.
• B-blockers with or without nitrates are used for primary prophylaxis of variceal bleed.
• Treatment of underlying disease.
 102

Ascites
Accumulation of fluid within the peritoneal cavity,.
Most common cause - Portal hypertension related to cirrhosis.
Pathogenesis of ascites.

Clinical features
Increase in abdominal girth Development of peripheral edema
Shortness of breath Weakness
Malnourishment Muscle wasting
Excessive fatigue
puddle sign - Dullness over dependent abdomen with pt on hands and knees
Periumbilical nodule (Sister Mary Joseph’s nodule) or supraclavicular node
(Virchow’s node) suggests an abdominal malignancy
 103
Investigation
Bulging flanks
Fluid wave
Presence of shifting dullness
USG or CT scan
Diagnostic paracentesis:- Determination of total protein and albumin content
Blood cells and differential count
Cultures

Algorithm for the diagnosis of ascites according to the serum-ascites albumin gradient (SAAG).

Minimum Volume of Ascitic Fluid required to for

following tests to be Positive
a. Diagnostic tappig - 10 - 20 ml
b. USG - < 100 ml
c. CT scan - 100 ml
d.Puddle sign - 120ml (>100ml)
e.Shifting dullness - 500ml
f. Fluid thrill - 1000 -1500ml

# High level of RBC signifies traumatic tap or hepaticellular C A or ruptured omental varix.
# Absolute level of PMNL is > 250/ul - ascitic fluid infection.
 104
Treatment
Small amount of ascitic fluid can be managed by dietary restriction of sodium.
Advise to eat fresh and frozen foods. Avoid canned or processed foods.
Moderate amount of ascitic - Diuretic therapy is necessary

Spironolactone 100-200mg /day started

Furosemide 40-80mg /day may be added if
peripheral edema is present

If compliance to dietary restriction is confirmed but still the

ascitic fluid is not mobilized,dose may be increased.

CIRRHOSIS
Cirrhosis is characterised by diffuse hepatic fibrosis and nodule formation,
Cirrhosis is the most common cause of portal hypertension and its complications.
Causes
• Alcohol • Biliary: primary or secondary biliary
• Chronic viral hepatitis (B or C) cirrhosis, cystic fibrosis
• Non-alcoholic fatty liver disease • Genetic: haemochromatosis, α1-
• Immune: primary sclerosing antitrypsin deficiency, Wilson’s disease
cholangitis, autoimmune liver disease • Chronic venous outflow obstruction
 105
The Child-Pugh score is calculated
by adding the scores of the five
factors and can range from 5–15.
Child-Pugh class is either A (a score
of 5–6), B (7–9), or C (10 or above).
Decompensation indicates
cirrhosis with a Child-Pugh score of
7 or more (class B). This level has
been the accepted criterion for
listing for liver transplantation.

Ascitis formation in cirrhosis

related CLINICAL question

Q. A 68-year-old man comes to the hospital due to abdominal distension. His waist has
progressively enlarged over the past few weeks, leading to a feeling of "heaviness." He
has a long history of heavy alcohol use. Scleral icterus is present on physical
examination as well as 2+ pitting edema in the bilateral lower extremities. Multiple
spider angioma are identified. The abdomen is grossly distended and mildly tender to
palpation. Shifting dullness is elicited. What is the probable diagnosis?

Clinical formula
Increase in abdominal Small amount of ascitic
girth, Shortness of breath, fluid can be managed by
Bulging flanks
Malnourishment dietary restriction of
Fluid wave
Ascites Excessive fatigue
Presence of shifting dullness sodium, Diuretic therapy
Development of peripheral with Spironolactone,
USG or CT scan
edema, Weakness, Furosemide , large
Diagnostic paracentesis
Muscle wasting volume paracentesis
 106
Hematology

Iron deficiency anemia (peripheral blood). Megaloblastic bone marrow. The majority of cells are
Hypochromia, microcytosis, anisocytosis and target megaloblastic erythroblasts showing failure of nuclear
cells are shown development and abnormal nuclear morphology of
lymphocyte are visible and platelets are scattered
through the film

Sickle hemoglobin disease (peripheral blood). In

homozygous disease (HbSS), sickle cells and target
cells are present together with occasional nucleated
Sickle cells—note the sickle shape due to the
red cells. Heterozygotes (HbAS) have a normal
presence of HbS (arrow)
peripheral blood

Burr cells—note short spiny margins

Beta thalassaemia—plenty of target cells
 107

Acanthocytes—note the thorn like projections Basophilic stipling—note the basophilic

dots in the RBC, often due to toxic injury

Howell-Jolly body Cabots ring which is remnant of nuclear

material (arrow)

HbH preparation showing golf-ball inclusions Reticulocyte preparation of a patient with

hemolytic anemia
 108

Anaemia

Clinical
manifestations of
Vit B 12 Deficiency

Clinical
Manifestations of
Aplastic anaemia

Clinical
Manifestations
of IDA

Other features in advanced stage:

Cheilosis (fissures at corners of mouth)
Koilonychia (spooning of fingers)

Clinical
manifestation
for
Hypoalbuminemia
 109

White nails

Hyperpigmented
Knuckles

Hyper-pigmented knuckles in
megaloblastic anemia

related CLINICAL question

Q. A 54-year-old vegetarian man comes to the opd due to several months of increased
fatigability. Physical examination reveals pale conjunctivae and hyperdynamic carotid
pulses. Hemoglobin level is 7.7 g/dL, leukocytes are 4,500/mm3, and platelets are
170,000/mm3. Folic acid therapy is initiated. Four weeks later the patient's hemoglobin
level is 9.1 mg/dL, but he has new tingling in his toes. What is the probable diagnosis?
Clinical formula
Tiredness, Mean corpuscular volume Blood transfusion,, Packed
Lightheadedness, (MCV), Mean corpuscular cells are preferred,
Breathlessness, Mucous haemoglobin (MCH), Mean Intravenous frusemide 20
Anaemia membrane pallor, corpuscular haemoglobin mg may be given prior to
Tachypnoea, Raised JVP, concentration (MCHC) transfusion, Prompt
Flow murmurs, Ankle Reticulocyte count, Reticulocyte
treatment of infections and
oedema, Postural index, Red cell distribution width
(ROW)
cardiac failure.
hypotension, Tachycardia.
 110

Thalassemia

Thalassemia is a heterogeneous disorder

; Caused by germline mutations that decrease the

synthesis of α-globin or β-globin
Leads to microcytic anemia, tissue hypoxia, and
red cell hemolysis

Pathogenesis of β-thalassemia major

 111
Clinical features
α-Thalassemia
-Anaemia
-Pale skin
-Weakness
-Fatigue
-Hepatosplenomegaly
-Heart defects
-Abnormalities of urinary system & genitalia
-Hb Bart Syndrome causing complications during
pregnancy: i. High BP
ii. Premature delivery
iii. Abnormal bleeding
iv. Jaundice.

β- Thalassemia

-Anaemia
-Pale skin/ Jaundice
-Weakness
-Fatigue
-Protruding abdomen with
-Hepatosplenomegaly Thalassemic/Chipmunk facies Hair on end appearance
-Dark urine
-Abnormal facial bone and poor growth
-Poor appetite
-Delayed puberty (severe)
 112

Investigations
Investigations done for Haemoglobin disorders:
i. Screening ☐ Haemoglobin electrophoresis

ii. Investigation of choice HPLC

iii. Definitive diagnosis : Globin Gene Sequencing

Molecular genetic testing (globin gene sequencing)

(a) Helps in identifying individuals carrying the thalassemia traits that could cause
adverse effect in the offspring
(b) Prenatal genetic testing can identify foetuses with severe globin phenotype.
(c) Used for both alpha and beta -Thalassemia diagnosis
Treatment
Transfusion therapy
Patient should receive red cells depleted of leukocytes and matched
for at least D,C,c,E,e and Kell antigens
Transfusions should generally be given at intervals of 3-4wks with goal being to
maintain a Pre transfusion Hb level of 9.5 - 10.5g/dl.
Iron overload and monitoring should be done.
Serial serum ferritin levels are a useful screening technique in assessing iron
balance trends.
Chelation therapy should be started as soon as patient become significantly iron
overloaded.
Serum ferrritn > 1000 ng / ml
Liver iron concentration of > 2500/g dry weight

3 available iron chelators are

i. Deferoxamine ii. Deferasirox iii. Deferiprone
•

Given as s/c or i.v •

Oral iron chelator •
Oral iron chelator
•
Adverse S/E : •
Side effects •
Effectively enters cardiac tissues
•

Ototoxicity •
GI symptoms - MC compared to others.
Retinal changes Kidney damage Most serious side effect :
•

Bone dysplasia with

Transient agranulocytosis
•

truncal shortening
 113

Hydroxyurea
•
DNA antimetabolite
•
Increases stress eryhtropoiesis which results in increased HbF production
•
Mean increase in hemoglobin of 1g ( range : 0.1 - 2.5g )
•
Initial starting dose for thalassemia intermedia is 10 mg/kg.
Hematopoeitic Stem cell Transplantation
Splenectomy
•
May be required in those who develop hypersplenism.
@
All patients should be fully immuniszed against encapsulated bacteria and on
long term penicillin prophylaxis.

Preventive Monitoring of
Thalassemia patients
•

Serial echocardiograms
•

Monitoring for endocrine dysfunction starts early around 5 yrs.

•
Most patients need Vitamin D,Calcium,Vit B,Vit C and zinc replacement.
•
Psychosocial support

related CLINICAL question

Q. A 14 months old baby Hb level of 6.3
gm% and multiple units of blood
transfusion were given during last 9
months. What is the definitive diagnosis of
this patient ?

Clinical formula

β- Thalassemia
α-Thalassemia -Anaemia Chelation therapy
-Anaemia -Pale skin/ Jaundice Haemoglobin Deferoxamine
-Pale skin -Weakness electrophoresis Deferasirox
-Weakness -Fatigue HPLC Deferiprone
Thalassemia -Fatigue -Protruding abdomen Globin Gene
-Hepatospleno -Hepatosplenomegaly Sequencing Hydroxyurea
megaly -Dark urine Hematopoeitic Stem
-Heart defects -Poor appetite cell Transplantation
-Delayed puberty Splenectomy
 114
Kawasaki disease
Medium vessel vasculitis involving coronary artery
Most common vasculitis in childhood
CREAM criteria
Conjunctivitis
Rash (Polymorphic truncal rash)
Edema (of extremities in acute phase; skin peeling in subacute phase)
Adenopathy (cervical lymphadenopathy; single >1.5 cm)
Mucosal involvement (Strawberry tongue, erythematous lips)

related CLINICAL question

Q. A 4 yr old boy was brought to the casualty with fever for past one week and
rashes over the trunk. Immunisations are up to date. Temperature is 40 C ( 104 F),
blood pressure is 100/70 mmHg, pulse is 120/min, RR is 18/min. On physical
examination, the child is awake and alert but very cranky. The conjunctival are
congested without discharge bilaterally . There is a scant nasal congestion. The lips,
tongue and oral mucosa are erythematous. S1 and S2 are normal without murmurs,
lungs are clear bilaterally, abdomen is soft, non tender and non distended. There is
non tender erythema and peeling of the skin in the perineum and inguinal folds and
several erythematous, blanching macules on the trunk.What is the probable
diagnosis?
 115

RAYNAUD’S PHENOMENON
Vasoconstriction of peripheral blood vessels in response to cold or stress exposure

Predisposing Factors Precipitating Factors

1. 15 and 40 years old. 1. Smoking
2. More in Women 2. Working with vibrating
3. Climate- winter machinery
3. Emotional distress
4. Exposure to the cold

Cold exposure

Stress

Digital artery
contraction spasm

Occlusion of
arteries vasoconstriction - white
cyanosis - blue
Tissue ischemia rapid blood reflow- red

Diagnosis Treatment
Complete blood count Calcium channel blockers-
ESR Nifidipine
Antinuclear antibody Topical nitroglycerin
Rheumatoid factor

related CLINICAL question

Q. A 28-year-old woman comes to the clinician with pain and numbness of
both hands over the last 6 months. Cold temperatures seem to precipitate
these episodes. Medical history includes exercise-induced asthma, lower
back pain, and hypothyroidism. The patient takes levothyroxine daily. She
does not use alcohol or illicit drugs but has a 10-pack-year smoking history.
Laboratory studies show normal complete blood count and chemistry panel.
TSH is 4.7 µU/mL. Antinuclear antibody screen is negative. What is the
probable diagnosis?
 116
Clinical formula
15 and 40 years old. Complete blood
Women vasoconstriction count Calcium channel
Smoking cyanosis ESR blockers- Nifidipine
RAYNAUD’S Working with vibrating Antinuclear Topical nitroglycerin
PHENOMENON rapid blood reflow
machinery antibody
Emotional distress Rheumatoid
Exposure to the cold factor

Transfusion reactions

Acute < 24hrs Delayed >24hrs

Immune Immune
Acute hemolytic transfusion reaction DHTR
PTP
Febrile non-hemolytic transfusion reactions GVHD
Allergic
TRALI Nonimmune
Nonimmune
Repeated transfusion
Sepsis Disease Thalasemia
- Acute
- Delayed Hemosiderosis
Transfusion associated circulatory overload

Acute hemolytic transfusion reaction

Cause: Mismatch, Bombay blood group
Present with hematuria
Febrile Non hemolytic transfusion reaction
> 1 C rise from baseline
Due to cytokine from donor lymphocytes

Allergic
Due to transfer of lymphocytes from donor

Delayed hemolytic transfusion reaction

Cause: Duffy mismatch

Post transfusion purpura

Antibodies against HpA
After 7 days
 117

TRALI
Transfusion associated lung injury
Usually occur due to plasma products

Antibodies are present in the donor plasma

against HLA/ Human neutrophil antigen

Neutrophil activation

Recruit IL-8
Damage endothelium of alveoli
Hyaline membranes
Acute lung injury

Transfusion associated circulatory overload

BP
Tachycardia
Testing done before blood transfusion
TTI testing Cross match
Hepatitis B Plasma
Hepatitis C (more important as antibodies present
HIV in plasma and destroy red cells)
Malaria Red cells
Syphilis
Complication after transfusion
Hypocalcemia
Citrate chelates calcium and causes Hypocalcemia
Hypomagnesaemia
Because of large volume of magnesium poor fluid and citrate overload
Hyperkalemia
Because of haemolysis of RBC from storage, irradiation or both
Hypokalemia
Because of re-entry into transfused RBC’s,
Release of stress hormones or metabolic alkalosis
 118
Massive transfusion
Replacement of >1 time the total blood volume within 24hrs or
Replacement of more than 50% of the blood volume in 3 hrs in an adult
Complications
Metabolic alkalosis > acidosis
Hyperkalemia. Ventricular arrhythmia/ cardiac arrest
Hypocalcemia/ citrate toxicity
Depletion of coagulation factors. Increased risk of DIC
Dilutional thrombocytopenia
Hypothermia
blood transfusion reaction protocol

related CLINICAL question

Q. A 27-year-old man with sickle cell anemia comes to the casualty due to increasing
dyspnea that started 3 hours ago. The patient was seen in the casualty 5 days ago for
symptomatic anemia, and his hemoglobin level was 6.2 g/dL. He received a blood
transfusion, after which his hemoglobin level improved to 8 g/dL, and he was sent home.
The patient appears pale; scleral icterus is present. What is the probable diagnosis?

Clinical formula
Fever, chills, back pain, Get a coagulation Stop the transfusion
pruritus, burning screen including partial immediately
Acute
Haemolytic sensation and chest pain. thromboplastin time, If hypotension develops,
Transfusion In unconscious patient, platelet count, fibrinogen administer fluids and if
Reaction hypotension, shock, levels and fibrin- required, vasopressors.
haemoglobinuria, oliguria degradation products to Administer furosemide to
and excessive bleeding. exclude DIC. maintain urine output.
 119

Nephrology and Urology

ACID-BASE DISORDERS
Henderson hasselbalch equation
HCO3-
pH= 6.1 + log10
0.03 x pCO2

Anion gap
Measure of acid-base balance
AG = (Na+) - [ (CL-) + (HCO3-) ]

NA+
CL- HCO3- ANION GAP

High anion gap Normal anion gap

metabolic acidosis metabolic acidosis

1. Methanol 1. Ureteroenterostomy
2. Uraemia 2. Small bowel fistula
3. Diabetic ketoacidosis 3. Extra chloride
4. Phenformin, Paraldehyde 4. Diarrhoea
5. INH, Iron 5. Carbonic anhydride inhibitor
6. Lactic acid 6. Addison’s disease
7. Ethanol, Ethylene glycol 7. Renal tubular acidosis
8. Salicylates 8. Pancreatic fistula

MNEMONIC MNEMONIC
MUD PILES USED CARP

Seizure activity especially a tonic clonic seizure can significantly raise serum
lactic acid levels due to skeletal muscle hypoxia and impaired hepatic lactic
acid uptake and cause High anion gap metabolic acidosis (HAGMA)
 120

DAVENPORT DIAGRAM

METABOLIC ACIDOSIS Acute respiratory alkalosis

FALL IN PH Rise in ph
FALL IN HCO3 Fall in pco2
Chronic respiratory alkalosis
METABOLIC ALKALOSIS Rise in ph
RISE IN PH Fall in pco2
RISE IN HCO3 Fall in hco3

acute Respiratory acidosis

Fall in ph
Rise in pco2 pH 7.35 - 7.45

Chronic respiratory acidosis PCO2 40mmHg

Fall in ph
Rise in pco2
Rise in HCO3 HCO3 24 mmHg
 121

RELATED CLINICAL QUESTION

Q. A 46 yr old man is brought to the casualty immediately after having a seizure. His
family describes a medical history of generalised tonic -clonic seizures. The patient
has been on valproate acid for the past 10years but stopped taking the drug 6 months
ago as he had no seizure in the last 9 years. The patient is afebrile, Blood pressure is
105/68 mm Hg, pulse is 96/min and RR is 18/min, SpO2 is 99% on room air. The patient
appears confused and lethargic. Chest auscultation is unremarkable, and the abdomen
is soft and non tender. A limited neurological examination is no focal. Laboratory
results are as follows.
Sodium 140 mEq/L
Potassium 4.0 mEq/L
Chloride 103 mEq/L
Bicarbonate 17 mEq/L
Blood urea nitrogen 20 mg/dL
Creatinine 0.8 mg/dL
Glucose 98 mg/dL
Arterial blood gas shows pH 7.24. Chest X-ray and CT scan of head is
unremarkable. What is the probable diagnosis?

Clinical formula
Step 1. Check the pH Step 3. Choose Step 5. If metabolic
pH< 7.36, acidosis appropriate compensation acidosis present,
pH> 7.44, alkalosis for acid-base disorder calculate the anion gap
ACID-BASE
DISORDERS Step 2. Is primary process Step 4. Determine if Step 6. If high anion
metabolic or respiratory? For degree of compensation gap acidosis, calculate
this, check pC02 and HC03 is appropriate or not delta-delta gap

Spectrum of glomerular diseases

 122

Kidney

Nephrotic Membranoproliferative Glomerulonephritis

syndrome glomerulonephritis

Ig A Nephropathy
Minimal change Most common cause in world
disease
(Child) Post streptococcal
glomerulonephritis
Most common cause in india
Focal segmented
glomerular sclerosis
(Adults) Rapidly progressive
glomerulonephritis
End stage- Aggressive
Membraneous
Nephropathy
(Elderly)

acute glomerulonephritis

The term glomerulonephritis signifies glomerular inflammation in which there is an

immunologically-mediated injury to the glomeruli.
CAUSES OF ACUTE GLOMERULONEPHRITIS
 123
Clinical features
• Haematuria • Hypertension
• Red blood eelI casts • Proteinuria
• Oliguria • Uraemia
• Oedema

Post-Streptococcal Glomerulonephritis
One of the common causes of acute nephritic syndrome is acute post-
streptococcal glomerulonephritis (PSGN)
• Onset is often abrupt with puffiness of face, oliguria, smoky urine or reddish
urine, hypertension and oedema.
• The oedema of acute glomerulonephritis tends to appear initially in areas of low
tissue pressure (periorbital areas), but subsequently progresses to involve
dependent portions of the body, and may lead to ascites and/or pleural effusion.

Investigations
• Urine microscopy Red cells (particularly dysmorphic-i.e. distorted
and fragmented red cells), red cell casts
• Cultures Throat swab and swab from inflamed skin may
grow group A 13-haemolytic streptococci
• Antistreptolysin-0 (ASO) titre Elevated
• C3 level (complement) May be reduced
• Urinary protein Increased
• Urea and creatinine May be elevated
• Renal biopsy Features of glomerulonephritis

Treatment
• Treatment of acute PSGN is supportive.
• The measures include rest, salt restriction, diuretics and antihypertensives.
• Antibiotics are given for presumed throat infection as this may result in milder
form of nephritis. Further, treatment of a carrier state may prevent spread to
other household members.
• Dialysis is required in severe oliguria, fluid overload and hyperkalaemia.
• Steroids and cytotoxic drugs are of no value.
• Complications include pulmonary oedema, hypertensive encephalopathy and
renal failure.
 124

IgA nephropathy
- Also known as IgA nephritis or Berger disease
- Most common glomerulonephritis worldwide and is a leading cause of chronic kidney
disease and renal failure.
Clinical features
• Characterised by predominant lgA deposition in the glomerular mesangium.
• Presents with painless haematuria, generally within 1-2 days of upper
respiratory infection.
• More common in children and young adults with peak incidence between 15
and 30 years.
Henoch-Schonlein purpura is a systemic disease which may have mesangial lgA
deposition. It is more common during childhood as compared to IgA nephropathy
A characteristic petechial rash (cutaneous vasculitis, typically affecting buttocks
and lower legs) and abdominal pain (GI vasculitis) usually dominate the clinical
picture, with mild glomerulonephritis indicated by haematuria.
May be detected on routine urine examination (microscopic haematuria).
Renal biopsy shows mesangial IgA deposition and appearances indistinguishable
from acute IgA nephropathy.
Management of IgA nephropathy is largely directed towards control of BP and
proteinuria reduction in an attempt to prevent or retard progressive renal disease.

Rapidly progressive glomerulonephritis (RPGN)

RPGN is defined as any glomerular disease characterised by extensive crescents
(usually >50%) as the principal histologic finding and by a rapid loss of renal function
(usually a 50% decline in the GFR within 3 months).
• Presents with moderate proteinuria, haematuria, oliguria, oedema and uraemia.
Classified on the basis of BM damage

type I RPGN Type II RPGN Type III RPGN

Anti GBM disease Immunocomplex mediated Pauci immune

disease ANCA mediated
 125
Causes of Rapidly Progressive Glomerulonephritis
Anti-GBM antibody
• Goodpasture syndrome
• Anti-GBM disease (only kidney involvement)
Pauci-immune
• Wegener granulomatosis
• Microscopic polyangiitis
• Renal-limited necrotizing crescentic glomerulonephritis
• Churg-Strauss syndrome
Immune complex
Post-infectious
• Post-streptococcaI
• Visceral abscess
• Collagen vascular disease
• Lupus nephritis
• Henoch-Schonlein purpura
• Mixed cryoglobulinaemia
• Primary renal disease
• lgA nephropathy
• Membranoproliferative glomerulonephritis
• Idiopathic

Goodpasture syndrome
- Referred as anti glomerular basement membrane (anti-GBM) antibody disease
- Autoimmune disease characterized by damage to the alveolar and renal
glomerular basement membranes by an antibody.
Goodpasture syndrome is defined by:
- Pulmonary hemorrhage
- Glomerulonephritis
- Circulating anti glomerular
basement membrane antibodies.
Immunofluorescence
- Smooth
- Diffuse linear pattern
 126
Investigations
• Leucocytosis and anaemia.
• Blood urea and serum creatinine levels usually elevated.
• Urinalysis shows modest proteinuria (1-4 g/day), microscopic haematuria, and RBC
and WBC casts.
• Complement levels (C3 and C4) may be decreased in patients with immune-complex
mediated RPGN.
• Circulating anti-GBM antibodies in Goodpasture syndrome.
• ANCA in patients with pauci-immune RPGN.
• Serum cryoglobulin levels may be elevated in cryoglobulinaemias.
• Abdominal ultrasound shows normal-sized kidneys.
• Chest X-ray in patients with Goodpasture syndrome and vasculitides may show
diffuse opacities if pulmonary haemorrhage occur.
• Kidney biopsy.
Treatment
• Control of infection
• Control of volume status (dialysis if required).
Immunosuppressive therapy (e.g. glucocorticoids, cyclophosphamide, azathioprine,
mycophenolate), plasma exchange (in patients presenting with life-threatening
pulmonary haemorrhage). Treatment of choice in anti-GBM antibody disease is
plasmapheresis combined with prednisolone and cyclophospharnide.
Infliximab and rituximab.

RELATED CLINICAL QUESTION

Q. A 22-year-old man comes to the casualty for evaluation due to dark urine that he
noticed earlier this morning. The patient is recovering from an upper respiratory tract
infection that started 3 days ago, Temperature is 37.7 C (99.9 F), blood pressure is
145/92 mm Hg, pulse is 80/min, and respirations are 14/min. Physical examination shows
no rash or joint abnormalities. Laboratory results are as follows:
Urinalysis
Glucosenegative White blood cells 3-6/hpf
Blood urea nitrogen 18 mg/dL
Protein 1+ Red blood cells 30-50/hpf
Serum creatinine 1.4 mg/dL
Leukocyte esterase negative Casts red blood cells
Serum complement levels (C3, C4) are within normal limits, and other serologic workup
is pending. Which of the following is the most likely diagnosis in this patient?
 127

Clinical formula

Post- Urine microscopy, Cultures,

Streptococ Puffiness of face, Rest, salt restriction, diuretics,
cal oliguria, smoky urine Antistreptolysin-0 (ASO) titre, antihypertensives, Antibiotics ,
Glomerulon or reddish urine, C3 level (complement), Urinary Dialysis in severe oliguria, fluid
ephritis hypertensio, oedema. protein, Urea and creatinine, overload, hyperkalaemia.
(PSGN) Renal biopsy

Pulmonary • Complement levels (C3 and C4) Control of infection, dialysis

hemorrhage, may be decreased in patients with if require, plasmapheresis
Glomerulonephritis, immune-complex mediated RPGN. combined with prednisolone
Circulating anti • Circulating anti-GBM antibodies in and cyclophospharnide.
Goodpasture glomerular Goodpasture syndrome.
syndrome basement • ANCA in patients with pauci-
membrane immune RPGN.
antibodies. • Serum cryoglobulin levels may be
elevated in cryoglobulinaemias.

nephrotic syndrome
The nephrotic syndrome is characterised by the following abnormalities
Proteinuria (>3.5 g in 24 hours)
Generalised oedema
Hypoalbuminaemia
Hyperlipidaemia
Causes

Minimal change disease:

• Most common cause of nephrotic syndrome in children (80%); responsible for
20% of all cases in adults.
• Normal-appearing glomeruli on light microscopy of a renal biopsy specimen.
• Effacement of foot processes of epithelial cells on electron microscopy.
 128

Focal and segmental glomerulosclerosis (FSGS):

• Accounts for one-third of cases of nephrotic syndrome in adults.
• May be idiopathic or develop secondary to HIV infection, heroin use, sickle
cell disease, obesity and reflux nephropathy.
• Patients usually present with nephrotic-range proteinuria, hypertension,
renal insufficiency and occasionally haematuria.
Membranous glomerulonephritis:
• One of the most common primary renal causes of nephrotic syndrome in adults.
• Male predominance, Incidence usually peaks between ages 30 and 50 years.
• Secondary causes include systemic lupus erythematosus, hepatitis B, malignancy
or drug-induced (e.g. chronic gold or penicillamine drug therapy).
• Approximately 75% of patients present with nephrotic-range proteinuria and 50%
present with microscopic haematuria
Investigations

Treatment
• Measures to reduce proteinuria
• Measures to control complications of nephrotic syndrome
• Treatment of underlying cause

RELATED CLINICAL QUESTION

Q. A 72-year-old woman is brought to the opd by her daughter for evaluation of
leg swelling and fatigue. She has had bilateral lower extremity swelling for the
past 3 months. Blood pressure is 116/72 mm Hg and pulse is 78/min and regular.
The lungs are clear on auscultation and heart sounds are normal. The abdomen is
soft and nontender. Examination of the lower extremities reveals 3+ pitting
edema. There are scattered ecchymoses, Albumin is 2.8 g/dL . Urinalysis reveals
4+ protein with no cells or casts. What is the probable diagnosis?
 129

Clinical formula
24-hour urinary protein • Measures to reduce
Proteinuria (>3.5 g in estimation, and estimation of proteinuria- ACE
24 hours) serum albumin and serum inhibitors,NSAIDs
nephrotic • Measures to control
syndrome Generalised oedema cholesterol concentrations.
Hypoalbuminaemia Red cells and red cell casts complications of nephrotic
Hyperlipidaemia may be present in the urine. syndrome- salt restriction, rest
and judicious use of diuretics

Acute kidney injury (AKI)

Acute renal failure (ARF) is defined as a rapid, potentially reversible deterioration in

renal function sufficient to result in accumulation of nitrogenous wastes in the body
(uraemia):
• An increase in serum creatinine of > 0.3 mg/dL within 48 hours; or
• An increase in serum creatinine of >: 1.5 times baseline, which is known
or presumed to have occurred within the prior seven days; or
• Urine volume <0.5 mL/kg per hour for more than six hours.

Causes of acute kidney injury

 130
Clinical features
• In ARF due to a pre-renal disorder the clinical features are those of the causal
condition together with those of rapidly developing uraemia. Patients often present
with a low blood pressure, poor peripheral perfusion and a falling urine output.
• Acute tubular necrosis (ATN) is the most important cause of ARF due to intrinsic
renal disease. The clinical course in ATN can be divided into an oliguric phase,
maintenance phase and a diuretic phase.
• Patients with glomerulonephritis typically have hypertension, proteinuria and
haematuria.
• Patients with drug-induced acute tubulo-interstitial nephritis may present
with fever, skin rash and arthralgias.
• ARF due to bilateral post-renal obstruction commonly causes anuria. The patient
may give a history of loin pain, hae maturia, renal colic or difficulty in micturition.

Investigations
 131
Treatment
• Therapy for ARF is directed at correcting fluid and electrolyte abnormalities, treating
the underlying cause and prevent ing complications including nutritional deficiencies.
• Emergency treatment should be started for hyperkalaemia (K+ >6 mmol/L) to prevent
life-threatening complications.
• Acidosis should be treated with intravenous or oral bicarbonate if serum bicarbonate
level is <15 mEq/L.
• Drugs such as loop diuretics, mannitol and dopamine have been used to increase urine
output and reduce the duration of renal failure but they have been shown to be of no value.
• Dietary proteins should be restricted
• If conservative measures fail, haemodialysis may be required.

RELATED CLINICAL QUESTION

Q. A 54-year-old man comes to the casualty due to progressive shortness of breath, lower
extremity swelling, and decreased urine output for the past week. The patient has a history
of nonischemic cardiomyopathy and heart failure with reduced ejection fraction. Physical
examination shows jugular venous distension. Crackles are heard at the bilateral lung
bases. The abdomen is distended and there is 2+ pitting lower extremity edema bilaterally.
Blood urea nitrogen 46 mg/dL. Serum creatinine 2.2 mg/dL
What is the probable diagnosis?
Clinical formula
Urea and creatinine Fluid and electrolyte
Low blood pressure, poor Electrolytes Calcium and abnormalities treatment ,
Acute peripheral perfusion and a
kidney phosphate, Albumin FBC, Emergency treatment for
falling urine output, CRP, Urinalysis, Urine hyperkalaemia, intravenous
injury hypertension, proteinuria or oral bicarbonate, loop
microscopy, Renal USS,
(AKI) and haematuria, fever, Cultures CXR, Serology, diuretics, mannitol and
skin rash and arthralgias. ECG dopamin, proteins restricted

CHRONIC KIDNEY DISEASE

Irreversible deterioration in renal function that classically develops over a period of years
Spectrum of different pathophysiologic processes associated with
- Abnormal kidney function
- Progressive decline in glomerular filtration rate (GFR).

• Glomerular filtration rate (GFR) of <60 ml/minute/1.73 m2 for 3 months

or more, with or without kidney
 132

Physical signs in chronic kidney disease.

(*Features of renal replacement therapy)

Staging of CKD
 133
Hyperkalemia in CKD
Hyperkalemia is is the most critical manifestation of Chronic kidney disease.
It may lead to Diastolic arrest.
K+ > 5.0 mEq/L
Acute reduction is required at levels >7.0 mEq/L
ECG - Tall peaked T waves
TREATMENT
i. IV Calcium - most rapid and effective way to antagonize myocardial toxic effect
ii. IV insulin
iii. B2 Adrenergic agonist
iv. Haemodialysis if hyperkalemia is persistent or severe

RELATED CLINICAL QUESTION

Q. A 34-year-old man with renal failure comes to the opd for follow-up. The patient
has a history of chronic kidney disease caused by diabetic nephropathy. Three months
ago, he had a prolonged hospitalization due to septic shock and required dialysis for
oliguric acute kidney injury from acute tubular necrosis. His renal function has failed
to improve, and the patient has been receiving intermittent hemodialysis for end-stage
renal disease. Other medical history includes type 1 diabetes mellitus, gastroparesis,
and diabetic neuropathy. What is the probable diagnosis??
Clinical formula
Pulsus paradoxus, Pallor, JVP raised, Urea and creatinine
Pericardial friction rub, Arteriovenous Electrolytes Calcium DASH diet (Dietary
CHRONIC fistulae, ‘Brown line’ pigmentation of and phosphate, Albumin Approaches to Stop
nails, FBC, CRP, Urinalysis, Hypertension)
KIDNEY Therapy for the
Excoriation of pruritus Bruising easily, Urine microscopy, Renal
DISEASE Peripheral neuropathy, Absent underlying cause of
USS, Cultures CXR,
reflexes, Paraesthesia ‘Restless legs’ Serology, ECG kidney disease

Urine Crystals

Uric acid crystals: Amber colored,

Struvite crystals: Coffin lid shaped.
Calcium phosphate stones: Rosette shaped.
Cystine stones: Hexagonal crystals.
Calcium oxalate: Envelope shaped
 134

Clinical features
- Some renal stones : Asymptomatic
- Most will result in pain.
- Small stones that arise in the kidney are more likely to pass into the
ureter where they may result in renal colic.
-Hematuria may also be present.
Plain radiograph
1)Calcium-containing stones are radiopaque:
- Calcium oxalate +/- calcium phosphate
- Struvite (triple phosphate) - usually opaque but variable
- Pure calcium phosphate
2)Lucent stones include:
- Uric acid
- Cystine
- Medication (indinavir) stones

lupus nephritis
 135
Nocturnal Enuresis
Refers to the occurrence of involuntary voiding at night after 5yrs of age.
Nocturnal enuresis
Primary Secondary
75-90% 10-25%
Urinary control never achieved Child was dry for few months
and then enuresis developed
Causes
i. Delayed maturation of cortical mechanism that allow voluntary control of
micturition reflex.
ii. Defective sleep arousal
iii. Sleep disorders
iv. Constipation

Treatment
Best approach is to reassure the child and parents that the condition is self limited and
avoid punitive measures that can affect child’s psychological development adversely
Fluid intake should be restricted after 6-7pm
Parents should be certain that child voids at bedtime
Conditioning therapy : involves use of loud auditory or vibratory alarm attached to
moisture sensor in undergarment.
Pharmacological therapy : 2nd line - Desmopressin acetate (Synthetic analogue of ADH )

RELATED CLINICAL QUESTION

Q. A 7 year old child presented with history of bed wetting for last 1 year, at a
frequency being twice a week. With thorough investigations, organic cause is
ruled out. What should be the initial treatment plan?

Clinical formula
i. Delayed maturation of cortical Reassure the child and
mechanism that allow voluntary parents
Involuntary voiding Fluid intake should be
Nocturnal at night after 5yrs control of micturition reflex.
ii. Defective sleep arousal restricted after 6-7pm
Enuresis of age. Conditioning therapy ,
iii. Sleep disorders
iv. Constipation Pharmacological therapy : 2nd
line - Desmopressin acetate
 136

Endocrinology including DM
anterior pituitary hormone deficiency
Hypopituitarism means the combined deficiency of any of the anterior pituitary hormones.
Causes

Sheehan's syndrome
• Results from infarction of pituitary gland during post-partum period.
• Post-partum pituitary infarction occurs because the enlarged pituitary gland of
pregnancy is more vulnerable to ischaemia of post-partum haemorrhage and systemic
hypotension.
• Failure to lactate is the earliest symptom.
• Another typical symptom is failure to regain menstruation after delivery and breast
involution.
• Other symptoms of hypopituitarism appear over months or years, though some
patients present acutely.
• Uncommonly, it can present acutely with circulatory collapse, severe hyponatraemia,
diabetes insipidus, hypoglycae mia, congestive cardiac failure, psychosis, finally leading to
coma and death.
• MRI may show hypertrophic pituitary in early stages, but later, atrophic pituitary and
empty sella develop. It also excludes a pituitary mass.
• Treatment is substitution of deficient hormones.
 137
Investigation of pituitary and hypothalamic disease

Treatment
Cortisol replacement: Hydrocortisone is used
Thyroid hormone replacement: Levothyroxine 50–150 µg once daily should be given.
Sex hormone replacement: for gonadotrophin deficiency in women < 50 and in men.
Growth hormone (GH) replacement

RELATED CLINICAL QUESTION

Q. A 31-year-old woman comes to the opd due to worsening fatigue and
abdominal pain for the last month since the birth of her child. She had an
emergency cesarean delivery complicated by significant hemorrhage that
required transfusion of multiple units of blood. The patient reports that she
has been unable to breastfeed and has switched to formula to feed her infant.
The patient has sparse axillary and pubic hair. What is the probable diagnosis?

Clinical formula
Failure to lactate , failure Short ACTH stimulation test; Hydrocortisone
to regain menstruation insulin tolerance test, serum Levothyroxine
after delivery , circulatory testosterone, LH, FSH;serum T4; Sex hormone
Sheehan's TSH , blood glucose, potassium
syndrome collapse, severe replacement
hyponatraemia, diabetes and calcium measurements; Growth hormone (GH)
insipidus, hypoglycaemia water deprivation test or 5% replacement
saline infusion test
 138

acromegaly
• GH hypersecretion occurring in adult life after epiphyseal closure results in
acromegaly (excess before epiphysis closure results in gigantism).
• Pituitary tumour (somatotroph pituitary adenoma) is the most common cause.
• Rare causes include excessive GH secretion from pancreatic islet cell tumour, or
excessive secretion of GR-releasing hormone from hypothalamic lesions, bronchial
carcinoid and small cell lung carcinoma.

Clinical features
• Soft tissue changes Thickening of skin, increased skin tags, acanthosis nigricans,
increased sweat and sebum resulting in moist and oily skin,
enlargement of lips, nose and tongue, increased heel pad
thickness, visceral enlargement-e.g. thyroid, heart and liver,
carpal tunnel syndrome, myopathy, sleep apnoea, Raynaud's
phenomenon
• Bone changes Large spade-like hands, large feet, prognathism, prominent
supraorbital ridges, large frontal sinuses, wide-spacing of the
teeth, arthropathy, kyphosis, osteoporosis
• Metabolic effects Glucose intolerance or clinical diabetes mellitus

• Cardiac effects Coronary heart disease, cardiomyopathy, hypertension, left

ventricular hypertrophy
Increased risk of colonic polyps and carcinoma

Skull in acromegaly. Note enlargement of sella

turcica and of frontal bones, generalized thickening
of skull bones and prognathism. Other causes of
enlarged sella – Primary hypothyroidism, pregnancy,
empty sella syndrome (classically in obese
hypertensive multipara)
 139
Investigations
• Investigations of pituitary tumour
• Elevated IGF-I levels.
• GH levels are measured during an oral glucose tolerance test (OGTT).
A failure of suppression or a paradoxical rise of GH indicates acromegaly.

Treatment
The primary treatment modality for acromegaly is transsphenoidal surgery
• Bromocriptine or cabergoline (dopamine receptor agonists) in mildly elevated IGF-1.
• Octreotide or lanreotide (somatostatin analogues)- act on pituitary somatostatin
receptors to produce inhibition of GH and IGF-1.
• Pegvisomant, a GH receptor antagonist, blocks peripheral IGF-1 action

RELATED CLINICAL QUESTION

Q, A 45-year-old man comes to the casualty due to a 4-week history of progressively
worsening shortness of breath. The patient has no history of cardiopulmonary disease,
although his wife, who accompanies him, states that he snores heavily at night. In
addition, over the last 6 months his hands and feet have become enlarged. On
examination, he has coarse facial features with prominent frontal bones and jaw and
crowding of the pharyngeal space. The extremities show enlarged, swollen hands and
feet. There are fine crackles at the lung bases. What is the probable diagnosis?

Clinical formula
Large spade-like hands, • Investigations of pituitary
large feet, prognathism, • Bromocriptine or
tumour
prominent supraorbital cabergoline
• Elevated IGF-I levels.
acromegaly ridges, large frontal sinuses, • Octreotide or
• GH levels are measured
wide-spacing of the teeth, lanreotide
during an oral glucose
arthropathy, kyphosis, • Pegvisomant,
tolerance test (OGTT).
osteoporosis

diabetes insipidus
Diabetes insipidus (DI) can be divided into following types:
• Deficient production of ADH.
Primary deficiency (neurogenic, pituitary, hypothalamic, cranial or central DI)
occurs due to agenesis or destruc tion of neurohypophysis.
Secondary deficiency occurs due to inhibition of ADH secretion (primary
polydipsia).
Deficient action of ADH (nephrogenic DI).
 140
Causes of diabetes insipidus

Clinical Features
• Polyuria, excessive thirst and polydipsia (with predilection for cold drinks)
are the cardinal manifestations of DI.
• Daily urine output >50 mL/kg/day and may reach as high as 10-15 L.
• In traumatic DI triphasic response may be seen: initial polyuria, prolonged
antidiuresis and final polyuria.
Diagnosis
• The urine is clear and of low specific gravity. The osmolality is low.
• Serum sodium is borderline high indicating water loss.
• Water deprivation test
• MRI of pituitary and hypothalamus.
Treatment
• Desmopressin 10-20 µg intranasally once or twice a day.
• Chlorpropamide enhances the renal responsiveness to vasopressin.
• Carbamazepine is an alternate drug with similar action.
• Thiazide diuretics (e.g. bendrofluazide) are the only effective drugs for nephrogenic DI.

RELATED CLINICAL QUESTION

Q. A 34-year-old woman comes to the opd due to excessive urination at night. For the past
2 weeks, the patient has been getting up at least 3 times at night to urinate. She has a
history of hypothyroidism treated with levothyroxine and bipolar disorder treated with
lithium carbonate.Physical examination shows decreased skin turgor and dry mucous
membranes. Sodium 146 mEq/L TSH 7.0 µU/mL Osmolality, urine 200 mOsmol/kg H2O
What is the probable diagnosis?
 141

Clinical formula
• The urine is clear and of
Polyuria, low specific gravity. • Desmopressin
excessive • Serum sodium is • Chlorpropamide
diabetes borderline high. • Carbamazepine
insipidus thirst and
polydipsia • Water deprivation test • Thiazide diuretics (e.g.
• MRI of pituitary and bendrofluazide)
hypothalamus.

adrenocortical insufficiency

Causes of adrenocortical insufficiency

Addison's disease
Clinical features of Addison's disease result from glucocorticoid deficiency,
mineralocorticoid deficiency, androgen deficiency and ACTH excess.
Manifestations include fatigue, weakness, anorexia, nausea and vomiting, weight loss,
abdominal pain, cutaneous and mucosal pigmentation, salt craving, hypo- tension
(especially orthostatic), and, occasionally, hypoglycemia.
Routine laboratory parameters may be normal, but typically serum Na is reduced and
serum K increased.
Extracellular fluid depletion accentuates hypotension.
In secondary adrenal insufficiency, pigmentation is diminished and serum potassium is
not elevated.
Serum Na tends to be low because of hemodilution stemming from excess vasopressin
secreted in the setting of cortisol deficiency.
 142
Investigations
• Elevated blood urea, hyponatraemia and hyperkalaemia.
• Low blood sugar levels.
• Mild anaemia, mild eosinophilia.
• Plasma cortisol measured between 8 and 9 am <3 mg/dL suggests adrenal insufficiency
• ACTH stimulation test
• Plasma ACTH levels are elevated (> 100 pg/dL) in primary adrenal insufficiency.
• PRA is high and plasma aldosterone levels are low or normal.
• Adrenal and other organ-specific antibodies (e.g. adrenal cortex antibodies, 21-
hydroxylase antibodies) may be detected in the serum in autoimmune adrenalitis.
Management
• Patients with Addison's disease require lifelong glucocorticoid and
mineralocorticoid replacement therapy.
• Cortisone is given at a dose of 20 mg on getting up in the morning and 10 mg in
the evening at 6 pm. Alternatively,Prednisolone is given in a dose of 5 mg in the
morning and 2.5 mg in the evening.
• Fludrocortisone (mineralocorticoid) 0.05-0.1 mg daily in patients with primary
adrenal insufficiency.
• During periods of stress and infections the patient should be told to take
additional doses of prednisolone.

RELATED CLINICAL QUESTION

Q. A 42-year-old woman comes to the casualty due to 2 syncopal episodes in the last
3 days. The patient was well until approximately a month ago when she began to feel
increasingly fatigued and weak. For the past 2 weeks, she has had anorexia, nausea,
and abdominal pain. Temperature is 36.7 C (98 F), blood pressure is 86/52 mm Hg,
pulse is 90/min, and respirations are 18/min. Cardiopulmonary examination is
normal. The abdomen is mildly tender with otherwise normal findings. The skin
shows hyperpigmentation in the palmar creases. What is the probable diagnosis?

Clinical formula
Fatigue, weakness, anorexia, Elevated blood urea,
nausea and vomiting, weight hyponatraemia and
loss, abdominal pain, Glucocorticoid and
Addison's hyperkalaemia, Low blood
mineralocorticoid
disease cutaneous and mucosal sugar levels, Mild anaemia,
pigmentation, salt craving, replacement therapy.
mild eosinophilia, Plasma
hypotension (especially cortisol, ACTH stimulation.
orthostatic), hypoglycemia.
 143
Cushing’s syndrome
Cushing’s syndrome refers to the clinical manifestations induced by, chronic
exposure to excess corticosteroid.
Cushing disease is corticosteroid excess due to pituitary dependent bilateral
adrenal hyperplasia.
Causes
Clinical features
 144

Buffalo hump Moonface

 145
Management

Management of the patient with suspected Cushing’s syndrome. ACTH, adrenocorticotropic hormone;
CRH, corticotropin-releasing hormone; DEX, dexamethasone.
 146
RELATED CLINICAL QUESTION
Q. A 34-year-old woman comes to the opd due to a 6-month history of easy bruising with
minimal or no trauma. She also has had difficulty climbing stairs due to muscle weakness and
frequent nocturnal muscle cramps and weight gain. Her lmp was 3 months ago. Examination
shows facial plethora with dark terminal hair on her upper lip and chin. There is inflammatory
acne on her face and back, extensive tinea versicolor on the trunk, and scattered bruises over
the extremities. What is the probable diagnosis?
Clinical formula
Most patients are
Weight gain, Hirsutism, 24hr urinary cortisol and serum treated surgically, and
Oligomenorrhoea, Central cortisol that fails to suppress corticosteroid
Cushing’s obesity ("lemon on match- either with a 1mg overnight biosynthesis can be
syndrome stick") dexamethasone suppression test inhibited by metyrapone
Buffalo hump, Moon face, or with the 48hr lowdose or ketoconazole pending
Purplish striae dexamethasone suppression test operation.

Hypothyroidism
Clinical condition resulting from reduced production of thyroid hormone.
Myxoedema indicates severe hypothyroidism in which there is accumulation of
hydrophilic mucopolysac charides in the ground substance of the dermis and other
tissues, leading to thickening of the facial features and doughy induration of the skin.
CAUSES OF HYPOTHYROIDISM
 147

Clinical features

Evaluation of hypothyroidism.

TPOAb+, thyroid
peroxidase antibodies
present; TPOAb–,
thyroid peroxidase
antibodies not present;
TSH, thyroid-
stimulating hormone.

Management
• Hypothyroidism is treated with T4• It is usually given at a dose of 50 µg/day for 3
weeks, followed by 100 µg/day for 3 weeks, followed by a maintenance dose of 150 µg/
day. The correct dose of T4 is that which restores serum TSH to below 3 mU/L. It
should be given on empty stomach in the morning.
• In elderly patients and those with ischaernic heart disease T4 is started at a lower
dose of 25 µg/day.
 148
RELATED CLINICAL QUESTION
Q. A 39-year-old woman with abnormal uterine bleeding. The patient underwent menarche
at age 15 and had irregular menses that normalized with oral contraceptives. She also has
had difficulty concentrating at work due to increasing irritability and depressed mood. She
has no headaches or hot flushes. Vital signs are normal. BMI is 26 kg/m2. Skin is cool and
dry. Pregnancy test is negative. This patient's laboratory results would most likely reveal
which of the following?
Clinical formula
Tiredness, SerumT4 levels are low
andTSH levels are high, T4 at a dose of 50 μg/
somnolence, cold
Serum sodium levels may day for 3 weeks,
Hypothyroi intolerance,
be low.ECG: sinus followed by 100 μg/day
dism hoarseness of
bradycardia, low voltage for 3 weeks, followed by
voice, low-pitched
QRS complexes and ST-T a maintenance dose of
voice, slurred
wave abnormalities. 150 μg/day.
speech, weight gain

THYROTOXICOSIS
The term thyrotoxicosis refers to the clinical syndrome of hypermetabolism and
hypersensitivity which result from excessive amount of thyroid hormones
Causes
 149
Evaluation of thyrotoxicosis

Evaluation of
thyrotoxicosis. aDiffuse
goiter, positive TPO
antibodies,
ophthalmopathy,
dermopathy; bcan be
confirmed by
radionuclide scan.
TSH, thyroid-
stimulating hormone.

Clinical features
Thyroid Diffuse or nodular enlargement
Gastrointestinal Weight loss, increased appetite, vomiting, increased stool
frequency, diarrhoea, steatorrhoea
Cardiorespiratory Exertional dyspnoea, exacerbation of asthma, palpitations,
angina, sinus tachycar dia, atrial fibrillation, wide pulse pressure,
cardiac failure, cardiomyopathy
Neuromuscular Nervousness, irritability, emotional ability, psychosis, fine
tremors, hyper-reflexia, ill-sustained clonus, muscle weakness,
proximal myopathy, bulbar myopathy
Dermatological Increased sweating, pruritus, palmar erythema, spider
naevi, onycholysis, alope cia, pigmentation
 150

Reproductive Menstrual disturbances (amenorrhoea or oligomenorrhoea),

infertility, repeated abortions, loss of libido, impotence

Miscellaneous Heat intolerance, fatigue, apathy, gynaecomastia, thirst

Graves' disease
Graves' disease is distinguished from other forms of hyperthyroidism by the
presence of diffuse thyroid enlargement with or without bruit, ophthalmopathy and
pretibial myxoedema.
Autoimmune disorder in which thyroid stimulating immunoglobulin (TSI) binds to
and stimulates thyroid stimulating hormone (TSH) receptor
on thyroid cell membrane resulting in excessive synthesis and secretion of thyroid
hormone.
- Excessive sweating, - Insomnia
- Fatigue - Tremors
- Palpations - Irritability

Thyrotoxic crisis
Thyrotoxic crisis, or thyroid storm, is rare, presents as a life-threatening exacer-
bation of hyperthyroidism, and can be accompanied by fever, delirium, seizures,
arrhythmias, coma, vomiting, diarrhea, and jaundice.
RELATED CLINICAL QUESTION
Q. A 58-year-old woman comes to the opd due to recent-onset tremor, palpitations,
weight loss, and fatigue.The patient's mother had hypothyroidism and osteoporosis.
On examination, there is diffuse, nontender enlargement of the thyroid gland.
Ocular examination shows bilateral proptosis, lid lag, and periorbital puffiness. The
patient has diplopia and ocular discomfort on extremes of lateral gaze. Laboratory
tests show a suppressed TSH and elevated thyroid hormone levels. What is the
probable diagnosis?
Clinical formula

- Excessive sweating, TSH , elevated levels ofbT3 and 1. Antithyroid drugs with
- Fatigue normal levels ofT4, AbsentTSH initial supplementation of
Graves' - Palpations response following a B-blocker.
disease - Insomnia intravenousTRH, Elevated 2. Surgicaltreatment.
- Tremors levels of antibodies toTPO, 3. Radioactive iodine.
- Irritability Measurement ofTRAb
 151

Diabetes mellitus
Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia due to
absolute or relative deficiency of insulin.
Type 2 DM is disorder characterized by insulin resistance and impaired insulin secretion.
Hyperglycaemia develops due to
(i) Peripheral resistance to action of insulin.
(ii) Increased hepatic glucose output.
(iii) Impaired pan- creatic β cell secretion of insulin.
Feature Type 1 DM Type2 DM

• Age of onset <40 years >40 years

• Duration of symptoms Days or weeks Months or years
• Body habitus Normal to wasted Obese
• Plasma insulin Low to absent Normal to high
• Plasma glucagon High, suppressible High, resistant
• Acute complication Ketoacidosis Hyperosmolar hyperglycaemic state
• Insulin therapy Responsive Responsive to resistant
• Sulphonylurea therapy Unresponsive Responsive
• Autoantibodies Yes No
• Other autoimmune diseases Yes No
• Family history of diabetes No Yes

Investigations
 152
Management

Glycemic management of type

2 diabetes. Agents that can be
combined with metformin
include insulin secretagogues,
thiazolidinediones, α-
glucosidase inhibitors, DPP-IV
inhibitors, GLP-1 receptor
agonists, SLGT2 inhibitors, and
insulin. HbA1c, hemoglobin
HbA1c.

Diabetic ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are

acute complications of diabetes mellitus (DM).
The cardinal biochemical features of DKA are:
● Hyperglycaemia. ● Hyperketonaemia. ● Metabolic acidosis.

Symptoms Signs
• Polyuria, thirst • Dehydration
• Weight loss • Hypotension (postural or supine), tachycardia
• Weakness • Cold extremities/peripheral cyanosis
• Nausea, vomiting • Air hunger (Kussmaul breathing)
• Blurred vision • Smell of acetone
• Abdominal pain, leg cramps • Hypothermia
• Confusion, drowsiness, coma (10%)
 153
Management

RELATED CLINICAL QUESTION

Q. A 28-year-old man with type 1 diabetes mellitus comes to the casualty due to
abdominal pain, nausea, and vomiting for the past 2 days. The patient has a history of
medical noncompliance and has not used insulin for the past 5 days. Examination
shows dry mucous membranes. Serum and urine are positive for ketones. What is the
probable diagnosis?
Glucose 400 mg/dL PaO2 84 mm Hg
pH 7.19 PaCO2 25 mm Hg
Clinical formula

U&Es, blood glucose, Insulin, Fluid

Polyuria, thirst, Weight loss, replacement, Potassium,
Diabetic Weakness, Blurred vision, plasma bicarbonate. Urine
and plasma for ketones, Cardiac rhythm should
ketoacid Dehydration, Hypotension, be monitored in severe
tachycardia, Cold extremities/ ECG, FBC,blood/urine
osis (DKA) culture,CRP, CXR, cases because of the
peripheral cyanosis, Kussmaul risk of arrhythmia,
breathing, Smell of acetone Leucocytosis
Bicarbonate:
 154

Rheumatology and Connective tissue disorders

Rheumatoid arthritis
Most common persistent inflammatory arthritis
The clinical course is prolonged, with intermittent exacerbations and remissions.
Clinical features
Insidious onset, multiple joint pain, stiffness and swelling
The typical presentation is with pain, joint swelling and stiffness
affecting the small joints of the hands, feet and wrists.
Morning stiffness, polyarthritis and pitting oedema
(more commonly in old age)

Characteristic deformities may develop with longstanding uncontrolled

disease, including ‘swan neck’ deformity, the boutonnière or ‘button hole’
deformity, and a Z deformity of the thumb
Tenosynovitis of the palms Trigger finger
Rheumatoid nodules occur almost exclusively in sero positive patients, usually
at sites of pressure or friction, such as the extensor surfaces of the
forearm , sacrum, Achilles tendon and toes.

Ulnar deviation of the fingers with wasting of the ‘Swan neck’ deformity of the fingers.
small muscles of the hands and synovial swelling
at the wrists, the extensor tendon sheaths, the
metacarpophalangeal and proximal interphalangeal
joints.
 155

Criteria for diagnosis of rheumatoid arthritis

(ACPA = Anti-citrullinated peptide antibodies;

CRP = C-reactive protein;
ESR = Erythrocyte sedimentation rate;
RF = Rheumatoid factor)
 156
Extra-articular manifestations of rheumatoid disease
Most common in patients with longstanding seropositive erosive disease
Anorexia, weight loss and fatigue
Cervical joint involvement Spine subluxation Spinal cord compression
Generalised osteoporosis and musclewasting result from systemic inflammation.
Increased levels of pro inflammatory cytokines, corticosteroid therapy and lack of
physical activity contribute to local or generalised loss of bone mass.

Osteoporosis, osteopenia and bone fractures.

Risk factors include low body weight, post menopausal women, family history of
osteoporosis, cigarette smoking and alcohol.
Degree of bone loss generally correlates with disease activity.

Laboratory investigations
Positive anti- CCP antibodies ( diagnostic)
High IgM rheumatoid Factor
High C- reactive protein & ESR
X-ray : Soft tissue swelling , joint space narrowing & bony erosions

Subluxation of cervical spine

Flexion, showing widening Extension, showing

of the space (arrow) reduction in this space. RA affecting small joints of hands
between the odontoid peg
of the axis (behind) and
the anterior arch of the
atlas (in front).
 157
Management of early rheumatoid arthritis.

ds
roi
ste
ar
Abatacept

cul

NS
Rituximab

AID
rti
Tocilizumab

a-a

a
nd
Anti-TNF #2

r
int

An
al
nd
Anti-TNF #1

ges
ra

ics
ula
usc

Combination DMARD
ram

Methotrexate + corticosteroids
Int

Diagnosis of RA
(DMARD = disease-modifying antirheumatic drug;
NSAID = non-steroidal anti-inflammatory drug;
TNF = tumour necrosis factor)

RELATED CLINICAL QUESTION

Q. A 43 yearly old woman comes to the OPD complaining of bilateral joint pain and
swelling in her hands for the past few months. She reports easy fatiguability and loss
of energy that has worsened insidiously. It is especially difficult for her to perform
daily activities in the morning due to prolonged stiffness. The patient also describes
frequent knee pain accompanied by a low grade fever. She takes over-the-counter
ibuprofen to relieve her symptoms. Her hematocrit is 33% and creatinine is normal.
The patient is at greatest risk for which of the following?
a. Avascular bone necrosis
b. Osteitis deformans
c. Osteitis fibrosis cystica
d. Osteoporosis
e. Osteosarcoma

Clinical formula

Insidious Spine
onset, Positive anti-
subluxation, Methotrexate + corticosteroids
Rheumatoid multiple joint CCP
Osteoporosis, DMARD
Arthritis pain, antibodies,
osteopenia Anti TNF
stiffness and High CRP &
and bone Abatacept, Rituximab, Tocilizumab
swelling ESR
fractures.
 158

Septic Arthritis
Most rapid and destructive joint disease
Due to haematogenous spread from either skin or upper respiratory tract;
infection from direct puncture wounds or secondary to joint aspiration
Risk factors include increasing age, preexisting joint disease , diabetes mellitus,
immunosuppression and intravenous drug misuse.
Clinical Features
Acute or subacute monoarthritis
Fever
Joint is usually swollen, hot and red, with pain at rest and on movement.
Lower limb joints, such as the knee and hip, are commonly targeted.
Patients with preexisting arthritis may present with multiple joint involvement.

In adults, particularly in patients with RA and diabetes. Staphylococcus aureus

The skin is a frequent portal of entry because of maceration

of skin between the toes due to joint deformity
In young, sexually active adults disseminated gonococcal infection,

Migratory arthralgia, lowgrade fever and tenosynovitis

Gramnegative bacilli or group B, C

In elderly and intravenous drug users and G streptococci

Laboratory investigations
Blood cultures - maybe negative
Joint aspiration
The synovial fluid is usually turbid or bloodstained but may appear normal.
Synovial fluid analysis shows inflammatory effusion with neutrophil predominance
Diagnosis is confirmed by Gram stain of synovial fluid , blood cultures, and
genital/ pharyngeal nucleus acid amplification test for Neisseria gonorrhoea
Leucocytosis with raised ESR and CRP
Serial measurements of CRP and ESR are useful in following the
response to treatment.
 159
Joint fluid characteristics
Non inflammatory Inflammatory
Normal (eg: crystals, RA)
Septic joint
(eg: OA)
Appearance Clear Clear Translucent or opaque Opaque

WBCs (mm )
3
<200 200 - 2,000 2,000 - 100,000 50,000 - 150,000

PMNs <25% 25% Often >50% >80% - 90%

Management
Admit patient to hospital and Perform urgent investigations
Synovial fluid for Gram stain and culture
Blood for culture, routine biochemistry and haematology, including ESR and CRP
IV antibiotics
Flucloxacillin (2 g IV 4 times daily) is the antibiotic of first choice
If at high risk of Gram-negative sepsis (elderly, frail, recurrent urinary
tract infection), add a cephalosporin
Relieve pain by IV analgesics, ice pack
Perform serial joint aspiration to dryness (1–3 times/day or as required)
Early regular passive movement, progressing to active movements once pain
controlled and effusion not re-accumulating

RELATED CLINICAL QUESTION

Q. A 28 yr old married woman comes to the OPD with acute pain in her left knee joint
and fever. She had mild discomfort and pain in her right wrist 4 days ago and left ankle
pain 2 days ago. The patient has had no recent respiratory illness, diarrhoea, urinary
symptoms or vaginal discharge. Temperature is 38.5 C (101.3 F), Blood pressure is
120/80mm Hg, pulse is 98/min, respiratory rate 15/min. Inspection of the knee shows
a moderate effusion and faint erythema. There is warmth and tenderness on palpating.
Range of motion is limited by significant pain. No skin lesions are present. Synovial
fluid analysis shows a white blood cell count of 50,000/mm3with a predominance of
neutrophils. What is the organism causing the diagnosis?
Clinical formula
Adults- with RA and diabetes Synovial fluid analysis Flucloxacillin
Monoarthritis Staphylococcus aureus - neutrophil
Septic Fever, Sexually active adults
Analgesics
Arthritis predominance, Joint aspiration
dermatitis, Neisseria gonorrhoea Leucocytosis with Physiotherapist
tenosynovitis Elderly and IV drug users raised ESR and CRP
Gram-ive bacilli or streptococci
 160

Gout
Inflammatory disease caused by deposition of monosodium urate monohydrate
crystals in and around synovial joints.
Hyperuricemia is the biologic hallmark of gout.
Causes of hyperuricaemia and gout

-86hPa

Clinical features
Acute monoarthritis:
Rapid onset, reaching maximum severity in 2–6 hours, and
often waking the patient in the early morning
During the attack, the joint shows signs of marked synovitis, swelling
and erythema with accom panying fever, malaise and even confusion,
especially if a large joint such as the knee is involved.
The first metatarso- phalangeal joint (podagra) is often involved.
Extraarticular tophi
Crystals may be deposited in the joints and soft tissues to produce irregular
firm nodules on extensor surfaces of fingers, hands, forearm, elbows, Achilles
tendons and sometimes the helix of the ear.
Renal impairment due to the development of interstitial nephritis as the
result of urate deposition in the kidney.
 161

Podagra. Acute gout causing swelling, erythema Tophus with white monosodium urate
and extreme pain and tenderness of the first monohydrate crystals visible beneath the skin.
metatarsophalangeal joint.

Laboratory investigations
Synovial fluid analysis : demonstration of both intra- cellular and extracellular
needle-shaped negatively birefringent MSU crystals by polarizing microscopy.
Gram stain and culture to rule out infection.
Serum uric acid: normal levels do not rule out gout.
Urine uric acid: excretion of >800 mg/d on regular diet in the absence of drugs
suggests overproduction.
Tophaceous gout may be accompanied by a modest but chronic elevation in
ESR and CRP.
Joint x-rays: may demonstrate cystic changes, erosions with sclerotic margins in
advanced chronic arthritis.

Management
ACUTE GOUTY ARTHRITIS
NSAIDs: Treatment of choice when not contraindicated.
Oral colchicine, which works by inhibiting microtubule assembly in
neutrophils, is usually given in doses of 0.5 mg twice or 3 times daily.
Joint aspiration and Intraarticular glucocorticoids ( rule out septic arthritis )
Oral or intra muscular corticosteroids can also be highly effective in
treating acute attacks.
 162
URIC ACID–LOWERING AGENTS
Indications
Recurrent frequent acute gouty arthritis, polyarticular gouty arthritis,
tophaceous gout, renal stones, prophylaxis during cytotoxic therapy.

1. Xanthine oxidase inhibitors (allopurinol, febuxostat):

Decrease uric acid synthesis.
2. Uricosuric drugs (probenecid, sulfinpyrazone):
Increases uric acid excretion by inhibiting its tubular reabsorption
Should not be used in
Age >60, renal stones, tophi, increased urinary uric acid excretion,
prophylaxis during cytotoxic therapy.
3. Pegloticase
Recombinant uricase that lowers uric acid by oxidizing urate to allantoin.

related CLINICAL question

Q. A 66 yr old man is admitted to the hospital for left lower quadrant abdominal pain,
fever and vomiting. CT scan of the abdomen reveals diverticulitis. The patient is started
on supportive care and antibiotics. His symptoms improve over 2 days , however on the
third day of hospitalisation he reports acute pain in the right ankle, which becomes
unbearable within a few hours. The patient had a similar pain 1 year ago that resolved with
over-the-counter medication. Medical history is notable for Type DM, hyperlipidemia and
hypertension. His temperature is 37 C (98.8 F), blood pressure is 140/90mmHg and pulse is
98/min. BMI is 36 kg/m. Examination shows a swollen, erythematous right ankle with
moderate restriction of movement due to pain. Both the ankles were normal at the time of
admission. What are the risk factors for the diagnosis?

Clinical formula
Synovial fluid NSAIDs,
Diuretics, analysis - Oral colchicine,
Low dose Aspirin, Negatively 1. Xanthine
Acute monoarthritis
alcohol, (Rapid onset)
birefringent MSU oxidase inhibitors
Recent Synovitis, Swelling crystals, (allopurinol,
Gout hospitalisation, Erythema Serum & Urine Uric febuxostat)
Low VIT C and Podagra, Tophus acid elevated 2. Uricosuric drugs
coffee intake, ^
CRP,ESR in (probenecid,
Lesch–Nyhan tophus, sulfinpyrazone)
syndrome Erosions in X-ray 3. Pegloticase
 163

Systemic lupus erythematosus

Disease of unknown etiology in which tissues and cells undergo damage

mediated by tissue-binding autoantibodies and immune complexes.

Clinical Features
• 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. Pts are
also at increased risk of myocardial infarction usually due to accelerated
atherosclerosis.
• Nephritis: classification is primarily histologic
• GI: peritonitis, vasculitis
• Neurologic: organic brain syndromes, seizures, psychosis, cerebritis

Severe secondary Raynaud’s phenomenon leading to

digital ulceration.
Butterfly (malar) rash of systemic lupus Examination of capillary nailfold loops using an
erythematosus, This is erythematous, raised and ophthalmoscope (and oil placed on the skin) may
painful or itchy, and occurs over the cheeks with help distinguish primary from secondary Raynaud’s.
sparing of the nasolabial folds Loss of the normal loop pattern, with capillary
‘fallout’ and dilatation and branching of loops,
supports connec tive tissue disease.
 164
Drug-Induced Lupus
Similar clinical and immunologic picture induced by drugs
Procainamide, hydralazine, isoniazid, chlorpromazine, methyldopa,
minocycline, anti-TNF agents.

Revised American Rheumatism Association criteria

A person has SLE if any 4 out of

these 11 features are present
serially or simultaneously

Laboratory investigations
Antibodies
ANA ( Sensitive)
Anti-dsDNA & anti- smith (specific)
A raised ESR, leucopenia and lymphopenia are typical of active SLE, along
with anaemia, haemo lytic anaemia and thrombocytopenia, proteinuria and
elevated creatinine
Renal biopsy if evidence of glomerulonephritis
 165
Management
Patients should be advised to avoid sun and UV light exposure and to
employ sun blocks (factor 25–50).
Mild to moderate disease
NSAID and hydroxychloroquine (200–400 mg daily)
Frequently, corticosteroids (prednisolone 5–20 mg/day), often in
combination with immunosuppressants such as methotrexate, azathio prine
or mycophenolate mofetil (MMF) are also necessary
Belimumab , B-lymphocyte stimulator (BLyS)-specific inhibitor ( limited to pts with
mild to moderate active disease.)
Life-threatening disease
Methyl prednisolone (10 mg/kg IV), coupled with cyclo phosphamide (15
mg/kg IV), repeated at 2–3weekly intervals for six cycles.
Mycophenolate mofetil has been used successfully in combination with
highdose steroids for renal involve ment in SLE
Related clinical question
Q. A 28 yr old woman comes to the casualty due to worsening headaches. She was first
evaluated for headache 4 weeks ago. At that time, examination was unremarkable and her
blood pressure was 132/86 mmHg. The patient was advised to take ibuprofen. However, she
continues to have worsening headache and reports fatigue. The patient has no fever ,
nausea, vomiting , abdominal pain, chest pain or dyspnea. She was treated for sunburn on
the face and arms 6 months ago and for sinus infection 4 weeks ago. Temperature is 37.2
C (99 F) , blood pressure is 170/110 mmHg, pulse is 82/ min and RR is 14/min. Examination
shows bilateral pitting ankle edema. Laboratory results are as follows
Complete blood count Serum chemistry
Hb 11 g/dL Blood urea nitrogen 40mg/dL
Platelets 75,000/mm Creatinine 2.5 mg/dL
Leukocytes 7,500/mm
Urinalysis
Protein 3+ C3( complement) 30 mg/dL
Bacteria none ( 88-206 mg/dL
Red blood cells 20-30/hpf
Casts Erythrocytes casts
What is the most likely diagnosis?
 166
Clinical formula

Systemic Malar “butterfly” Mild to moderate

ANA ( Sensitive)
lupus rash NSAID and hydroxychloroquine
Anti-dsDNA & anti-
erythema Photosensitivity Belimumab
smith (specific)
Life-threatening disease
-tosus Glomerulonephritis Low levels of C3
Corticosteroids with
Thromboembolic and C4
SLE events immunosuppressants
Proteinuria
Mycophenolate mofetil

Vasculitis

polyarteritis nodosa (PAN)

Multisystem, necrotising vasculitis of small and medium-sized muscular arteries.
The organ systems commonly involved are kidneys, heart, liver and
gastrointestinal tract. It does not involve pulmonary arteries.
Hepatitis B is a risk factor for PAN.
Clinical Features
Skin involvement, hypertension, renal failure, polyarthritis, myalgia,
peripheral neuropathy and mononeuritis multiplex.
Skin manifestations include tender erythematous nodules, palpable
purpura and ulcers.
Renal involvement leads to renal ischaemia, infarcts, hypertension
and renal insufficiency
Diagnosis is confirmed by finding multiple aneurysms and narrowing of the
mesenteric, hepatic or renal vessels on angiography. Muscle or sural nerve biopsy
may also be diagnostic.
Treatment is with high-dose steroids and immunosuppressants, as for SLE.

Takayasu’s disease
Granulomatous large-vessel vasculitis affecting the aorta and its major
branches, and occasionally the pulmonary arteries.
The typical age at onset is between 25 and 30 yrs, female preponderance.
The usual presentation is with claudication, fever, arthralgia and weight loss.
Examination may reveal loss of pulses, bruits and aortic incompetence.
Diagnosis is based on angiographic findings of coarctation, occlusion and
aneurysmal dilatation.
Treatment is with high-dose steroids and immunosuppressants, as for SLE.
 167

Churg-Strauss syndrome (CSS)

Allergic granulomatous angiitis or eosinophilic granulomatosis with polyangiitis is
a rare syndrome that affects small and medium-sized arteries and veins.
It is a systemic disorder characterised by asthma, transient pulmonary
infiltrates, hypereosinophilia and a systemic vasculitis.

Kawasaki disease
Vasculitis that mostly affects the coronary vessels.
Usually affecting children under 5 years

Clinical Features
Fever > 5 days + > 4 of the following
r r

Bilateral non exudate Conjunctivitis

Inflamed oral mucosa, strawberry tongue
Cervical lymphadenopathy
Generalised erythematous rash
Erythema and edema of hands/feet’s

Laboratory investigations
C- reactive protein and ESR are the inflammatory markers
that are elevated in KD which has to be done when < 3
diagnostic criteria are met in a child with > 5 days fever
Echocardiogram to rule out cardiac sequelae initially
and follow up after 2-6 weeks of treatment.
Treatment
Aspirin (5 mg/kg daily for 14 days) and intravenous
gammaglobulin (400 mg/kg daily for 4 days).
Aspirin reduces systemic inflammation and IVIg
significantly decreases risk of cardiac sequelae
Complication
Coronary artery aneurysm
Myocardial infarction & Ischemia
 168

Strawberry tongue

Peeling of skin

Related clinical question

Q. A 4 yr old boy was brought to the casualty with fever for past one week and rashes over
the trunk. Immunisations are up to date. Temperature is 40 C ( 104 F), blood pressure is
100/70 mmHg, pulse is 120/min, RR is 18/min. On physical examination, the child is awake
and alert but very cranky. The conjunctival are congested without discharge bilaterally .
There is a scant nasal congestion. The lips, tongue and oral mucosa are erythematous. S1
and S2 are normal without murmurs, lungs are clear bilaterally, abdomen is soft, non
tender and non distended. There is non tender erythema and peeling of the skin in the
perineum and inguinal folds and several erythematous, blanching macules on the trunk.
What are the diagnostic investigations to be done?

Clinical formula
Fever, generalised
rash, including Coronary
Aspirin with artery
palms and soles, CRP , ESR
Kawasaki and conjunctival Echocardiogram
intravenous aneurysm
disease injection, inflamed
immunoglobulin Myocardial
oral mucosa, infarction &
cervical Ischemia
lymphadenopathy
 169

Osteogenesis imperfecta
Autosomal dominant connective tissue disorder

Mutations in the COL1A1 and COL1A2 genes, which

encode the proteins that make up type I collagen.

mild OI severe OI
Reduced collagen production Formation of abnormal collagen
chains that are rapidly degraded

Clinical Features
Frequent fractures due to defective collagen in osteoid, osteoporosis.
Blue sclera due to thinning of sclera.
Dentinogenesis imperfecta- blue grey or yellow brown discolouration of
dentin though translucent weak enamel.
Joint hypermobility due to Ligamentous laxity
Conductive hearing loss and short stature.

The main radiographic features are osteopenia, bone fractures and bone deformities. They
result from constitutional bone fragility (cortical bone thinning, trabecular bone rarefaction)
but also from acquired bone fragility due to muscle wasting and immobilisation.
 170

Management
Surgical reduction and fixation of fractures and correction of limb deformities,
Physiotherapy for rehabilitation of patients with bone deformity.
Bisphosphonates especially IV pamidronate in children (limited evidence)

related CLINICAL question

Q. A 7 year old boy is brought to the casualty due to right leg pain. His mother says
that he was running around in the house and fell on the carpet an hour ago. The
patient has been crying and experiencing thigh pain after that. He did not hit his head
or lose consciousness. Medical history is notable for 3 fractures after seemingly
minor injuries. Temperature is 37.7 C (98 F), Blood pressure is 100/60 mmHg. Pulse
is 148/min, and RR is 20/min. On physical examination,his teeth appear translucent
and grey. There is hyperlaxity of the joints. The right thigh is markedly tender on
palpation with obvious deformity. X- ray demonstrates fracture of the proximal
femur and does not involve the growth plate which appears normal. What is the
mutation defect for this diagnosis?
Clinical formula
Mutations in History
Frequent fractures, Surgical
the COL1A1 Clinical
Osteogenesis and COL1A2 Blue sclera, reduction and
imperfecta Dentinogenesis presentation fixation of
genes
Brittle bone imperfecta, X-ray findings of fractures,
disease Joint hypermobility Fractures & bone Physiotherapy
Type 1 deformities
Osteoporosis Bisphosphonate
collagen defect

Systemic sclerosis
Multisystem disorder characterized by thickening of the skin (scleroderma) and
distinctive involvement of multiple internal organs
Diffuse cutaneous SSc Limited cutaneous SSc
Rapid development of Long-standing Raynaud’s phenomenon
symmetric skin thickening Skin involvement limited to fingers
of proximal and distal (sclerodactyly), extremity distal to
extremity, face, and trunk. elbows, and face
At high risk for May have ‘CREST’ syndrome (Calcinosis,
development of visceral Raynaud’s, oEsophageal involvement,
disease early in course. Sclerodactyly and Telangiectasia).
 171

Hands showing tight, shiny skin, sclerodactyly, Typical facial appearance in the CREST syndrome
flexion contractures of the fingers and thickening
of the left middle finger extensor tendon sheath.
Laboratory investigations
ESR is usually elevated and raised levels of IgG,
CRP values - increased in severe organ involvement or coexisting infection.
ANA is positive in about 70%,
30% of patients with DCSS have antibodies to topoisomerase 1 (Scl70).
60% of patients with CREST syndrome have anticentromere antibodies

Management
Raynaud’s should be treated by avoidance of cold exposure and calcium antagonists
Oesophageal reflux should be treated with proton pump inhibitors and antireflux agents.
Hypertension should be treated with ACE inhibitors
Joint involvement may be treated with analgesics and/or NSAID.
Pulmonary hypertension may be treated with bosentan.

Related clinical question

Q. A 36 year old woman comes to the casualty with complaints of a severe, throbbing
headache that began several hours ago. She also has acute onset of blurred vision and
nausea. She took acetaminophen, which did not provide any relief. She was diagnosed
with Raynaud phenomenon a few years ago. She recently started having heartburn, for
which she takes over-the-counter ranitidine. Her temperature is 36.7 C ( 98 F) , blood
pressure is 200/110 mmHg and pulse is 94/min. Pulse oximetry showed 94% in room
air. Ophthalmic examination demonstrates bilateral papilledema.
All her laboratory investigations were normal during her previous visit, her BP was
140/100 then. What is the most likely diagnosis?
 172
Clinical formula
Diffuse cutaneous SSc Antibodies to Calcium antagonists
Rapid symmetric topoisomerase 1 (Scl70). Proton pump inhibitors
Systemic skin thickening and antireflux agents
sclerosis Limited cutaneous SSc Anticentromere antibodies ACE inhibitors
‘CREST’ syndrome Elevated ESR, IgG, Analgesics/NSAID
ANA is positive Bosentan

Sjögren’s syndrome
Lymphocytic infiltration of salivary and lachrymal glands, leading to
glandular fibrosis and exocrine failure.
Clinical Features Risk factor
• Keratoconjunctivitis sicca • Non-erosive arthritis • Age of onset 40–60
• Xerostomia • Raynaud’s phenomenon • Female > male.
• Salivary gland enlargement • Fatigue • HLA-B8/DR3
Laboratory investigations
• Presence of autoantibodies (ANA, RF, anti-Ro/SS-A, anti- La/SS-B)
Elevated ESR and hypergammaglobulinaemia
Labial salivary gland biopsy, Schirmer’s test, Rose bengal staining.
Management
• Dry eyes: artificial tears, ophthalmic lubricating ointments
• Xerostomia: frequent sips of water, sugarless candy.
• Pilocarpine or cevimeline: may help sicca manifestations
• Hydroxychloroquine , Glucocorticoids for extraglandular manifestations

Related clinical question

Q. A 65yr old female presents to your office with a 6months history of dry mouth. She
says that she feels dry all day along and has to drink water. She also complaints of a
sandy sensation in her eyes, especially after watching TV for a while. Her past medical
history is significant for long term hypertension that is controlled with metoprolol. She
does not smoke or consume alcohol. Her recent fasting blood glucose level was normal.
The physical examination findings are within normal limits. What is the next step in
management of this patient?
Clinical formula
Keratoconjunctivitis Presence of Artificial tears
40–60 sicca autoantibodies Frequent sips of water
Sjögren’s Female. Xerostomia (ANA, RF, Pilocarpine or cevimeline
syndrome HLA-B8/DR3 Raynaud’s anti-Ro/SS-A, Hydroxychloroquine ,
phenomenon anti- La/SS-B) Glucocorticoids
 173
SARCOIDOSIS
Multisystem, chronic granulomatous inflammatory disorder of unknown aetiology.
Characterised by the accumulation of T lymphocytes and mononuclear phagocytes
and non-caseating epithelioid granulomas in the affected organs.
Two syndromes have been identified in the acute form of disease
1. Lofgren's syndrome characterised by fever, erythemanodosum, joint
symptoms and radiographic evidence of bilateral hilar adenopathy. Uveitis may
occur in some patients. It resolves over 6 months-2 years with NSAIDs.
2. Heerfordt-Waldenstrom syndrome or uveoparotid fever characterised
by anterior uveitis, parotid enlargement, fever and facial palsy.
Scadding Scoring
Stage 1: Hilar adenopathy alone, as
shown in x ray bilateral hilar
adenopathy
Stage 2: Adenopathy plus infiltrates
Stage 3: Infiltrates alone
Stage 4: Fibrosis

Extra pulmonary manifestations of sarcoidosis

 174
Investigations
1) Raised Serum ACE levels
2) Chest Xray reveals eggshell calcification.
3) Serum Vitamin D3,Calcium levels are raised.
4) KVEIM test is used to detect sarcoidosis
Management

Related clinical question

Q. A 30-year-old man comes to the office due to shortness of breath, nonproductive
cough, and fatigue for the past 3-4 weeks. He also has been urinating more than
usual. The patient has no other medical issues and currently takes no medications. He
has smoked a pack of cigarettes daily for 8 years. Vital signs are normal.
Cardiopulmonary examination shows scattered crackles but is otherwise
unremarkable. Chest x-ray reveals bilateral hilar fullness and interstitial infiltrates.
What is the most likely diagnosis?
Clinical formula
1. Lofgren's syndrome
fever, erythemanodosum, Stage 1: Hilar 1) Raised Serum Stage I : no
joint symptoms Uveitis adenopathy ACE levels treatment
2. Heerfordt-Waldenstrom Stage 2: 2) Xray eggshell Stage II &III:
SARCOIDOSIS syndrome or Adenopathy plus calcification. Prednisolone,
uveoparotid fever infiltrates 3) Serum Vit If cannot be
anterior uveitis, parotid Stage 3: Infiltrates D3,Calcium levels maintained
enlargement, fever and alone are raised. Azathioprine &
facial palsy. Stage 4: Fibrosis 4) KVEIM test methotrexate
 175

Infectious diseases including STD and HIV

pyrexia of unknown origin

Fever of at least 3 weeks' duration with daily temperature elevation above 101°F and
remaining undiagnosed after 1 week of intensive study in the hospital.

• Classic PUO: Fever of at least 3 weeks' duration with temperature recorded as more than 101
°F (38.3°C) on several occasions, and the cause is not found despite three outpatient visits or 3
days of hospitalisation or 7 days of "intelligent" ambulatory investigations.
• Nosocornial PUO: A temperature of more than 38.3°C (101°F) developing on several
occasions in a hospitalised patient who is receiving acute care and in whom infection is not
manifest or incubating on admission.
• Neutropenic PUO: A temperature of more than 38.3°C (101°F) developing on several
occasions in a patient whose neutrophil count is below 500/mL or is expected to fall to that level
in 1 or 2 days.
• HIV-associated PUO: A temperature of more than 38.3°C (101°F) developing on several
occasions over a period of more than 4 weeks for outpatients or more than 3 days for hospitalised
patients with HIV infection.

Aetiology
 176

Additional investigations in PUO

• Serological tests: autoantibodies, complement, immunoglobulins, cryoglobulins
• Echocardiography
• USS of abdomen
• CT/MRI of thorax, abdomen and/or brain
• Skeletal imaging: X-rays, CT/MRI spine, isotope bone scan
• Labelled white-cell scan
• PET scan
• Biopsy: bronchoscopic, lymph node, liver, bone marrow, temporal artery, laparoscopic

Treatment
• Treatment of underlying causes detected after investigations.
• Empirical broad-spectrum antibiotics.
• Empirical antitubercular treatment.
• Rheumatic fever and Still's disease respond dramatically to aspirin and NSAIDs.
• Temporal arteritis and polymyalgia rheumatic respond to glucocorticoids dramatically.

Dengue Fever
a.k.a Break Bone Fever
Caused by Dengue viruses 1-4 ( Flavirisues )
Principal Reservoir - Non human primates
Vectors - Mosquitos ( Aedes aegypti , A.albopictus )
Syndromes associated
i. Dengue Shock Syndrome
ii. Dengue hemorrhagic fever
IP - 4 - 7 days
Symptoms Signs
Sudden Onset fever ( High grade - 40 C) Transient Macular Rash on 1st day
Frontal Headache Adenopathy
Retroorbital pain Palatal vesicles
Back pain with severe myalgias Scleral injection

At the time of defervescence on days 3 - 5 Maculopapular rash begins on the

trunk and spreads to the extremities and the face.
Epistaxis and scattered petechiae can also be present
 177

Lab Diagnosis
Leukopenia
Thrombocytopenia
Elevated Serum Amino Transferases
4 fold rise in Anti - Dengue Ig G antibody
IgM ELISA
Antigen detection by ELISA or RTPCR

Severe Dengue
Dengue Hemorrhagic Fever and Dengue Shock Syndrome are most severe
manifestations.
Usually occurs several weeks after convalescence when transient protection against
reinfection with heterotypic dengue virus wanes.
Identified by bleeding tendencies or overt bleeding in the absence of underlying causes.
Shock is results from increased vascular permeability.

Milder cases Severe cases

Restlessness Shock is apparent lasts for 1 or 2 days
Lethargy Low pulse pressure
Thrombocytopenia ( < 1 lakh/ul ) Cyanosis
Hemoconcentration Hepatomegaly
Pleural effusions
Ascites
Treatment
Symptomatic treatment.
Advise to take rest and drink plenty of oral fluids
Most patients with shock respond to close monitoring,Oxygen administration and
infusion i.v fluids ( crystalloids or colloids )

RELATED CLINICAL QUESTION

Q. A case of Dengue was admitted and is having no pyrexia for last 24hrs and good
appetite.His BP = 110/70 mmHg. Work up shows hematocrit of 44%, TLC of 4K and
platelet count of 14K.He is having epistaxis on blowing nose that has resolved
spontaneously.What is the next best step in management of this patient ?
 178

Clinical formula

Sudden Onset fever, Frontal Leukopenia,

Symptomatic treatment.
Headache, Retroorbital pain, Thrombocytopenia
Dengue Advise to take rest and
Back pain with severe Elevated Serum Amino
drink plenty of oral fluids
Fever myalgias, Transient Macular Transferases, rise in Anti -
Oxygen administration
Rash , Adenopathy, Palatal Dengue Ig G antibody,
and infusion i.v fluids
vesicles, Scleral injection ELISA or RTPCR

MEASLES (RUBEOLA)
• Measles is caused by a paramyxovirus (RNA virus) infection.
• Mode of spread is by droplet infection.
• Incubation period is of about 10 days.
• Period of infectivity is from 4 days before and 2 days after the onset of rash. People with
compromised immunity can continue to shed virus for the entire duration of illness.
Clinical Features
• An erythematous, nonpruritic, maculopapular rash begins at the hairline and behind
the ears, spreads down the trunk and limbs to include the palms and soles, can become
confluent, and begins to fade (in the same order of progression) by day 4.
• Koplik’s spots are pathognomonic for measles and consist of bluish-white dots ~1
mm in diameter surrounded by erythema. They appear on the buccal mucosa ~2 days
before the rash appears and fade with the onset of rash.
 179
Diagnosis
• Serologic testing is the most common method of laboratory diagnosis. Measles-
specific IgM is usually detectable within 1–3 days of rash onset.
• Viral culture and reverse-transcription PCR analysis of clinical specimens are
used occasionally to detect measles.
TREATMENT
• Supportive care is the mainstay of treatment, as there is no specific antiviral
therapy for measles. Prompt antibiotic therapy for pts with secondary bacterial
infections helps reduce morbidity and mortality risks.
• Vitamin A (for children ≥12 months: 200,000 IU/d for 2 days) is recommended by
the World Health Organization (WHO) for all children with measles.

RELATED CLINICAL QUESTION

Q. A 5 yr old boy was brought to the casualty with complaints of high fever and cough
for the past 3 days. The boy had red and watery eyes. He had now developed rash over
the trunk which spreads to the limbs. On examination, erythematous, nonpruritic,
maculopapular rash present. High grade fever (104 F) . Eyes is congested, white lesions
are present on the buccal mucosa opposite the lower 1st & 2nd molars. What is the
probable diagnosis?

Clinical formula
• Serologic testing:
Erythematous, Measles- specific IgM Vitamin A (for
nonpruritic, within 1–3 days of rash children ≥12
MEASLES maculopapular rash onset. months: 200,000
Koplik’s spots • Viral culture and IU/d for 2 days)
reverse-transcription PCR

ZIKA FEVER
i. Causative agent : Zika virus (Flaviviridae)
ii. Spread by Aedes aegypti and A.albopictus
iii. Mode of transmission :
- Zika can be transmitted from men and women to their sexual partners.
- Can spread by vertical (mother to child) transmission.
- Can be transmitted through blood transfusion.
 180
Symptoms iv. Lab diagnosis : RT-PCR
Acute onset of Fever v. Prevention and control : relies on reducing mosquitoes
Red eyes (conjunctivitis) through source reduction (removal and modification of
Joint pains breeding sites) and reducing contact between mosquitoes
Headache & malaise and people.
Maculopapular rash

Maculopapular rash

Transplacnetal transmission to
baby can cause :
i. Severe microcephaly
ii. Decreased brain tissue with a specific pattern of brain damage - Microencephaly
iii. Damage to the back of the eye - Macular scarring
iv. Joints with limited range of motion, such as club foot - CTEV
v. Too much tone restricting body movements after birth - Hypertonia

RELATED CLINICAL QUESTION

Q. Transplacental transmission of the

organism given in the image which
causes microcephaly ?
 181

Clinical formula
Reducing mosquitoes
Acute onset of Fever Severe microcephaly
through source reduction
Red eyes Microencephaly (removal and modification of
ZIKA (conjunctivitis) Macular scarring Lab diagnosis : breeding sites) and
FEVER Joint pains CTEV RT-PCR reducing contact between
Headache & malaise Hypertonia
mosquitoes
Maculopapular rash
and people.

Hansen's disease (leprosy)

Chronic granulomatous disease affecting skin and nerve, and is caused by
Mycobacterium leprae.
The clinical form of the disease is determined by the degree of cell- mediated
immunity (CMI) expressed by that individual towards M. leprae.

The cardinal features are skin lesions

with anaesthesia, thickened
peripheral nerves and acid-fast
bacilli on skin smear or biopsy.

The most common skin lesions are

macules or plaques. Tuberculoid
patients have a few hypopigmented
lesions. In lepromatous leprosy,
papules, nodules or diffuse infiltration
of the skin occur. Confluent lesions
on the face can lead to a ‘leonine
facies’ Lepromatous leprosy. Widespread nodules
and infiltration with loss of the eyebrows.
This man also has early collapse of the nose.
 182
Leprosy reactions
Type 1 (reversal) reactions:
These occur in 30% of borderline patients (BT, BB, BL) and are delayed
hypersensitivity reactions.
Skin lesions become erythematous; peripheral nerves become tender and painful
with sudden loss of nerve function.
Type 2 (erythema nodosum leprosum – ENL) reactions:
Partly due to immune complex deposition, these occur in BL and lepromatous
patients who produce antibodies and have a high antigen load.
They manifest with malaise, fever and crops of small pink nodules on face and
limbs. Iritis and episcleritis are common.

Investigations
● Slit skin smears: dermal material is scraped on to a glass slide and acid-
fast bacilli may be seen on microscopy.
● Skin biopsy: histological examination may aid diagnosis.
● Neither serology nor PCR testing for M. leprae DNA is sensitive or specific
enough for diagnosis.
Management

RELATED CLINICAL QUESTION

Q. A 30 yr old women presents to the opd with pale patche on the skin and loss
of sensation over that area. On examination hypopigment hypoaesthetic patch
present on the forearm. Granulomatous inflammations is seen on
histolopathological examination.what is the probable diagnosis?
 183

Clinical formula
Macules or plaques. Tuberculoid Dapsone 2 mg/kg daily, not
exceeding 100 mg
patients have a few hypopigmented
Slit skin Clofazimine 50 mg daily or 100 mg
lesions. In lepromatous leprosy,
three times a week
leprosy papules, nodules or diffuse smears, Skin
Rifampicin, 450 mg (for those who
infiltration of the skin occur. biopsy are <35 kg) or 600 mg (for those who
Confluent lesions on the face can are <35 kg), on 2 consecutive
lead to a ‘leonine facies’ days a month.

Hydatid disease
Parasitic infection caused by Echinococcus granulosus (EG)
Characterized by cystic lesions
The liver is the most common site of echinococcal cyst, followed by the lungs
Clinical Features
Hepatic lesions often present as palpable masses or abdominal pain.
Obstruction of bile duct may result in obstructive jaundice.
Intrabiliary extrusion of calcified hepatic cysts can present with recurrent
cholecystitis.
Rupture of a hydatid into the bile duct, peritoneal cavity, lung, pleura or bronchus
may produce fever, pruritus, urticarial rash or an anaphylactoid reaction that may
be fatal.
A pulmonary hydatid may rupture producing cough, chest pain or haemoptysis.
Central nervous system involvement may produce epilepsy or blindness.

IMAGING FINDINGS
CHEST X-RAY- RUPTURE CYST
HOMOGENOUS ROUND OR OVAL EVACULATION OF CONTENTS IN
MASSES WITH SMOOTH BORDERS PARTIAL RUPTURE
SURROUNDED BY NORMAL LUNG AIR/FLUID LEVEL CAN BE SEEN
TISSUE
 184

serpent sign Water lily sign

After partial expectoration, the collapsed hydatid membranes
cyst empties and the collapsed floating on top of the residual
membranes can be seen inside the hydatid fluid.
cyst.

Treatment
• Surgical excision of the cysts is the treatment of choice.
• In inoperable cases, "high-dose" albendazole (7.5 mg/kg twice daily)
should be given for 1-3 months.
• In selected cases, percutaneous aspiration, infusion of scolicidal agents
(e.g. 95% ethanol or hypertonic saline) and reaspiration (PAIR) can be
done. It is followed by albendazole treatment for 1 month.

RELATED CLINICAL QUESTION

Q. 40 yr old smoker patient with c/c
cough,dyspnea and pleuritis chest pain for
last 2 yrs. HRCT chest is shown
below.Comment on the diagnosis ?

Clinical formula
Palpable masses or
abdominal pain, obstructive Radiological signs Surgical excision
Hydatid jaundice. Rupture cyst: Air fluid level of the cysts
disease fever, pruritus, urticarial serpent sign high-dose
rash, cough, chest pain or Water lily sign albendazole
haemoptysis, epilepsy or
blindness.
 185

Hepatitis B infection

Serological responses to hepatitis B virus infection.

(HBsAg = hepatitis B surface

antigen; anti-HBs = antibody
to HBsAg; HBeAg = hepatitis
B e antigen; anti-HBe =
antibody to HBeAg; anti-HBc
= antibody to hepatitis B core
antigen.)

Interpretation
 186

COVID-19
Causative agent : SARS-CoV-2 virus

Transmission :
- Asymptomatic carriers
- Respiratory droplets
(Coughing, sneezing)
- Contact
- Aerosols in closed spaces
Clinical features :
- Fever
- Cough
- Sore throat
- Anosmia
- Shortness of breath
- Rhinorrhea - infrequent
Complications :
(a) ARDS
(b) Acute respiratory failure
(c) Acute liver/ kidney injury
(d) DIC
(e) Secondary infection
(f) Neurological complications
Laboratory diagnosis :
a. NAATs
b. rRT-PCR : gold standard
c. True Naat : Not that sensitive (50 ~ 80 %)
d. Serological tests :
(i) Ig M and Ig G antibodies (blood samples) (iv) Elevated CRP
(ii) ELISA, immunochromatography (v) Elevated LDH, AST
(iii) Accurately assess prior infection and (vi) Lymphopenia
immunity to SARS-CoV-2 (vii) Elevated ESR
(viii) Increased bilirubin
(ix) Elevated D-dimer
 187

Management
COVID-19 Positve case

Asymptomatic/ Moderate case Severe case

very mild to ( Pneumonia with no
mild case ( Respiratory rate > 30min,
sign of severe disease ) SpO2 <90% on room air )
( Fever /URTI )
( RR 15 to 30/min,
SpO2 90 -94% )
Covid care centre

Home isolation Hospitalisation

( Consent for home
isolation be ensured )
Dedicated Covid hospital
Dedicated Covid ( Tertiary care Hospitals )
health centre
( 2 care hospitals
with O2 supply )

RELATED CLINICAL QUESTION

4.When would you admit a COVID - 19 patient aged 75yrs to a dedicated COVID health
center ?
c. RR of 25/min
a. Presence of chest discomfort
d. Presence of serious co-morbidities
b. SpO2 < 93% in room air
 188

Clinical formula
- Fever Isolate yourself
rRT-PCR : gold standard Use a mask,
- Cough Elevated CRP, Elevated
- Sore throat Take rest and drink a lot of
LDH, AST, Lymphopenia, fluids to maintain adequate
COVID 19 - Anosmia Elevated ESR, Increased
- Shortness of breath hydration.
bilirubin, Elevated D- Frequent hand washing
- Rhinorrhea dimer Alcohol-based sanitizer.

Acquired immunodeficiency syndrome (AIDS)

Acquired immunodeficiency syndrome (AIDS) is caused by a single-stranded RNA

human retrovirus known as human immunodeficiency virus. It possesses the RNA-
dependent DNA polymerase [reverse transcriptase (RT) enzyme].
HIV is transmitted:
● By sexual contact.
● By exposure to blood or blood products (e.g. drug users, patients with
haemophilia or occupationally in health- careworkers).
● Verticallyfrommothertochildinutero,duringbirth or by breastfeeding.
Routes not Involved in Transmission of HIV
• Close personal contact including kissing
• Household contact
• Contact at school, swimming pool
• Sharing of utensils and insect bites

WHO Clinical Staging of HIV Infection

Clinical stage 1
Asymptomatic
Persistent generalised lymphadenopathy
Clinical stage 2
Moderate unexplained weight loss (<10% of presumed or measured body weight)
Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis)
Herpes zoster
Angular cheilitis
Recurrent oral ulceration
Seborrhoeic dermatitis
 189

Clinical stage 3
Fungal nail infections
Unexplained severe weight loss (>10% of presumed or measured body weight)
Unexplained chronic diarrhoea for longer than one month
Unexplained persistent fever (above 37.6°C intermittent or constant for >1
month)
Persistent oral candidiasis
Oral hairy leucoplakia
Pulmonary tuberculosis
Severe bacterial infections
Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
Unexplained anaemia (<8 g/dL), neutropenia (<500/µL) or chronic
thrombocytopenia (<50,000/µL)
Clinical stage 4
HIV wasting syndrome
Pneumocystis pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection
Oesophageal candidiasis
Extrapulmonary tuberculosis
Oral Kaposi’s sarcoma.
Kaposi's sarcoma
Cytomegalovirus infection
Central nervous system toxoplasmosis
HIV encephalopathy
Extrapulmonary cryptococcosis including meningitis
Disseminated non-tuberculous mycobacterial infection
Progressive multifocal leucoencephalopathy
Chronic cryptosporidiosis (with diarrhoea)
Chronic isosporiasis
Disseminated mycosis (coccidiomycosis or histoplasmosis)
Recurrent non-typhoidal Salmonella bacteraemia
Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-associated
tumours Invasive cervical carcinoma
Atypical disseminated leishmaniasis
 190
Laboratory diagnosis :

Virological and immunological progression of HIV infection.

 191

Correlations between CD4 count and HIV-associated diseases

Treatment

Commonly used antiretroviral drugs

RELATED CLINICAL QUESTION

A 36-year-old man comes to the opd due to a month of diarrhea, nausea, and abdominal
cramps. He has also had night sweats, arthralgias, and weight loss of 6.8 kg during this
period. Pink, oval lesions developed on the patient's upper chest, neck, and face at the
beginning of the illness but have now resolved. Temperature is 38.2 C (100.8 F), blood
pressure is 112/74 mm Hg, pulse is 104/min, and respirations are 16/min. Nontender
lymphadenopathy is present in the cervical and inguinal lymph nodes. What is the
probable diagnosis?

Clinical formula

Acute seroconversion illness, Nucleoside reverse transcriptase

Asymptomatic viral carriage, inhibitors (NRTIs) Non-nucleoside
Thrombocytopenia
Persistent generalised reverse transcriptase inhibitors
AIDS lymphadenopathy, AIDS-related
Elevated liver
(NNRTIs) Protease inhibitors
enzymes
complex, Opportunistic (PIs) Integrase inhibitors
infections, Malignancies Chemokine receptor inhibitor
 192

Neurology
CSF analysis
CSF is formed from mainly the choroid plexuses of lateral, third and fourth ventricles.
Some may originate as tissue fluid formed in the brain substance.
It leaves the ventricular system through the apertures in the roof of the fourth
ventricle and flows through the cerebral and spinal subarachnoid spaces.
It is returned into venous sinuses by the arachnoid villi
Analysis of CSF is of diagnostic value. Disorders of central nervous system
and some peripheral nervous system may be made out by CSF examination.
Functions
Serves as a cushion between the CNS and surrounding bones, thus protecting CNS
against mechanical trauma.
Serves as a reservoir and assists in the regulation of intracranial volume as a buffer
Nourishment of the nervous tissue.
Removal of products of neuronal metabolism.

Components of normal CSF

CSF findings in different cuses of meningitis

 193

lumbar puncture

Diagnostic indications Therapeutic indications

Absolute Methotrexate in leukaemia
Meningitis Spinal anaesthesia
Encephalitis Benign intracranial hypertension
SAH (if CT normal) [to reduce intracranial pressure
Guillain-Barre syndrome (GB syndrome) (ICP)]
Acute demyelinating diseases
Acute disseminated encephalomyelitis
Transverse myelitis (TM)
Unexplained coma
Unexplained dementia
Relative
Multiple sclerosis
Pyrexia of unknown origin
Neurosyphilis

Contraindications
Raised ICP
Spinal deformity
Local infections
Coagulation disorders

Proper positioning of a pt
in the lateral decubitus
position. Note that the
shoulders and hips are in a
vertical plane; the torso is
perpendicular to the bed.
 194
Subacute combined degeneration of spinal cord

Also known as Lichtheim's disease or Putnam-Dana syndrome

Degeneration of the dorsal columns and lateral corticospinal tracts
Due to i. Vitamin B12 deficiency
ii. Vitamin E deficiency
iii. Copper deficiency
CLINICAL FEATURES
1. Paresthesias, sensory loss- LE>UE
2. Ataxia
3. Loss of ankle jerk
4. Memory loss
5. Reduced vision, central scotoma
6. Sphincter disturbance

+VE BABINSKI SIGN = eXTENSOR PLANTAR REFLEX

+VE RHOMBERG TEST

INVERTED V /RABBIT EAR SIGN MYELOPATHIES SHOWING

INVERTED V SIGN
MRI of the cervical spinal cord at C2 1. VIT B12 DEFICIENCY
level demonstrates bilateral 2. NITROUS OXIDE TOXICITY
symmetric signal high intensity within 3. COPPER DEFICIENCY
the dorsal columns (inverted V sign) 4. HIV VACUOLAR MYELOPATHY
5. TABES DORSALIS
6. DIABETIC MYELOPATHY

TREATMENT
Vit B12 supplementation
 195

RELATED CLINICAL QUESTION

Q. A 60 yr old man presented to opd with loss of sensation in hands and feet and
muscle weakness, especially of the legs.He has been having memory loss for the past
few months.He is a vegetarian. On examination there is loss of vibration and
proprioception in the hands and feet. Gait is affected. What is the probable diagnosis?

Clinical formula

1. Paresthesias, sensory loss- LE>UE

Subacute MRI : bilateral
2. Ataxia
combined symmetric signal high
degenerati 3. Loss of ankle jerk Vit B12
intensity within the
on of spinal 4. Memory loss supplementation
dorsal columns
cord 5. Reduced vision, central scotoma
(inverted V sign)
6. Sphincter disturbance

Neurocysticercosis
Most common parasitic disease of the nervous system
By the ingestion of food contaminated with the eggs of the parasite T. solium.
Leading cause of adult onset epilepsy
Clinical Features
• Presence of adult worm in the intestine is generally asymptomatic.
• Superficially placed cysts may be palpable under the skin or mucosa as pea-like ovoid
bodies.
• The dead larvae may invoke marked tissue response with muscular pain, weakness,
fever and eosinophilia.
• Neurocysticercosis results from brain cysts. It may manifest as meningoencephalitis,
epilepsy, personality changes, staggering gait, space-occupying lesion, stroke (due to
inflammatory changes in the wall of intracranial arteries located in the vicinity of
cysticerci) or hydrocephalus.

MRI T2 image showing neurocysticercosis Diagnosis Multiple neurocysticercosis showing 'starry sky appearance'
 196

Stages Inflammatory Cyst wall Scolex

rection
Remarks
Mild Non enhancing, Viable
Vesicular inflammatory well defined Hole with dot
stage appearance larva
reaction

Severe
Colloidal Larval
inflammatory Ring enhancing, Degenerating degeneration
stage reaction perilesional edema scolex

Eosinophilia
Focal nodular
Granular Astro enhancing necrotic Degenerating structure,
gliosis scolex bladder
stage lesion also with scolex in
edema disintegration

Calcified
calcified nodule Small hyper dense nodules without
stage Intense gliosis perilesional edema

Diagnosis
• Eggs and proglottids in stool.
• Soft tissue radiographs may show calcified cysts (cigar-shaped) in muscles.
• CT scan of the brain may show calcified spots, solid nodules, cystic lesions containing a
scolex or hydrocephalus.
• CT scan is more sensitive than MRI in identifying calcified lesions, while MRI is better
for identifying cystic lesions and enhancement.
• CSF shows mononuclear pleocytosis and presence of eosinophils.
• In CSF, specific enzyme-linked immunoelectrodiffusion transfer blot (EITB) using
lentil lectin purified glycoproteins is highly sensitive and specific.
• Histological examination of the excised subcutaneous nodule can establish a specific
diagnosis.
Treatment
IV DEXAMETHASONE- along with Mannitol followed by oral prednisolone
Antiparasitic agents- PRAZIQUNTEL, ALBENDAZOLE

RELATED CLINICAL QUESTION

Q. A 46-year-old man is brought to the casualty due to a generalized tonic-clonic
seizure. He has spent 3 months with rural pig farmers. The patient is drowsy and
postictal. EEG shows epileptiform activity. MRI of the brain demonstrates several
intraparenchymal, 5- to 10-mm cystic lesions with surrounding edema. There is no mass
effect or midline shift. A rapid HIV test is negative.what is the probable diagnosis?
 197

Clinical formula
CT scan of the brain,mCSF
Meningoencephalitis, shows mononuclear pleocytosis
epilepsy, personality and presence of eosinophils, In IV DEXAMETHASONE
Neurocysti changes, staggering
cercosis CSF, specific enzyme-linked PRAZIQUNTEL,
gait, space-occupying immunoelectrodiffusion transfer ALBENDAZOLE
lesion, stroke or blot (EITB) using lentil lectin
hydrocephalus. purified glycoproteins

Bell's palsy.
Bell’s palsy is an acute, apparently isolated, lower motor neuron facial palsy for
which no cause can be found. Presumed to be viral due to HSV 1 (viral genomic
sequences detected).
Clinical features
• Paralysis of all the muscles of facial expression on the side of palsy.
• Drooping of corner of mouth, effacement of creases and skin fold on the affected side.
• Weakness of frowning and eye closure as the upper facial muscles are weak.
• Drooling of saliva from angle of mouth.
• On asking the patient to show his teeth, the angle of mouth deviates away from the
side of lesion.
• Upon attempted closure of the eyelid, the eye on the paralysed side rolls upwards
(Bell's phenomenon).
• Corneal ulceration due to inability to close the eye during sleep.
 198

Investigations
• No specific confirmatory diagnostic procedure.
• Electrophysiological tests (EMG or electromyography) may help in prognostication.
• To rule out alternate diagnosis, appropriate diagnostic procedures maybe necessary.

Treatment
• If patient is seen early (within 3 days), a short course of prednisolone maybe given.
Usually, prednisolone is given at 1 mg/kg/day for the 1st week, with the dosage
tapering off over the 2nd week.
• Addition of acyclovir does not alter recovery.
• Adhesive tape to keep the eye closed so as to prevent corneal ulceration.

Ramsay Hunt syndrome

Aetiology
Herpes zoster of geniculate ganglion

Clinical Features
• Onset is with severe pain in external ear,
followed by appearance of vesicles in the
external auditory meatus, and occasionally on
tongue and pharynx, along with LMN facial
paralysis.
Eighth nerve palsy maybe associated leading
to nausea, vomiting, vertigo, nystagmus,
tinnitus and hearing loss.
• Complete recovery is less likely than in
Bell's palsy.
Treatment
• Analgesics.
• Oral acyclovir 800 mg five times a day is useful if started early (within 72 hours)
along with corticosteroids.
• Other agents are famciclovir (500 mg three times a day) and valaciclovir (1 g
three times a day).
• ldoxuridine (5% solution) maybe applied over the vesicles in early stages.
 199
RELATED CLINICAL QUESTION
Q.A 48-year-old man comes to thecasualty due to facial drooping and he had difficulty
closing the left eye to the sunlight while driving to work. Four hours later, he was unable
to sip drinks through a straw.On physical examination, there is left facial asymmetry
with drooping of the left corner of the mouth and flattening of the nasolabial fold. He is
unable to fully close the left eye.What is the probable diagnosis?
Clinical formula
Paralysis of all the muscles of EMG or Prednisolone,
facial expression, Drooping of electromyography acyclovir.
Bell’s corner of mouth, Weakness of To rule out alternate Adhesive tape to
palsy frowning and eye closure, diagnosis, appropriate keep the eye closed
Drooling of saliva from angle of diagnostic procedures so as to prevent
mouth, angle of mouth maybe necessary. corneal ulceration.
deviates, Bell's phenomenon.

EPILEPSY
Brief recurrent disorder of cerebral function that is usually associated with
disturbance of consciousness and accompanied by a sudden, excessive electrical
discharge of cerebral neurones..
 200
status epilepticus
• Status epilepticus denotes sustained epileptic activity, and is clinically diagnosed with
one of the following two:
• Two fits occur without recovery of consciousness in between.
• A single fit lasts longer than 30 minutes with or without loss of consciousness.
• Condition is fatal or results in severe morbidity if not treated rapidly.
Causes
• Sudden antiepileptic withdrawal
• Metabolic disorders-hypoglycaemia and hyponatraemia
• Alcohol or benzodiazepine withdrawal
• Infections-encephalitis and meningitis
• Occasionally, brain tumour or trauma
• Priority should be to control seizures as fast as possible, along with
identification of an underlying cause and its correction.
• Simultaneously, BP, acidosis, ventilation and electrolyte balance are taken care of.
Underlying cause should be rectified appropriately.

Investigations
Cerebral imaging: After a single seizure, head CT or MRI is advisable
EEG: performed very soon after a seizure than after an interval. help establish the
type of epilepsy and guide therapy;
Other investigations: These should identify any metabolic, infective, inflammatory or
toxic causes. They include FBC, ESR, CRP, U&Es, glucose, LFTs, CXR, syphilis serology,
HIV, tests for collagen disease and CSF examination.

Guidelines for choice of anti-epileptic drugs

 201
Management
 202
RELATED CLINICAL QUESTION
Q. A 23-year-old man is brought to the casualty for a seizure. According to a witness, he
fell on the sidewalk while leaving a pub and had rhythmic movements of the extremities for
about 2 minutes. In the emergency department, the patient is lethargic and confused but
follows simple commands. His temperature is 37.3° C (99.2° F), blood pressure is 122/70
mm Hg, and pulse is 97/min. The pupils are equal and reactive to light. He moves all his
extremities, and the deep-tendon reflexes are symmetric. What is the probable diagnosis?

Clinical formula
Altered consciousness , epileptic cry. Fit starts 1st line
Head CT or MRI, Focal onset GTCS
simultaneously with gener alised tonic state,
EEG, FBC, ESR, Lamotrigine
unconscious and cyanosed, does not breathe, pupils GTCS
are dilated followed by clonic state where rhythmic CRP, U&Es,
EPILEPSY jerks appear,, Tongue maybe bitten and urinary or glucose, LFTs,
Sodium valproate
Levetiracetam
bowel incontinence may occur followed by postictal CXR, CSF Absence Myoclonic
phase where patient passes off into sleepy state and examination. Ethosuximide Sodium
may have headache and vomiting. valproate

STROKE
An ischemic deficit that resolves rapidly without radiologic evidence of an infarction is
termed a transient ischemic attack
risk factors
 203

Clinical features
Unilateral weakness is the classical presentation of stroke. The weakness starts
suddenly, and progresses rapidly in a hemiplegic pattern.
Dysphasia and dysarthria are the usual speech manifestations in stroke.
Monocular blindness in stroke can be caused by reduced blood flow in the internal carotid
or ophthalmic arteries.
Stroke causing damage to the cerebellum and its connections can present as acute
ataxia.
Sudden severe headache is the cardinal symptom of subarachnoid haemorrhage but also
occurs in intracerebral haemorrhage.
Seizure is unusual in acute stroke but may occur in cerebral venous disease.
Coma is an uncommon feature of stroke, though it may occur with a brainstem event.

Rounded boxes are

diagnoses; rectangles
are interventions.
Numbers are
percentages of stroke
overall. ABCs, airway,
breathing, circulation;
bp, blood pressure;
CEA, carotid
endarterectomy; ICH,
intracerebral
hemorrhage; SAH,
subarachnoid
hemorrhage; TIA,
transient ischemic
attack.
 204
Acute stroke management

Wallenberg's syndrome
(lateral medullary syndrome)
Due to an infarct that is located at dorsolateral medulla and occurs due to occlusion
of posterior inferior cerebellar artery, its branch or parent vertebral artery itself.
Symptoms consist of sudden onset vertigo, vomiting, dysphagia and ataxia.

ipsilateral signs Contralateral signs

• Facial numbness (VII) • Analgesia over trunk and extremities
• Diplopia (VI) (spinothalamic)
• Nystagmus • Hemiparesis (mild, unusual)
• Ataxia (cerebellar)
• Homer's syndrome
• Palatal palsy (IXth and Xth nerve lesions)
 205
Glasgow Coma Scale
Conscious level should be measured using the Glasgow Coma Scal
Useful for grading severity of brain injury.

Coma score = E + M + V. Patients

scoring 3 or 4 have an 85%
chance of dying or remaining
vegetative, whereas scores >11
indicate only a 5–10% likelihood
of death or vegetative state and
85% chance of moderate
disability or good recovery.
Intermediate scores correlate with
proportional chances of recovery.

RELATED CLINICAL QUESTION

Q. A 68-year-old man is brought to the casualty for acute right-sided hemiplegia,
headache, and impaired consciousness. His symptoms started an hour ago and are
progressively getting worse. His medical problems include obesity, gout, benign prostatic
hyperplasia, benign essential tremor, hypertension, and hypercholesterolemia. The
patient's medications include allopurinol, tamsulosin, propranolol, amlodipine, and
simvastatin.Neurological examination shows right-sided weakness and hemi-sensory loss.
There is a carotid bruit on his left side. What is the probable diagnosis?

Clinical formula
Full blood count, ESR, Blood
Unilateral weakness glucose, urea, proteins, Chest X- Antiplatelet agents-
Dysphasia and dysarthria ray, ECG Combination of aspirin and
STROKE Monocular blindness, CT scan or diffusion weighted MRI clopidogrel
acute ataxia. of head,Carotid Doppler Correction of risk factors,
Sudden severe headache Arteriography, CT or MR Anticoagulants, Surgery-
Seizure , Coma angiography, Antinuclear factors, carotid endarterectomy.
Cholesterol, Coagulation studies
 206
Subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) accounts for about 10% of strokes. In more

than 80% of cases, it is due to rupture of aneurysms located at circle of Willis or
its main branches.
Clinical Features
Sudden, severe ‘thunderclap’ headache (often occipital), which lasts for hours or even
days, often accompanied by vomiting.
Physical exertion, straining and sexual excitement are common antecedents.
Usually the patient is distressed and irritable, with photophobia, but there may be
loss of consciousness.
Neck stiffness, focal hemisphere signs and subhyaloid haemorrhage on fundoscopy
may be found.

Investigations
CT Scan- shows blood in the subarachnoid space (if done in the first few days) and
presence of intracerebral haematoma, hydrocephalus, associated brain ischaemia and
occasionally location of aneurysm itself.
Lumbar Puncture- CSF will be uniformly blood stained in the initial hours and becomes
xanthochromic in later days (first appears after 4-6 hours of the bleed).
Angiography- It is needed to locate the site of aneurysm
CT Angiography- A rapid, readily available, less invasive alternative to catheter
angiography and is equivalent to conventional angiography for demonstrating larger
aneurysms.
Management
Immediate administration of antifibrinolytic agent tranexamic acid (1 g IV, followed
by 1 g every 6 hours) maybe useful to reduce the rate of early aneurysm re-
bleeding.
Pain management, sedation and control of hypertension are also important in the
prevention of aneurysm re-bleeding.
In conscious patients without evidence of raised ICP, active hypertension treatment
is indicated.
Calcium blocking agent nimodipine (60 mg orally every 4 hours) provides a modest
but significant improvement in outcome by reducing cerebral arterial vasospasm.
Anticonvulsants are recommended for prophylaxis.
Absolute bed rest for 4 weeks is advised
 207

RELATED CLINICAL QUESTION

Q. A 40-year-old man comes to the casualty due to severe
headache associated with photophobia and nausea for the
past several hours. The patient reports mild cold
symptoms a week ago. He has a 2-year history of
hypertension and has smoked a pack of cigarettes daily for
15 years. His father died of stroke at the age of 75.
Temperature is 37.7 C (100 F), blood pressure is 170/100
mm Hg, and pulse is 92/min and regular. He appears to be
uncomfortable and had an episode of nonbilious vomiting in
the casualty. Neurologic examination shows 4/5 motor
strength and 2+ deep tendon reflexes bilaterally in the
upper and lower extremities. What is the diagnosis?
Clinical formula
Sudden, severe Antifibrinolytic agent
‘thunderclap’ CT Scan tranexamic acid
headache, vomiting. Lumbar Puncture Pain management, sedation
Subarachnoid
haemorrhage distressed and Angiography and control of hypertension
irritable, with CT Angiography Calcium blocking agent
photophobia, Neck nimodipine
stiffness Anticonvulsants
 208

Wernicke's encephalopathy.
Wemicke's encephalopathy is an acute neuropsychiatric condition due to an initially
reversible biochemical brain lesion caused by depletion of vitamin B1 (thiamine).
Causes
• Chronic alcohol use
• Protein-calorie malnutrition from malabsorption or forced/self-imposed inadequate diet
• Patients with protracted vomiting
• Carbohydrate loading (intravenous or oral) when thiamine stores are minimal
• Chronic renal failure
• Hyperalimentation, AIDS, and drug misuse
• Genetic abnormality of transketolase enzyme

Clinical Features
• Mental disturbances:
• Progressive depression of the state of consciousness.
• Global confusional apathetic state, profound listlessness,
inattentiveness and disorientation.
• Paralysis of eye movements:
• Vlth nerve palsy and diplopia.
• Nystagmus.
• Internuclear ophthalmoplegia.
• Ataxia of gait-this affects stance and gait predominantly.
Management
• Immediate administration of thiamine.
• Magnesium is often required as it is a cofactor required for normal functioning of
thiamine-dependent enzymes.
• Intravenous glucose solutions should not be given particularly in malnourished
patients, as they may exhaust the patient's reserve of B vitamins and either
precipitates Wernicke's disease in a previously unaffected patient or cause a rapid
worsening of an early form of the disease.

Korsakoff's psychosis is the psychic component of Wernicke's encephalopathy.

When both the ocular ataxic and amnesic symptoms can be recognised the
disease is designated as Wernicke-Korsakoff syndrome.
 209

NEURODEGENERATIVE DISEASES

Alzheimer’s disease
Progressive neurodegenerative disease resulting in decline in cognitive functions
together with declining activities of daily living (ADL) and behavioural disturbances.
It is the most common cause of cognitive impairment in elderly persons.
Aetiology
Genes that increase the probability of sporadic Alzheimer's disease include the
allele E4 of apolipoprotein E (APOE) and the sortilin-related receptor l . (SORL
l ) gene (which is involved in cholesterol transport, 13-amyloid formation and
APP processing).
Early onset of Alzheimer's disease (onset < 60 years) is uncommon and is usually
autosomal dominant. Three gene mutations have been identified: APP gene located on
the chromosome 21; the presenilin-1 (PSI) and presenilin-2 (PS2) genes located on
chromosomes 14 and 1 respectively.
Clinical features
The key feature is impairment of the ability to remember new information.
Memory impairment is gradual and usually associated with disorders of other cortical
functions.
Both short-term memory and long-term memory are affected.
Later in the disease, patients commonly deny their disabilities, and additional
features are apraxia, visuo-spatial impairment, depression and aphasia.
management
Investigation is aimed at excluding the less common treatable causes of dementia
Anticholinesterases (donepezil, rivastigmine, galantamine) and the NMDA receptor
antagonist memantine have been shown to be of some benefit.
Depression should be treated with antidepressants. Support for carers is crucial.

Parkinson’s Disease
Parkinsonism is a clinical syndrome involving bradykinesia, plus at least one of
the following three features: tremor, rigidity and postural instability.
All patients with Parkinson's disease have parkinsonism, but not all patients with
parkinsonism have Parkinson's disease.
 210
Causes

Clinical features
The presentation is usually asymmetrical, e.g. a resting tremor in an upper limb.
Typical features of an established case include:
Bradykinesia: Slowness in initiating or repeating movements, impaired fine
movements (causing small handwriting) and expressionless face. The patient is slow to
start walking, with reduced arm swing, rapid small steps and a tendency to run
(festination).
Tremor: Present at rest (4–6 Hz), diminished on action; it starts in the fingers/thumb
and may affect arms, legs, feet, jaw and tongue.
Rigidity: Cogwheel type mostly affects upper limbs; plastic (lead-pipe) type mostly
affects legs.
Non-motor symptoms may precede typical motor symptoms and include:
● Depression
● Anxiety TRAP:
● Cognitive impairment Tremor at rest,
Rigidity,
Akinesia (or bradykinesia)
Postural instability.

Investigations
Diagnosis is clinical.
CT may be needed if any features suggest pyramidal, cerebellar or autonomic
involvement, or if the diagnosis is in doubt, but is usually normal for age.
Patients <50 yrs should be tested for Wilson’s disease and Huntington’s disease.
 211

Management

RELATED CLINICAL QUESTION

Q. A 57-year-old man comes to the opd due to involuntary shaking of his hands. It
started on the right side, but now his left hand shakes as well. The shaking
disappears with purposeful activity and worsens with emotional stress. He does not
have a family history of tremors. Physical examination reveals a resting hand
tremor with a frequency of 5-7 cycles/sec. There is some muscle rigidity of both
arms. His gait and posture are normal.what is the probable diagnosis?

Clinical formula

Tremor at rest, Levodopa together with a

CT may be needed if any
Rigidity, peripheral-acting dopa-
Parkinson’s features suggest
Akinesia (or decarboxylase inhibitor.
Disease pyramidal, cerebellar or
bradykinesia) Levodopa is particularly
autonomic involvement
Postural instability. effective at improving
bradykinesia and rigidity.
212
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