Tell me details about every investigation with normal values in each and every disease conditions starting from normal fever to advance pathology

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Investigations in Common Fever & Infectious Conditions - Quick Reference

Below is a structured reference covering the key investigations used in fever workup, their normal values, and how they change across conditions - from simple viral fever through advanced bacterial and parasitic infections.

CORE INVESTIGATIONS - NORMAL VALUES

Investigation	Normal Value
Temperature	36.1 - 37.2°C (97 - 99°F)
WBC (Total Leukocytes)	4,000 - 11,000 cells/µL
Neutrophils	50 - 70% (2,500 - 7,500/µL absolute)
Lymphocytes	20 - 40% (1,000 - 4,800/µL)
Eosinophils	1 - 4% (100 - 400/µL)
Monocytes	2 - 8%
Basophils	0 - 1%
Hemoglobin (Male)	13.5 - 17.5 g/dL
Hemoglobin (Female)	12.0 - 15.5 g/dL
Hematocrit (Male)	41 - 53%
Hematocrit (Female)	36 - 46%
Platelets	150,000 - 400,000/µL
MCV	80 - 100 fL
ESR (Male)	< 15 mm/hr (Westergren)
ESR (Female)	< 20 mm/hr
CRP	< 0.5 - 1.0 mg/dL (< 10 mg/L)
Procalcitonin (PCT)	< 0.1 ng/mL
Serum Sodium	135 - 145 mEq/L
Serum Potassium	3.5 - 5.0 mEq/L
Serum Creatinine	0.7 - 1.2 mg/dL (male); 0.5 - 1.0 (female)
BUN	7 - 20 mg/dL
ALT (SGPT)	7 - 56 U/L
AST (SGOT)	10 - 40 U/L
Total Bilirubin	0.3 - 1.2 mg/dL
Serum Albumin	3.5 - 5.0 g/dL
Blood Glucose (fasting)	70 - 100 mg/dL
Urine Specific Gravity	1.005 - 1.030
Urine WBC	0 - 4 cells/HPF

CONDITION-BY-CONDITION INVESTIGATION GUIDE

1. SIMPLE VIRAL FEVER (e.g., Common Cold, Influenza, Adenovirus)

Investigation	Expected Finding	Significance
WBC	Normal or low (3,000 - 8,000)	Viral-induced leukopenia is common
Differential	Lymphocytosis (>40%), neutropenia	Classic viral pattern
Platelets	Normal or mildly decreased	Non-specific
CRP	Mildly elevated (1 - 20 mg/L)	Non-specific inflammation
ESR	Mildly elevated	Non-specific
Procalcitonin (PCT)	< 0.5 ng/mL - KEY FINDING	Low PCT strongly argues against bacterial sepsis
LFTs	Normal
Urine	Normal
Throat swab / Rapid Ag test	Positive (e.g., Flu A/B antigen)	Confirms influenza

Pattern to remember: WBC normal or LOW + lymphocytosis + low PCT = viral fever

2. BACTERIAL FEVER / SEPSIS (e.g., Pneumonia, UTI, Cellulitis)

Investigation	Expected Finding	Significance
WBC	Elevated (>11,000), often 15,000 - 25,000+	Leukocytosis
Neutrophils	>70-80% with left shift (band forms >10%)	Bands = immature neutrophils, severe infection
Toxic granulations / Döhle bodies	Present on blood film	Marker of severe bacterial infection
CRP	Markedly elevated (>50 - 200+ mg/L)	Rises within 6 hrs, peaks at 48 hrs
ESR	Elevated (often >40 mm/hr)	Lags behind CRP
Procalcitonin (PCT)	>0.5 - 2.0 ng/mL (moderate); >2.0 (severe sepsis)	Best biomarker for bacterial vs. viral
Blood Culture	Positive organism in bacteremia	Gold standard - collect BEFORE antibiotics
Urine C&S	Bacteria + WBCs if UTI
Chest X-ray	Consolidation/infiltrate in pneumonia
Lactate	>2 mmol/L = sepsis; >4 = septic shock	Tissue hypoperfusion marker
Serum Creatinine	May rise if organ dysfunction

PCT cut-offs: < 0.1 = unlikely bacterial | 0.1 - 0.5 = possible | 0.5 - 2.0 = probable | >2.0 = severe sepsis/bacteremia

3. TYPHOID FEVER (Salmonella typhi)

Investigation	Week 1	Week 2	Week 3-4
WBC	Low-normal (2,000 - 6,000)	Leukopenia continues	Leukopenia
Neutrophils	Normal or low	Relatively low	Low
Eosinophils	Absent (eosinopenia) - classic finding	Absent	Returning eosinophils = recovery sign
Platelets	Mildly low	May drop further	Normalizing
Blood Culture	Positive (80% sensitivity)	50% sensitivity	30% sensitivity
Urine Culture	25% positive	Higher yield
Stool Culture	Lower yield	Higher yield (week 2-3)
Widal Test (Felix-Widal)	Usually negative	O antibodies rise (day 6-8); H antibodies (day 10-12)	Significant titer
Significant Widal titer	O ≥1:80, H ≥1:160 (endemic area); O ≥1:40 (non-endemic)	Fourfold rise in paired sera = definitive
CRP	Elevated	Elevated
LFTs	Mildly elevated ALT/AST (~2-3x ULN)	Hepatomegaly
Rapid tests (Typhidot, Tubex)	IgM positive from day 4-5	More reliable

Key: Blood culture is gold standard (highest yield in Week 1). Widal test has 30% false-negative rate and cross-reacts with malaria, typhus, cirrhosis - so use with caution. Park's Textbook of Preventive and Social Medicine, p. 278

4. MALARIA

Parameter	P. vivax / P. ovale	P. falciparum	P. malariae
WBC	Normal or mildly low	Normal or low	Normal
Platelets	Low (<150,000) - often 50,000-100,000	Severely low (<50,000 in severe disease)	Mildly low
Hemoglobin	Mildly low (anemia develops)	Severely low (hemolytic anemia)	Mild anemia
Bilirubin (indirect)	Elevated (hemolysis)	Markedly elevated	Mild rise
LDH	Elevated	Very high	Elevated
Blood film (thick + thin smear)	Ring forms + Schuffner's dots	Ring forms + banana-shaped gametocytes, multiple rings/cell	Basket/band trophozoites
RDT (HRP-2 antigen)	Negative for falciparum	Positive (HRP-2)	Negative (use pan-Ag)
Parasite density (thin smear)	% parasitized RBCs; >5% = severe in falciparum
Serum creatinine	Usually normal	May rise (blackwater fever, acute kidney injury)	Nephrotic syndrome (chronic)
Blood glucose	Normal	Hypoglycemia in severe falciparum	Normal
CSF	Normal	Abnormal in cerebral malaria	Normal
Urine	Normal	Hemoglobinuria (blackwater fever - dark urine)	Proteinuria in P. malariae nephropathy

Harrison's 22E, Diagnosis of Malaria block: "If the blood smear is negative when examined by an experienced microscopist, the patient does not have malaria."

5. DENGUE FEVER

Phase	Day 1-3 (Febrile)	Day 4-6 (Critical)	Day 7-10 (Recovery)
WBC	Normal or mildly low	Leukopenia (often 2,000-4,000)	Rising back to normal
Neutrophils	Low	Very low	Normalizing
Lymphocytes	Increasing	Atypical lymphocytes	High
Platelets	Borderline low	Severely low (<100,000 = dengue fever; <20,000 = dengue hemorrhagic)	Rising - recovery sign
Hematocrit	Normal	Rising >20% from baseline = plasma leakage (dengue hemorrhagic fever)	Falls as plasma re-absorbed
NS1 Antigen	Positive (days 1-5) - high sensitivity early	Becoming negative	Negative
IgM antibody	Negative	Positive from day 5	Persists weeks
IgG antibody	Negative (primary infection) or positive early (secondary infection)	Rising	High
AST/ALT	Mildly elevated	Can be markedly elevated	Normalizing
PT/aPTT	Normal	Prolonged in DHF/DSS
Fibrinogen	Normal	Low in DIC (severe DHF)

WHO dengue criteria: Thrombocytopenia (<100,000) + hemoconcentration (hematocrit rise >20%) = dengue hemorrhagic fever (DHF). Platelet <20,000 + spontaneous bleeding = dengue shock syndrome (DSS). Dermatology 5e / Harrison's

6. LEPTOSPIROSIS

Investigation	Leptospiremic Phase (days 1-7)	Immune Phase (days 7-14)
WBC	Elevated (10,000-15,000), neutrophilia	Elevated, then normalizing
Platelets	Mildly low	Low-normal
Creatinine	Rising	Markedly elevated (Weil's disease = AKI)
Bilirubin	Rising	Markedly elevated - conjugated (jaundice)
CPK (creatine kinase)	Markedly elevated	Elevated - myalgia/myositis
Urinalysis	Proteinuria, hematuria, casts	Worse - acute tubular necrosis pattern
LFTs	AST/ALT elevated	ALT may normalize; bilirubin very high
Dark-field microscopy of blood	Can see leptospires (rarely used)	Negative
MAT (Microscopic Agglutination Test)	Negative early	Positive (titer >1:100 significant, >1:400 diagnostic)
ELISA IgM	Positive from day 5-7	Highly positive
Blood culture (EMJH medium)	Positive in first 5-7 days	Negative
Urine culture	Negative	Positive (weeks 2-4)

Weil's disease triad: Jaundice + acute kidney injury + bleeding tendency

7. URINARY TRACT INFECTION (UTI)

Investigation	Simple Cystitis	Pyelonephritis	Urosepsis
Urinalysis	WBC >5/HPF, bacteria, nitrite positive	WBC casts (pathognomonic), WBC >10/HPF	Same + may be dilute
Urine culture	>100,000 CFU/mL (symptomatic: >1,000)	>100,000 CFU/mL	Blood culture also positive
WBC	Normal or mildly elevated	12,000-20,000	>20,000 with left shift
CRP	Normal or mildly elevated	Elevated (>50 mg/L)	Very high
PCT	< 0.5 ng/mL	0.5-2.0 ng/mL	>2.0 ng/mL
Creatinine	Normal	May rise	Rising (septic AKI)
Blood culture	Negative	Usually negative	Positive (E. coli most common)

8. PNEUMONIA

Investigation	Viral Pneumonia	Typical Bacterial (Pneumococcal)	Atypical (Mycoplasma, Legionella)
WBC	Normal or low	15,000-30,000, neutrophilia	Normal or mildly elevated
CRP	Mild-moderate elevation	Very high (>100 mg/L)	Moderate elevation
PCT	< 0.25 ng/mL	>0.5 - 2.0 ng/mL	Variable (0.1 - 0.5)
Chest X-ray	Bilateral interstitial/ground-glass	Lobar consolidation, air bronchograms	Patchy bilateral infiltrates, worse than exam suggests
Sputum Gram stain	No bacteria (or normal flora)	Gram-positive cocci in pairs (diplococci)	No typical organism on Gram stain
Sputum culture	Viral PCR if needed	S. pneumoniae	Culture or serology
Urine Legionella Ag	Negative	Negative	Positive in Legionella pneumophila type 1
Urine Pneumococcal Ag	Negative	Positive	Negative
Cold agglutinins	Normal	Normal	Elevated in Mycoplasma (>1:32)
Mycoplasma IgM	Negative	Negative	Positive (>1:16 significant)
Sodium	Normal	Hyponatremia common in severe pneumonia	Hyponatremia classic in Legionella
LFTs	Normal	Mildly elevated	Elevated in Legionella (hepatitis)
LDH	Mildly elevated in viral		Very elevated in Legionella/PCP

9. MENINGITIS

Investigation	Viral (Aseptic)	Bacterial	Tuberculous	Fungal (Cryptococcal)
WBC (CSF)	10-500, mostly lymphocytes	>500 - 2,000+, mostly neutrophils (>80%)	100-500, mostly lymphocytes	10-200, lymphocytes
CSF Glucose	Normal (>45 mg/dL; >60% serum)	Very low (<40 mg/dL)	Low (20-45 mg/dL)	Very low
CSF Protein	Normal-mildly high (45-100 mg/dL)	Very high (>100-500 mg/dL)	High (100-500 mg/dL)	High (100-500 mg/dL)
CSF appearance	Clear	Turbid/cloudy	Clear (xanthochromic)	Clear, viscous
CSF Gram stain	Negative	Positive in ~70% (bacteria seen)	Negative (AFB rarely seen on ZN)	Negative; India ink positive
CSF Culture	Viral PCR	Bacterial culture	LJ medium (slow - 6-8 weeks)	Fungal culture; CrAg positive
Opening pressure	Normal (7-18 cmH2O)	Markedly elevated	Mildly-moderately elevated	Very high
Blood WBC	Normal	High with neutrophilia	Normal or mildly elevated	Low (immunocompromised)
Serum CRP	Mild	Very high	Elevated	Low-moderate
Serum PCT	Low	High (>2.0 ng/mL)	Low-moderate	Low
CSF Lactate	<3.5 mmol/L	>3.5 mmol/L (high)	Elevated	Elevated

CSF glucose normal = 45-80 mg/dL; should be >2/3 of blood glucose

10. INFECTIVE ENDOCARDITIS

Investigation	Expected Finding
Blood cultures (3 sets)	Positive in >90% (gold standard); S. viridans most common
WBC	12,000-20,000, neutrophilia
ESR	Very high (>60-100 mm/hr)
CRP	Very high
Hemoglobin	Low (normochromic normocytic anemia of chronic inflammation)
Rheumatoid factor	Positive in ~50% of subacute IE
Urinalysis	Microscopic hematuria, RBC casts (immune complex glomerulonephritis)
Echocardiography (TTE/TEE)	Vegetations, valve incompetence - major Duke criterion
ECG	PR interval prolongation = aortic root abscess
Complement (C3/C4)	Low (immune complex consumption)

11. TUBERCULOSIS (TB)

Investigation	Primary TB	Active Pulmonary TB	Miliary TB
WBC	Normal	Normal or mildly elevated, lymphocytosis	Elevated; pancytopenia in bone marrow involvement
Hemoglobin	Normal	Mildly low (anemia of chronic disease)	Low
ESR	Elevated	Very high (>80-100 mm/hr)	Very high
CRP	Elevated	Elevated	Very high
Sputum AFB smear	Negative	Positive in ~60% (ZN stain; require ≥5,000 bacilli/mL)	Usually negative
Sputum culture (LJ)	Gold standard	Positive in 80-85%	May need BAL or bone marrow
GeneXpert MTB/RIF	Detects M. tuberculosis + rifampicin resistance within 2 hrs	Sensitivity ~88% smear+, ~67% smear-
Tuberculin test (Mantoux)	>10 mm induration after 48-72 hrs (5 mm in HIV+)	Positive	May be negative (anergy in miliary)
IGRA (Quantiferon Gold)	Positive	Positive	May be negative
Chest X-ray	Ghon complex, hilar lymphadenopathy	Cavitation, upper lobe infiltrates	Miliary shadowing (1-3 mm nodules throughout)
Serum Sodium	Normal	SIADH in advanced disease (hyponatremia)
LFTs	Normal	Mildly elevated (drug monitoring during treatment)
Serum Albumin	Normal	Low in chronic disease	Very low
ADA (Adenosine Deaminase)	-	Elevated in TB pleural effusion (>40 U/L)	Elevated in CSF/ascites TB

SUMMARY PATTERN CHEAT SHEET

Pattern	Think Of
WBC low + lymphocytosis + low PCT	Viral fever (influenza, EBV, dengue early)
WBC high + neutrophilia + high PCT (>0.5)	Bacterial infection / sepsis
WBC low + eosinopenia + low-normal CRP	Typhoid fever
Thrombocytopenia + rising hematocrit	Dengue hemorrhagic fever
Thrombocytopenia + hemolytic anemia + blood film parasites	Malaria
Jaundice + AKI + elevated CPK + fever	Leptospirosis (Weil's disease)
CSF: high neutrophils + low glucose + high protein	Bacterial meningitis
CSF: lymphocytes + low glucose + high protein (weeks)	TB meningitis
Persistent bacteremia + new murmur + hematuria	Infective endocarditis
ESR very high + low albumin + upper lobe cavitation	Active pulmonary TB
Lobar consolidation + urine Legionella Ag + hyponatremia	Legionella pneumonia

KEY BIOMARKER CUT-OFFS AT A GLANCE

Biomarker	Normal	Viral Infection	Bacterial Infection	Sepsis
PCT	<0.1 ng/mL	<0.25 ng/mL	0.5-2.0 ng/mL	>2.0 ng/mL (>10 = severe)
CRP	<10 mg/L	10-40 mg/L	40-200 mg/L	>200 mg/L
WBC	4-11 x10³/µL	3-8 (low-normal)	12-25 (high)	>25 or <4 (SIRS extremes)
Lactate	<2.0 mmol/L	Normal	Normal-mildly elevated	>2 mmol/L (sepsis); >4 (shock)
Neutrophil %	50-70%	Low (<50%)	High (>80%)	>80% with bands

Sources: Park's Textbook of Preventive and Social Medicine (typhoid, p. 278) | Harrison's Principles of Internal Medicine 22E (malaria diagnosis) | Tintinalli's Emergency Medicine (malaria blood smear) | Henry's Clinical Diagnosis and Management by Laboratory Methods (CBC, reference ranges) | Goldman-Cecil Medicine | Rosen's Emergency Medicine

Explore advanced pathology: investigations in chronic infections & immune complications

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Here is the complete advanced pathology reference, organized from chronic infections through immune system complications:

Advanced Pathology: Investigations in Chronic Infections & Immune Complications

MASTER REFERENCE - ADVANCED NORMAL VALUES

Investigation	Normal Value	Clinical Significance
CD4+ T-cell count	500 - 1,500 cells/µL	Immune competence marker
CD8+ T-cell count	300 - 1,000 cells/µL	Cytotoxic T-cells
CD4:CD8 ratio	1.5 - 2.5	Inverted (<1.0) in HIV/immunosuppression
HIV RNA viral load	Undetectable (0 copies/mL) in treated patients	>1,000 = replicating virus; >100,000 = high risk
HBsAg	Negative	Positive = HBV infection
Anti-HBs	Negative (or >10 IU/L = immune)	Protective after vaccination/recovery
HCV RNA	Undetectable	Any detectable = active HCV
Serum IgG	700 - 1,600 mg/dL
Serum IgA	70 - 400 mg/dL
Serum IgM	40 - 230 mg/dL
Serum IgE	< 100 IU/mL
Complement C3	90 - 180 mg/dL
Complement C4	16 - 47 mg/dL
CH50 (total complement)	41 - 90 U/mL
ANA (antinuclear Ab)	Negative (<1:40 titer)
Anti-dsDNA	< 7 IU/mL (negative)
RF (Rheumatoid Factor)	< 14 IU/mL
Anti-CCP	< 20 U/mL (negative)
Ferritin	12 - 300 ng/mL (male); 12 - 150 (female)
LDH	140 - 280 U/L
Beta-2 microglobulin	0.8 - 2.4 mg/L
Fibrinogen	200 - 400 mg/dL
D-dimer	< 0.5 µg/mL (< 500 ng/mL)
PT	11 - 13 seconds (INR 0.9 - 1.1)
aPTT	25 - 35 seconds
ADA (Adenosine Deaminase)	Serum: < 20 U/L	Elevated in TB, lymphoma, hemolysis

PART 1 - HIV/AIDS: STAGING & MONITORING

HIV Disease Progression by CD4 Count

CD4 Count	Stage	OI Risk	Prophylaxis Needed
> 500 cells/µL	Asymptomatic HIV	None significant	None
200 - 500 cells/µL	Symptomatic HIV (Category B)	TB, Herpes Zoster, oral thrush, bacterial pneumonia	TB screening; pneumococcal vaccine
< 200 cells/µL	AIDS-defining	PCP (Pneumocystis jirovecii)	TMP-SMX prophylaxis
< 150 cells/µL	Advanced AIDS	Histoplasmosis, Cryptococcal meningitis
< 100 cells/µL	Severe AIDS	Toxoplasmosis, MAC (Mycobacterium avium complex)	Azithromycin prophylaxis for MAC
< 50 cells/µL	End-stage AIDS	CMV retinitis, PML (JC virus), disseminated MAC	Valganciclovir for CMV

HIV Monitoring Panel (per Harriet Lane / Harrison's)

Investigation	At Diagnosis	Every 3-6 Months on ART	Target on ART
CD4+ count	Baseline	Every 3-6 months	>500 cells/µL
HIV RNA viral load	Baseline	Monitor suppression	<50 copies/mL (undetectable)
Genotype resistance testing	At diagnosis	If virologic failure	-
CBC with differential	Baseline	Monitor (ART toxicity)	Normal
LFTs (ALT, AST, bilirubin)	Baseline	Monitor	Normal
Serum creatinine / GFR	Baseline	Monitor (tenofovir nephrotoxicity)	Normal
Fasting lipids	Baseline	Annually (ART-related dyslipidemia)	LDL <100 mg/dL
Fasting glucose	Baseline	Monitor (protease inhibitor-related DM)	<100 mg/dL
*HLA-B5701**	Before abacavir	Once only	Negative = safe to use
HBsAg, HBsAb, HBcAb	At diagnosis	Recheck if negative and at-risk	-
HCV antibody	At diagnosis	Recheck if at-risk	-
VDRL / RPR (syphilis)	At diagnosis	Annually if sexually active	Non-reactive
Toxoplasma IgG	At diagnosis	If CD4 <100	-
CMV IgG	At diagnosis	If CD4 <50, add CMV PCR	-
Urinalysis	Baseline	Monitor	Normal

Opportunistic Infections by CD4 - Specific Investigations

OI	CD4 Threshold	Key Investigation	Diagnostic Value
PCP (Pneumocystis)	<200	BAL with GMS/immunofluorescence; serum LDH; Beta-D-glucan	LDH >300 U/L; BDG positive; LDH rises with severity
Cryptococcal Meningitis	<100	CSF India ink; serum/CSF CrAg (cryptococcal Ag); CSF culture	CrAg sensitivity >95%
CMV Retinitis	<50	CMV PCR (blood); fundoscopy; CMV pp65 antigenemia	>500 copies/mL significant
MAC (M. avium complex)	<50	Blood culture (lysis-centrifugation); blood AFB culture	Takes weeks; high-volume bacteremia
Toxoplasmosis	<100	Serum Toxoplasma IgG (if negative, low risk); MRI brain (ring-enhancing lesions)	IgG positive + CD4<100 + ring lesions = treat empirically
PML (JC virus)	<50	CSF JC virus PCR; MRI (T2 white matter lesions no mass effect)	JC PCR positive in CSF
Histoplasmosis	<150	Urine/serum Histoplasma Ag; blood culture; bone marrow biopsy	Urine Ag sensitivity >90% in disseminated disease
Kaposi Sarcoma	Any (AIDS)	Clinical + skin/mucosal biopsy; HHV-8 PCR	HHV-8 DNA confirmed by PCR

IRIS (Immune Reconstitution Inflammatory Syndrome)

Feature	Finding
Trigger	ART initiation when CD4 <100
Timing	Weeks to months after ART start
CD4 trend	Rising (paradox: worsening despite immunological improvement)
HIV viral load	Falling
CRP / ESR	Markedly elevated
Ferritin	Often very high (>500-1,000 ng/mL)
Common presentations	TB-IRIS, Cryptococcal IRIS, Herpes Zoster IRIS
TB-IRIS	New lymphadenopathy, fever, pulmonary infiltrates after ART start

Sources: Harriet Lane Handbook 23e, p. 625; Firestein & Kelley's Rheumatology; Goldman-Cecil Medicine

PART 2 - VIRAL HEPATITIS: CHRONIC DISEASE MARKERS

Hepatitis B - Complete Serology Map

Marker	Acute HBV	Chronic HBV (Active)	Chronic HBV (Inactive Carrier)	Resolved HBV	Vaccinated
HBsAg	+	+	+	-	-
Anti-HBs	-	-	-	+	+
Anti-HBc IgM	+ (high titer)	- (or low)	-	-	-
Anti-HBc IgG	-	+	+	+	-
HBeAg	+	+	-	-	-
Anti-HBe	-	-	+	+	-
HBV DNA (PCR)	High (>200,000 IU/mL)	High (>2,000 IU/mL)	Low (<2,000 IU/mL)	Undetectable	Undetectable
ALT	Very high (>10x ULN)	Elevated or fluctuating	Normal	Normal	Normal
Interpretation	Active acute infection	Active chronic, infectious	Carrier state	Past infection, immune	Immune (vaccine)

Window period: HBsAg cleared but anti-HBs not yet detectable - ONLY anti-HBc IgM is positive. This is the sole serologic marker during the window period. Henry's Clinical Diagnosis, p. 1477

Hepatitis B - Liver Disease Staging

Investigation	Normal	Chronic Hepatitis B	Cirrhosis	HCC
HBV DNA	Undetectable	>2,000 IU/mL	May be low or high	Variable
ALT	7-56 U/L	Elevated (1.5-5x ULN)	May normalize (burnt out)	May rise again
AST:ALT ratio	<1.0	Usually <1.0	>1.0 (AST>ALT = cirrhosis pattern)	>2.0
GGT	9-48 U/L	Mildly elevated	Elevated	High
Bilirubin	<1.2 mg/dL	Mildly elevated	Elevated (>2.5 mg/dL in decompensation)	High
Albumin	3.5-5.0 g/dL	Normal	Low (<3.0 g/dL decompensated)	Very low
PT/INR	INR <1.2	Normal	Prolonged INR >1.5	Prolonged
Platelet count	150,000-400,000	Normal	Low (<100,000 = portal hypertension)	Low
AFP (alpha-fetoprotein)	<10 ng/mL	Mildly elevated	10-100 ng/mL (watch)	>400 ng/mL strongly suggestive
Liver biopsy (Metavir)	F0	F1-F2	F3-F4	N/A
FibroScan (kPa)	<7 kPa	7-10 kPa	>12 kPa (F3-F4)	>17 kPa (cirrhosis)

Hepatitis C - Diagnosis & Treatment Monitoring

Investigation	Initial Screening	Confirmation	Pre-Treatment	SVR (Cure)
Anti-HCV antibody	Positive (ELISA)	Must do RNA next	-	Stays positive for life (not useful)
HCV RNA (PCR)	-	Positive = active infection	Quantify viral load	Undetectable at 12 weeks post-Rx = SVR
HCV Genotype	-	-	Types 1-6; guides DAA selection	-
ALT	Elevated	-	Severity of inflammation	Normal (cure)
Platelet count	-	-	Low = cirrhosis/portal HTN	Rising after cure
Cryoglobulins	-	-	Positive in 40-50% chronic HCV	Resolve after SVR
Serum IgM	-	-	Elevated (cryoglobulinemic vasculitis)	Falls after SVR
Rheumatoid Factor	-	-	May be positive (cryoglobulin-related)	Falls after SVR
Urinalysis	-	-	Proteinuria + hematuria = MPGN	Resolves after SVR

Henry's Clinical Diagnosis (Hepatitis B & C, p. 1477-1882)

PART 3 - FUNGAL & PARASITIC CHRONIC INFECTIONS

Aspergillosis (in Immunocompromised)

Investigation	Normal	Invasive Aspergillosis	Chronic Pulmonary	Allergic (ABPA)
Serum Galactomannan (GM)	<0.5 ODI	>0.5-1.0 (positive, two consecutive)	May be positive	Usually negative
Beta-D-glucan (BDG)	<60-80 pg/mL	Positive (>80 pg/mL)	Positive	Negative
Serum Aspergillus IgG	Negative	May be low (immunocompromised)	Positive	Positive
Serum Aspergillus IgE (specific)	<0.35 kU/L	-	-	Elevated (>0.35)
Total IgE	<100 IU/mL	Normal	Normal	Very high (>1,000 IU/mL)
Eosinophils	1-4%	Normal	Normal	Elevated (>500/µL)
BAL GM	<1.0	>1.0 (high sensitivity)	-	-
CT chest	Normal	"Halo sign" (early), "air-crescent sign" (late), cavitation	Cavitation + aspergilloma	Mucoid impaction, central bronchiectasis
WBC	Normal	Often low (neutropenic patient)	Normal	Normal-high

Cryptococcosis

Investigation	Normal	Cryptococcal Meningitis	Disseminated
Serum CrAg (cryptococcal Ag)	Negative	Positive (sensitivity >95%)	Positive
CSF CrAg	Negative	Very high titer (1:1,024 or more)	-
CSF India ink	Negative	Encapsulated yeast with clear halo	-
CSF Opening pressure	7-18 cmH2O	Very high (>25-40 cmH2O)	-
CSF WBC	<5 cells/µL	Mild lymphocytosis (10-50) or even normal in severe AIDS	-
CSF Glucose	45-80 mg/dL	Low to normal	-
CSF protein	15-45 mg/dL	Elevated	-
CD4 count	>500	Usually <100 cells/µL	<50 cells/µL
Urine Ag	Negative	Positive (disseminated)	Positive

Leishmaniasis (Visceral / Kala-azar)

Investigation	Finding
WBC	Very low (leukopenia 1,000-3,000)
Hemoglobin	Low (<8 g/dL, normochromic normocytic)
Platelets	Very low (<50,000) - pancytopenia pattern
ESR	Very high (>100 mm/hr)
Serum globulins (IgG)	Markedly elevated (hypergammaglobulinemia - reversed A:G ratio)
Serum albumin	Low (<3.0 g/dL)
LFTs	AST/ALT elevated, bilirubin elevated
Bone marrow / splenic aspirate	Leishman-Donovan (LD) bodies (intracellular amastigotes) - gold standard
rK39 rapid antibody test	Positive (sensitivity ~97% in South Asia)
Aldehyde test (Napier's)	Positive (gel-like coagulation due to hypergammaglobulinemia) - historical

PART 4 - SEPSIS & ADVANCED ORGAN DYSFUNCTION

SOFA Score - Laboratory Components

Organ System	Investigation	SOFA 0 (Normal)	SOFA 1	SOFA 2	SOFA 3	SOFA 4
Respiration	PaO2/FiO2 ratio	>400	300-400	200-300	100-200	<100
Coagulation	Platelets (/µL)	>150,000	100-150k	50-100k	20-50k	<20,000
Liver	Bilirubin (mg/dL)	<1.2	1.2-2.0	2.0-6.0	6.0-12.0	>12.0
Cardiovascular	MAP / vasopressors	MAP >70	MAP <70	Low-dose dopamine	High-dose dopamine	Norepinephrine +
Renal	Creatinine (mg/dL)	<1.2	1.2-2.0	2.0-3.5	3.5-5.0	>5.0
CNS	GCS	15	13-14	10-12	6-9	<6

SOFA ≥2 = organ dysfunction. SOFA rise >2 = sepsis (Sepsis-3 criteria, 2016).

Disseminated Intravascular Coagulation (DIC)

Investigation	Normal	DIC (Active/Overt)	DIC (Chronic/Low-grade)
PT	11-13 sec	Prolonged (>14 sec)	Mildly prolonged
aPTT	25-35 sec	Prolonged (>40 sec)	Normal or mildly prolonged
Fibrinogen	200-400 mg/dL	Very low (<150 mg/dL)	Normal-low (compensated)
D-dimer	<0.5 µg/mL	Very high (>4-10 µg/mL)	Elevated (>1-2 µg/mL)
FDPs (fibrin degradation products)	<5 µg/mL	Very high	Elevated
Platelets	150,000-400,000	Rapidly falling (<50,000 in severe)	Low-normal
Schistocytes (blood film)	0-<1%	>1% (microangiopathic hemolysis)	May be present
Antithrombin III	80-120%	Very low (<50%)	Moderately low
Factor V / VIII levels	50-150%	Very low	Low
Common causes	-	Gram-negative sepsis, trauma, obstetric crises, AML-M3	Malignancy, chronic infection

Symptom to Diagnosis 4th Ed: DIC = thrombocytopenia + prolonged PT + reduced fibrinogen + elevated D-dimer

PART 5 - IMMUNE COMPLICATIONS: AUTOIMMUNITY

Systemic Lupus Erythematosus (SLE) - EULAR/ACR 2019

Investigation	Normal	SLE (Active)	SLE (Remission)	Clinical Weight (EULAR score)
ANA (ELISA/IIF)	Negative (<1:40)	Positive ≥1:80 (>95% sensitivity - entry criterion)	May stay positive	Entry criterion
Anti-dsDNA	Negative (<7 IU/mL)	Highly positive; titre correlates with disease activity	Falls in remission	+6 points
Anti-Sm (Smith)	Negative	Positive in ~30% - highly specific (>99%)	Persists	+6 points
Anti-Ro/SSA	Negative	Positive in ~50-70%	Persists	-
Anti-La/SSB	Negative	Positive in ~30-40%	Persists	-
Anti-phospholipid Ab (aCL, LAC, anti-B2GP1)	Negative	Positive in ~40%	Variable	+2 points each
C3	90-180 mg/dL	Low (<90 mg/dL) - active nephritis	Normalizes with treatment	+3 points (low C3 or C4)
C4	16-47 mg/dL	Very low (<16 mg/dL)	Normalizes	+4 points (both low)
CH50	41-90 U/mL	Very low or undetectable	Normalizes	-
CBC	Normal	Hemolytic anemia (+4), leukopenia <4,000 (+3), thrombocytopenia <100,000 (+4)	May normalize	+3 to +4
Direct Coombs test	Negative	Positive (autoimmune hemolytic anemia)	-	+4
Urinalysis	Normal	Proteinuria >0.5g/day, RBC casts = lupus nephritis	Minimal protein	+4-8
ESR	<20 mm/hr	Very high (>60-100 mm/hr) during flare	Mildly elevated	-
CRP	<10 mg/L	Notably: CRP is often NORMAL or only mildly elevated in SLE flare (unlike RA)	-	Key differentiator

Clue: High ESR + normal/low CRP in a febrile patient = think SLE flare (not sepsis, where CRP is always high) Goldman-Cecil Medicine; Fuster & Hurst's The Heart 15e

Rheumatoid Arthritis (RA)

Investigation	Normal	Early RA	Established RA	Severe/Extra-articular RA
RF (IgM Rheumatoid Factor)	<14 IU/mL	Positive in ~70%	Positive	Very high titers
Anti-CCP (ACPA)	<20 U/mL	Positive in ~70-80% - more specific than RF	Positive	High
CRP	<10 mg/L	Elevated (20-100 mg/L)	Elevated correlates with activity	Very high in flare
ESR	<20 mm/hr	Elevated	Elevated (50-100 mm/hr)	Very high
CBC - Anemia	Hb 12-17 g/dL	Normal early	Normochromic normocytic (ACD)	Severe ACD; also drug-related
Platelet count	150-400k	Normal	Elevated (reactive thrombocytosis)	Elevated
WBC	4-11k	Normal or mildly elevated	Normal	Low (Felty syndrome: RA + splenomegaly + neutropenia)
ANA	Negative	May be weakly positive (30%)	-	-
Complement	Normal	Normal (RA = normocomplementemic)	Normal	Consumed in RA vasculitis
Synovial fluid WBC	<200 cells/µL	2,000-50,000 (inflammatory)	Inflammatory	>50,000 = septic arthritis must be ruled out
X-ray	Normal	Periarticular osteopenia, soft tissue swelling	Juxta-articular erosions	Severe erosions, joint destruction

Sjögren's Syndrome

Investigation	Finding
Anti-Ro/SSA	Positive in ~70-80% (most specific)
Anti-La/SSB	Positive in ~40-60%
ANA	Positive in ~80%
RF	Positive in ~75% (high levels - cryoglobulin-associated)
Serum IgG	Elevated (hypergammaglobulinemia)
Serum IgM	Elevated (cryoglobulins)
Complement (C3, C4)	Low in those with cryoglobulinemia
CBC	Mild lymphopenia, mild anemia
ESR	Elevated
CRP	Mildly elevated
Schirmer's test	<5 mm wetting in 5 min = dry eyes
Salivary gland biopsy	Focal lymphocytic sialadenitis (focus score >1)
Serum protein electrophoresis	Polyclonal hypergammaglobulinemia

PART 6 - PRIMARY IMMUNODEFICIENCIES

Antibody Deficiency Disorders

Condition	IgG	IgA	IgM	B-cells	Key Investigation	Clinical Pattern
XLA (Bruton's agammaglobulinemia)	Very low (<2 g/dL)	Very low	Very low	Absent	BTK gene mutation; absent B-cells (flow cytometry)	Recurrent bacterial infections from infancy; no viral susceptibility
CVID (Common Variable ID)	Low (<7 g/dL; <2 SD below mean)	Low	Low or normal	Normal or low number, dysfunctional	Vaccine response absent; B-cell phenotyping	Presents in 2nd-3rd decade; also autoimmunity, lymphoma risk
IgA Deficiency	Normal	Very low (<7 mg/dL)	Normal	Normal	Serum IgA level	Recurrent sinopulmonary infections; anaphylaxis to blood products
Hyper-IgM Syndrome	Very low	Very low	Normal or elevated	Normal	CD40L expression (flow cytometry); gene testing	Pneumocystis, Cryptosporidium infections; neutropenia
Steroid-induced hypogammaglobulinemia	Moderately low (>400 mg/dL)	May be low	Normal	Normal	Clinical context; dose-dependent	Dose and duration-dependent

Goldman-Cecil Medicine (Common Variable ID); Murray & Nadel's Respiratory Medicine (antibody deficiencies)

T-Cell / Combined Immunodeficiency

Condition	CD4	CD8	B-cells	NK cells	Ig Levels	Key Test
SCID (Severe Combined ID)	Absent or very low	Absent or very low	Present or absent	Variable	Very low all	Absent thymic shadow on CXR; lymphocyte proliferation assay - absent
DiGeorge Syndrome	Very low	Very low	Normal	Normal	Normal or low	FISH for 22q11.2 deletion; low PTH + hypocalcemia
Wiskott-Aldrich	Progressively low	Normal	Normal	Low	IgM low; IgA/E elevated; IgG normal	WASp protein by flow cytometry; WAS gene
Ataxia-Telangiectasia	Low	Normal	Normal	Normal	IgA very low; IgE low; IgG may be low	AFP very high (>10 ng/mL) - hallmark; chromosomal breakage studies
Chronic Granulomatous Disease (CGD)	Normal	Normal	Normal	Normal	Normal	DHR (dihydrorhodamine) flow cytometry - absent oxidative burst; NBT test

PART 7 - HAEMATOLOGICAL IMMUNE COMPLICATIONS

Haemophagocytic Lymphohistiocytosis (HLH)

This is a life-threatening hyperinflammatory syndrome triggered by infections (EBV most common), malignancy, or autoimmune disease.

Investigation	Normal	HLH (HScore/HLH-2004 criteria)	Significance
Ferritin	12-300 ng/mL	>500 ng/mL (>10,000 = highly specific)	Most sensitive marker; tracks disease activity
Temperature	36.1-37.2°C	>38.5°C (persistent)	Criterion
Spleen	Normal	Splenomegaly	Criterion
CBC - Cytopenia	Normal	≥2 cell lines low (Hb <9g/dL; Plt <100k; Neutrophils <1,000)	Criterion
Triglycerides (fasting)	<150 mg/dL	>265 mg/dL (≥3 mmol/L)	Criterion
Fibrinogen	200-400 mg/dL	Low (<150 mg/dL)	Criterion
Bone marrow biopsy	Normal	Haemophagocytosis (macrophages engulfing RBCs, WBCs, platelets)	Criterion
NK cell activity	Normal	Very low or absent	Criterion
sCD25 (soluble IL-2 receptor)	<2,400 U/mL	Very high (>2,400 U/mL; often >10,000)	Criterion; correlates with T-cell activation
LDH	140-280 U/L	Very high (>600-1,000 U/L)	Tissue destruction
CRP	<10 mg/L	Very high (>100-300 mg/L)	Inflammation
EBV PCR	Undetectable	Positive in EBV-HLH	Identifies trigger
AST/ALT	<40 U/L	Markedly elevated	Hepatitis from haemophagocytosis

5 of 8 HLH-2004 criteria = diagnosis. Ferritin >10,000 + cytopenia + high triglycerides = strong suspicion.

Macrophage Activation Syndrome (MAS) - Overlap with HLH in Rheumatic Disease

Investigation	Normal	MAS (complicating SLE/sJIA)
Ferritin	<300 ng/mL	Rapid rise >500 ng/mL; often >10,000
ESR	<20 mm/hr	Paradoxically FALLS (fibrinogen being consumed) - key differentiator from SLE flare
CRP	<10 mg/L	Markedly elevated
Platelets	>150k	Rapidly falling
Fibrinogen	200-400	Falling
D-dimer	<0.5	Rising
WBC	4-11k	Falling (leukopenia)
LDH	140-280	Very high
AST/ALT	Normal	Elevated

Clinical clue: A patient with active autoimmune disease who develops FALLING ESR + RISING ferritin + pancytopenia = think MAS before thinking disease flare.

MASTER PATTERN RECOGNITION TABLE

Lab Pattern	Think First	Also Consider
CD4 <200 + lymphocytosis (atypical) + LDH very high + BDG positive	PCP pneumonia	Cryptosporidiosis
Pancytopenia + very high ferritin (>10,000) + splenomegaly + haemophagocytes on BM	HLH	MAS, disseminated TB
HBsAg+ >6 months + HBeAg+ + high HBV DNA + elevated ALT	Active chronic hepatitis B	Needs antiviral therapy
Anti-HCV+ but HCV RNA undetectable	Cleared/resolved HCV (no treatment needed)	False-positive Ab screen
High ANA + high anti-dsDNA + low C3/C4 + proteinuria + normal CRP	Active SLE (nephritis)	Drug-induced lupus (no low complement)
High RF + high anti-CCP + high CRP + elevated platelet	Rheumatoid Arthritis	-
Reversed albumin:globulin ratio + pancytopenia + splenomegaly + fever in endemic area	Visceral Leishmaniasis
Rising CD4 + falling viral load + NEW fever/lymphadenopathy + high CRP	IRIS (immune reconstitution)	ART drug reaction
PT prolonged + aPTT prolonged + fibrinogen very low + D-dimer very high + schistocytes	DIC (sepsis, trauma, obstetric)	TTP (normal PT/fibrinogen; schistocytes + very low platelets)
IgG very low + IgA very low + IgM very low + absent B-cells in male infant	XLA (Bruton's)	SCID
IgA isolated low + recurrent sinopulmonary infections + normal other Ig	Selective IgA deficiency	-
AFP very high + cerebellar ataxia + telangiectasias	Ataxia-Telangiectasia	-

BIOMARKER SEVERITY LADDER - AT A GLANCE

Biomarker	Mild Disease	Moderate	Severe	Life-Threatening
Ferritin	300-1,000	1,000-5,000	5,000-10,000	>10,000 (HLH/MAS)
D-dimer	0.5-1.0 µg/mL	1-4 µg/mL	>4 µg/mL	>10 µg/mL (overt DIC)
LDH	280-500	500-1,000	1,000-2,000	>2,000 (HLH, PCP, severe hemolysis)
Beta-2 microglobulin	2.5-4 mg/L	4-6 mg/L	>6 mg/L	(lymphoma, CKD staging, HIV severity)
sCD25 (IL-2R)	Mildly elevated	2,400-5,000 U/mL	5,000-10,000	>10,000 (HLH)
CD4 count	200-500 (HIV)	100-200	50-100	<50 (end-stage AIDS)

Sources: Harrison's Principles of Internal Medicine 22E | Goldman-Cecil Medicine | Harriet Lane Handbook 23e | Henry's Clinical Diagnosis and Management by Laboratory Methods | Firestein & Kelley's Textbook of Rheumatology | Murray & Nadel's Respiratory Medicine | Dermatology 5e (EULAR/ACR SLE criteria) | Symptom to Diagnosis 4th Ed | Tietz Textbook of Laboratory Medicine 7e

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