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Harrison Textbook Updates

Hematology
PRIMARY HEMOSTATIC (PLATELET PLUG) DISORDERS

Defects of Platelet Adhesion


Von Willebrand disease
Bernard-Soulier syndrome (absence or dysfunction of platelet Gp Ib-IX-V)
Defects of Platelet Aggregation
Glanzmann‟s thrombasthenia (absence or dysfunction of platelet glycoprotein [Gp] IIb/IIIa)
Afibrinogenemia
Defects of Platelet Secretion
Decreased cyclooxygenase activity
Drug-induced (aspirin, nonsteroidal anti-inflammatory agents, thienopyridines)
Inherited
Granule storage pool defects
Inherited
Acquired
Nonspecific drug effects
Uremia
Platelet coating (e.g., paraprotein, penicillin)
Defect of Platelet Coagulant Activity
Scott‟s syndrome

DISEASES ASSOCIATED WITH MASSIVE SPLENOMEGALYa


Chronic myeloid leukemia GAUCHER‟S DISEASE
Lymphomas CHRONIC LYMPHOCYTIC LEUKEMIA
Hairy cell leukemia SARCOIDOSIS
Myelofibrosis with myeloid metaplasia AUTOIMMUNE HEMOLYTIC ANEMIA
Polycythemia vera DIFFUSE SPLENIC HEMANGIOMATOSIS
a
The spleen extends > 8 cm below the left costal margin and/or weighs > 1000 g.

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Physiological Classification of Anemia Based on Reticulocyte Production Index

Anemia

CBC, reticulocyte count

Index < 2.5


Index < 2.5

Hemolysis/hemorrhage
Red cell morphology

Blood loss
Normocytic Intravascular hemolysis
Micro or
Normochromic
macrocytic
Metabolite defect

Hypoproliferative Maturation disorder Membrane abnormality

Hemoglobinopathy
Marrow damage Cytoplasmic defects
 Infiltration/fibrosis  Iron deficiency Immune destruction
 Aplasia  Thalassemia
Iron deficiency  Sideroblastic anemia Fragmentation hemolysis

 Stimulation Nuclear defects


 Inflammation  Folate deficiency
 Metabolic defect  Vitamin B12 deficiency
 Renal disease Drug toxicity
 Refractory anemia

IMPORTANT POINTS

 The World Health Organization defines anemia as a hemoglobin level <13 g/dL in men and <12
g/dL in women.
 Normal reticulocyte count is 1-2%
 Prematurely released reticulocytes into the circulation are called “shift cells”.
 The normal serum iron range from 50-150 µmol/dL, whereas the normal TIBC is 300-360 g/dL;
the normal transferring saturation ranges from 25 to 50%.
 The minimum number of stem cells necessary to support hematopoiesis is estimated to be 400-
500 at any one time.

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Hematopoietic disorders
CLASSIFICATION OF PURE RED CELL APLASIA

Self-limited
Transient erythroblastopenia of childhood
Transient aplastic crisis of hemolysis (acute B19 parvovirus infection)
Fetal red blood cell aplasia
Nonimmune hydrops fetalis (in utero B19 parvovirus infection)
Hereditary pus red cell aplasisa
Congenital pure ted cell aplasia (Diamond Blackfan anemia)
Acquired pure red cell aplasia
Cancer
Thymoma
Lympjhoid malignancies (and more rarely other hematologic diseases)
Parancoplastic to solid tumors.
Connective Tissue Disorders
SLE
JRA,RA
Viruses
Persistent Parvovirus B19,hepatitis,EBV
DRUGS
Phenytoin,azathioprine,chloramphenicol,INH,Procainamide

DISORDERS CAUSING MYELOFIBROSIS

Malignant Nonmalignant
Acute leukemia (lymphocytic, myelogenous, megakaryocytic) HIV infection
Chronic myeloid leukemia Hyperparathyroidism
Hairy cell leukemia Renal osteodystrophy
Hodgkin‟s disease Systemic lupus
Primary myelfibrosis erythematous

Lymphoma Tuberculosis

Multiple myeloma Vitamin D deficiency

Myebdysplasia. Thorium dioxide exposure

Metastatic carcinoma Gray platelet syndrome

Polycythemia vera
Systsemic mastocytosis
Systemic mastocyrosis

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DIAGNOSIS OF MICROCYTIC ANEMIA

Tests Iron Deficiency Inflammation Thalassemia Sideroblastic


Anemia
Smear Micro/hypo Normal Micro/hypo with Variable
micro/hypo targeting
Serum iron <30 <50 Normal to high Normal to high
(g/dL)
TIBC (g/dL) >360 <300 Normal Normal
Percent <10 10-20 30-80 30-80
saturation
Ferritin (g/L) <15 30-200 50-300 50-300
Hemoglobin Normal Normal Abnormal with 2 Normal
pattern on thalassemia; can
electrophoresis be normal with a
Thalassemia

CLASSIFICATION OF ACQUIRED IMMUNE HEMOLYTIC ANEMIAS

TYPE OF ANITBODY
Clinical Setting Cold, Mostly IgM, Optimal Warm, Mostly IgG, Optimal
Temperature 4-30oC temperature 37oC; or mixed
Primary CAD AIHA (idiopathic)
Secondary to viral infection EBV HIV
CMV Viral vaccines
Other
Secondary to/associated with CAD in : AIHA in :
other disease Waldenstrom‟s disease SLE
Lymphoma CLL
Other malignancy
Chronic inflammatory disorders
(e.g., IBD)
After allogeneic HSCT
Secondary to drugs : Small minority (e.g., with Majority: currently most
Drug-induced immune lenalid-drugs : common culprit drugs are
cefotetan, ceftriaxone,
Hemolytic anemia piperacillin
Drug-dependent: antibody destroys red cells only when drug
present (e.g., rarely penicillin)
Drug-independent : antibody can destroy red cells even when drug
no longer present (e.g., methyldopa)

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Abbreviations : AIHA-autoimmune hemolytic anemia; CAD-Cold agglutinin disease; CLL-Chronic
lymphocytic leu7kemia; CMV-cytomegalovirus; EBV-Epstein-Bar virus HIV human
immunodeficiency virus. HSCT. Hematopoietic stem cell transplantation IBD-inflammatory bowel
disease: SLE-Systemic lupus erythematosus.

DIFFERENTIAL DIAGNOSIS OF PANCYTOPENIA

Pancytopenia with Hypocellular Bone Marrow


Acquired aplastic anemia
Constitutional aplastic anemia (Fanconi anemia, dyskeratosis congenital)
Some myelodysplasia
Rate aleukemic leukemia
Some acute lymphoid leukemia
Some lymphomas of bone marrow

Pancytopenic with Cellular Bone Marrow

Primary bone marrow diseases


Myelodysplasia
Paroxysmal nocturnal
Hemoglobinuria
Myelofibrosis
Some aleukemic leukemia
Myelophthisis
Bone marrow lymphoma
Hairy cell leukemia
Secondary to systemic diseases
Systemic lupus erythematosus
Hypersplenisms
B12, folate deficiency
Overwhelming infections
Alcohol
Brucellosis
Sarcoidosis
Tuberculosis
Leishmaniasis
Hypocellular Bone Marrow + cytopenia
Q fever
Legionnaires‟ disease

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Anotexia nervosa, starvation


Mycobacterium

CAUSES OF THROMBOCYTOSIS

Tissue inflammation, collagen vascular disease, Hemorrhage


inflammatory bowel disease
Malignancy Iron-deficiency anemia
Infection Surgery
Myeloproliferative disorders: polycytemia vera, Rebound : Correction of vitamin B12, or folate
primary myelofibrosis, essential thrombocytosis, deficiency, post, ethanol abuse
chronic myelogenous leukemia
Myelodysplastic disorder : 5q-syndrom,idiopathic Hemolysis
refractory sideroblastic anemia
Prostsplenectomy or hyposplatnim Familial : Thrombopoietin over-production, MPL
mutations.

INFECTIOUS AGENTS ASSOCIATED WITH THE DEVELOPMENT OF LYMPHOID


MALIGNANCIES

Infectious Agent Lymphoid Malignancy


Epstein-Barr virus Burkitt‟s lymphoma
Post-organ transplant lymphoma
Primary CNS diffuse large B-cell lymphoma
Hodgkin‟s lymphoma
Extranodal NK/T-cell lymphoma, nasal type

HTLV-1 Adult T-cell leukemia/lymphoma


HIV Diffuse large B-cell lymphoma
Burkitt‟s lymphoma

Hepatitis C virus Lymphoplasmacytic lymphoma


Helicobacter pylori Gastric MALT lymphoma
Human herpesvirus 8 Primary effusion lymphoma
Multicentric Castleman‟s disease
Abbreviations: CNS, centrla nervous system; HIV, human immunodeficiency virus; HTLV, human
T-cell lymphotropic virus; MALT, mucosa-associated lymphoid tissue; NK, natural killer.

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THE ANN ARBOR STAGING SYSTEM FOR HODGKIN’S LYMPHOMA

Stage Definition
I Involvement of a single lymph node region or lymphoid structure (eg., spleen, thymus,
Waldeyer‟s ring)
II Involvement of two or more lymph node regions on the same side of the diaphragm (the
mediastinum is a single site; hilar lymph nodes should be considered “lateralized” and, when
involved on both sides, constitute stage I disease)
III Involvement of lymph node regions or lymphoid structure on both sides of the diaphragm
III1 Subdiaphragmatic involvement limited to spleen, splenic hilar nodes, celiac nodes, or portal
nodes
III2 Subdiaphragmatic involvement includes paraaortic, iliac, or mesenteric nodes plus structures
in III1
IV Involvement of extranodal site(s) beyond that designated as “F” More than one extranodal
deposit at any location Any involvement of liver or bone marrow
A No symptoms
B Unexplained weight loss of > 10% of the body weight during the 6 months before staging
investigation
Unexplained, persistent, or recurrent fever with temperatures >38oC during the previous
month
Recurrent drenching night sweats during the previous month
E Localized, solitary involvement of extra lymphatic tissue, excluding liver and bone marrow

IMPORTANT POINTS
 Most common type of Non-Hodgkin‟s lymphoma is Diffuse large B cell lymphoma.
 Most common presentation of mantle cell lymphoma is palpable lymphadenopathy
 Most common presentation for follicular lymphoma is with new, painless lymphadenopathy
 Most common site of MALT lymphoma is stomach.
 Most common lymphoid leukemia is B cell CLL/small lymphocytic lymphoma.
 Patients with hairy cell leukemia are prone to unusual infections, including infection by
Mycobacterium avium intracellulare.
 In Adult T-cell lymphoma/leukemia, peripheral smear reveals characteristic, pleomorphic
abnormal CD4-positive cells with indented nuclei, which have been called “flower” cells.
 Most common initial manifestation of Hodgkin‟s lymphoma is mediastinal lymphadenopathy.
 Most important cytokine involved in myeloma cell proliferation is IL-6
 Most common symptom of myeloma is bone pain.
 Most common infections in myeloma patients are pneumonias and pyelonephritis
 Most common cause of renal failure in myeloma patients is hypercalcemia.
 Earliest manifestation of renal tubular damage in multiple myeloma is Fanconi‟s syndrome.
 Normocytic normochromic anemia occurs in ~80% of myeloma patients.

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 Most common serum M component in multiple myeloma is IgG.
 Serum Beta 2 microglobulin is the single most powerful predictor of survival in multiple
myeloma
 International Staging System (ISS) for myeloma is based on serum Beta 2-microglobulin and
albumin levels.

DIAGNOSTIC CRITERIA FOR MULTIPLE MYELOMA, MYELOMA VARIANTS, AND


MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE

Monoclonal Gammopathy of Undetermined Significance (MGUS)


M protein in serum <30 g/L
Bone marrow clonal plasma cells <10%
No evidence of other B cell proliferative disorders
No myeloma – realated organ or tissue impairment (no end organ damage, including bone lesions)a
Smoldering Multiple myeloma (Asymptomatic Myeloma)
M protein in serum >30g/L and/or
Bone marrow clonal plasma cells >10%
No myeloma – related organ or tissue impairment (no end organ damage, including bone lesions)a or
symptoms
Symptomatic Multiple Myeloma
M protein in serum and / or urine
Bone marrow (clonal) plasma cellsb or plasmacytoma
Myeloma – related organ or tissue impairment (end organ damage, including Bone lesions)
Non secretory Myeloma
No M protein in serum and/or urine with immunofixation
Bone marrow clonal plasmacytosis >10% or plasmacytoma
Myeloma-related organ or tissue impairment (end organ damage, including bone lesions)
Solitary Plasmacytomsa of Bone
No M protein in serum and/or urinef
Single area of bone destruction due to clonal plasma cells
Bone marrow not consistent with multiple mycloma
Normal skeletal survey (and magnetic resonance imaging of spine and pelvis if done)
No related organ or tissue impairment (no end organ damage other than solitary bone lesion)a
POEMS Syndrome
All of the following four criteria must be met
1. Polyneuropathy
2. Monoclonal plasma cell proliferative disorder
3. Any one of the following: (a) organomegaly (splenomegaly, hepatomegaly, or lymph-
adenopathy); (b) extravascular volume overload (edema, pleural effusion, or ascites); (c)
endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, and pancreatic); (d) skin
changes (hyperpigmentation, hypertrichosis, glomeruloid hemangiomata, plethora, acrocyanosis,

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flushing, and white nails); (e) papilledema; (f) thrombocytosis/polycythemiad
a
Myloma-related organ or tissue impairment (end organ damage); calcium levels increased serum
calcium >0.25 mmol/L above the upper limit of hormal or >2.75 mmol/L; renal insufficiency:
creatinine >173 mmol/L; anemia: hemoglobin 2 g/dL below the lower limit of normal or hemoglobin
>10g/dL; bone lesions: lytic lesions or osteoporosi with compression fractures (magnetic resonance
imaging or computed tomography may clarigy); other: symptomatic hyperviscosity, amyloidosis,
recurrent bacterial infection (>2 episodes in 12 months). bIf flow cytometry is performed, most plasma
cells (>90%) will show a “neoplastic” phenotype. cA small M component may sometimes be present.
d
These features should have no attributable other causes and have temporal relation with each other.

FEATURES OF GPIIB/IIA ANTAGONISTS

Feature Abciximab Eptifibatide Tirofiban


Description Fab fragment of Cyclical KGD Nonpeptidic RGD
humanized mouse containing mimetic
monoclonal antibody heptapeptide
Specific for Gp IIb/IIa No Yes Yes
Plasma half life Short (min.) Long (2.5 h) Long (2.0 h)
Platelet bound half life Long (days) Short (s) Short (s)
Renal clearance No Yes Yes

FEATURES OF HEPARIN-INDUCED THROMBOCYTOPENIA

Features Details
Thrombocytopenia Platelet count of < 100,000/L or a decrease in platelet
count of > 50%
Timing Platelet count falls 5-10 days after starting heparin
Type of heparin More common with unfractionated heparin than
low-molecular-weight heparin
More common in surgical patients and patients with
cancer than general medical patients; more common
in women than in men
Thrombosis Venous thrombosis more common than arterial
thrombosis

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MANAGEMENT OF HEPARIN-INDUCED THROMBOCYTOPENIA

Stop all heparin


Give an alternative anticoagulant, such as lepirudin, argatroban, bivalirudin, or fondaparinux.
Do not give platelet transfusions.
Do not give warfarin until the platelet count returns to its baseline level. If warfarin was administered,
give vitamin K to restore the INR to normal.
Evaluate for thrombosis, particularly deep vein thrombosis.

ADVANTAGES OF LMWH OVER HEPARIN

Advantage Consequence
Better bioavailability and longer half-life Can be given subcutaneously once a twice daily for both
after subcutaneous injection prophylaxis and treatment
Dose-independent clearance Simplified dosing
Predictable anticoagulant response Coagulation monitoring is unnecessary in most patients
Lower risk of heparin-induced Safer than heparin for short or long term
thrombocytopenia administration
Lower risk of osteoporosis Safer than heparin for extended administration

COMPARISON OF THE PHARMACOLOGIC PROPERTIES OF THE NEW ORAL


ANTICOAGULANTS

Characteristic Rivaroxaban Apixaban Endoxaban Dabigatran


Target Factor Xa Factor Xa Factor Xa Thrombin
Prodrug No No No Yes
Bioavailability 80% 60% 50% 6%
Dosing qd (bid) Bid qd Bid (qd)
Half-life 7-11 h 12 h 9-11 h 12-17 h
Renal 33% (66%) 25% 35% 80%
Monitoring No No No No
Interactions 3A4/P-gp 3A4/ P-gp P-gp
p-gp
Abbreviations: bid, twice a day; P-gp, P-glycoprotein, qd., once a day

COMMON CLINICAL CAUSES OF DISSEMINATED INTRAVASCULAR COAGULATION

Sepsis Immunologic Disorders


 Bacterial  Acute hemolytic transfusion reaction
Staphylococci, streptococci, pneumococci,  Organ or tissue transplant rejection

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meningococci, gram negative bacilli  Immunotherapy
 Viral  Graft versus host disease
 Mycotic
 Parasitic
 Rickettsial
Trauma and Tissue Injury Drugs
 Brain injury (gunshot)  Fibrinolytic agents
 Extensive burns  Aprotinin
 Fat embolism  Warfarin (especially in neonates with protein
C deficiency)
 Rhabdomyolysis
 Prothrombin complex concentrates
 Recreational drugs (amphetamines)
Vascular Disorders Envenomation
 Giant hemangiomas (Kasabach Merritt  Snake
syndrome)  Insects
 Large vessel aneurysms (eg. aorta)
Obstetrical Complications Liver Disease
 Abruptio placentae  Fulminant hepatic failure
 Amniotic fluid embolism  Cirrhosis
 Dead fetus  Fatty liver of pregnancy
 Septic abortion
Cancer Miscellaneous
 Adenocarcinoma (prostate, pancreas, etc)  Shock
 Hematologic malignancies (acute  Respiratory distress syndrome
promyelocytic leukemia)  Massive transfusion

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Cardiovascular System
CLASSIFICATION OF MYOCARDIAL INFARCTION

Type 1 : Spontaneous Myocardial Infarction


Spontaneous myocardial infarction related to atherosclerotic plaque rupture, ulceration, fissuring,
erosion, or dissection with resulting intraluminal thrombus in one or more of the coronary arteries
leading to decreased myocardial blood flow or distal platelet emboli with ensuring myocyte necrosis.
The patient may have underlying severe coronary artery disease (CAD) but on occasion
nonobstructive or no CAD
Type 2 : Myocardial Infarction Secondary to an Ischemic Imbalance
In Instances of myocardial injury with necrosis where a condition other than CAD contributes to an
imbalance between myocardial oxygen supply and/or demand, e.g. coronary endothelial dysfunction,
coronary artery spasm, coronary embolism. Tachybrady- arrhythmias, anemia respiratory failure,
coronary embolism, tachybradyarrthymias, anemia, respiratory failure, hypotension, and hypertension
with or without left ventricular hypertrophy.
Type 3 : Myocardial Infarction resulting in Death When biomarker valves are Unavailable
Cardiac Death with symptoms suggestive of myocardPrevalence of extra\
ial ischemia and presumed new ischemic electrocardiogram (ECG) changes or new left bundle branch
block (LBBB), but death occurring before blood samples could be obtained or before cardiac
biomarker could rise, or in rare cases, cardiac biomarkers were not collected.
Type 4 a : Myocardial Infarction Related to Percutaneous Coronary Intervention (PCI)
Myocardial infarction associated with PCI is arbitrarily defined by elevation of cardiac troponin (cTn)
values (s99th percentile URL) or a rise of cTn value > 20% if the baseline values are elevated and are
stable or falling. In addition, either (i) symptoms suggestive of myocardial ischemia, or (ii) new
ischemic ECG changes or new LBBB, or (iii) angiographic loss of patency of a major coronary artery
or a side branch or persistent slow or no flow or ambolization, or (iv) imaging demonstration of new
loss of viable myocardium or new regional wall motion abnormality is required
Type 4 b : Myocardial Infarction Related to stent Thrombosis
Myocardial infarction associated with stent thrombosis is detected by coronary angiography or
autopsy in the setting of myocardial ischemia and with a rise and/or fall of cardiac biomarker values
with at least one value above the 99th percentile URL.
Type 5 : Myocardial Infarction Related to Coronary Artery Bypass Grafting (CABG)
Myocardial infarction associated with CABG is arbitrarily defined by alevation of cardiac biomarker
values > 10* 99th percentile URL in patients with normal baseline cTn values (99 percentile URL). In
addition, either (i) new pathologic Q waves or new LBBB, or (ii) angiographic documented new graft
or new native coronary artery occlusion, or (iii) imaging evidence of new loss of viable myocardium
or new regional wall motion abnormality.

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IMP POINTS

 Differential cyanosis refers to isolated cyanosis affecting the lower but not the upper extremities
in a patient with a large patent ductus arterious (PDA) and secondary pulmonary hypertension
with rightto-left to shunting at the great vessel level.
 Palmar crease xanthomas are specific for type III hyperlipoproteinemia.
 Pseudoxanthoma elasticum, a disease associated with premature atherosclerosis, is manifested
by a leathery, cobblestoned appearance of the skin in the axilla and neck creases and by angioid
streaks on fundoscopy.
 Bifid uvula has been described in patients with Loeys-Dietz syndrome.
 Straight back syndrome refers to the loss of the normal kyphosis of the thoracic spine and has
been described in patients with mitral valve prolapsed (MPV) and its variants,
 Patients with the Holt-Oram syndrome have an unopposable, fingerized thumb.
 Kussamaul’s sign is defined by either a rise or a lack of fall of the JVP with inspiration and is
classically associated with constrictive pericarditis, although it has been reported in patients with
restrictive cardiomyopathy, massive pulmonary embolism, right ventricular infarction, and
advanced left ventricular systolic heart failure.
 The length and width of the blood pressure cuffbladder should be 80% and 40% of the arm‟s
circumference, respectively.
 Orthostatic hypotension is defined by a fall in systolic pressure > 20 mmHg or in diastolic
pressure > 10 mmHg in response to assumption of the upright posture from a supine position
within 3 min.
 The character of the pulse is best appreciated at the carotid level.
 A weak and delayed pulse (pulsus parvus et tardus) defines severe aortic stenosis (AS).
 Some patients with AS may also have a slow, notched, or interrupted upstroke (anacrotic pulse)
with a thrill or shudder.
 With chronic severe AR, the carotid upstroke has a sharp rise and rapid fall-off (Corrigan’s or
water-hammer pulse).
 Some patients with advanced AR may have a bifid or bisferiens pulse in which two systolic peaks
can be appreaciated. A bifid pulse is also described in patients with hypertrophic obstructive
cardiomyopathy (HOCM), with inscription of percussion and tidal waves. A bifid pulse4 is easily
appreciated in patients on intraaortic balloon counterpulsation (IABP), in whom the second pulse
is diastolic in timing.
 Pulsus paradoxus refers to a fall in systolic pressure > 10 mmHg with inspiration that is seen in
patients with pericardial tamponade but also is described in those with massive pulmonary
embolism, hemorrhagic shock, severe obstructive lung disease, and tension pneumothorax.
 Pulsus alternans, is defined by beat-to-beat variability of pulse amplitude. It is seen in patients
with severe left ventricular systolic dysfunction and is thought to be due to cyclic changes in
intracellular calcium and action potential duration.
 Most common acquired cause of thrombophilia is Antiphospholipid antibody syndrome and is
associated with venous or arterial thrombosis

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 Most common gas exchange abnormalities in pulmonary embolism are arterial hypoxemia and an
increased alveolar-arterial O2 tension gradient.
 The sensitivity of the D-dimer is >80% for DVT (including isolated calf DVT) and >95% for PE.
The D-dimer is less sensitive for DVT than for PE because the DVT thrombus size is smaller.
 Most specific ECG finfing in pulmonary embolism is the S1Q3T3 sign : an S wave in lead 1, a Q
wave in lead III, and an inverted T wave in lead III.
 The best-known indirect sign of pulmonary embolism on transthoracic echocardiography if
McConnell‟s sign : hypokinesis of the RV free wall with normal or hyperkinetic motion of the RV
apex.
 A normal or nearly normal chest x-ray often occurs in Pulmonary embolism. Well-
established abnormalities include focal oligemia (Westermark‟s sign), a peripheral wedged-
shaped density above the diaphragm (Hampton‟s hump), and an enlarged right descending
pulmonary artery (Palla‟s sign).
 May Thurner syndrome – Left iliac vein is occluded or stenosed by extrinsic compression
from the overlapping right common iliac artery.
 Most common presenting symptom of pulmonary hypertension is dyspnea.

EFFECTS OF PHYSIOLOGIC AND PHARMACOLOGIC INTERVENTIONS ON THE


INTENSITY OF HEART MURMURS AND SOUNDS
 Respiration : Right-sided murmurs and sounds generally increased with inspiration, except
for the PES. Left-sided murmurs and sounds are usually louder during expiration.
 Valsalva maneuver: most murmurs decrease in length and intensity; Two exceptions are the
systolic murmur of HOCM, which usually becomes much louder, and that of MVP, which
becomes longer and often louder. After release of the Valsalva maneuver, right-sided
murmurs tend to return to control intensity earlier than do left-sided murmurs.
 After VPS or AF Murmurs originating at normal or stenotic semilunar valves increase in the
cardiac cycle after a VPB or in the circle after a long cycle length in AF. By contrast, systolic
murmurs due to AV valve regurgitation do not change, diminish {papillary muscle
dysfunction), or become shorter (MVP).
 Positional changes with standing, most murmurs diminish, with two exceptions being the
murmur of HOCM, which becomes louder, and that of MVP, which lengthens and often is
intensified. With squatting, most murmurs become louder, but those of HOCM and MVP
usually soften and may disappear. Passive leg raising usually produces the same results.
 Exercise Murmurs due to blood flow across normal or obstructed valves (e.g., PS, MS)
become louder with both isotonic and submaximal isometric (hand grip) exercise. Murmurs of
MR, VSD, and AR also increase with hand grip exercise. However, the murmur of HOCM
often decreases with nearly maximum hand grip exercise. Left-sided S4 and S3 sounds are
often accentuated by exercise, particularly when due to ischemic heart disease.

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DIFFERENTIAL DIAGNOSIS OF ST-SEGMENT ELEVATIONS

Ischemia/myocardial infarction
Noninfarction, transmural ischemia (Prinzmetal‟s angina, and probably Tako-tsubo syndrome, which
may also exactly simulate classical acute infarction)
Acute myocardial infarction
Postmyocardical infarction (ventricular aneurysm pattern)
Acute pericarditis
Normal variants (including benign “early repolarization” patterns)
Left ventricular hypertrophy/left bundle branch blocka
Other (rarer)
Acute pulmonary embolisma
Brugada patterns (right bundle branch block-like pattern with ST elevations in right precordial leads)a
DC cardioversion
Hypercalcemiaa
Hyperkalemiaa
Hypothermia (J [Osborn] waves)
Nonischemic myocardial injury
Myocarditis
Tumor invading left ventricle
Trauma to ventricles
a
Usually localized to V1-V2 or V3.

PRESENTATION WITH SYMPTOMATIC CARDIOMYOPATHY

Dilated Restrictive Hypertrophic

Ejection fraction Usually <30% when 25-50% >60%


(normal >55%) symptoms severe

Left ventricular >60 mm <60 mm (may be Often decreased


diastolic dimension decreased)
(normal <55 mm)

Left ventricular wall Normal or decreased Normal or increased Markedly increased


thickness

Atrial size Increased, may also Increased, may be Increased; related to


be primarily affected massive elevated filing
pressures

Valvular regurgitation Related to annular Related to endocardial Related to valve-

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dilation; mitral appears involvement; frequent septum interaction;
earlier during mitral and tricuspid mitral regurgitation
decompensation: regurgitation, rarely
tricuspid regurgitation severe
with right ventricular
dysfunction

Common first Exertional intolerance Exertional Exertional


symptoms intolerance, fluid intolerance; may have
retention early, may chest pain
have dominant right
sided symptoms

Congestive symptomsa Left before right, Right often dominates Left-sided congestion at
except right prominent rest may develop late
in young adults

Arrhythmias Ventricular Ventricular Ventricular


tachyarrhythmia; uncommon except in tachyarrhythmias;
conduction block in sarcoidosis, atrial fibrillation
Chagas’ disease, and conduction block in
some families. Atrial sarcoidosis and
fibrillation amyloidosis. Atrial
fibrillation
a
Left-sided symptoms of pulmonary congestion: dyspnea on exertion, orthopnea, paroxysmal
nocturnal dyspnea. Right sided symptoms of systemic venous congestion: hepatic and abdominal
distention, discomfort on bending, peripheral edema.

FEATURES THAT DISTINGUISH CARDIAC TAMPONADE FROM CONSTRICTIVE


PERICARDITIS AND SIMILAR CLINICAL DISORDERS

Characteristic Tamponade Constrictive Restrictive RVMI Effusive


Pericarditis Cardiomyopathy Constrictive
Pericarditis
Clinical
Pulsus +++ + + + +++
paradoxus
Jugular veins
Prominent y – ++ + + –
descent
Prominent x +++ ++ +++ + +++
descent
Kussmaul’s sign – +++ + +++ ++
Third heart sound – – + + +
Pericardial – ++ – – –

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knock
Electrocardiogram
Low ECG ++ ++ ++ – ++
voltage
Electrical ++ – – – +
alternans
Echocardiogram
Thickened – +++ – – ++
pericardium
Pericardial – ++ – -
calcification
Pericardial +++ – – ++
effusion
RV size Usually Usually Usually normal Enlarged
small normal
RA and RV +++ – – –
Exaggerated +++ – +++ +++
respiratory
variation in (flow
velocity)
CT/MRI
Thickened ++ – +++ –
pericardium
Cardiac
catheterization
Equalization of ++ – +++ +++
diastolic pressures

Abbreviations : +++, always present: ++, usually present. +, rare; DC diastolic collapse; ECG
electrocardiograph: RA, right atrium, RV, right ventricle; RVMI, right ventricular myocardial
infarction.

SYSTOLIC HYPERTENSION WITH WIDE PULSE PRESSURE

1. Decreased vascular compliance (arteriosclerosis)


2. Increased cardiac output
a. Aortic regurgitation
b. Thyrotoxicosis
c. Hyperkinetic heart syndrome
d. Fever
e. Arteriovenous fistula
f. Patent ductus arteriosus

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CLASSIFICATION OF RAYNAUD’S PHENOMENON


Primary or idiopathic Raynaud’s phenomenon
Secondary Raynaud’s phenomenon
Collagen vascular disease: scleroderma, systemic lupus erythematosus, rheumatoid arthritis,
dermatomyositis, polymyositis, mixed connective tissue disease, Sjögren‟s syndrome.
Arterial occlusive diseases: atherosclerosis of the extremities, thromboangitis obliterans, acute arterial
occlusion, thoracic outlet syndrome
Pulmonary hypertension
Neurologic disorders: intervertebral disk disease, syringomyelia, spinal cord tumors, stroke,
poliomyelitis, carpal tunnel syndrome, complex regional pain syndrome
Blood dyscrasias: cold agglutinins, cryoglobulinemia, cryofibrinogenemia, myeloproliferative
disorders, lymphoplasmacytic lymphoma
Trauma : vibration injury, hammer hand syndrome, electric shock, cold injury, typing piano playing
Drug and toxins: ergot derivatives, methysergide, 2-adrenergic receptor blockers, bleomycin,
vinblastine, cisplatin, gemcitabine, vinyl chloride.

Five Categories of Pulmonary Hypertension (WHO)


 Group 1 : Pulmonary arterial hypertension
 Group 2 : Pulmonary hypertension due to left heart disease
 Group 3 : Pulmonary hypertension due to chronic lung disease
 Group 4 : Pulmonary hypertension due to chronic thromboemboli
 Group 5 : Miscellaneous causes

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Kidney and urinary tract


IMPORTANT POINTS
 In Chronic Kidney Disease, kidneys are usually smaller unless the patient has diabetic
nephropathy, HIV associated nephropathy, or infiltrative diseases.
 Peak GFR in a normal adult is achieved during third decade of life, following which there is
decline.
 Cardiac troponin levels are frequently elevated in CKD without evidence of acute ischaemia.
 Calciphylaxis (calcific uremic arteriolopathy) is a devastating condition seen almost
exclusively in patients with advanced CKD.It is heralded by livedo reticularis and advances to
patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts.
Pathologically, there is evidence of vascular occlusion in association with extensive vascular
and soft tissue calcification.
 Patients with lupus nephritis class V are predisposed to renal vein thrombosis and
other thrombotic complications.
 The renal biopsy in poststreptococcal glomerulonephritis demonstrates
hypercellularity of mesangial and endothelial cells, glomerular infutrates of
polymorphonuclear leukocytes, granular subendothelial immune deposits of IgG,
IgM, C3, C4 and C5-9 and subepithelial deposits (which appear as “humps”)
 Goodpasture‟s syndrome appears in two age groups: in young men in their late
twenties and in men and women in their sixties and seventies.
 IgA nephropathy is one of the most common forms of glomerulonephritis worldwide.
 Most common cause of nephritic syndrome is elderly is membranous
glomerulonephritis.
 Do and fleck retinopathy is seen in Alport‟s syndrome
 The lesion in HIV associated nephropathy (HIVAN) is FSGS, characteristically
revealing a “collapsing glomerulopathy”.
 The renal lesions most commonly seen in hepatitis C, in order of decreasing
frequency, are cryoglobulinemic glomerulonephritis, MGN, and type I MPGN.
 The schistosoma strain most commonly associated with clinical renal disease is
Schistosoma mansoni.
 Serum lipid profiles in humans are greatly affected by apolipoprotein E
polymorphisms; the E4 allele is accompanied by increases in serum cholesterol and is
more closely associated with atherogenic profiles in patients with renal failure.
Mutations in E2 alleles, particularly in Japanese patients, produce a specific renal
abnormality called lipoprotein glomerulopathy associated with glomerular lipoprotein
thrombi and capillary dilation.
 Autosomal dominant polycystic kidney disease is caused mutations in PKD1 and
PKD2 genes on chromosome 16p and 4q respectively.
 ADPKD is the most common adult-onset, single-gene form of kidney disease.
 Autosomal recessive polycystic kidney disease is caused by mutations in the gene
PKHD1 gene located on chromosome 6p.

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 Most common renal lesion in tuberous sclerosis is angiomyolipoma.


 Most common inherited childhood form of kidney failure requiring kidney
replacement therapy is Nephronophthisis.
 Most common renal manifestation of Sjogren‟s syndrome is tubulointerstitial
nephritis with a predominant lymphocytic infiltrate.
 Inherited TTP is also known as Upshaw Schulman syndrome
 Scleroderma renal crisis occurs in 12% of patients with diffuse systemic sclerosis but
in only 2% of those with limited systemic sclerosis.
 Renal vein thrombosis more commonly involves the left renal vein, and two-third of
cases are bilateral.
 Most common renal stones are calcium oxalate stones.
 The two most common and well-characterized rare monogenic disorders that lead to
stone formation are primary hyperoxaluria and cystinuria.
 Struvite stones, also known as infection stones or triplephosphate stones, form only
when the upper urinary tract is infected with urease-producing bacteria such as
Proteus mirabilis, Klebsiella pneumonia, or Providencia species.
 Struvite stones may grow quickly and fill the renal pelvis producing staghorn calculi

THE MOST COMMON OPPORTUNISTIC INFECTIONS IN RENAL TRANSPLANT


RECEIPIENTS

Peritransplant (<1 month) Late (>6 months)


Wound infections Aspergillus
Herpesvirus Nocardia
Oral candidiasis BK virus (polyoma)
Urinary tract infection Herpes zoster
Early (1-6 months) Hepatitis B
Pneumocystis jiroveci Hepatitis C
Cytomegalovirus
Legionella
Listeria
Hepatitis B
Hepatitis C

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MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

Type I Disease (Most Common)


Idiopathic
Subacute bacterial endocarditis
Systemic lupus erythematosus
Hepatitis C + cryoglobulinemia
Mixed cryoglobulinemia
Hepatitis B
Cancer : Lung, breast, and ovary (germinal)
Type II Disease (Dense Deposit Diseases)
Idiopathic
C3 nephritic factor associated
Partial lipodystrophy
Type III Disease
Idiopathic
Compliment receptor deficiency

INDICATIONS FOR CORTICOSTEROIDS AND IMMUNOSUPPRESSIVES IN


INTERSTITIAL NEPHRITIS

Absolute indications

 Sjögren‟s syndrome
 Sarcoidosis
 SLE interstitial nephritis
 Adults with TINU
 Idiopathic and other granulomatous interstitial nephritis

Relative Indications

 Drug-induced or idiopathic AIN with :


 Rapid progression of renal failure
 Diffuse infiltrates on biopsy
 Impending need for dialysis
 Delayed recovery
 Children with TINU
 Postinfectious AIN with delayed recovery (?)
Abbreviations: AIN, acute interstitial nephritis; SLE, systemic lupus erythematosus; TINU,
tubulointerstitial nephritis with uveitis.

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CLASSIFICATION FOR LUPUS NEPHRITIS
Class I Minimal mesangial Normal histology with mesangial deposits
Class II Mesangial proliferation Mesangial hypercellularity with expansion of
the mesangial matrix
Class III Focal nephritis Focal endocapillary + extracapillary
proliferation with focal subendothelial
immune deposits and mild mesangial
expansion
Class IV Diffuse nephritis Diffuse endocapillary + extracapillary
proliferation with diffuse subendothelial
immune deposits and mesangial alterations
Class V Membranous nephritis Thickened basement membranes with diffuse
subepithelial immune deposits; may occur
with class III or IV lesions and is sometimes
called mixed membranous and proliferative
nephritis.
Class VI Sclerotic nephritis Global sclerosis of nearly all glomerular
capillaries

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Respiratory System
IMPORTANT POINTS
 The excess frequency of lung cancer in asbestos workers is associated with a minimum latency of
15-19 years between first exposure and development of the disease.
 Relatively shortterm asbestos exposures of < 1-2 years, occurring up to 40 years in the past, have
been associated with the development of mesotheliomas.
 The clinical and pathologic features of acute silicosis are similar to those of pulmonary alveolar
proteinosis.
 In Silicosis, the chest radiograph may show profuse military infiltration of consolidation and there
is a characteristic HRCT pattern knows as “crazy paving”.
 Calcification of hilar nodes may occur in as many as 20% of cases of silicosis and produces a
characteristic “eggshell” pattern.
 Because silica is cytotoxic to alveolar macrophages, patients with silicosis are at greater risk of
acquiring lung infections that involve these cells as a primary defense (Mycobacterium
tuberculosis, atypical myobacteria and fungi)
 Caplan syndrome, first described in coal miners but subsequently in patients with silicos, is the
combination of pneumoconiotic nodules and seropositive rheumatoid arthritis.
 Byssinosis is characterized clinically as occasional (early-stage) and then regular (late-stage)
chest rightness toward the end of the first day of the workweek (“Monday chest tightness”).
 Bronchiectasis is more common among women than among men.
 The most common form of bronchiectasis is cylindrical or tubular.
 Bronchiectasis seen in associated with cystic fibrosis and post radiation fibrosis mostly involves
the upper lung fields.
 Bronchiectasis resulting from infection by nontuberculous mycobacteria (NTM), most commonly
the Mycobacterium avium-intracellulare complex (MAC), often preferentially affects the midlung
fields.
 Congenital bronchiectasis in association with immotile cilia syndrome involves predominantly the
midlung fields.
 Allergic Bronchopulmonary aspergillosis also is associated with central bronchiectasis.
 Most common cause of superior vena cava syndrome is small cell carcinoma lung.
 Erosion of the pedicles (the “winking owl” sign) is the earliest radiologic finding of vertebral
metastatic tumor.
 Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia,
hyperphosphatemia, and hypocalcemia and is caused by the destruction of a large number of
rapidly proliferation neoplastic cells.

• Most common form of Idiopathic Interstitial Pneumonia is Idiopathic Pulmonary Fibrosis.


• Acute Intersitial Pneumonia is also known as Hamman-Rich-Syndrome
• Desquamative Intersitial Pneumonia is the form of ILD that is exclusively found in smokers.
• Pulmonary Alveolar Proteinosis is an autoimmune disease with a neutralizing antibody of
immunoglobulin G isotype against granulocyte-macrophage colonystimulating factor (GM-CSF).
• Pulmonary Lymphangioleiomyomatosis is a rare condition that afflicts premenopausal women
and should be suspected in young women with emphysema, recurrent pneumothorax, or chylous
pleural effusion.

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• Hermansky-Pudlak syndrome is an autosomal recessive disorder in which granulomatous colitis
and ILD may occur.
• Lymphocytic Interstitial Pneumonitis is a rare form of ILD, that has been reported in Sjogren
syndrome and HIV infection.
• Light‟s criteria for differentiating exudative and transudative pleural effusion. Exudative pleural
effusions meet at least one of the following criteria, whereas transudative pleural effusions meet
none.
1. Pleural fluid protein/serum protein > 0.5
2. Pleural fluid LDH/serum LDH > 0.6
3. Pleural fluid LDH more than two-thirds the normal upper limit for serum.
• A pleural fluid N=terminal pro-brain natriuretic peptide (NT-proBNP) >1500 pg/mL is virtually
diagnostic that the pleural effusion is secondary to congestive heart failure.
• The three tumors that cause – 75% of all malignant pleural effusions are lung carcinoma, breast
carcinoma and lymphoma.
• The most common cause of chylothorax is trauma (most frequently thoracic surgery)

DIAGNOSTIC VALUE OF BRONCHOALVEOLAR LAVAGE IN INTERSTITIAL LUNG


DISEASE

Conduction Bronchoalveolar Lavage Finding


Sarcoidosis Lymphocytosis; CD4; CD8 ratio >3.5 most
specific of diagnosis
Hypersensitivity pneumonitis Marked lymphocytosis (>50%)
Organizing pneumonia Foamy macrophages; mixed pattern of increased
cells characteristic; decreased CD4:CD8 ratio
Eosinophilic lung disease Eosinophils >25%
Diffuse alveolar bleeding Hemosiderin laden macrophages, red blood cells
Diffuse alveolar damage, drug toxicity Atypical hyperplastic type 1 penumocytes
Opportunistic infections Pneumocystis carinii, fungi, cytomegalovirus
transformed cells
Lymphangitic carcinomatosis, alveolar cell Malignant cells
carcinoma, pulmonary lymphoma
Alveolar proteinosis Milky effluent, foamy macrophages and
lipoprotein aceous intraalveolar material
(periodic acid-Schiff stain-positive)
Lipoid pneumonia Fat globules in macrophages
Pulmonary Langerhans cell histiocytosis Increased CD1+ Langerhans cells, electron
microscopy demonstrating Birbeck granule in
lavaged macrophage (expensive and difficult to
perform)
Asbestos related pulmonary disease Dust particles, ferruginous bodies
Beryllosis Positive lymphocyte transformation test to

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beryllium
Silicosis Dust particles by polarized light microscopy
Lipoidosis Accumulation of specific lipopigment in alveolar
macrophages.

OBSTRUCTIVE SLEEP APNEA/HYPOPNEA SYNDROME (OSAHS) : QUANTIFICATION


AND SEVERITY SCALE

 Apnea-hypopnea index (AHI)a Number of apneas plus hypopneas per hour of sleep
 Respiratory disturbance index (RDI) : Number of apneas plus hypopneas plus RERAs per hour
of sleep
Mild OSAH: AHI of 5-14 events/h
Moderate OSAHS : AHI of 15-29 events/h
Severe OSAHS : AHI of >30 events/h

GOLD CRITERIA FOR SEVERITY OF AIRFLOW OBSTRUCTION IN COPD

GOLD Stage Severity Spirometry


I Mild FEV1/FVC <0.7 and FEV1,
> 80% predicted
II Moderate FEV1/FVC <0.7 and FEV1,
> 50% but <80% predicted
III Severe FEV1/FVC <0.7 and FEV1,
>30% but <50% predicted
IV Very severe FEV1/FVC <0.7 and FEV1,
<30% predicted
Abbreviations : COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Lung
Disease

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CLINICAL DISORDERS COMMONLY ASSOCIATED WITH ARDS

Direct Lung Injury Indirect Lung Injury


Pneumonia Sepsis
Aspiration of gastric contents Severe trauma
Pulmonary contusion Multiple bone fractures
Near-drowning Flail chest
Toxic inhalation injury Head trauma
Burns
Multiple transfusions
Drug overdose
Pancreatitis
Postcardiopulmonary bypass

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Alimentary tract , LIVER AND BILIARY


TRACT DIEASE
DIEULAFOY’s Lesion
 It is a large-caliber arteriole that runs immediately beneath the gastrointestinal mucosa and bleeds
through a pinpoint mucosal erosion.
 It is also called persistent caliber artery.
 Seen most commonly on the lesser curvature of the proximal stomach.
 C/F – Impulsive arterial hemorrhage.
 Endoscopic therapy, such as thermal coagulation or band ligation, is typically effective for control
of bleeding and ablation of the underlying vessel once the lesion has been identified.

DIFFERENT CLINICAL ENDOSCOPIC, AND RADIOGRAPHIC FEATURES


Ulcerative Crohn’s Diseases
Clinical
Gross blood in stool Yes Occasionally
Mucus Yes Occasionally
Systemic symptoms Occasionally Frequently
Pain Occasionally Frequently
Abdominal mass Rarely Yes
Significant perineal disease No Frequently
Fistulas No Yes
Small intestinal obstruction No Frequently
Colonic obstruction Rarely Frequently
Response to antibiotics No Yes
Recurrence after surgery No Yes
Endoscopic
Rectal sparing Rarely Frequently
Continuous disease Yes Occasionally
“Cobblestoning” No Yes
Granuloma on biopsy No Occasionally
Radiographic
Small bowel significantly No Yes
abnormal
Abnormal terminal ileum No Yes
Segmental colitis No Yes
Asymmetric colitis No Yes
Stricture Occasionally Frequently

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DIAGNOSTIC CRITERIA FOR IRRITABLE BOWEL SYNDROMEa
Recurrent abdominal pain or discomfortb at least 3 days per month in the last 3 months associated
with two or more of the following :
1. Improvement with defecation
2. Onset associated with a change in frequency of stool
3. Onset associated with a change in form (appearance of stool)
a
Criteria fulfilled for the 3 months with symptom onset at least 6 months prior to diagnosis.
Discomfort means an uncomfortable sensation not described as pain In pathophysiology research and
clinical trials, a pain/discomfort frequency of at least 2 days a week during screening evaluation is
required for subject eligibility.

COMMONLY ENCOUNTERED SEROLOGIC PATTERNS OF HEPATITIS B INFECTION


HBsAg ANTI-HBs Anti-HBc HBeAg Anti-HBe Interpretation
+ – IgM + – Acute hepatitis B, high
infectivity
+ – IgG + – Chronic hepatitis B, high
infectivity

+ – IgG – + 1) Late acute or chronic


hepatitis B, low
infectivity
2. HBeAg negative
(“precore mutant”)
hepatitis B (chronic or,
rarely, acute)
+ + + +/– +/– 1. HBsAg of one subtype
and heterotypic anti-HBs
(common)
2. Process of
seroconversion from
HBsAg to anti-HBs (rare)
– – IgM +/– +/– 1. Acute hepatitis B
2. Anti-HBc “window”
– – IgG – +/– 1. Low level hepatitis B
carrier
2. Hepatitis B in remote
past
– + IgG – +/– Recovery from hepatitis B

– + – – – 1. Immunization with
HBsAg (after
vaccination)

2. Hepatitis B in the remote


past (?)
3. False positive

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SIMPLIFIED DIAGNOSTIC APPROACH IN PATIENTS PRESENTING WITH ACUTE
HEPATITIS
Serologic Tests of Patient’s Serum
HBsAg IgM Anti-HAV IgM Anti-HBc Anti-HCV Diagnostic
Interpretation
+ – + – Acute hepatitis B
+ – – – Chronic hepatitis B
+ + – – Acute hepatitis A
super-imposed on
chronic hepatitis B
+ + + – Acute hepatitis A
and B
– + – – Acute hepatitis A
– + + – Acute hepatitis A
and B (HB-sAg
below detection
threshold
– – + – Acute hepatitis B
(HBsAg below
detection
threshold)
– – – – + Acute hepatitis C

CLINICAL AND LABORATORY FEATURES OF CHRONIC HEPATITIS

Type of Hepatitis Diagnostic Test(s) Autoantibodies Therapy


Chronic hepatitis B HBsAg, IgG anti- Uncommon IFN-a, PEG IN-a
HBc, HBeAg, HBV Oral agents;
DNA First line entecavir,
tenofovir
Second lime ; lami-
vudine, adefovir,
telbivudine
Chronic hepatitis C Anti-HCV, HCV Anti-LKM1a PEG IFN-α plus
RNA ribavirin
Telaprevir
Boceprevir b
Chronic hepatitis D Anti-HDV, HDV Anti LKM3 IFN-a, PFG IFN-ac
RNA, HBsAg
IgGandi HBc
Autoimmune hepatitis ANAd ANA, anti-LKMI anti Prednisone,
(homogeneous), anti- SLAa azathioprine
LKMI (+)
Drug associated – Uncommon Withdraw drug
Cryptogenic All negative None Prednisone (?)
Azthoprine (?)

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a
Antibodies to liver kidney microsomes type 1 (autoimmune hepatitis type 1 and some cases of
hepatitis C). bAdministered as a triple drug combination with PEG IFN and ribavirin. 2 additional
drugs are also approved for hepatitis C, simeprevir and sofosbuvir (see www.hcvguidelines.org)
„Early clinical trials suggested benefit of IFN-a therapy, PEG IFN-α is as effective, if not more so, and
has supplanted standard IFN-α dAntinuclear antibody (autoimmune hepatitis type 1). “Antibodies to
soluble liver antigen (autoimmune hepatitis type III).

CHILD-PUGH CLASSIFICATION OF CIRRHOSIS

Factor Units Points Toward Total Score


1 2 3
Serum bilirubin µmol/L <34 34-51 >51
mg/dL <2.0 2.0-3.0 >3.0
Serum albumin g/L >35 30-35 <30
g/dL >3.5 3.0-3.5 <3.0
Prothrombin time Seconds <4 4-6 >6
prolonged
INRa <1.7 1.7-2.3 >2.3
Ascites None Easily controlled Poorly controlled
Hepatic None Minimal Advanced
encephalopathy
a
International normalized ratio
Note : The Child-Pugh score is calculated by adding the scores for the five factors and can range from
5 to 15. The resulting Child-Pugh class can be A (a score of 5-6), B(7-9), or C (> 10).
Decompensation indicates cirrhosis, with a Child-Pugh score of >7 (class B). This level has been the
accepted criterion for listing a patient for liver transplantation.

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Treatment Algorithm For Alcoholic Hepatitis

Alcoholic Hepatitis

Alcoholic abstinence
Nutritional support

Discriminant function > 32 or


MELD > 21
(with absence of co-morbidity)

Treatment options

Preferred Alternative

Prednisolone 32 mg Pentoxifylline 400 mg


p.o. daily for 4 weeks, p.o. TID for 4 weeks
then taper for 4 weeks

As identified by a calculated discriminant function >32 patients with severe alcoholic hepatitis,
without the presence of gastrointestinal bleeding or infection, would be candidates for either
glucocorticoids or pentoxifylline administration.
A discriminant function calculated as; 4.6× (the prolongation of the prothrombin time above control
[seconds]) + serum bilirubin (mg/dL) can identify patients with a poor prognosis (discriminant
function > 32). The drug of choice for alcoholic hepatitis with poor discriminant function is steroids.
 Zieve‟s syndrome is a unique form of hemolytic anemia that occurs in patients with severe
alcoholic hepatitis.

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CONTRAINDICATIONS LIVER TRANSPLANTATION
Absolute Relative
Uncontrolled extrahepatobiliary infection Age >70
Active, untreated sepsis Prior extensive hepatobiliary surgery
Uncorrectable, life-mimiting congenital Portal vein thrombosis
anomalies Renal failure not attributable to liver disease
Active substance or alcohol abuse Previous extrahepatic malignancy (not including
Advanced cardiopulmonary disease nonmelanoma skin cancer)
Extrahepatobiliary malignancy (not including Severe obesity
non-melanoma malignancy skin cancer) Severe malnutrition/wasting
Metastatic malignancy to the liver Medical noncompliance
Cholangiocarcinoma HIV seropositivity with failure to control HIV
AIDS viremia or CD4 <100/µl
Life threatening systemic diseases Intrahepatic sepsis
Severe hypoxemia secondary to right to left
intrapulmonary shunts (PO2, <50 mm Hg)
Severe pulmonary hypertension (mean
pulmonary artery pressure >35 mm Hg)
Uncontrolled psychiatric disorder

CLINICAL FEATURES OF AUTOIMMUNE PANCREATITIS (AIP)


 Mild symptoms, usually abdominal pain, but without frequent attacks of acute pancreatitis
 Diffuse swelling and enlargement of the pancreas
 Two-thirds of patients present with either obstructive jaundice or a “mass” in the head of the
pancreas mimicking carcinoma
 Diffuse irregular narrowing of the pancreatic duct (MRCP or ERCP)
 Increased levels of serum gamma globulins, especially IgG4
 Presence of other auto-antibodies (ANA), rheumatoid factor (RF)
 Can occur with other autoimmune diseases: Sjögren‟s syndrome, primary sclerosing cholangitis,
ulcerative colitis, rheumatoid arthritis
 Extrapancreatic bile duct changes such as stricture of the common bile duct and intra-hepatic
ducts
 Pancreatic calcifications (rare)
 Pancreatic biopsies reveal extensive fibrosis and lymphoplasmacytic infiltration
 Glucocorticoids are effective in alleviating symptoms, decreasing size of the pancreatic and
reversing histopathologic changes.

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NEUROLOGY
FEATURES THAT DISTINGUISH GENERALIZED TONIC-CLONIC SEIZURE FROM
SYNCOPE

Features Seizure Syncope


Immediate precipitating factors Usually none Emotional stress, Valsalva,
orthostatic hypotension, cardiac
etiologies
Premonitory symptoms None or aura (e.g., odd odor) Tiredness, nausea, diaphoresis,
tunneling of vision
Posture at onset Variable Usually erect
Transition to unconsciousness Often immediate Gradual over secondsa
Duration of unconsciousness Minutes Seconds
Duration of tonic or clonic 30-60 s Never more than 15 s
movements
Facial appearance during event Cyanosis, frothing at month Pallor
Disorientation and sleepiness Many minutes to hours <5 min
after event
Aching of muscles after event Often Sometimes
Biting of tongue Sometimes Rarely
Incontinence Severe Somtimes
Headacahe Sometimes Rarely

Cerebrovascular Diseases

 A stroke, or cerebrovascular accident, is defined as an abrupt onset of a neurologic deficit that is


attributablew to a focal vascular cause.
 The definition of TIA requires that all neurologic signs and symptoms resolve within 24 h without
evidence of brain infarction on brain imaging.
 Stroke has occurred if the neurologic signs and symptoms last for >24 h or brain infarction is
demonstrated.
 A decrease in cerebral blood flow to zero causes death of brain tissue within 4-10 min; values
<16-18 ml/100 g tissue per minute cause infarction within an hour; and value <20 ml/100 g tissue
per minute cause ischemia without infarction unless prolonged for several hours or days.
 Fever dramatically worsens brain injury during ischemia, as does hyperglycemia.

 Dementia associated with cerebrovascular disease can be divided into two general categories:
multi-infarct dementia and diffuse white matter disease (also called leukoaraiosis, subcortical
arteriosclerotic leukoencephalopathy, or Binswanger‟s disease.)

Management of Acute ischaemic Stroke

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 First goal is to prevent or reverse brain injury.


 Attend to the patient‟s airway, breathing, and circulation (ABCs), and treat hypoglycemia or
hyperglycemia if identified.
 Perform an emergency NCCT head to differentiate between ischaemic stroke and haemorrhagic
stroke.
 Blood pressure should be lowered if there is malignant hypertension or concomitant myocardial
ischemia, or if blood pressure is > 185/110 mmHg and thrombolytic therapy is anticipated.
 Cerebral edema can be managed with mannitol.
 INTRAVENOUS THROMBOLYSIS

CLASSIFICATION OF SEIZURES

1. Focal seizures
(Can be further described as having motor, sensory, autonomic, cognitive, or other features)
2. Generalized seizures
a. Absence
Typical
Atypical
b. Tonic clonic
c. Clonic
d. Tonic
e. Atonic
f. Myoclonic
3. May be focal, generalized, or unclear
Epileptic spasms

 Focal seizure – Focal seizures are usually associated with structural abnormalities of the brain. In
contrast, generalized seizures may result from cellular, biochemical, or structural abnormalities
that have a more widespread distribution.
 With the new classification system, the subcategories of “simple focal seizures” and “complex
focal seizures” have been eliminated. Instead, depending on the presence of cognitive impairment,
they can be described as focal seizures with or without dyscognitive features.
 Remember three additional features of focal motor seizures :
1. JACKSONIAN MARCH – Abnormal motor movements may begin in a very restricted
region such as the fingers and gradually progress (overseconds to minutes) to include a larger
portion of the extremity. Thisphenomenon represents the spread of seizure activity over a
progressively larger region of cerebral cortex.
2. TODD’s PARALYSIS – Localized paresis for minutes to many hours in the involved region
following the seizure.
3. EPILEPSY PARTIALIS CONTINUA – Seizure may continue for several hours or days.

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ADMINISTRATION OF INTRAVENOUS RECOMBINANT TISSUE PLASMINOGEN
ACTIVATOR (rtPA) FOR ACUTE ISCHEMICF STROKE I (AIS)
Indication Contraindication

Clinical diagnosis of stroke Sustained BP > 185/110 mmHg despite treatment

Onset of symptoms to time of drug Platelets <100,000; HCT <25%; glucose <50 or >400 mg/dL
administration < 4.5 h
Use of heparin within 48 h and prolonged PTT, or elevated
CT scan showing no hemorrhage or INR
edema of > 1/3 of the MCA territory
Rapidly improving symptoms
Age 18 > years
Prior stroke or head injury within 3 months; prior intracranial
Consent by patient or surrogate hemorrhage

Major surgery in preceding 14 days

Minor stroke symptoms

Gastrointestinal bleeding in preceding 21 days

Recent myocardial infarction

Coma or stupor

GRADING SCALES FOR SUBARACHNOID HEMORRHAGE

Grade Hunt-Hess Scale World Federation of Neurosurgical Societies


(WFNS) scale
1 Mild headache, normal mental GCS score 15, no motor deficits
status, no cranial nerve or motor
findings
2 Severe headache, normal mental GCS score 13-14, no motor deficits
status, may have cranial nerve
deficit
3 Somnolent, confused, may have GCS score 13-14, with motor deficits
cranial nerve or mild motor deficit
4 Stupor, moderate to severe motor GCS score 7-12, with or without motor deficits
deficit, may have intermittent
reflex posturing
5 Coma, reflex posturing or flaccid GCS score 3-6, with or without motor deficits

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SIMPLIFIED DIAGNOSTIC CRITERIA FOR MIGRAINE

Repeated attacks of headache lasting 4-72 h in patients with a normal physical examination, no
other reasonable cause for the headache, and :
At Least 2 of the Following Features : Plus at Least 1 of the Folloiwng Features :
Unilateral pain
Throbbing pain
Aggravation by movement Nausea/vomiting
Moderate or severe intensity Photophobia and phonophobia
 Calcitonin gene related peptide is an important vasoactive neuropeptide implicated in the
pathogenesis of migraine.
 CGRP receptor antagonists 9gepants) have now been shown to be effective in the acute treatment
of migraine, and monoclonal antibodies to CGRP have been shown effective in two early phase
clinical trials.
 Data also support a role for dopamine in the pathophysiology of migraine.
 Most drugs effective in the treatment of migraine are members of one of three major
pharmacologic classes : nonsteroidal anti-inflammatory drugs, 5-HT1B/1D receptor agonists, and
dopamine receptor antagonists.

Trigeminal autonomic cephalalgias

 The trigeminal autonomic cephalalgias (TACs) describe a grouping of primary headaches


including cluster headache, paroxysmalhemicranias, SUNCT (short-lasting unilateral
neuralgiform headache attacks with conjunctival injection and tearing)/SUNA (short-lasting
unilateral neuralgiform headache attacks with cranial autonomic symptoms) and hemicrania
continua.
 TACs are characterized by relatively short-lasting attacks of head pain associated with cranial
autonomic symptoms, such as lacrimation, conjunctival injection, or nasal congestion.

CLINICAL FEATURES OF THE TRIGEMINAL AUTONOMIC CEPHALALGIAS

Cluster headache Paroxysmal SUNCT/SUNA


Hemicrania
Gender M>F F=M F~M
Pain
Type Stabbing, boring Throbbing, boring, Burning, stabbing,
stabbing sharp
Severity Excruciating Excruciating Severe to excruciating
Site Orbit, temple Orbit, temple Periorbital
Attack frequency 1/alternate day-8/d 1-20/d (>5/d for more 3-200/d
than half the time)
Duration of attack 15-180 min 2-30 min. 5-240 s
Autonomic features Yes Yes Yes (prominent con-
junctival injection and

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Cluster headache Paroxysmal SUNCT/SUNA


Hemicrania
lacrimation)
Migrainous features Yes Yes Yes
Alcohol trigger Yes No No
Cutaneous triggers No No Yes
Indomethacin effect – Yes –
Abortive treatment Sumatriptan injection No effective treatment Lidocaine (IV)
or nasal spray Oxygen
Prophylactic treatment Verapamil Indomethacin Lamotrigine
Methysergide Lithium Topiramate
Gabapentin

Alzhemer’s Disease

 Most common cause of dementia in the elderly (though it can manifest as young as the third
decade).
 The most important risk factors are old age and a positive family history.
 The major genetic risk for AD is apolipoprotein E4 (Apo E4).
 Several genes play an important role in the pathogenesis of AD One is the APP gene on
chromosome 21. Adults with trisomy 21 (Down‟s syndrome) consistently develop the typical
neuropathologic hallmarks of AD if they survive beyond age 40 years.
 The other risk factors are female sex, history of head trauma, low educational status, diabetes
mellitus.
 Elevated homocysteine and cholesterol levels; hypertension; diminished serum levels of folic
acid; low dietary intake of fruits, vegetables and red wine; and low levels of exercise are all being
explored as potential risk factors for AD.
 Patients most often present with an insidious loss of episodic memory followed by a slowly
progressive dementia that evolves over years.
 At autopsy, the earliest and most severe degeneration is usually found in the medial temporal lobe
(entorhinal/perirhinal cortex and hippocampus), lateral temporal cortex, and nucleus basalis of
Meynert.
 The characteristic microscopic findings are neuritic plaques and neurofibrillary tangles.
 Increaisng evidence suggests that soluble amyloid species called oligomers may cause cellular
dysfunction and represent the early toxic molecule in AD.
 Donepezil, Rivastigmine, Galantamine and Memantine are approved by PDA for treatment of
AD.

Progressive Supranucelar Palsy

 Also known as Steele – Richardson – Olszewski syndrome


 Degenerative disorder that involves the brainstem, basal ganglia, limbic structures, and selected
areas of cortex.
 Clinical features
 Begins with falls and executive or subtle personality changes (such as mental rigidity,

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impulsitivity, or apathy)
 Shortly thereafter, a progressive oculomotor syndrome ensues that begins with square wave jerks,
followed by slowed saccades 9vertical worse than horizontal) before resulting in progressive
supranuclearophthalmoparesis.
 Dysarthria, dysphagia, and symmetric axial rigidity can be prominent features that emerge at any
point in the illness.
 A stiff unstable posture with hyperextension of the neck and a slow, jerky, toppling gait are
characteristic.
 Frequent unexplained and sometimes spectacular falls are common secondary to a combination of
axial rigidity, inability to look down, and poor judgment.
 The dementia overlaps with behavioural FTD, featuring apathy, frontal-executive dysfunction,
poor judgement, slowed through processes, impaired verbal fluency, and difficulty with sequential
actions and with shifting from one task to another.
 Response to L-dopa is limited or absent; no other treatments exist.
 RADIOLOGY : Hummingbird sign and Mickey mouse sign are MRI signs (occurs due to
midbrain atrophy).

IMPORTANT POINTS

 Commonest cause of familial Parkinson disease is LRRK2 mutation.


 Mutations in the parkin gene should be considered in parkinsonian patients with onset prior to 40
years of age.
 Atypical and secondary parkinsonism is typically characterized by early speech and gait
impairment, absence of rest tremor, no more asymmetry, poor or no response to levodopa, and an
aggressive clinical course.
 Synuclein constitutes the major component of Lewy bodies in patients with sporadic PD.
 Mutations in the glucocerebrosidase (GBA) gene associated with Gaucher‟s disease numerically
represent the most important risk factor for the development of PD.
 Levodopa remains the most effective symptomatic treatment for PD and the gold standard against
which new therapies are compared.
 No current medical or surgical treatment provides antiparkinsonian benefits superior to what can
be achieved with levodopa.
 Levodopa benefits the classic motor features of PD, prolongs independence and employ ability,
improves quality of life, and increases life span.

SPINOCEREBELLAR ATAXIA – imp POINTS


 Spinocerebellar ataxia type 3 is known as Machado Joseph disease.
 SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17 are caused by CAG triplet repeat expansions in
different genes.
 SSCA8 is due to an untranslated CTG repeat expansion.
 SCA12 is linked to an untranslated CAG repeat.
 SCA10 is caused by an untranslated pentanucleotide repeat.

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IMPORTANT POINTS
 Tangier disease is caused by mutations in the ATP-binding cassette transporter 1 (ABC1) gene,
which leads to markedly reduced levels of high-density lipoprotein (HDL) cholesterol levels,
whereas triacylglycerol levels are increased. The tonsils may appear swollen and yellowish-
orange in color.
 Most common cause of Familial Amyloid Polyneuropathy is mutation in the gene coding for
transthyretin.
 Distal Symmetric Sensory and Sensorimotor Polyneuropathy (DSPN) is the most common form
of diabetic neuropathy.
 Most common cranial nerve affected in sarcoidosis is seventh nerve.
 Most common cranial nerve affected in Lyme disease is seventh nerve.
 Distal Symmetric Polyneuropathy (DSP) is the most common form of peripheral neuropathy
associated with HIV infection and usually is seen in patients with AIDS.
 Lumbosacral polyradiculoneuropathy in AIDS patients is usually secondary to CMV infection.
 INH related peripheral neuropathy is more common among the slow acetylators.
 Vitamin B6, or pyridoxine, can produce neuropathic manifestations from both deficiency and
toxicity.
 The neuropathy affecting lateral femoral cutaneous nerve is called Meralgiaparesthetica.
 Immune-Mediated Brachial Plexus Neuropathy is also known as acute brachial plexitis,
neuralgicamyotrophy or Parsonage-Turner syndrome.
 The most common surgical procedures associated with brachial plexopathy as a complication are
those that involve median sternotomines (e.g: open-heart surgeries and thoracotomies).
 Polyclonal antineuronal antibodies (IgG) directed against the so called “Hu antigen”, are found in
the sea or CSF in the majority of patients with paraneoplastic sensory neuropathy.

 World Federation of Neurology has established diagnostic guidelines for ALS. Essential for
the diagnosis is simultaneous upper and lower motor neuron involvement with progressive
weakness and the exclusion of all alternative diagnoses. The disorder is ranked as : “definite”
ALS when three or four of the following are involved: bulbar, cervical, thoracic, and
lumbosacral motor neurons.When two sites are involve, the diagnosis is “probable” and when
only one site is implicated, the diagnosis is “possible.”

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SUBTYPES OF GUILLAIN-BARRE SYNDROME (GBS)

Subtype Features Electrodiagnosis Pathology

Acute inflammatory Adults affected more Demyelinating First attack on


demyelinating poly- than children; 90% OF Schwann cell surface;
neuropathy (AIDP) CASES IN Western widespread myelin
world; recovery rapid; damage, macrophage
andi-GM1 antibodies activation, and
(<50%) lymphocytic
infiltration variable
secondary axonal
damage

Acutemotore axonal Children and young Axonal First attack motor


neuropathy (AMAN) adults; prevalent in nodes of Ranvier;
China and Mexico; may macrophage
be seasonal; recovery activation, few
rapid; anti-GD1a lymphocytes, frequent
antibodies periaxonal
macrophages; extent
of axonal damage
highly variable

Acute motor sensory Mostly adults; Axonal Same AMAN, but also
axonal neuropathy uncommon; recovery affects sensory nerves
(AMSAN) slow, often incomplete; and roots; axonal
closely related to damage usually severe
AMAN

Miller Fisher Adults and children; Axonal or Few cases examined;


Syndrome (MFS) ophthalmoplegia, ataxia demyelinating resembles AIDP
and areflexia; anti-
GQ1b antibodies (90%)

DRUGS WITH INTERACTIONS IN MYASTHENIA GRAVIS (MG)

Drugs that may Exacerbate MG

Antibiotics

Aminoglycosides: e.g., streptomycin, tobramycin, kanamycin


Quinolones: e.g., ciprofloxacin, Levofloxacin, ofloxacin, gatifloxacin

Macrolides: e.g., erythromycin, azithromycin

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Nondepolarizing muscle relaxants for surgery

D-tubocurarine (curare), pancuronium, vecuronium, atracurium

Beta-blocking agents

Propranolol, atenolol, metoprolol

Local anesthetics and related agents

Procaine, Xylocaine in large amounts


Procainamide (for arrhythmias)

Botulinum toxin

Botox exacderbates weakness

Quinine derivatives

Quinine, quinidine, chloroquine, mefloquine (Lariam)

Magnesium

Decreases acetylcholine release

Penicillamine

May cause MG

Drugs with Important Interactions in MG

Cyclosporine

Broad range of drug interactions, which may raise or lower cyclosporine levels..

Azathioprine

Avoid allopurinol–combination may result in myelosuppression.

MYASTHENIA GRAVIS LAMERT EATON SYNDROME

Post-synaptic defect Presynaptic defect

Normal reflexes Diminished or absent

No autonomic dysfunction Autonomic changes like dry mouth

Decremental response to repeated nerve Incremental response


stimulation

Ptosis and diplopia Ptosis and diplopia present, but proximal


weakness of legs predominate.

NEUROMUSCULAR CAUSES OF PTOSIS OR OPHTHALMOPLEGIA

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Peripheral Neuropathy

Guillain-Barre syndrome
Miller Fisher syndrome

Neuromuscular Junction

Botulism
Lambert-Eaton syndrome
Myasthenia gravis
Congenital myasthenia

Myopathy

Mitochondrial myopathies
Kearns-Sayre syndrome
Progressive external ophthalmoplegia
Oculopharyngeal and oculopharyngodistal muscular dystrophy
Myotonic dystrophy (ptosis only)
Congenital myopathy
Myotubular
Nemaline (ptosis only)
Hyperthyroidism/Graves‟ disease (ophthalmoplegia without ptosis)
Hereditary inclusion body myopathy type 3

PROGRESSIVE MUSCULAR DYSTROPHIES

Type Inheritanc Defective Onset Clinical OTHER


e Gene/Protei Age Features ORGAN
n SYSTEMS
INVOLVED
Duchenne XR Dystrophin Before 5 Progressive Cardiomyopathy
years weakness of Mental
girdle muscles impairment
Unable to walk
after age 12
Progressive
kyphoscoliosis
Respiratory
failure in second
or third decade
Becker XR Dystrophin Early Progressive Cardiomyopathy
childhood weakness of

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to adult girdle muscles
Able to walk
after age 15
Respiratory
failure may
develop by fourth
decade
Limb-girdle AD/AR Several Early Slow progressive + Cardiomyo-
childhood weakness of pathy
to early shoulder and hip
adult girdle muscles
Emery-Dreifuss XR/AD Emerin. Childhoo Elbow/knee/ankl Cardiomyopathy
Lamin A/C d to adult e contractures,
Nesprin-1, humeral and
nesprin 2, peroneal
TMEM43 weakness
Congenital AR AR Several At birth Hypotonia, CNS
or within contractures, abnormalities
first few delayed (hypomyelination
months milestones , malformation)
Progression to Eye abnormalities
respiratory
failure in some;
static course in
others
Myotonic(DM1, AD DM1 : Childhoo Slowly Cardiac
DM2) Expansion d to adult; progressive conduction
CTG repeat possibly weakness of face, defects
DM2 : infancy if shoulder girdle, Mental
Expansion mother and foot impairment
CCTG repeat affected dorsiflexion Cataracts
(DM1 Preferential Frontal baldness
only) proximal
Gonadal atrophy
weakness in
DM2
FSHD1 AD DUX44q Childhoo Slowly Deafness
d to adult progressive
weakness of face,
shoulder girdle,
and foot
dorsiflexion
FSHD2 AD SMCHD1 Coats‟ (eye)
disease
Oculopharyngea AD Expansion, Fifth to Slowly

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l poly A RNA sixth progressive
binding decade weakness of
protein extra-ocular,
pharyngeal, and
limb muscles

KEARNS-SAYRE SYNDROME is a widespread multiorgan system disorder with the following


triad of clinical findings ;
1. Onset before age 20 years
2. CPEO
3. Pigmentary retinopathy

PLUS one or more of the following features


 Complete Heart Block
 CSF protein >100 mg/dl
 Cerebellar ataxia

CLINICAL FEATURES OF PERIODIC PARALYSIS AND NONDYSTROPHIC


MYOTONIAS

Calcium Channel Sodium Channel Potassium


Channel
Feature Hypokalemic PP Hyperkalemic PP Paramyotonia Andersen-Tawil
Congenita Syndromea
Mode of AD AD AD AD
inheritance
Age of onset Adolescence Early childhood Early childhood Early childhood
b
Myotonia No Yes Yes No
Episodic Yes Yes Yes Yes
weakness
Frequency of Daily to yearly May be 2-3/d With cold, usually Daily to yearly
attacks of rare
weakness
Duration of 2-12 h From 1-2 h to >1 d 2-24 h 2-24 h
attacks of
weakness
Serum K+ level Decreased Increased or Usually normal Variable
during attacks of normal
weakness
Effect of K+ No change Increased Increased No change
loading myotonia, then myotonia
weakness

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Effect of muscle No change Increased Increased No change


cooling myotonia myotonia, then
weakness
Fixed weakness Yes Yes Yes Yes
a b
Dysmorphic features and cardiac arrhythmias are distinguishing features. May be paradoxical in
paramyotonia congenital.Abbreviations : AD, Autosomal dominant; PP, periodic paralysis

DRUG-INDUCED MYOPATHIES

Drugs Major Toxic Reaction

Lipid-lowering agents Drugs belonging to all three of the major classes of lipid-lowering
Fibric add derivatives agents can produce a spectrum of toxicity, asymptomatic serum
creatine kinase elevation, myalgias, exercise-induced pain,
HMG-CoA reductase inhibitors
rhabdomyolysis, and myoglobinuria.
Niacin (nicotinic acid)

Glucocorticoids Acute, high-dose glucocorticoid treatment can cause acute


quadriplegic myopathy. These high doses of steroids are often
combined with nonderolarizing neuromuscular blocking agents but
the weakness can occur without their use. Chronic steroid
administration produses predominantly proximal weakness

Nondepolazing neuromuscular Acute quadriplegic myopathy can occur with or without


blocking agents concomitant glucocorticoids.

Zidovudine Mitochondrolal myopathy with ragged red fibers

Drugs of abuse
Alcohol All drugs in this group can lead to widespread muscle breakdown,
Amphetamines rabdomyolysis, and myoglobinauria.

Cocaine Local injections cause muscle necrosis, skin induration, and limb
comtractures
Heroin
Phencyclidine
Meperidine

Autoimmunie toxic myopathy - Use of this drug may cause polymyositis and myasthenia gravis.
Penicillamine

Amphophilic cationic drugs All amphophilic drugs have the potential to produce painless,
Amiodarone proximal weakness associated with autophagic vacuoles in the
muscle biopsy.
Chloroquine
Hydroxychloroquine

Antimicrotubular drugs This drug produces painless, proximal weakness especially in the
Colchicine setting of renal failure. Muscle biopsy shows autophagic vacuoles.

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ENDOCRINOLOGY & METABOLISM


ANTERIOR PITUITARY HORMONE EXPRESSION AND REGULATION
Cell Corticotrope Somatotrope Lactotrope Thyrotrope Gonadotrope
Tissue- T-Pit Prop-1, Pit-1 Prop-1, Pit-1 Prop-1, Pit-1, SF-1, DAX-1
specific TEF
transcription
factor
Fetal 6 week 8 weeks 12 weeks 12 weeks 12 weeks
appearance
Hormone POMC GH PRL TSH FSH, LH
Protein Polypeptide Polypeptide Polypeptide Glycoprotein Glycoprotein
M4! subunits M4! Subunits

Stimulators CRH, AVP, gp- GHRH, Estrogen, TRH GnRH,


130 cytokines ghrelin TRH, VIP activins,
estrogen
Inhibitors Glucocorticoids Somatostatin, Dopamine T3, T4, Sex steroids,
IGF-1 dopamine, inhibin
somatostatin,
glucocorticoids
Target gland Adrenal Liver, bone Breast, other Thyroid Ovary, testis
other tissues tissues
Trophic effect Steroid IGF-I Milk T4 synthesis Sex steroid
production production, production and secretion production,
growth follicle
induction, growth, germ
insulin cell maturation
antagonism
Normal range ACTH, 4-22 <0.5 µg/La M<15µg/L 0.15 mU/L M, 5-20 IU/L,
pg/L F<20 F (basal), 5-20
µg/L IU/L
a
Hormone secretion integrated over 24 h.

IMPORTANT POINTS
 Prolactin is unique among the pituitary hormones in that the predominant central control
mechanism is inhibitory reflecting dopamine mediated suppression of PRL release.
 Most abundant anterior pituitary hormone is growth hormone, and GH-secreting somatotrope
cells constitute up to 50% of the total anterior pituitary cell population.
 Growth hormone receptor antagonist (Pegvisomant) is approved for the treatment of acromegaly.
 Most common hormone deficiency after cranial irradiation is growth hormone.
 Homozygous or heterozygous mutations of the GH receptor are associated with partial or
complete GH insensitivity and growth failure (Laron‟s syndrome).
 Hypogonadism is the most common presenting feature of adult hypopituitarism even when other
pituitary hormones are also deficient.

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 Pituitary adenomas are the most common cause of pituitary hormone hypersecretion and
hyposecretin syndromes in adults.
 Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men
and women.
 Amenorrhea, galactorrhea, and infertility are the hallmarks of hyperprolactinemia in women.
 In men with hyperprolactinemia, diminished libido, infertility, and visual loss (from optic nerve
compression) are the usual presenting symptoms.
 The female-to-male ratio for microprolactinomas (<1 cm) is 20:1, whereas the sex ratio is near 1:1
for macroadenomas (>1 cm).
 Children with GnRH producing hypothalamic hamartomas present with precocious puberty,
psychomotor delay, and laughing-associated seizures. (gelastic seizures)
 MEDNIK syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthyosis,
keratodermia) is a rare multi-system disorder of copper metabolism with both features of
Menkes and Wilson‟s disease.

CRANIOPHARYNGIOMAS
 Benign, suprasellar cystic masses derived from the Rathke‟s pouch
 They are often large, cystic, and locally invasive
 Many are partially calcified, exhibiting a characteristic appearance on skull x-ray and CT images.
 More than half of all patients present before age 20, usually with signs of increased intracranial
pressure, including headache, vomiting, papilledema, and hydrocephalus.
 Associated symptoms include visual field abnormalities, personality changes and cognitive
deterioration, cranial nerve damage, sleep difficulties, and weight gain.
 Hypopituitarism can be documented in about 90%, and diabetes insipidus occurs in about 10% of
patients
 About half of affected children present with growth retardation.
 MRI is generally superior to CT for evaluating cystic structure and tissue components of
craniopharyngiomas. CT is useful to define calcifications and evaluate invasion into surrounding
bony structures and sinuses.

FAMILIAL PITUITARY TUMOR SYNDROMES

Gene Mutated Clinical Features


Multiple endocrine neoplasia 1 MEN 1 Hyperparathyroidism
(MEN 1) (11Q13) Pancreatic neuroendocrine tumors
Foregut carcinoids
Adrenal adenomas
Skin lesions
Pituitary adenomas (40%)
Multiple endocrine neoplasia 4 CDKNIB Hyperparathyroidism
(MEN 4) (12P13) Piituitary adenomas
Other tumors
Carney complex PRKARIA Pituitary hyperplasia and adenomas
(17Q23-24) (10%)
Atrial myxomas

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Gene Mutated Clinical Features


Schwannomas
Adrenal hyperplasia
Lentigines
Familial pituitary adenomas AIP (11Q13.3) Acromegaly/gigantism (~15% of
afflicted families)

CAUSES OF CUSHING’S SYNDROME

Female : Male %
Causes of Cushing’s Syndrome Ratio
ACTH-Dependent Cushing’s 90
Cushing‟s disease (=ACTH-producing pituitary adenoma) 4:1 75
Ectopic ACTH syndrome (due to ACTH secretion by bronchial or 1:1 15
pancreatic carcinoid tumors, small-cell lung cancer, medullary thyroid
carcinoma, pheochromocytoma and others)
ACTH-Independent Cushing’s 4:1 10
Adrenocortical adenoma 5-10
Adrenocortical carcinoma 1
Rare causes: macronodular adrenal hyperplasia; primary pigmented <1
nodular adrenal disease (micro-and/or macronodular); McCune-Albright
syndrome

CLINICAL FEATURES ASSOCIATED WITH PHEOCHROMOCYTOMA, LISTED BY


FREQUENCY OF OCCURRENCE

1. Headaches
2. Profuse sweating
3. Palpitations and tachycardia
4. Hypertension, sustained or paroxysmal
5. Anxiety and panic attacks
6. Pallor
7. Nausea
8. Abdominal pain
9. Weakness
10. Weight loss
11. Paradoxical response to antihypertensive drugs
12. Polyuria and polydipsia
13. Constipation
14. Orthostatic hypotension

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15. Dilated cardiomyopathy
16. Erythrocytosis
17. Elevated blood sugar
18. Hypercalcemia

 The classic “rule of tens” for pheochromocytoma states that ~10% are bilateral, ~10% are
extraadrenal and ~10% are malignant.

Multiple Endocrine Neoplasia


 Four major forms of MEN are recognized and referred to as Men types 1-4 (MEN 1-4).
 Each type of MEN is inherited as an Autosomal dominant syndrome or may occur sporadically.
 In addition to MEN 1-4, at least six other syndromes are associated with multiple endocrine and
other organ neoplasias 9MEONs).
 These MEONs include the hyperparathyroidism-jaw tumor syndrome, Carney complex, von
Hippel-Lindau disease, neurofibromatosis type q, Cowden‟s syndrome, and Mc-Cune-Albright
syndrome; all of these are inherited as Autosomal dominant disorders, except for McCune-
Albright syndrome, which is caused by mosaic expression of a postzygotic somatic M1 mutation.

Multiple Endocrine Neoplasia Type 1


 Also referred to as Wermer‟s syndrome.
 Characterized by the triad of tumors involving the parathyroids, pancreatic islets, and anterior
pituitary.
 In addition, adrenal cortical tumors, carcinoid tumors usually of the foregut, meningiomas, facial
angiofibromas, collagenomas, and Lipomas may also occur in some patients with MEN 1.
 Primary hyperparathyroidism is the most common feature of MEN 1.
 Gastrinoma is the most common pancreatic neuroendocrine tumor in MEN 1.
 Most common cause of death is usually a malignant tumor, often from a pancreatic
neuroendocrine tumor (NET) or foregut carcinoid.
Multiple Endocrine Neoplasia Type 2 & 3
 Also referred to as Sipple‟s syndrome.
 Characterised by association of medullary thyroid carcinoma, pheochromocytomas and
parathyroid tumors.
 Three clinical variants of MEN 2 are recognized : MEN 2A, MEN 2B and MTC only. MEN 2A,
which is often referred to as Men 2 is the most common variant.
 In MEN 2A, MTC is associated with pheochromocytomas in 50% of patients and with
parathyroid tumors in 20% of patients.
 MEN 2A may rarely occur in association with Hirschsprung‟s disease, caused by the absence of
autonomic ganglion cells in the terminal hindgut, resulting in colonic dilatation, severe
constipation, and obstruction.
 MEN 2A may also be associated with cutaneous lichen amyloidosis, which is a pruritic lichenoid
lesion that is usually located on the upper back.
 MEN 2B, which is also referred to as MEN 3, represents 5% of all cases of Men 2 and is
characterized by the occurrence of MTC and pheochromocytoma in association with a marfanoid
habitus; mucosal neuromas of the lips, tongue, and eyelids; medullated corneal fibers; and
intestinal autonomic ganglion dysfunction leading to multiple diverticulae and megacolon.
Parathyroid tumors do not usually occur in MEN 2B.

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 MTC only (FMTC) is a variant in which MTC is the some manifestation of the syndrome.
 MTC is the most common feature of MEN 2A and MEN 2B and occurs in almost all affected
individuals.

Multiple Endocrine Neoplasia Type 4

 Patients with MEN 1 associated tumors such as pituitary adenomas, and pancreatic NETs,
occurring in association with gonadal, adrenal, renal and thyroid tumors have been reported to
have mutations in the gene encoding the 196 amino acid cyclin-dependent kinase inhibitor (CK1)
p27kipl (CDNKIB). Such families with MEN 1 associated tumors and CDNKIB mutations are
designated to have MEN-4.

ETIOLOGIC CLASSIFICATION OF DIABETES MELLITUS

I. Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)
A. Immune-mediated
B. Idiopathic

II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly insulin secretory defect with insulin resistance)

III. Other specific type of diabetes

A. Genetic defects of beta cell development or function characterized by mutations in :


1. Hepatocyte nuclear transcription factor (HNF) 4 M (MODY 1)
2. Glucokinase (MODY 2)
3. HNF-1 M (MODY 3)
4. Insulin promoter factor-1 (IPF-1; MODY 4)
5. HNF-14! (MODY 5)
6. Neuro D1 (MODY 6)
7. Mitochondrial DNA
8. Subunits of ATP-Sensitive potassium channel
9. Proinsulin or insulin
10. Other pancreatic islet regulators/proteins such as KLF11, PAX4, BLK, GATA4,
GATA6, SLC2A2 (GLUT2), RFX6, GUS3

B. Genetic defects in insulin action


1. Type A insulin resistance
2. Leprechaunism
3. Rabson-Mendenhall syndrome

C. Diseases of the exocrine pancreas–Pancreatitis, pancreatectomy, neoplasia, cystic fibrosis,


hemochromatosis, fibrocalculous pancreatopathy, mutations in carboxyl ester lipase.
D. Endocrinopathies–acromegaly, Cushing‟s syndrome, glucagonoma, pheochromocytoma,
hyperthyroidism, somatostatinorma, aldosteronoma.

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E. Drug or chemical-induced–glucocorticoids, vacor (a rodenticide), pentamidine, nicotinic acid,
diazoxide, adrenergic agonists, thiazides, calcineurin and mTOR inhibitors, hydantoins,
asparaginase, interferon, protease inhibitors, antipsychotics (atypicals and others),
epinephrine
F. Infections–congenital rubella, cytomegalovirus, coxsackievirus
G. Uncommon forms of immune-mediated diabetes–“stiff-person” syndrome, anti-insulin
receptor antibodies
H. Other genetic syndromes sometimes associated with diabetes–Wolfram‟s syndrome, Down‟s
syndrome, Klinefelter‟s syndrome, Turner‟s syndrome, Huntington‟s chorea, Laurence-
Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-Willi syndrome.

IV. Gestational diabetes mellitus (GDM)

Abbreviations: MODY, maturity-onset diabetes of the young

Maturity onset diabetes of the young (MODY) and monogenic diabetes are subtypes of DM
characterized by Autosomal dominant inheritance, early onset of hyperglycemia (usually <25 years;
sometimes in neonatal period), and impaired insulin secretion.

CRITERIA FOR THE DIAGNOSIS OF DIABETES MELLITUS


 Symptoms of diabetes plus random blood glucose concentration >11.1 mmol/L (200 mg/dL)a or
 Fasting plasma glucose >7.0 mmol/L (126 mg/dL)b or
 Hemoglobin A1c > 6.5%c or
 2-h plasma glucose > 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance testd
a
Random is defined as without regard to time since the last meal, bfasting is defined as no caloric
intake for at least 8 h. cHemoglobin A1c test should be performed in a laboratory using a method
approved by the National Glycohemoglobin Standardization Program and correlated to the reference
assay of the Diabetes Control and Complications Trial. Point of care hemoglobin A1c should not be
used for diagnostic purposes. dThe test should be performed using a glucose load containing the
equivalent of 75 g anhydrous glucose dissolved in water, not recommended for routine clinical use.

TREATMENT GOALS FOR ADULTS WITH DIABETESa

Index Goal
Glycemic controlb
HbA1c <7.0%c
Preprandial capillary plasma glucose 4.4-7.2 mmol/L (80-130 mg/dL)
Peak postprandial capillary plasma glucosed <10.0 mmol/L (<180 mg/dL)
Blood pressure <140/90 mmHge
Lipidsf

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Low-density lipoprotein <2.6 mmol/L (100 mg/dL)g


High-density lipoprotein >1 mmol/L (40 mg/dL) in men
>1.3 mmol/L (50 mg/dL) in women
<1.7 mmol/L (150 mg/dL)

As recommended by the American Diabetes Associateion; goals should be individualized for each
patient. Goals may be different for certain patient populations. bHbA1c is primary goal. cDiabetes
Control and Complications Trial-based assay. d1-2h after beginning of a meal. eGoal of <130/80
mmHg may be appropriate for younger individualsf in decreasing order of priority. Recent guidelines
from the American College of Cardiology and American Heart Association no longer advocate
specific LDL and HDL goals. gGoal of 1.8 mmol/L (70 mg/dL) may be appropriate for individuals
with cardiovascular disease.

NCEP : ATPIII 2001 AND HARMONIZING DEFINITION CRITERIA FOR THE


METABOLIC SYNDROME.

NCEP : ATPIII 2001


Three or more of the following :
 Central obesity: waist circumference >102 cm (M), >88 cm (F)
 Hypertriglyceridemia : triglyceride level > 150 mg/dL, or specific medication
 Low HDL cholesterol : <40 mg/dL and <50 mg/dL for men and women, respectively, or specific
medication.
 Hypertension: blood pressure >130 mmHg systolic or > 85 mmHg diastolic or specific medication
 Fasting plasma glucose level > 100 mg/dL or specific medication or previously diagnosed type 2
diabetes

Harmonizing Definition CRITERIA FOR THE METABOLIC SYNDROME.

Three of the following :

 Waist circumference (cm)


Men Women Ethnicity
> 94 > 80 Europid, sub-Saharan African,
Eastern and Middle Eastern
> 90 > 80 South Asian, Chinese, and ethnic
South and Central American
> 85 > 90 Japanese
 Fasting triglyceride level >150 mg/dL or specific medication
 HDL cholesterol level <40 mg/dL and <50 mg/dL for men and women,
respectively, or specific medication
 Blood pressure >130 mm systolic or >85 mm diastolic or previous diagnosis or
specific medication.

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 Fasting plasma glucose level >100 mg/dL (alternative indication: drug


treatment of elevated glucose levels)

USEFUL TESTS FOR WILSON’S DISEASE

Test Usefulness Normal Value Heterozygous Wilson’s Disease


Carriers
Serum + 180-350 mg/L Low in 20% Low in 90%
ceruloplasmin (18-35 mg/dL)
Kayser-Fleischer ++ Absent Absent Present in >99% if
rings neurologic/psychiatric
symptoms are present
Present in 30-50% in
hepatic presentation
and presymptomatic
state
Urine copper +++ 0.3-0.8 mol Normal to 1.3 >1.6 mol (>100 g)
(24h) (20-50 g) mol (80 g) in symptomatic
patients; 0.9 to > 1.6
mol (60 to > 100
g) in
presymptomatic
patients
Liver copper ++++ 0.3-0.8 mol/g Normal to 2.0 >3.1 mol (>200 g)
(20-50 g/g of mol (125 g) (Obstructive liver
tissue) disease can cause
false-positive results.)
Haplotype ++++ (siblings 0 matches 1 match 2 matches
analysis only)
a
Usefulness range : + (somewhat useful) to ++++ (very useful)

First step in evaluating patients presenting with hepatic decompensation is to establish disease
severity, which can be estimated with the Nazer Prognostic Index. Patients with scores <7 can usually
be managed with medical therapy. Patients with scores >0 should be considered immediately for liver
transplantation. For patients with scores between 7 and 9, clinical judgment is required in deciding
whether to recommended trans plantation or medical therapy.

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PROGNOSTIC INDEX OF NAZER

Score (in Points)


Laboratory Normal 0 1 2 3 4
Measurement Value
Serum bilirubina 0.2-1.2 <5.8 5.8-8.8 8.8-11.7 11.7-17.5 >17.5
mg/dL
Serum aspartate 10-35 IU/L <100 100-150 151-200 201-300 >300
aminotransferase
Prolongation of – <4 4-8 9-12 13-20 >20
prothrombin
time (sec)
a
If hemolysis is present, serum billirubin cannot be used as a measure of liver function until the
hemolysis subsides.

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DISEASES OF IMMUNITY
COMPLEMENT DEFICIENCIES AND ASSOCIATED DISEASES
Component Associated Diseases
Classic Pathway
Clq, Clr, Cls, C4 Immune-complex syndromes,a pyogenic infections
C2 Immune-complex syndromes,a few with pyogenic infections
C1 inhibitor Rare immune-complex disease, few with pyogenic infections
C3 andAlternative Pathway C3
C3 Immune-complex syndromes,a pyogenic infections
D Pyogenic infections
Properdin Neisseria infections
I Pyogenic infections
H Hemolytic-uremic syndrome
Membrane Attack Complex
C5, C6, C7, C8 Recurrent Neisseria infections, immune-complex disease
C9 Rare Neisseria infections
a
Immune-complex syndromes include systemic lupus-erythematosus (SLE) and LSE-like syndromes,
glomerulonephritis, and vasculitis syndromes.

SIGNIFICANT HLA CLASS I AND CLASS II ASSOCIATION WITH DISEASE


Marker Strength of Association
Spondyloarthropathies
Ankylosing spondylitis B27 ++++
Reactive arthritis (Reiter‟s) B27 ++++
Acute anterior uveitis B27 +++
Reactive arthritis (Yersnia, B27 +++
Salmonella, Shigella,
Chamydia)
Psoriatic spondylitis B27 +++
Collagen Vascular Diseases
Juvenile arthritis, DR8 ++
pauciarticular
DR5 ++
Rheumatoid arthritis DR4 +++
Sjögren‟s syndrome DR3 ++
Systemic lupus
erythematosus
White DR3 +
Japanese DR2 ++
Autoimmune Gut and Skin

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Gluten sensitive DQ2


enteropathy (ceiliac DR3 +++
disease)
Chronic active hepatitis DR3 ++
Dermatitis herpetiformis Cw6 +++
Psoriasis vulgaris DR4 ++
Pemphigus vulgaris DQ1 +++
Bullous pemphigoid DQ7 +
variant
Autoimmune Endocrine
Type I diabetes mellitus DQ8 +++
DR4 ++
DR3
DR2 –a
Hyperthyroidism BB +
(Graves)
DR3 +
Hyperthyroidism B35 +
(Japanee)
Adrenal insufficiency DR3 ++
Autoimmune Neurologic
Myasthenia gravis B8 +
Multiple sclerosis DR2 +
DR2 ++
Other
Bechcet‟s disease B51 ++
Congenital adrenal B47 +++
hyperplasia
Narcolepsy DR2 ++++
Goodpasture‟s DR2 ++
syndrome (anti GBM)
Abacavir B57 ++++
hypersensitivity
a
Strong negative association, i.e. genetic association with protection from diabetes

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CLASSIFICATION CRITERIA FOR RHEUMATOID ARTHRITIS
SCORE
Joint involvement 1 large joint (shoulder, elbow, hip, knee, ankle) 0
2-10 large joints 1
1-3 small joints (MCP PIP, thumb IP MTP wrists) 2
4-10 small joints 3
>10 joints (at least 1 small joint) 5
Serology Negative RF and negative ACPA 0
Low-positive RB or low-positive anti-CCP 2
antibodies
(<3 times ULN) 3
High-positive RF r high-positive and – CCP
antibodies (>3 times ULN
Actual-phase reactants Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
Durartion of symptoms <6 weeks 0
>6 weeks 1

Note : These criteria are aimed at classification of newly presenting patients who have at least one
joint with definite clinical synovitis that is not better explained by another disease A score of
>6fulfills requirements for definite RA.
Abbreviatins : ACPA, anti-circullinated peptide antibiotics; CCP, cyclic circullinated peptides: CRP,
C-reactive protein; ESR, erythrocyte sedimentation rate; IP, interphalanagitis joint; MCR
metacarpohalangeal joint. MTP metatarsophalangel joint; PIP, Proximal interphalangeal, joint; RF,
rheumatoid factor, ULN, upper limit of normal.

AUTOANTIBODIES AND ASSOCIATED FEATURES IN SYSTEMIC SCLEROSIS (SSC)


Target Antigen SSc Subset Characteristic Clinical
Association
Topoisomerase 1 dcSSc Tendon friction rubs, early ILD,
cardiac involvement,
scleroderma renal crisis
Centromere proteins IcSSc Digital ischemic ulcers,
calcinosis cutis, isolated PAH,
overlap syndromes; renal crisis
rare
RNA polymerase III dcSSc Rapidly progressive skin
involvement, tendon friction
rubs, joint contractures, GAVE,
renal crisis, contemporaneous
cancers
U3 RNP (fibrillarin) dcSSc PAH, ILD, scleroderma renal
crisis, myositis
Th/T0 IcSSc ILD, PAH
PM/Scl IcSSc Calcinoma cutis, ILD myositis
overlap
Ku Overlap SLE,Myositis

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Target Antigen SSc Subset Characteristic Clinical


Association
U1-RNP MCTD PAH,arthritis myositis

PREVALENCE OF EXTTRAGLANDULAR MANIFESTATIONS IN PRIMARY


SJOGREN’S SNDROME
Clinical Manifestation Percent Remarks
Arthralgias/arthritis 60 Usually non erosive, leading to
Jaccoud‟s arthropathy
Raynaud‟s phenomenon 37 In one third of patients, precedes
sicca manifestations
Lymphadenopathy 14 Lymphoma should be excluded
Lung involvement 14 Small airway disease is the
predominant pathology
Vasculitis 11 The most common clinical
manifestation is cutaneous
palpable purpura
Kidey involvement 9 Interstitial kidney disease is
usually asymptomatic.
Glomerulonepyhritis is
associated with
cryoglobulinemia
Liver involvement 6 Primary biliary cirrhosis stage I.
Lymphoma 6 Glandular MALT lymphoma is
most common
Peripheral neuropathy 2 Polyneuropathy, either sensory
or or sensorimotor
Myositis 1 Sporadic causes of myolitis and
inclusion body myositis have
been reported

CLINICAL MANIFESTATIONS RELATED TO ORGAN SYSTEM INVOLVEMENT IN


POLYARTERITIS NODOSA
Organ system Percent Incidence Clinical Manifestations
Renal 60 Renal failure, hypertension
Musculoskeletal system 64 Arthritis, arthralgia, myalgia
Peripheral nervous system 51 Peripheral neuropathy, mononeuritis
multiplex
Gastrointstinal tract 44 Abdominal pain, nausea and vomiting,
bleeding, bowel infarction and perforation,
cholecystitis, hepatic infarction, pancreatic
infarction
Skin 43 Rash, purpura, nodules, cutaneous infarcts,
livedo reticularis, Raynaud‟s phenomenon
Cardiac 36 Congestive heart failure, myocardial

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Organ system Percent Incidence Clinical Manifestations


infarction, pericarditis
Genitourinary 25 Testicular, ovarian, or epididymal pain
Central nervous system 23 Cerebral vascular accident, altered mental
status, seizure

FEATURES ASSOCIATED WITH INFLAMMATORY MYOPATHIES


Characteristic Polymyositis Dermatomyositis Inclusion Body
Myositis
Age at onset >18 years Adulthood and >50 years
childhood
Familial association No No Yes, in some rare cases
Extramuscular Yes Yes Yes
manifestations
Associated conditions Yes Scleroderma and mixed Yes, in u p to 20% of
Connective tissue Frequent connective tissue cases
diseases No disease (overlap Infrequent
Systemic syndromes No
Yes
autoimmune diseases Infrequent Yes
Yes
Malignancy Yes, in up to 15% of No
Yes
Viruses cases
No
Drugs Unproven
Parasites and bacteria Yes, rarely
No

ANTINUCLEAR ANTIBODY (ANA) PATTERNS AND CLINICAL ASSOCIATIONS


ANA Pattern Antigen Identified Clinical Correlate
Diffuse Deoxyribonucleoprotein Nonspecific
Histones Drug-induced lupus, lupus
Peripheral (rim) ds-DNA 50% of SLE (specific)
Speckled U1-RNP >90% of MCTD
Sm 30% of SLE (specific)
Ro (SS-A) Sjogren‟s 60%, SCLE, neonatal lupus,
La (SS-B) ANA(-) lupus
Scl-70 50% of Sjogren‟s 15% lupus
PM-1 40% of diffuse scleroderma
Jo-1 Polymyositis (PM), dermatomyositis
PM w/pneumonitis + arthritis
Nucleolar RNA polymerase 1, 40% of PSS
others
Centromere Kinetochore 75% CREST (limited scleroderma)

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DISORDERS ASSOCIATED WITH RELAPSING POLYCHONDRITISa

Systemic vasculitis
Rheumatoid arthritis
Systemic lupus erythematosus
Overlapping connective tissue disease
Spondyloarthritides
Bechcet‟s disease
Polymyalgia rheumatic
Primary biliary cirrhosis
Pulmonary fibrosis
Hashimoto‟s thyroiditis
Myelodysplastic syndrome
a
Systemic vasculitis is the most common association, followed by rheumatoid arthritis and systemic
lupus erythematosus.

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ONCOLOGY
TUMOR MARKERS

Tumor Markers Cancer Nonneoplastic Conditions


Hormones
Human chorionic gonadotropin Gestational trophoblastic Pregnancy
disease, gonadal germ cell
tumor
Calcitonin Medullary cancer of the
thyroid
Catecholamines Pheochromocytoma
Oncofetal Antigens
K Fetoprotein Hepatocellular carcinoma, Cirrhosis, hepatitis
gonadal germ cell tumor
Carcinoembryonic antigen Adenocarcinomas of the Pancreatitis, hepatitis, inflammatory
colon, pancreas, lung, bowel disease, smoking
breast, ovary
Enzymes
Prostatic acid phosphatase Prostate cancer Prostatitis, prostatic hypertrophy
Neuron specific enolase Small cell cancer of the
long, neuroblastoma
Lactate dehydrogenasse Lymphoma, Ewing‟s Hepatitis, hemolytic anemia, many
sarcoma others
Tumor-Associated Proteins
Prostate specific antigen Prostate cancer Prostatitis,prostatic hypertrophy
Monoclonal immunoglobulin Myeloma Infection, MGUS
CA-125 Ovarian cancer some Menstruation,peritonitis,
lymphomas pregnancy,Endometriosis
CA19-9 Colon, pancreatic, breast Pancreatitis, ulcerative colitis
cancer
CD30 Hodgkin‟s disease, –
anaplastic large cell
lymphoma
CD25 Hairy cell leukemia, adult –
T cell leukemia/lymphoma
Abbreviations : MGUS, monoclonal gammopathy of uncertain significance

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ANTIBODIES USED IN CANCER TREATMENT

Drug Target Indications and Features of


Use
Tumor Regulatory Antibodies
Rituximab CD20 B cell neoplasms (also emerging
role in autoimmune disease);
chimerk antibody with frequent
mouse-derived sequences;
frequent infusion reactions,
particularly on initial doses;
reactivation of infections,
particularly hepatitis; progressive
multifocal leukoencephalopathy;
tumor lysis syndrome
Ofatumumab CD20 Active in CLL; fully human
antibody with distinct binding
site compared to rituximab;
decreased intensity infusion
reactions
Trastuzumab HFR2/neu Active in breast cancer and Gl
cancers expressing HFR2/neu;
cardiotoxicity, particularly in
s3etting of prior anthracyclines,
requires monitoring infusion
reactions
Pertuzumab HER2/neu Breast cancer; targets distinct
binding site from trastuzumab,
inhibiting dimerization of HER2
family members; infusion
reactions; cardiac toxicity
Cetuximab EGFR Colorectal cancers with wild-
type Ki-ras oncoprotein; head
and neck cancers with radiation;
rash, diarrhea, infusion reactions
Panitumumab EGFR Colorectal cancers with wild-
type Ki-ras oncoprotein; fully
humanized; decreased infusion
reactions; different IgG subtype
than cetuximab
Bevacizumab VEGF Metastatic colorectal cancer and
non-small-cell lung cancer
(nonsquamous) with
chemotherapy; renal cancer and
glioblastoma as single agents;
prominent HBP, proteinuria, Gl
perforations, hemorrhage,
thrombosis (venous and arterial)

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Immunoregulatory Antibodies
Alemtuzumab CD52 CLL, T cell lymphomas;
activates complement after
binding to cell surface; infusion
reactions, hypersensitivity, tumor
lysis, activation of infections,
dcytopenias
Ipilimumab CTLA4 Melanoma inhibits the negative
proliferative signal to T cells
acting through CTLA4, resulting
in prominent T cell activation;
side effects include immune-
mediated toxicity to liver, skin,
pituitary, gut, which if severe
calls for steroids, which inhibit
antineoplastic effect
Pembrolizumab PD-1 Melanoma unresectable or
metastatic and if B-RAF V600
mutated, refractory to a B-BAF
inhibitor; also can cause immune
related colitis, hepatitis,
hypophysitis, nephritis, and
altered thyroid function; also
consider steroids for treatment of
severe adverse events.
Abbreviations : CLL-Chronic Lymphocytic Leukemia: EGFR-Epidermal growth factor receptor; GI-
Gastrointestinal; HBP-High blood pressure; VEGF-Vascular Endothelial Growth Factor.
 Tumor-regulatory antibodies target tumor cells directly or indirectly to modulate intracellular
functions of attract immune or stromal cells.
Immunoregulatory antibodies target antigens expressed on the tumor cells or host immune cells to
modulate primarily the host‟s immune responsiveness to the tumor.

HEREDITABLE (AUTOSOMAL DOMINANT) GASTROINTESTINAL POLYPOSIS


SYNDROMES

Syndrome Distribution of Histologic Type Malignant Associated


Polyps Potential Lesions
Familial Large intestine Adenoma Common None
adenomatous
polyposis
Gardner‟s Large and small Adenoma Common Osteomas,
syndrome intestines fibromas, lipomas,
epidermoid cysts,
ampullary cancers,
congenital
hypertrophy of
retinal pigament
epithelium

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Syndrome Distribution of Histologic Type Malignant Associated


Polyps Potential Lesions
Turcot‟s Large intestine Adenoma Common Brain tumors
syndrome
MYH-associated Large intestine Adenoma Common None
polyposis
Nonpolyposis Large intestine Adenoma Common Endometrial and
syndrome (often proximal) ovarian tumors
(Lynch‟s (most frequently)
syndrome) gastric,
genitourinary,
pancreatic, biliary
cancers (less
frequently)
Peutz-Jeghers Small and large Hamartoma Rare Mucocutaneous
syndrome intestines, pigmentation;
stomach tumors of the
ovary, breast,
pancreas,
endometrium
Juvenile polyposis Large and small Hamartoma, Rare Various congenital
intestines, rarely progressing abnormalities
stomach to adenoma

CLASSIFICATION OF EPITHELIAL NEOPLASMS ARISING FROM THE KIDNEY

Carcinoma Type Growth Pattern Cell of Origin Cytogenetics


Clear cell Acinar or sarcomatoid Proximal tubule 3p–, 5q+, 14q–
Papillary Papillary or Proximal tubule +7, +17, –Y
sarcomatoid
Chromophobe Solid, tubular, or Distal tubules/cortical Whole arm losses (1, 2,
sarcomatoid collecting duct 6, 10, 13, 17, and 21)
Oncocytic Tumor nests Cortical collecting Undetermined
Collecting duct Papillary or Medullary collecting Undetermined
sarcomatoid duct

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PARANEOPLASTIC HEMATOLOGIC SYNDROMES

Syndrome Proteins Cancers Typically Association


with Syndrome
Erythrocytosis Erythropoietin Renal cancers, hepatocarcinoma,
cerebellar hemangioblastomas
Granulocytosis `G-CSF, GM-CSF, IL-6 Lung cancer, gastrointestinal
cancer, ovarian cancer,
genitourinary cancer, Hodgkin‟s
disease
Thrombocytosis IL-6 Lung cancer, gastrointestinal
cancer, breast cancer, ovarian
cancer, lymphoma
Eosinophilia IL-5 Lymphoma, leukemia, lung
cancer
Thrombophlebitis Unknown Lung cancer, pancreatic cancer,
gastrointestinal cancer, breast
cancer, genitourinary cancer,
ovarian cancer, prostate cancer,
lymphoma
Abbreviations : G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte
macrophage colony-stimulating factor; IL, interleukin

ANTIBODIES TO INTRACELLULAR ANTIGENS, SYNDROMES, AND ASSOCIATED


CANCERS

Antibody Associated Neurologic Tumors


Syndrome(s)
Anti-Hu (ANNA1) Encephalomyelitis, subacute SCLC
sensory neuronopathy
Anti-Yo (PCA1) Cerebellar degeneration Ovary, breast
Anti-Ri (ANNA2) Cerebellar degeneration, Breast, gynaecologic, SCLC
opsoclonus, brainstem
encephalitis
Anti-Tr Cerebellar degeneration Hodgkin‟s lymphoma
Anti-CRMP5 (CV2) Encephalomyelitis, chorea, optic SCLC, thymoma, other
neuritis, uveitis, peripheral
neuropathy
Anti-Ma proteins Limbic, hypothalamic, brainstem Testicular (Ma2), other (Ma)
encephalitis
Anti-amphiphysin Stiff-person syndrome, Breast, SCLC
encephalomyelitis
Recoverin, bipolar cell Cancer-associated retinopathy SCLC (CAR) melanoma
antibodies, othersa (CAR) (MAR)
Melanoma associated

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Antibody Associated Neurologic Tumors


Syndrome(s)
retinopathy (MAR)
Anti-GAD Stiff-person, cerebellar Infrequent tumor association
syndromes, limbic encephalitis (thymoma)
a
A variety of target antigens have been identified
Abbreviations : CRMP, collapsing response-mediator protein : SCLC, small-cell lung cancer.

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INFECTIOUS DISEASES
TYPICAL CSF PROFILES MENINGITIS AND ENCEPHALITS

Normal Bacterial Viral Fungal Parasitic Tuber- Ence-


Meningitis meningitis meningitis meningitis culosis pha-
menin- litis
gitis
WBC count <5 > 1000 25-500 40-600 150-2000 25-100 50-500
(per  L)
Differential 60-70%  PMNs Predomi- Lymphocytes  Eosino- Predomi- Pre-
of WBC lympho- (> 80%) nantly or PMNs, phils (> nantly domi-
cytes, lymphocytes depending on 50%) lympho- nantly
<30% specific cytes lympho-
mono- organism cytes
cytes /
macro-
phages
Gram‟s Negative Positive (in Negative Rarely positive Negative Occa- Negative
stain >60% of sionally
cases) positive
Glucose 40-85 <40 Normal  to normal Normal <50 in Normal
(mg/dL) 75% of
cases
Protein 15-45 >100 20-80 150-300 50-200 100-200 50-100
(mg/dL)
Opening 50-180 >300 100-350 160-340 Normal 150-280 Normal
pressure to 
(mmH2O)
Common – Strepto- Entero- Candida, Angiostron Mycobac- Herpes
causes coccus viruses Cryptococcus, glylus terium viruses,
pneumonia, and cantonensis, tuberculo- entero-
Neisseria Aspergillus Gnatho- sis viruses,
meningitidis spp. stoma influenz
spinigerum, a virus,
Baylisa- rabies
scaris virus
procytonis

EXAMPLES OF MICROBIAL LIGAND RECEPTOR INTERACTIONS

Microorganism Type of Microbial Ligand Host Receptor


Viral Pathogens
Influenza virus Hemagglutinin Sialic acid
Measles virus
Vaccine strain Hemagglutinin CD46/moesin

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Microorganism Type of Microbial Ligand Host Receptor


Wild type strains Hemagglutinin Signaling lymphocytic
activation molecule (SLAM)
Human herpesvirus type 6 ? CD46
Herpes simplex virus Glycoprotein C Heparan sulfate
HIV Surface glycoprotein CD4 and chemokine receptors
(CCR5 and CXCR4)
Epstein-Barr virus Envelope protein CD21 (CR2)
Adenovirus Fiber protein Coxsackie-adeno virus receptor
(CAR)
Coxsackievirus Viral coat proteins CAR and major histo
compatibility class I antigens
Bacterial Pathogens
Neisseria spp Pili Membrane cofactor protein
(CD46)
Pseudomonas aeruginosa Pili and flagella Asialo-GMI
Lipopolysaccharide Cystic fibrosis trans membrane
conductance regulator (CFTR)
Escherichia coli Pili Ceramides/mannose and
digalactosyl residues
Streptococcus pyogenes Hyaluronic add capsule CD44
Yersinia spp Invasin/accessory invasion 21ss Integrins
locus
Bordetetta pertussis Filamentous hemag glutinin CR3
Legionella pneumophila Adsorbed C3bi CR3
Mycobacterium tuberculosis Adsorbed C3bi CR3; DC-SIGNa
Fungal Pathogens
Blastomyces dermatitidis WI-1 Possibly matrix proteins and
integrins
Candida albicans Intlp Extracellular matrix proteins
Protozoal Pathogens
Plasmodium vivax Merozoie form Duffy Fy antigen
Plasmodium falciparum Erythrocyte-binding protein 17S Glycophorin A
(FBA-175)
Entomoeba histolytica Surface lectin N-Acetylglucosamine
a
A novel dendritic cell-specific C type lectin

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EPIDEMIOLOGIC FACTORS SUGGESTING POSSIBLE CAUSES OF COMMUNITY-
ACQUIRED PNEUMONIA

Factor Possible Pathogen(s)


Alcoholism Streptococcus pneumoniae, oral anaerobes,
Klebsiella pneumoniae, Acinetobacter spp.,
Mycobacterium tuberculosis
COPD and/or smoking Haemophilus influenzae, Pseudomonas
aeruginosa, Legionella spp., S. pneumoniae,
Moraxella catarrhalis, Chlamydia pneumoniae
Structural lung disease (e.g., bronchiectasis) P. aeruginosa, burkholaderia cepacia,
Staphylococcus aureus
Dementia, stroke, decreased level of Oral anaerobes, gram-negative enteric bacteria
consciousness
Lung abscess CA-MRSA, oral anaerobes, endemic fungi, M.
tuberculosis, atypical mycobacteria
Travel to ohio or St. Lawerence river valleys Histoplasma capsulatum
Travel to southwestern United States Hantavirus, Coccidioides spp.
Travel to Southeast Asia Burkholderia pseudomallei, avian influenza virus
Stay in hotel or on cruise ship in previous 2 Legionella spp.
weeks
Local influenza activity Influenza virus, S. pneumoniae, S. aureus
Exposure to bats or birds H. capsulatum
Exposure to birds Chlamydia psittaci
Exposure to rabbits Francisella tularensis
Exposure to sheep, goats, parturient cats Coxiella burnetii
Abbreviations : CA-MRSA, community-acquired methicillin-resistant Staphylococcus aureus;
COPD, chronic obstructive pulmonary disease.

CAUSES OF AN EXTREMELY ELEVATED ERYTHROCYTE SEDIMENTATION RATE


(>100 mm/h)

Etiologic Category (% of Cases) Specific Causes


Infectious diseases (35-40) Subacute bacterial endocarditis
Abscesses
Osteomyelitis
Tuberculosis
Urinary tract infection
Inflammatory diseases (15-20) Giant cell arteritis
Rheumatoid arthritis
Systemic lupus erythematosus

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Malignancies (15-20) Multiple myeloma


Leukemias
Lymphomas
Carcinomas
Other (20-35) Drug hypersensitivity reactions (drug fever)
Ischemic tissue injury/trauma
Renal diseases

IMPORTANT POINTS
Organisms Causing Major Clinical Forms of Endocarditis
 Most common cause of native valve endocarditis – Staph aureus
 Most common cause of prosthetic valve endocarditis < 1 year after valve surgery – Coagulase
negative Staph
 Most common cause of prosthetic valve endocarditis > 1 year after valve surgery – Strep viridans
 Most common cause of right sided endocarditis in i.v drug users – Staph aureus
 Most common cause of left sided endocarditis in i.v drug users – Enterococci > Staph aureus
 Most common cause of endocarditis in i.v drug users overall – Staph aureus

THE MODIFIED DUKE CRITERIA FOR THE CLINICAL DIAGNOSIS OF INFECTIVE


ENDOCARDITISa

Major Criteria
1. Positive blood culture
Typical microorganism for infective endocarditis from two separate blood cultures
Viridans streptococci, streptococcus gallolyticus, HACEK group organisms,
staphylococcus aureus, or
Community acquired enterococci in the absence of a primary focus,
Or
Persistently positive blood culture, defined as recovery of a microorganism consistent with
infective endocarditis from Blood cultures drawn > 12 h apart, or
All of 3 or a majority of >4 separate blodd cultures, with first and last drawn at least 1 h
apart
Or
Single positive blood culture for Caxiellaburnetti or phase 1 IgG antibody titer of >1800
2. Evidence of endocardial involvement
Positive echocardial involvement
Positive echocardiogramb
Oscillating intracardiac mass on valve or supporting structures or in the path of
regurgitant jets or in implanted material, in the absence of an alternative anatomic
explanation, or
Abscess, or

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New partial dehiscence of prosthetic valve,


Or
New valvular regurgitation (increase or change in preexisting murmur not sufficient).
Minor Criteria
1. Predisposition: Predisposing heart conditionsc or injection drug use
2. Fever >38.0oC (>100.4oF)
3. Vascular phenomena: major arterial emboli, septic pulmonary infacts, mycotic
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions.
4. Immunologic phenomena: glomerulonephritis Osler’s nodes, Both’s spots, rheumatoid
factor
5. Microbiologic evidence : positive blood culture but not meeting major criterion, as noted
previouslyd, or serologic evidence of active infection with an organism consistent with
infective endocarditis.
a
Definite endocarditis is defined by documentation of two major criteria, of one major criteion and
three minor criteria, or of five minor criteria.
b
Transophageal echocardiography is required for optimal assessment of possible prosthetic valve
endocarditis or complicated endocarditis.
c
Valvular disease with stenosis or regurgitation, presence of a prosthetic valve, congenital heart
disease including corrected or partially, corrected conditions (except isolated artial septal defect,
repaired ventricular septal defect, or closed patent ductus arteriosus) prior endocarditis, or
hypertrophic cardiomyopathy.
d
Excluding single positive cultures for coagulase-negative staphylococci and diphtheroids, which are
common culture contaminants, or for organisms that doe not cause endocarditis frequently, such as
gram –negative bacii.

ANTIBIOTICS USED IN EMPIRICAL THERAPY OF BACTERIAL MENINGITIS AND


FOCAL CENTRAL NERVOUS SYSTEM INFECTIONSa

Indication Antibiotic
Preterm infants to infants <1 month Ampicillin + cefotaxime
Infants 1-3 months Ampicillin + cefotaxime or ceftriaxone
Immunocompetent children >3 months and adults Cefotaxime, ceftriaxone, or cefepime +
<55 vancomycin
Adults >55 and adults of any age with alcoholism Ampicillin + cefotaxime, ceftriaxone or
or other debilitating illnesses cefepime + vancomycin
Hospital acquired meningitis, posttraumatic or Ampicillin + ceftazidime or meropenem +
postneurosurgery meningitis, neutropenic vancomycin
patients, or patients with impaired cell-mediated
immunity

CEREBROSPINAL FLUID (CSF) ABNORMALITIES IN BACTERIAL MENINGITIS

Opening pressure >180 mmH2O


White blood cells 10/L to 10,000/L; neutrophils predominate

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Red blood cells Absent in nontraumatic tap


Glucose <2.2 mmol/L (<40 mg/dL)
CSF/serum glucose <0.4
Protein >0.45 g/L (>45 mg/dL)
Gram‟s stain Positive in >60%
Culture Positive in >80%
Latex agglutination May be positive in patients with meningitis due
to Streptococcus pneumoniae, Neisseria
meningitides, Haemophilus influenzae type b,
Escherichia coli, group B streptococci
Limulus lysate Positive in cases of gram-negative meningitis
PCR Detective bacterial DNA

COMMON INFECTIONS AFTER SOLID ORGAN TRANSPLANTATION, BY SITE OF


INFECTION

Infected Site Early (<1 Month) Middle (1-4 Months) Late (>6 Months)
Donor organ Bacterial and fungal CMV infection EBV infection (may
infections of the graft, present in allograft
anastomotic site, and organ)
surgical wound
Systemic Bacteremia and CMV infection (fever, CMV infection,
candidemia (often bone marrow especially in patients
resulting from central suppression) given early post-
venous catheter transplantation
colonization) prophylaxis; EBV
proliferative syndromes
(may occur in donor
organs)
Lung Bacterial aspiration Pneumocystis infection; Pneumocystis infection;
pneumonia with CMV pneumonia granulomatous lung
prevalent nosocomial (highest risk in lung diseases (nocardial and
organisms associated transplantation), reactivated fungal and
with intubation and Aspergillus infection mycobacterial diseases)
s3edation (highest risk (highest risk in lung
in lung transplantation) transplantation)
Kidney Bacterial and fungal Kidney transplantation; Kidney transplantation:
(Candida) infections BK virus infection bacterial infections
(cystitis, (associated with (late urinarty tract
pyelonephritis) nephropathy); JC virus infections, usually not
associated with urinary infection associated with
tract catheters (highest bacteremia); BK virus
risk in kidney infection (nephropathy,
transplantation) graft failure,
generalized

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Infected Site Early (<1 Month) Middle (1-4 Months) Late (>6 Months)
vasculopathy)
Live and biliary tract Cholangitis CMV hepatitis CMV hepatitis
Heart Toxoplasma gondii t. gondii (highest risk in
infection (highest risk heart transplantation)
in heart
transplantation);
endocarditis
(Aspergillus and gram-
negative organisms
more common than in
general population)
Gastro-intestinal tract Peritonitis, especially Colitis secondary to Colitis secondary to C
after liver Clostridium difficile difficile infection (risk
transplantation infection (risk can can persist)
persist)
Central nervous Listeria infection Listerial meningitis;
system (meningitis); T. gondii cryptococcal
infection; CMV meningitis; nocaridal
infection abscess; JC virus-
associated PML

IMPORTANT POINTS
 Most common cause of septic arthritis in native joints in both adults and children is Staph.
Aureus.
 Most common coagulase negative staph causing human infection is Staph epidermidis.
 Most abundant bacterial species in normal skin flora of humans is Staph epidermidis.
 Drug of choice for listeriosis is Ampicillin.
 Granulomatosis infantiseptica is an overwhelming listerial fetal infection with military
microabscesses and granulomas, most often in the skin, liver and spleen.
 Most common clinical manifestation of gonorrhea in male patients is acute urethritis.
 Most common bacterial cause of exacerbation of COPD is non-typhable H.influenzae.
 Most common species isolated from cases of HACEK endocarditis is Haemophilus
parainfluenzae.
 Most common mode of transmission of Legionella is aspiration > aerosolization.
 Urinary antigen test is highly sensitive and specific for detection of legionella.
 Most common heart valve affected in Bartonella endocarditis is aortic valve.
 Most common form of nocardial disease in the respiratory tract is pneumonia.
 Most common extra-pulmonary site of dissemination of nocardia is brain.
 Drug of choice for nocardiosis is sulfonamide.
 Most common site of post-primary disease in tuberculosis is apical and posterior segments of
upper lobe.

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 Most common site of spinal TB in children-upper thoracic spine.
 Most common site of spinal TB in adults – lower thoracic and upper lumbar vertebrae.
 First bacterium to be etiologically associated with human disease was Mycobacterium leprae.
 “Fish tank granuloma” is associated with Mycobacterium marinum.
 First antimicrobial agent used for the treatment of tuberculosis was Streptomycin.
 Least potent first line drug against Mycobacterium tuberculosis is Ethambutol.
 Pyrazinamide is more active against slowly replicating M. tuberculosis than against actively
replicating organisms.
 Most common causative organism of nongonococcal arthritis and postgonococcal arthritis is
Chlamydia trachomatis.
 Most common clinical manifestations of first episode of HSV-1 infection is gingivostomatitis and
pharyngitis.
 Most common clinical manifestation of reactivation of HSV-1 infection is recurrent herpes
labialis.
 Most common cause of recurrent lymphocytic meningitis (Mollaret meningitis) is HSV.
 Neonatal HSV infection is more commonly caused by HSV-2 >HSV-1.
 Most common infectious complication of varicella is secondary bacterial superinfection of the
skin, which is usually caused by Streptococcus pyogenes or Staphylococcus aureus.
 Most common extracutaneous site of involvement of chickenpox in children is the CNS.\
 Most common clinical manifestation of CMV infection in immunocompetent hosts beyond the
neonatal period is heterophile-antibody negative mononucleosis syndrome.
 Most common viral pathogen complicating organ transplantation is CMV.
 Most common hematologic abnormalty in HIV infected patients is anemia.
 Most common abnormal fundus finding in HIV infection are cotton wool spots.
 Most common aspergillus species implicated in fungal ball (aspergilloma) is A. fumigatus
 Most common form of mucormycosis is rhino-orbito-cerebral mucormycosis.
 Primary amebic meningoencephalitis is caused by Naegleria fowleri.
 Granulomatous amebic encephalitis is caused by Acanthamoeba species.
 Enlargement of the nodes of the posterior cervical triangle, or Winterbottom‟s sign is a classic
finding in sleeping sickness.
 Cutaneous larva migrans is also known as “creeping eruption”.
 Most common cause of human eosinophilic meningitis is Angiostrongylus cantonensis.
 Angiostrongylus cantonensis is also known as “rat lungworm”.
 Largest intestinal nematode parasite of humans is Ascaris lumbricoides.
 Most common cestode infection is Hymenolepiasis nana.
 Hymenolepiasis nana is also known as “dwarf tapeworm”.

RADIOLOGY OF THE SPINE : DIFFERENTIATION OF BRUCELLOSIS FROM


TUBERCULOSIS

Brucellosis Tuberculosis

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Brucellosis Tuberculosis
Site Lumbar and others Dorsolumbar
Multiple or contiguous Contiguous
Diskitis Late Early
Body Intact until late Morphology lost early
Canal compression Rare Common
Epiphysitis Anterosuperior (Pom‟s sign) General : upper and lower disk
regions, central, subperiosteal
Osteophyte Anterolateral (parrot beak) Unusual
Deformity Wedging uncommon Anterior wedge, gibbus
Recovery Sclerosis, whole-body Variable
Paravertebral abscess Small, well-localized Common and discrete loss,
transverse process
Psoas abscess Rare More likely

CMV DISEASE IN THE IMMUNOCOMPROMISED HOST

Population Risk Factors Principal Treatment Prevention


Syndromes
Fetus Primary maternal Cytomegalic Ganciclovir for Avoidance of
infection/early inclusion disease symptomatic exposure;
pregnancy neonates possibly, maternal
treatment with
CMV
immunoglobulin
during pregnancy
Organ transplant Seropositivity of Febrile Ganciclovir or Prophylaxis or
recipient donor and/or leucopenia: valganciclovir preemptive
recipient: potent gastrointestinal therapy with
immunosuppressive disease; ganciclovir or
regiment treatment pneumonia valganciclovir
of rejection
Hematopoietic Graft vs. host Pneumonia: Ganciclovir or Prophylaxis or
stem cell disease; older age gastrointestinal valganciclovir or preemptive
transplant of recipient; disease foscarnet, + CMV therapy with
recipient seropositive immunoglobulin ganciclovir or
recipient; viremia valganciclovir
Person with <100 CD4+ T Retinitis; Ganciclovir, Oral
AIDS cells/µ L; CMV gastrointestinal valganciclovir, valganciclovir
seropositivity disease; foscarnet, or
neurologic cidofovir

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disease

CDC STAGE 3 (AIDS) DEFINING OPPORTUNISTIC ILLNESSES INFECTION

Bacterial infections, multiple or recurrenta


Candidiasis of bronchi, trachea, or lungs
Candidiasis of esophagus
Cervical cancer, invasiveb
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (>1 month‟s duration)
Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month
Cytomegalovirus retinitis (with loss of vision) Encephalopathy attributed to HIV
Herpes simplex chronic ulcers (>1 month‟s duration) or bronchitis, pneumonitis, or esophagitis (onset
at age >1 month)
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (>1 month‟s duration)
Kaposi‟s sarcoma
Lymphoma, Burkitt‟s (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis of any site, pulmonary,b disseminated, or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jirovecii (previously known as Pneumocystis carnii) pneumonia
Pneumonia, recurrentb
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain, onset at age >1 month
Wasting syndrome attributed to HIV
a
Only among children <6 years. bOnly among adults, adolescents and children age >6 years.

CHARACTERISTICS OF IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME


(IRIS)

 Paradoxical worsening of an existing clinical condition or abrupt appearance of a new clinical


finding (unmasking) is seen following the initiation of antiretroviral therapy
 Occurs weeks to months following the initiation of antiretroviral therapy
 Is most common in patients starting therapy with a CD4+ T cell count <50/µ L who experience a
precipitous drop in viral load
 Is frequently seen in the setting o0f tuberculosis; particularly when ART is starting soon after
initiation of anti-TB therapy

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WELL-RECOGNIZED FACTORS AND CONDITIONS PREDISPOSING TO


HEMATOGENOUSLY DISSEMINATED CANDIDIASIS

Antibacterial agents Abdominal and thoracic surgery


Indwelling intravenous catheters Cytotoxic chemotherapy
Hyperalimentation fluids Immunosuppressive agents for organ
transplantation
Indwelling urinary catheters Respirators
Parenteral glucocorticoids Neutropenia
Severe burns Low birth weight (neonates)
HIV-associated low CD4+ T cell counts Diabetes

CHARACTERISTICS OF PLASMODIUM SPECIES INFECTING HUMANS

Finding for indicated Species


Characteristic P. falciparum P. vivax P. ovale P. malariae
Duration of 55 8 9 15
intrahepatic phase
(days)
Number of 30,000 10,000 15,000 15,000
merozoites
released per
infected
hepatocyte
Duration of 48 48 50 72
erythrocytic cycle
(hours)
Red cell Younger cells Reticulocytes and Reticulocytes Older cells
preference (but can invade cells up to 2
cells of all ages) weeks old
Morphology Usually only ring Irregularly shaped Infected Band or
forms; banana- large rings and erythrocytes, rectangular forms
shaped trophozoites; enlarged and oval of trophozoites
gametocytes enlarged with tufted ends; common
erythrocytes; Schiiffner‟s dots
Schuffner‟s dots
Pigment color Black Yellow-brown Dark brown Brown-black
Ability to cause No Yes Yes No
relapses

CDC classifies potential biologic threats into three categories: A, B, and C


Category A

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Anthrax (Bacillus anthracis)


Botulism (Clostridium botulinum toxin)
Plague (Yersinia pestis)
Smallpox (Variola major)
Tularemia (Francisella tularensis)
Viral hemorrhagtic fevers:
Arenaviruses: Lassa, New World (Machupo, Junin, Guanarito, and Sabia)
Bunyaviridae: Crimean-Congo, Rift Valley
Filoviridae: Ebola, Marburg
Category B
Brucellosis (Brucella spp.)
Epsilon toxin of Clostridium perfringens
Food safety threats (e.g. Salmonella spp., Escherichia coli 0157:H7, Shigella)
Glanders (Burkholderia mallei)
Melioidosis (Burkholderia pseudomallei)
Psittacosis (Chlamydophila psittaci)
Q fever (Coxidla burnetii)
Ricin toxin from Ricinus communis (castor beans)
Staphylococcal enterotoxin B
Typhus fever (Rickettsia prowazekii)
Viral encephalitis (alphaviruses [e.g., Venezuelan, eastern, and western equine encephalitis])
Water safety threats (e.g., Vibrio cholera, Cryptosporidium parvum)
Category C
Emerging infectious disease threats such as Nipah, hantavirus, SARS or MERS coronavirus, and
pandemic influenza
Abbreviations: MERS-Middle East Respiratory Syndrome; SARS-Severe Acute Respiratory
Syndrome.

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Miscellaneous
WELLS CLINICAL PREDICTION RULE FOR PULMONARY EMBOLISM

Clinical Feature Points

Clinical signs of deep vein thrombosis 3

Alternative diagnosis is less likely than pulmonary embolism 3

Heart rate >100 beats/min 1.5

Immobilization > 3days or surgery in previous 4 weeks 1.5

History of deep vein thrombosis or pulmonary embolism

Hemoptysis 1.5

Malignancy (with treatment within 6 months) or palliative 1

Interpretation

Score > 6.0 High

Score 2.0-6.0 Intermediate

Score <2.0 Low

HORMONES THAT DECREASE, REMAIN STABLE, AND INCREASE WITH AGING

Decrease No Change Increase

Growth hormone Prolactin Cholecystokinin

Luteinizing hormone (men) Thyrotropin Luteinizing hormone


(women)

Insulin growth factor 1 Thyroid hormones

Testosterone Epinephrine Follicle-stimulating hormone

Estradiol Glucagon-like Cortisol


peptide I

Dehydroepiandrosterone Gastric inhibitory Prolactin


polypeptide

Pregnenolone Norepinephrine

25-Hydroxyvitamin D Insulin

Aldosterone Parathormone

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Decrease No Change Increase

Vasoactive intestinal peptide

Melanonin

PAINFUL CONDITIONS THAT RESPOND TO TRICYCLIC ANTIDEPRESSANTS

Postherpetic neuralgia
Diabetic neuropathy
Tension headache
Migraine headache
Rheumatoid arthritis
Chronic low back pain
Cancer
Central poststroke pain

IMPORTANT POINTS
 Anomic aphasia is the single most common language disturbance seen in head trauma,
metabolic encephalopathy, and Alzheimer‟s disease.

 Apraxia designates a complex motor deficit that cannot be attributed to pyramidal,


extrapyramidal, cerebellar, or sensory dysfunction and that does not arise from the patient‟s
failure to understand the nature of the task.

 Aphemia is a severe form of acute speech apraxia that presents with severely impaired
fluency (often mutism).

 In approximately 90% of right-handers and 60% of left-handers, aphasia occurs only after
lesions of the left hemisphere.

- Gerstmann’s syndrome – combination of acalculia (impairment of simple arithmetic),


dysgraphia (impaired writing), finger anomia (an inability to name individual fingers
such as the index and thumb), and right-left confusion (an inability to tell whether a
hand, foot, or arm of the patient or examiner is on the right or left side of the body). When
Gerstmann‟s syndrome arise acutely and in isolation, it is commonly associated with
damage to the inferior parietallobule (especially the angular gyrus) in the left hemisphere.

- Bilateral involvement of the network for spatial attention, especially its parietal
components, leads to a state of severe spatial disorientation known as Balint’s syndrome.
It involves :
i. Deficits in the orderly visuomotor scanning of the environment (oculomotor
apraxia).
ii. Accurate manual reaching toward visual targets (optic ataxia)and

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iii. The ability to integrate visual information in the center of gaze with more
peripheral information (simultanagnosia).

 Narcolepsy is a disorder of REM sleep.


 Narcolepsy is caused by loss of the hypothalamic neurons that produce the orexin
neuropeptides (also known as hypocretins).
 Narcolepsy has the strongest known HLA association. HLA DQBI*06:02 is found in about
90% of people with narcolepsy.

 In Nothnagel’s syndrome, injury to the superior cerebellar peduncle causes ipsilateral


oculomotor palsy and contralateal cerebelar ataxia.
 In Benedikt’s syndrome, injury to the red nucleus results in ipsilateral oculomotor palsy and
contralateral tremor, chorea, and athetosis.
 Claude’s syndrome incorporate features of both of these syndromes, by injury to both the
red nucleus and the superior cerebellar peduncle.
 In Weber’s syndrome, injury to the cerebral peduncle causes ipsilateral oculomotor palsy
with contralateral hemiparesis.
 Foville’s syndrome – occurs after dorsal pontine injury, includes lateral gaze palsy,
ipsilateral facial palsy, and contralateral hemiparesis incurred by damage to descending
corticospinal fibers.
 Millard-Gubler syndrome - results from ventral pontine injury is similar to Foville‟s
syndrome, except for the eye findings. There is lateral rectus weakness only, instead of gaze
palsy, because the abducens fascicle is injured rather than the nucleus.
 Most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis.
 One-and-a-half syndrome is due to a combined lesion of the medial longitudinal fasciculus
and the abducens nucleus on the same side. The patient‟s only horizontal eye movement is
abduction of the eye on the other side.

Parinaud’s Syndrome
 This is a distinct supranuclear vertical gaze disorder caused by damage to the posterior
commissure.
 Also known as dorsal midbrain syndrome.
 It is a classic sign of hydrocephalus from aqueductal stenosis. Pineal region or
midbraintumors, cysticercosis, and stroke also cause Parinaud‟s syndrome.
 Features include lo0ss of upgaze (and sometimes downgaze), convergence-retraction
nystagmus on attempted upgaze, downward ocular deviation (“setting sun” sign), lid
retraction (Collier’s sign). Skew deviation, pseudoabducens palsy, and light-near dissociation
of the pupils.

 Syndromes associated with hearing loss are :


- Alport‟s syndrome
- Branchiootorenal (BOR) syndrome

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- Jevell and Lange Neilson syndrome
- Norrie‟s disease
- Pendred‟s syndrome
- Treacher Collins syndrome
- Usher‟s syndrome
- Waardenburg‟s syndrome

 The rash of measles typically spares palms and soles.


 Forcheimer spots (palatal petechiae) are seen in german measles, infectious mononucleosis and
scarlet fever.
 Most common causative organism of hand-foot-and mouth disease is Coxsackievirus A16.
 „Pastia lines‟ are accentuated petechiae in body folds seen in scarlet fever.
 “Hot-tub folliculitis” is caused by pseudomonas.

 Oliguria refers to 24 hour urinary output < 400 ml


 Anuria refers to 24 hour urinary output <100 ml
 Hematuria is defined as two to five RBCs per high-power field (HPF)
 Persistent or significant hematuria means >3 RBCs/HPF on three urinalyses, a single urinalysis
with >100 RBCs, or gross hematuria.
 Polyuria refers to 24 hour urine output >3 litres.

SIGNS THAT DISTINGUISH THE ORIGIN OF WEAKNESS

Sign Upper Lower Myopathic Psychogenic


motor motor
neuron neuron
Atrophy None Severe Mild None
Fasciculations None Common None None
Tone Spastic Decreased Normal/decreased Variable/paratonia
Distribution Pyramidal/regional Distal/segmental Proximal Variable/inconsistent
of weakness with daily activities
Muscle Hyperactive Hypoactive/absent Normal/hypoactive Normal
stretch
reflexes
Babinski sign Present Absent Absent Absent

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CAUSES OF EPISODIC GENERALIZED WEAKNESS
1. Electrolyte disturbances, e.g., hypokalemia hyperkalemia, hypercalcemia, hypernatremia,
hyponatremia, hypophosphatemia, hypermagnesemia

2. Muscle disorders
a. Channelopathies (periodic paralyses)
b. Metabolic defects of muscle (impaired carbohydrate or fatty acid utilization; abnormal
mitochondrial function

3. Neuromuscular junction disorders


a. Myasthenia gravis
b. Lambert Eaton myasthenic syndrome

4. Central nervous system disorders


a. Transient ischaemic attacks of the brainstem
b. Transient global cerebral ischemia
c. Multiple sclerosis
5. Lack of voluntary effort
a. Anxiety
b. Pain or discomfort
c. Somatization disorder

FEATURES OF CEREBELLAR ATAXIA, SENSORY ATAXIA AND FRONTAL GAIT


DISORDERS

Features Cerebellar Ataxia Sensory Ataxia Frontal Gait


Base of support Wide-based Narrow base, looks Wide-based
down
Velocity Variable Slow Very slow
Stride Irregular, lurching Regular with path Short, shuffling
deviation
Romberg test +/- Unsteady, falls +/-
Heel  shin Abnormal +/- Normal
Initiation Normal Normal Hesitant
Turns Unsteady +/- Hesitant, multistep
Postural instability ++++ +++ +
Poor postural
synergies rising
from a chair

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CLINICAL DIFFERENTIATION OF THE MAJOR DEMENTIAS

Disease First Symptom Mental Status Neuropsychiatry Neurology Imaging


AD Memory loss Episodic memory Irritability, Initially Entorhinal
loss anxiety, normal contex and
depression hippocampal
atrophy
FTD Apathy; Frontal/executive Apathy; May have Frontal,
poorjudgment/insig and/or language; disinhibition, vertical gaze insular,
ht, speech/language; spares drawing overeating, palsy, axial and/or
hyperorality compulsivity rigidity, temporal
dystonia, atrophy;
alien hand, or usually
MND spares
posterior
parietal lobe
DLB Visual Drawing and Visual Parkinsonism Posterior
hallucinations, frontal/executive; hallucinations, parietal
REM sleep behavior spares memory; depression, sleep atrophy;
disorder, delirium, delirium-prone disorders, hippocampi
Capgras syndrome, delusions larger than in
parkinsonism AD
CJD Dementia, mood, Variable, Apathy, delusions, Usually Cortical
anxiety, movement frontal/executive, anxiety motor ribboning and
disorders cognitive slowing, basal ganglia
slowing; can spasticity; or thalamus
spare memory can be hyperintensity
normal on diffusion /
FLAIR MRI
Vascular Offer but not Frontal/executive, Apathy, delusions, Usually Cortical
always sudden; cognitive anxiety motor and/or
variable; apathy; slowing; can slowing, subcortical
falls, focal spare memory spasticity; infarctions,
weakness can be confluent
normal white matter
disease
Abbreviation: AD-Alzheimer‟s disease; CBD-Cortical basal degeneration; CJD-Creutzfeldt-Jakob
disease; DLB-Dementia with Lewy bodies; FLAIR-Fluid-attenuated Inversion recovery; FTD-
Frontotemporal dementia; MND-Motor Neuron Disease;PSP-Progressive supranuclear palsy; REM-
Rapid Eye Movement.

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CLINICAL FEATURES OF APHASIAS AND RELATED CONDITIONS COMMONLY
SEEN IN CEREBROVASCULAR ACCIDENTS

Comprehension Repetition of Naming Fluency


spoken language
Wernick‟s Impaired Impaired Impaired Preserved of
increased
Broca‟s Preserved (except Impaired Impaired Decreased
grammar)
Global Impaired Impaired Impaired Decreased
Conduction Preserved Impaired Impaired Preserved
Nonfluent Preserved Preserved Impaired Impaired
(anterior)
transcortical
Fluent (posterior) Impaired Preserved Impaired Preserved
transcortical
Isolation Impaired Echolalia Impaired No purposeful
speech
Anomic Preserved Preserved Impaired Preserved except
for word-finding
pauses
Pure word Impaired only for Impaired Preserved Preserved
deafness spoken language
Pure alexia Impaired only for Preserved Preserved Preserved
reading

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Algorithm for the diagnosis of ascites according to the serum-ascites


albumin gradient (SAAG)

SAAG

> 1.1 g/dl < 1.1 g/dl

Ascitic protein < 2.5 g/dl Ascitic protein > 2.5 g/dl

Cirrhosis Heart failure/constrictive Biliary leak


Late Budd-Chiari syndrome pericarditis Nephrotic syndrome
Massive liver metastases Early Budd-Chiari syndrome Pancreatitis
IVC obstruction Peritoneal carcinomatosis
Sinusoidal obstruction syndrome Tuberculosis

DIAGNOSTIC APPROACH TO HYPONATREMIA

Assessment of volume status

Hypovolemia Euvolemia (no edema) Hypervolemia


 Total body water   Total body water   Total body water 
 Total body sodium   Total body sodium   Total body sodium 

UNa > 20 UNa < 20 UNa > 20 UNa > 20 UNa < 20

Renal losses Extrarenal losses Glucocorticoid Acute or Nephrotic


Diuretic excess Vomiting deficiency chronic renal syndrome
Mineral corticoid deficiency Diarrhea Hypothyroidism failure Cirrhosis
Salt-losing deficiency Third spacing of Stress Cardiac failure
Bicarbonaturia with renal fluids Drugs
tubal acidosis and metabolic Burns Syndorome of
alkalosis Pancreatitis inappropriate
Ketonuria Trauma andtidiuretic
Osmotic diuresia hormone
Cerebral salt wasting secretion
syndrome

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CAUSES OF HIGH-ANION GAP METABOLIC ACIDOSIS

Lactic acidosis Toxins

Ketoacidosis Ethylene glycol


Diabetic Methanol
Alcoholic Salicylates
Starvation Propylene glycol
Pyroglutamic acid (5-oxoproline)

Renal failure (acute and chronic)

CAUSES OF NON-ANION GAP ACIDOSIS

I. Gastrointestinal bicarbonate loss


A. Diarrhea
B. External pancreatic or small-bowel drainage
C. Ureterosigmoidostomy, jejuna loop, ileal loop
D. Drugs
1. Calcium chloride (acidifying agent)
2. Magnesium sulfate (diarrhea)
3. Cholestyramine (bile acid diarrhea)
II. Renal acidosis
A. Hypokalemia
1. Proximal RTA (type 2)
Drug induced : acetazolamide, topiramate
2. Distal (classic) RTA (type 1)
Drug induced: amphotericin B, ifosfamide

B. Hyperkalemia
1. Generalized distal nephron dysfunction (type 4 RTA)
a. Mineralocorticoid deficiency
b. Mineralocorticoid resistance (PHA 1, autosomal dominant)
c. Voltage defect (PHA I, autosomal recessive, and PHA II)
d. Tubulointerstitial disease
C. Normokalemia
1. Chronic progressive kidney disease
III. Drug-induced hyperkalemia (with real insufficiency)
A. Potassium-sparing diuretics (amiloride, triamterene spironolactone eplerenone)
B. Trimethoprim
C. Pentamidine
D. ACE-Is and ARBs
E. Nonsteroidal anti-inflammatory drugs

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F. Calcineuria inhibitors
IV. Other
A. Acid loads (ammonium chloride, hyperalimentation)
B. Loss of potential bicarbonate: ketosis with ketone excretion
C. Expansion acidosis (rapid saline administration)
D. Hippurate
E. Cation exchange resins

Abbreviations : ACE-1- Angiotensin converting enzyme inhibitor: ARB – Angiotensin receptor


blocker; PHA-Pseudohypoaldosteronism; RTA – Renal tubular acidosis.

GENETIC PROGEROID SYNDROMES

They are syndromes associated with premature aging. They include:


 Werner‟s syndrome
 Hutchinson-Gilford progeria syndrome
 Cockayne syndrome

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