Lab Medicine 👨🔬 Flashcards
1
Q
Blood elements
A
2
Q
What does a CBC measure?
A
3
Q
What is Hematocrit?
A
- The ratio of the volume of red blood cells to the total volume of blood.
4
Q
What is Mean corpuscular volume (MCV)?
A
The average volume of single RBC
5
Q
What is Mean corpuscular Hemoglobin (MCH)?
A
The average amount of Hb present in single RBC
6
Q
What is Mean corpuscular Hemoglobin Concentration (MCHC)?
A
The % ratio of Hb concentration in a single RBC in relation to its volume
7
Q
What is the definition of anemia?
A
- Reduction of the red cell mass due to decrease in Hb concentration And, or RBCs count below the normal for age & sex.
8
Q
Classification of anemia
A
9
Q
Examples of Microcytic, Hypochromic anemia
A
- Iron deficiency
- Thalassemia.
- Sideroblastic anemia.
- Anemia of chronic disease.
10
Q
Examples of Normocytic, Normochromic anemia
A
- Hemolytic anemia: Except thalassemia.
- Aplastic anemia.
- Acute hemorrhage.
11
Q
Examples of Macrocytic anemia
A
Megaloblastic anemia:
* B12 & folic acid deficiency.
Non-megaloblastic anemia:
* Liver disease.
* Acute hemolysis.
* Acute blood loss.
* Hypothyroidism.
12
Q
What is the most common form of anemia?
A
IRON DEFICIENCY ANEMIA
13
Q
Pathophysiology of iron deficiency anemia
A
Iron deficiency leads to decrease in the Production of hemoglobin.
14
Q
Lab diagnosis of iron deficiency anemia
A
- Blood exam
- BM Exam
- Iron Studies
15
Q
Blood exams in iron deficiency anemia
A
Anemia: typically, Microcytic Hypochromic.
Blood indices: Decrease in (MCV + MCH + MCHC).
16
Q
Bone marrow exam in iron deficiency anemia
A
- Erythroid hyperplasia.
- Absence of iron stores.
17
Q
Iron studies in iron deficiency anemia
A
18
Q
What are the best test for iron deficiency anemia?
A
Serum ferritin
19
Q
Classification of megaloblastic anemia
A
- Vit B12 deficiency.
- Folic acid deficiency.
20
Q
Pathophysiology of megaloblastic anemia due to vitamin B12 deficiency
A
B12 deficiency —> Impaired nucleic acid synthesis in all cells (including RBCs) —> Defect in maturation of RBCs (Megaloblastic erythropoiesis) & Neurological damage (so called pernicious anemia).
21
Q
Blood exam of megaloblastic anemia
A
Hemogram shows:
* Macrocytic anemia (MCV > 100 fl).
* Moderate neutropenia (Dec in Neutrophil).
* Thrombocytopenia (Dec in Platelet count).
22
Q
Laboratoey Diagnosis of megaloblastic anemia
A
- Blood Exam
- BM Exam
23
Q
What does blood film of megaloblastic anemia show?
A
- Howell -Jolly bodies.
- Oval macrocytes.
- Anisopoikilocytosis: RBCs different sizes & shapes.
- Large hyper segmented neutrophils.
- Giant platelets.
24
Q
What does bone marrow exam show for megaloblastic anemia?
A
- Hypercellular (Due to erythroid hyperplasia).
- Megaloblasts (Large than normoblast, with large nucleus).
- Atypical megakaryocytes (With hyper-segmented nuclei).
25
Types of hemolysis
26
What is the structure of hemoglobin?
- 4 globin chains + 4 heme molecule.
27
What are hemoglobin variants?
28
What is thalassemia and what causes it?
- Inherited (Autosomal recessive) & chronic hemolytic anemia
- Due to globin chain imbalance.
29
Classification of thalassemia
- Acc to the type of the globin chain that is produced at reduced rate into Alpha & Beta Thalasemia
30
Blood exam of beta thalassemia major
31
Compare between alpha thalassemia, and Beta thalassemia
32
Bone marrow exam of beta thalassemia major
- Intense erythroid hyperplasia.
- With marked ineffective erythropoiesis.
33
Definitive tests for diagnosis of beta thalassemia major
- Hb electrophoresis --> Inc in Hb F (10-90%)
- Molecular characterization of globin gene mutation.
34
Blood exam of Thalassemia minor
Blood indices: decrease in (MCV + MCH) & Normal RDW.
35
Definitive tests for Thalassemia minor
36
What is Sickle cell anemia?
- Autosomal recessive disorder due to amino acid substitution in beta globin chain.
37
Pathophysiology of Sickle cell anemia
Point mutation in the B-globin gene (chromosome 11) ---> glutamic acid replaced with valine (single amino acid substitution) ---> 2 a-globin & 2 mutated B-globin subunits create pathological hemoglobin S (HbS).
38
Clinical features of Sickle cell anemia
**Carriers (sickle cell trait):**
- are usually normal (symptom-free).
**Patient:**
- suffer from many types of crises:
* Hemolytic.
* Aplastic.
* Vaso-occlusive.
* Spleen sequestration.
39
Lab diagnosis of Sickle cell anemia
- Blood Exam
- RBCs fragility test
- Definitive tests
40
Blood exam of Sickle cell anemia
CBC shows Normocytic normochromic anemia.
41
RBCs osmotic fragility test for Sickle cell anemia
Decreases
42
Definitive tests for diagnosis of Sickle cell anemia
43
Pathophysiology of hereditary Spherocytosis
Abnormality in membrane cytoskeleton leads to decrease in RBC deformability (flexibility).
44
Presentation of hereditary Spherocytosis
- At neonatal, adult or even old age.
45
Lab diagnosis of hereditary Spherocytosis
- Blood Exam
- RBCs osmotic fragility test
46
Blood exam of hereditary Spherocytosis
47
RBCs osmotic fragility test for hereditary Spherocytosis
- Increases
**(Specific test for spherocytosis)**
48
Enzymopathies related to blood disorders
- G6PD deficiency (Favism)
- Pyruvate kinase deficiency
49
What is the most common hemolytic anemia?
- G6PD enzyme deficiency (favism)
50
Inheritance of G6PD deficiency (Favism)
X- linked recessive: So most often affects males.
51
Presentation of G6PD deficiency (Favism)
- Neonatal or infancy period
- In Between attacks the child is completely normal.
52
Risk factors of G6PD deficiency (Favism)
Precipitating agents of hemolytic crisis:
- Drugs.
- Acidosis.
- Infection.
- Fava beans or their pollens.
53
Definitive tests for diagnosis of G6PD deficiency (Favism)
Assay for G6PD enzyme activity
54
Blood exam of G6PD deficiency (Favism)
55
Definition of anemia due to Pyruvate kinase deficiency
- Congenital non-spherocytic hemolytic anemia
56
CBC of Pyruvate kinase deficiency
CBC shows:
- Hb: usually 7-10 g/dI.
- Blood smear: No characteristic changes
57
definitive test for pyruvate kinase deficiency
Determination of pyruvate kinase enzyme activity.
58
Why are white blood cells called leukocytes?
as they are colorless, Due to lack of Hemoglobin.
59
Lifespan of white blood cells
- Few hours to a few days.
60
Total leukocytic count
61
Differential leukocytic count
62
Compare between white blood cells and red blood cells in stained preparation
63
What are blood cells derived from?
hematopoietic stem cells
64
Differentiation of hematopoietic stem cells
65
Definition of acute leukemias
A heterogeneous group of malignant neoplasms of the precursors of blood cells resulting in appearance of the blast cells in the blood & bone marrow.
**(Blast cells = partially developed WBCs)**
66
Classification of acute leukemia
67
Etiology of acute leukemias
It is unknown but theories are implicated:
- lonizing radiation.
- Drugs & chemicals: as immunosuppressive agents & benzene.
- Genetics: chromosomal abnormalities.
- Infection: Retrovirus.
- Immune status: increased incidence of immunosuppressed individuals
68
Types of acute leukemia
- According to the type of the affected blast cells)
1. (Acute Lymphoblastic Leukemia (ALL) -› Mainly in infants.
2. (Acute Myeloblastic Leukemia (AML) -> Mainly In adults.
69
FAB classification of acute lymphoblastic leukemia (ALL)
70
Pathophysiology of acute leukemias
mutation (e.g. chromosomal translocation) in the blast in bone marrow ---> Which affect cell division & function.
71
FAB classification of acute myeloblastic leukemia (AML)
72
Cytochemistry of acute lymphoblastic leukemia (ALL)
- MPO (Myeloperoxidase): Negative.
- PAS stain (Periodic Acid Schiff): Positive.
73
Cytochemistry of acute myeloblastic leukemia (AML)
- MPO: Positive.
- PAS: Negative.
74
Immunophenotyping for acute Lymphoblastic leukemia (ALL)
75
Immunophenotyping for acute myeloblastic leukemia (AML)
CD13, CD33, CD117 & others.
76
Cytogenes of acute Lymphoblastic leukemia (ALL)
t (12;21)] & [t (8;14)].
77
Cytogenes for acute myeloblastic leukemia (AML)
- M3: [t(15;17) ]. & Other cytogentic abnormalities in different FAB Subtypes e.g. inv 16: [t(8;21 )].
78
Hematological Findings of acute leukemia
79
Bone marrow findings of acute leukemia
- Hypercellular & infiltrated with blast cells (>20%).
80
Biochemical findings in acute leukemia
- Increased Serum uric acid.
- Increased Serum LDH.
81
What are Lymphoproliferative disorders (LPDS)?
- A group of both malignant (clonal) lymphoid disorders.
82
What should Lymphoproliferative disorders (LPDS) Be diffrentiated from?
from reactive (polyclonal) lymphoid disorders
83
What do Lymphoproliferative disorders (LPDS) Include?
- Chronic lymphocytic leukemia (CLL).
- Hairy cell leukemia (HCL).
- Plasma cell leukemia (PCL).
- Non-Hodgkin's lymphoma (NHL).
- Large granular lymphocytosis.
84
Epidemiology of Chronic Lymphocytic leukemia (CLL)
**Age:**
- Affect older people (>50 years old).
- Incidence increases with age.
**Sex:**
- Male predominance.
85
Diagnostic criteria for Chronic Lymphocytic leukemia (CLL)
- Peripheral blood: Absolute lymphocytosis > 5.0 × 10°9 /L.
- Bone marrow: Lymphocytosis > 30% of total bone marrow cells.
86
What is the difference between absolute lymphocytosis and relative lymphocytosis?
87
Definition of plasma cell dyscrasias
- A group of disorders characterized by abnormal proliferation of the same type (=single clone =monoclonal) of a plasma cell (Immunoglobulin-selecting cells).
- That may also secrete a single homogenous immunoglobulin (ig) and/or immunoglobulin fragment (e.g., light chain) -› increase in their serum level.
88
What do plasma cells Dyscrasias include?
- Multiple Myeloma.
- Waldenstrom's macroglobulinemia.
- Solitary Plasmacytoma.
- Others.
89
What are myeloproliferative disorders?
- Related hematopoietic stem cell malignancies from myeloid lineage.
90
Diagnostic criteria for multiple myeloma (plasma cell myeloma)
91
Classification of myeloproliferative disorder
92
Diagnostic criteria for chronic myeloid leukemia (CML)
93
Philadelphia chromosome
94
Definition of polycythemia vera
- Increased Erythrocyte cell mass leads to increase in hematocrit, blood volume & blood viscosity with subsequent thrombotic or hemorrhagic problems.
95
Diagnostic criteria for polycythemia vera
96
Etiology of myloid metaplasia (myelofibrosis)
- Unknown so called agnogenic
97
Pathophysiology of myloid metaplasia (myelofibrosis)
98
What characterizes (symptoms) myloid metaplasia (myelofibrosis)?
- Extramedullary hematopoiesis (Formation of blood outside the BM as in spleen).
- Splenomegaly.
99
Natural History of myloid metaplasia (myelofibrosis)
Two phases:
- Initial cellular phase (early phase).
- Pancytopenic phase (late phase): due to progressive bone marrow failure (fibrosis.
100
Diagnostic criteria for myloid metaplasia (myelofibrosis)
101
Clinical features of essential Thrombocytopenia
The increased blood platelets lead to episodic symptoms:
- Thrombosis.
- Bleeding (as majority of newly formed platelets are dysfunctional).
- Acute leukemia (in < 1 %).
102
Diagnostic criteria for essential Thrombocytopenia
103
Janus kinase (JAK)
- An intracellular tyrosine kinase
- Mutations in the JAK2 gene are associated with certain myeloproliferative neoplasms, including polycythemia vera, primary myelofibrosis, and essential thrombocythemia.
104
Definition of hemoglobin electrophoresis
- It is a test that measures the different types of hemoglobin in the blood.
- It also looks for abnormal types of hemoglobin.
105
Principle of hemoglobin electrophoresis
106
What is the charge of hemoglobin in electrophoresis?
Negatively charged at alkaline pH
107
Results of hemoglobin electrophoresis (interpretation)
108
Steps of sickling test
- Mixing blood with reducing agent --> **(Sodium metabisulphite)**
- This will induce sickling insusceptible cells.
109
Results of sickling test
110
Steps of sickle solubility test
Mix Hb with a reducing solution
**(sodium dithionite)**
111
Results of solubility test
112
Definition of osmotic fragility test
- A measure of the resistance of erythrocytes to hemolysis by osmotic stress.
113
Results of osmotic fragility test
114
Principle of immunophenotyping analysis
115
Steps of immunophenotyping analysis
116
Definition of cytogenetics
- The study of chromosome & the related disease states caused by abnormal chromosome number and/or structure.
117
Definition of bone marrow aspiration
- The removal of a small amount of Bone Marrow (in semi-liquid form for examination)
118
Sites of bone marrow aspiration
- Iliac crest.
- Sternum.
- Tibial plateau.
119
Tool used in bone marrow aspiration
120
Definition of bone marrow biopsy
- The removal of a small amount of:
* Bone.
* Fluid & cells.
(From inside the bone.)
121
Sites of bone marrow biopsy
122
Tool used in bone marrow biopsy
123
Definition of normal hemostasis
- Mechanism by which bleeding from an injured vessel is arrested by formation of a thrombus.
124
Function of normal hemostasis
- To maintain the blood in fluid state.
- In intact vessels → Prevent clots.
- In injured vessels → Arrest bleeding
125
Components of normal hemostasis
126
Diagnosis of bleeding disorders
- History
- Clinical examination
- Laboratory investigation
127
Precautions during sample collection
128
Steps of blood sample collection
129
Which anti-coagulant is used during blood sample collection?
Trisodium citrate (1:9)
130
What are lab tests related to hemostasis?
131
Read notes about intrinsic and extrinsic pathways of coagulation
132
Significance of prothrombin time (PT)
Reflects: efficiency of extrinsic pathway.
133
Principle of prothrombin time (PT)
134
What is prothrombin time (PT) Sensitive to?
* Change in factor V - VII - X (Mostly)
* Change in factor I - Il (Lesser)
135
What causes prolonged prothrombin time (PT)?
* Deficiency of factor VII - X - V - II - I.
* Vit K Deficiency.
* DIC.
* Oral anticoagulant.
* Liver disease especially obstructive jaundice.
136
Range of prothrombin time (PT)
- With rabbit thromboplastin → 11 - 16 sec
- With human thromboplastin → 10 - 12 sec
137
Why should **activated partial thromboplastin time (APTT)** be done without the addition of tissue thromboplastin?
138
Significance of activated partial thromboplastin time (APTT)
Reflects: efficiency of intrinsic pathway
139
What is activated partial thromboplastin time (APTT) Sensitive to?
Sensitive to:
* Changes in factor VIII - IX - XI - XII.
* Heparin & circulating anticoagulant.
140
Range of ** activated partial thromboplastin time (APTT)**
26 to 40 sec.
141
What causes prolonged APTT?
* Deficiency of Factor VIII (Hemophilia A).
* Deficiency of FIX (Hemophilia B).
* DIC.
* Heparin therapy.
* Circulating anticoagulant.
* Liver disease.
* Massive transfusion of plasma depleted blood.
142
Significance of **Bleeding time**
Assess: primary hemostatic defect (vessel wall or platelet)
143
What does **Bleeding time** Depend on?
Adequate functioning of platelet
& Blood Vessels.
144
Method of **Bleeding time**
- Ivy's method.
- Duke's (not recommended).
- Template method.
145
Ranges of **Bleeding time**
- Ivy's method →2 to 7 mins.
- Template method → 2.5 to 9.5 mins.
146
Causes of prolonged **Bleeding time**
* VWD = Von Willebrand Disease.
* Thrombocytopenia.
* Platelet function disorder.
* Disorders of blood vessels.
147
Tests for bleeding disorders
148
what is the most common cause of bleeding disorders?
vascular
149
Definition of **blood transfusion**
- Injection of a volume of blood or blood products obtained from a healthy person (donor) into the circulation of a patient (recipient) whose blood is deficient in quantity or quality.
150
What is **donated blood** subjected to after collection?
- Donated blood is usually subjected to processing after collection & separated into blood components by differential centrifugation.
151
Blood components
- Whole blood (donor & recipient must be ABO identical).
- Packed RBCs.
- Platelet concentrates.
- Fresh frozen plasma.
- Cryoprecipitate.
- Protein solution.
- Factor concentrate.
- Granulocyte concentration.
152
Blood after centrifugation
153
Storage of **whole blood**
- At 4°C.
- For up to 35 days.
154
Indications of **whole blood**
- Hemorrhage: Sudden loss of 25% or more of blood volume.
- Patients undergoing exchange transfusion.
155
Storage of **Packed RBCs**
- At 4°C.
- For up to 42 days.
156
Benefits of **Packed RBCs**
1 unit of packed cell: increases the level of
- Hb by 1g/dl.
- Hematocrit by 3%.
157
Indications of **Packed RBCs**
- Acute blood loss: Sudden loss of 30% or more of blood volume.
- Symptomatic chronic anemia without hemorrhage.
- Cardiac failure.
158
Storage of **Platelets**
- At 20-24°C (room temp)
- For up to 5 days.
159
Benefits of **Platelets**
1 unit /10kg of body weight → increases count of platelet by 50,000.
160
Preparation of **Platelets**
- It is the precipitate after platelet-rich plasma is centrifugated at 3000 rev/min.
161
Indications of **Platelets**
- Patients with thrombocytopenia or platelet function defect.
- correction of coagulopathy (if platelet count <50,000/ml).
162
Storage of **fresh frozen plasma**
- At -18 °C or colder.
- For up to 12 months.
163
Preparation of **fresh frozen plasma**
It is the supernatant liquid portion when fresh blood is centrifugation at 3000 rev/min.
164
Indications of **fresh frozen plasma**
- Deficiencies of coagulation factors.
- Emergency TTT of vit k deficiency.
- TTT of TTP.
- TTT of DIC.
165
What are TTP & DIC short for respectively?
TTP = Thrombotic Thrombocytopenic Purpura
DIC = Disseminated Intravascular Coagulation
166
Preparation of **Cryoprecipitate transfusion**
Precipitate formed when Fresh Frozen Plasma (FFP) is thawed at 4°C
167
Importance of **Cryoprecipitate transfusion**
168
Types of blood transfusion complications
- Acute transfusion reaction
- Delayed transfusion reaction
169
Duration of acute transfusion reaction
Within 24hrs
170
Types of acute transfusion reactions
**Immunologic**
- Hemolytic transfusion reaction.
- Febrile non-hemolytic reaction.
- Allergic reaction.
- TRALI = Transfusion - Related Acute Lung injury
**Non-immunologic**
- Bacterial contamination.
- Transfusion - associated circulatory overload.
- Acute hypotensive reaction.
- Physical hemolysis: Hypothermia, Hyperkalemia & Acidosis
171
Duration of delayed transfusion reactions
After 24hrs
172
Types of delayed transfusion reactions
**Immunologic**
- DHTR = Delayed Hemolytic Transfusion Reaction.
- Post-transfusion thrombocytopenic purpura.
- Alloimmunization (RBCs - WBCs - platelet)
- GVHD = Graft Versus Host
**Non-immunologic**
- Hemosiderosis = Iron overload.
- Citrate
173
What are Transfusion related infections?
- Viral hepatitis (A-B-C-D).
- Syphilis.
- Malaria.
- HIV (AIDS).
- CMV infection
174
| How will lab imact this patient care??
175
Urine analysis
176
What is **Neutrophil Estrase**?
- an enzyme produced by WBC.
177
What forms Nitrite in urine?
- Formed by reducing nitrate by the action of gram -ve bacteria (e.g., E. Coli).
178
Interpreration of urine tests
179
TTT of UTI
- antibiotic with dose adjustment
180
What are renal function tests?
181
What are tubular functions tests?
- Water deprivation test
- DDAVP test
- Urine acedification test
182
Principle of **Water Deprivation test**
The ability of the tubules to reabsorb water (Concentrate the urine)
183
Importance of **Water Deprivation test**
- Indicates the Prescence or absence of diabetes insipidus.
184
Principle of **DDAVP test**
- DDAVP is a synthetic analogue of desmopressin.
185
Importance of **DDAVP test**
- Determine the type of diabetes insipidus (Neurogenic or
Nephrogenic)
186
Principle of **Urine Acidification test**
- The ability of the tubules to excrete H (Excrete acidic urine).
187
Importnace of **Urine Acidification test**
- Indicates if the cause of metabolic acidosis is tubular or not.
188
What are glomerular function tests?
Clearance test
189
Def of GFR
- Amount of the plasma that filtered through the glomeruli each minute.
190
Normal Range of GFR
- 100-125 ml/min for a body surface area of 1.74 m2
191
Factors that decrease GFR
192
Def of **Substance Clearance**
- The volume of plasma in ml. cleared of this substance in 1 min through urine.
193
What are factors that affect **Substance Clearance**?
194
Substance used in **Substance Clearance**
Creatinine & not inulin is preferred why?
- As creatinine is an endogenous substance.
195
Calculation of **Substance Clearance**
196
Importance of **Creatinine Clearence**
Assessment of GFR.
197
Calculation of **Creatinine Clearence**
CLcr Equation
198
Normal Range of **Creatinine Clearence**
90-110 ml / min
199
Sample collection for **Creatinine Clearence**
- Urine sample: (24h sample collection).
- Blood sample: Serum Creatinine analysis.
200
Interpretation of **Creatinine Clearence**
Decrease in CLcr ---> decrease in GFR ----> (So decrease drug dose)
201
Relation between **Creatinine Clearence** And Antibiotic dosing
202
What are **Blood Estimates**?
203
Blood Urea
- Formation
- Excretion
- Test
- Increases in cases of
204
Uric Acid
- Formation
- Excretion
- Test
- Increases in Cases of
205
What happens to plasma proteins in **Nephrotic Syndrome**?
- accompanied by a marked lowering of the plasma, protein concentration, particularly albumin
206
Def of **Arterial Blood Gas (ABG)**
- A test used to measure 02 saturation, Co2 & bicarbonate blood levels.
207
Significance of **Arterial Blood Gas (ABG)**
- It provides quick assessment of acid-base balance.
208
Normal level of **Plasma pH**
7.4 (Range 7.35 - 7.45).
- Corresponding to H+ concentration of 40 nmol/L (range 36 - 43 nmol/L.)
209
How is **Plasma pH** Maintained?
maintained within these narrow limits through strict regulations by:
- Body buffers.
- Respiratory mechanisms.
- Renal tubular mechanisms.
210
What are acid-base disorders?
211
How are Acid-Base Disorders maintained?
212
Collection of ABG sample
213
What are requirments for MI diagnosis?
Requirements of MI diagnosis:
- Panel of markers.
- Serial measurement.
- Timing of sample from onset of chest pain is important.
**Sample Collection:**
1. A venous blood sample was withdrawn into plain tube without additive.
2. Then clotting of blood sample & serum is separated.
214
What are **Cardiac markers**?
215
Lab tests of Cardiac markers
216
What is **POCT**?
(Point Of Care Testing):
* Rapid test performed where healthcare is provided close to or near the patient.
217
Kinetics of Cardiac markers after AMI
218
What is **Troponin**?
- A regulatory protein in striated muscle.
219
What is the most sensitive & Specific **(Definitive)** Cardiac Marker?
Troponin
220
What is the last marker to dissapear?
Troponin
221
What is the first marker to appear?
Myoglobin (4 Hrs after AMI)
222
Why isn’t Myoglobin specific?
as it increases in...
* Acute myocardial infarction (AMI).
* Muscle damage.
* Renal failure.
223
CK
224
LDH
225
What are **Acute Phase Proteins**?
Plasma proteins whose concentrations If by enhanced synthesis & release following inflammations.
226
What causes increase in **Acute Phase Proteins**?
227
What are Commonly measured **Acute Phase Proteins**?
* C-reactive protein. (Especially hs-CRP)
* Complement.
* a1 antitrypsin.
* Fibrinogen.
* Haptoglobins.
* a 2 macroglobulin.
228
Serum Creatinine
- Formation
- Excretion
- Test
- Increases in Cases of
229
Synthetic Liver Function tests
- Plasma proteins.
- Prothrombin time.
230
Test for integrity of hepatocytes
- Transaminases (ALT & AST).
231
Liver Function tests
- Excretory
- Synthetic
- Integrity of hepatocytes
- Tests for cholestasis
232
Tests for **cholestasis**
- Alkaline Phosphatase (ALP).
- Gamma Glutamyl Transferase (GGT).
233
Excterory Liver Function tests
- Serum bilirubin.
- Urinary Bile Pigment.
- Bile acids.
234
Metabolism of Hb
235
How does Bilirubin exist in the serum?
- Unconjugated (indirect) bilirubin
- Conjugated (Direct) bilirubin
236
Compare between unConjugated & Conjugated bilirubin in terms of:
- Normal Site
- Solubility
- Fate
237
What is the Fate of urobilinogen?
- Most of it converted into stercobilin & excreted in feces (brown color).
- Part of it oxidized to urobilin & excreted in urine (yellow color).
238
Def of **Delta-Bilirubin**
- Conjugated bilirubin covalently bound to albumin.
239
Level of **Delta-Bilirubin**
- Normally: Absent or present in very small amount.
- Increases in: cholestasis (in parallel with other fractions).
240
Clearence of **Delta-Bilirubin**
- Cleared slowly from circulation to urine so:
- When jaundice resolves the delta fraction (which is not filtered) still present & bilirubin testing may become -ve in spite of high serum level.
241
Causes of increased unconjuguated bilirubin
242
Causes of increased Conjugated bilirubin
243
What is **Gilberts Syndrome**?
**Most common cause of Unconjugated hyperblirubinemia**
- Deficiency of uridinediphosphoglucuronyl transferase enzyme (UDP-GT).
- There is defect in the uptake by hepatocytes.
244
What is **Dubin-Johnson Syndrome**?
- A defect in excretion of bilirubin by hepatocyte.
245
Site of formation of plasma proteins
**Most of them:** in liver.
**Except gamma globulins:** in plasma cells.
246
Level of albumin
- Represent: 60% of total serum protein.
- Level: 3.5 - 5.0 g/di.
247
What happens to synthetic liver function tests in advanced hepatic affection?
248
What happens in patients with hepatocellular damage?
**Concerning Blood coagulation factors**
Decrease in Coagulation factors → Increase Prothrombin time [PT] (an early abnormality in this disease).
249
What forms blood coagulation factors?
- Most of coagulation factors (except factor VIII) & fibrinolytic enzymes → by the liver.
- Factor VIII → by spleen.
250
Normal site of **ALT & AST**
Inside Hepatocytes
251
What hapens to serum Levels of **ALT & AST** in hepatitis?
252
What is **Preicteric phase**?
- the period prior to appearance of jaundice
253
What happens to serum level of **ALP** in Obstructive Jaundice?
In obstructive jaundice "serum level is markedly elevated (>3 URL)"
254
What are other causes of elevated **GGT**?
Alcohol & barbiturates
255
What happens to serum level of **GGT** in cholestasis & Liver cirrhosis?
Serum Level: Inc. in cholestasis & liver cirrhosis (but the rise is marked in cholestasis).
256
257
Types of **Plasma amaylase**
- Salivary (S-isoenzyme)
- Pancreatic (P-isoenzyme): More specific & sensitive for diagnosis of acute pancreatitis.
- Total amylase activity > 10 times URL is virtually diagnostic of acute pancreatitis.
258
Definition of **Tumor Markers**
- A substance found in an increased amount in (blood - other body fluids - body tissues) that may suggest the presence of a type of cancer.
259
Method of measurment of **Tumor Markers**
- Qualitatively or quantitatively by chemical, immunological or molecular biological methods (PCR) to identify the presence of cancer.
260
Uses of **Tumor Markers**
**Screening in general population:**
- It is of limited value as it doesn't confirm diagnosis.
- May aid diagnosis in high-risk people.
**Differential diagnosis in symptomatic individuals:**
- But must be in conjunction with clinical & radiological evidence.
**Prognostic indicator of disease progression:**
- As the plasma concentration correlates with the tumor mass.
**Monitoring of response to therapy & detecting recurrence.**
261
Categories of **Tumor Markers**
- Enzymes
- Hormones
- Oncofetal Antigens
- Blood Group Antigens
- In addition to : Proteins, Hormone Receptors, Genetic markers
262
Enzyme **Tumor Markers**
263
Oncofetal antigins as **Tumor Markers**
264
Hormonal **Tumor Markers**
265
Blood group antigens as **Tumor Markers**
266
What is a **Sample**?
A biological material taken from a patient for diagnostic, prognostic or therapeutic monitoring.
267
Types of samples
- Blood.
- Sweat.
- Urine & other fluids.
- Semen.
Feces.
Tissue.
268
Collection site of blood samples
269
Types of blood samples
- Venous sample.
- Capillary sample.
- Arterial sample.
270
In Blood sample collection, Avoid the hand with ……
- Extensive scarring.
- Burn.
- Hematoma.
- Containing I.V. access for I.V. infusion.
- Infection.
- On the side of mastectomy.
- Edema.
271
Cleansing of venipuncture site
272
Types of urine samples
273
Outcomes of Improper sample collection
274
Specimen Quality & Markers for rejection
275
Tests to assess thyroid function
TSH (Thyroid Stimulating Hormone).
Free T3.
Free T4.
276
What are other tests to assess the function of thyroid gland?
TSI
277
Aim of **TSI Testing**
to determine the cause of the disease.
278
Lab results of **TSI**
279
Thyroid Disorders and T4,T3 & TSH levels
280
What are Variables affecting (T3- T4 - TSH) testing?
- Hospitalized patient & recovery from Iliness.
- Pediatric & neonate.
- Pregnancy.
- Drug treatment.
- Assay interference.
- Reference range.
- Follow up test selection.
281
Def of **Euthyrold sick syndrome (ESS)**
- Abnormal levels of thyroid hormones despite normal thyroid gland function.
282
Synonyms of **Euthyrold sick syndrome (ESS)**
- Sick Euthyroid Syndrome (SES).
- Non-Thyroidal tilness syndrome (NTI).
283
Etiology of **Euthyrold sick syndrome (ESS)**
Occurs in severe illness or severe physical stress Most common in intensive care patients"
284
Pathophysiology of **Euthyrold sick syndrome (ESS)**
285
Patterns of **Euthyrold sick syndrome (ESS)**
286
Neonatal Thyroxine Levels at birth
287
Clinical features of **Euthyrold sick syndrome (ESS)**
No symptoms of hypothyroidism (as It Is a temporary state).
288
TTT of **Euthyrold sick syndrome (ESS)**
Once the person recovers from the Iliness → thyrold hormone returns to normal.
289
Neonatal Thyroxine Levels then
290
Examples of **Conditions causing Increase of plasma TBG**
Cases associated with Increased estrogen:
* Pregnancy.
* Oral contraceptives.
291
Effect of **Conditions causing Increase of plasma TBG**
Lead to false inc. of Total T4 & T3.
292
Reliable test in **Conditions causing Increase of plasma TBG**
Free T3 & Free T4 reliable In these cases.
293
Effect of **Conditions causing Decrease of plasma TBG**
Cause a false dec of Total T4 & T3.
294
Examples of **Conditions causing Decrease of plasma TBG**
Protein losing states
295
What are Drugs that interfere with thyroid function leading to thyroid disfunction (Hypo or hyperthyroidism)?
296
Reliable test in cases of **Conditions causing Decrease of plasma TBG**
Free T3 & Free T4 reliable In these cases.
297
Def of **Assay Interference**
- A nonspecific binding with assay reagents leading to false increase in concentration of the measured substance.
298
Thyroid assay interference
299
What is **Thyroid Assay**?
An animal anti-body against thyroid hormones used to determine their serum level.
300
Def of **reference Range**
A set of values that Includes upper & lower limits of a lab test based on a group of otherwise healthy people.
301
Is **reference Range** Age related?
yes
302
**reference Range** Must be trimester related in pregnancy
..
303
What test is used in follow up in cases of thyroid dysfunction?
304
Refer to Liver Case Scenario in Notes
..
305
Refer to Thyroid Case Scenario in Notes
..
306
Diurnal Variation in tests
- Time of day, month or year may affect lab test results
- Some tests must be collected at specific times or days in order to provide meaningful clinical information.
307
Examples of diurnal variation in tests
308
What are adrenal disorders?
- Hyperfunction: Cushing syndrome.
- Hypofunction: Adrenal insufficiency.
309
Levels of cortisol And ACTH in blood
- Cortisol & ACTH levels fluctuate throughout the day
**Peak levels**: In the early morning.
**Lowest levels** in the late evening around bedtime.
310
sample collection for cortisol
We collect 2 samples:
- 1st sample: At 8:00 AM.
- 2nd sample: At 8:00 PM "in the same day"
311
Serum cortisol levels & salivary cortisol in late night in patients with cushing syndrome
Elevated
312
Besides time, name other biologic variables that may affect lab test results
1. Age.
2. Gender.
3. Race.
4. Exercise.
5. Diet.
6. Posture.
7. Stress (venipuncture).
8. Genetic predisposition.
313
Tests to diagnose adrenal insufficiency
- Basic chemistry profile.
- CBC (Complete Blood Count).
- Urinalysis.
314
315
Other Variables affecting cortisol and ACTH testing
- Emotional stress.
- Estrogens containing oral contraceptive.
- Steroid therapy:
* Stopped within 12 h before the test.
* If not possible (as in Addison disease dexamethasone should be prescribed (As it doesn't cross react with cortisol assay) & not-prednisolone.
316
Time of sample collection for cortisol & ACTH
- 2 Samples (because of daily circadian rhythm).
* Morning: 8 - 10 AM.
* Evening: 10 - 12 PM.
317
Time of sample collection for Sex hormones & Gonadotropins
Monthly circadian rhythm in female.
318
Blood sample Collection
- Additive on sample
- Test done on
319
insulin sample collecion
separated immediately and kept in fridge
320
Def of **Competitive binding techniques**
The method where the hormone competes with labelled one for binding sites in vitro.
321
Binding sites in **Competitive binding techniques**
1. Antibody.
2. Binding proteins.
3. Receptor.
322
Labelling in **Competitive binding techniques**
- Radioisotope.
- Enzymes.
- Fluorochrome.
323
Examples of **Competitive binding techniques**
1. Radioimmunoassay (RIA)
2. Enzyme linked immunosorbent assay (ELISA)
3. Fluoro immunoassay (FIA)
324
Chromatography
This is a reference method.
325
Samples for **Catecholeamines Testing**
Blood & Urine
326
Blood sample for **Catecholeamines Testing**
- Measurement of plasma catecholamines.
- A sensitive test that needs specialized equipment's.
327
Urine sample for **Catecholeamines Testing**
- The reliable test: Measurement of urinary vanillymandelic acid (VMA).
- VMA: Is the end stage metabolite of catecholamines,
Excreted in urine.
328
blood Sample collection for **Catecholeamines Testing** * In patients with paroxysmal attacks of hypertension
Basal measurements should be made once in between attacks & another estimation, when the next attack occurs.
329
Cautions during collection & timing of urine specimens (24 hours) for VMA for catecholeamines testing
The diet excluded the following Items:
1. Caffeine as in (coffee - tea - cocoa - chocolate)
2. Amines as in (bananas - walnuts - avocados - fava beans - cheese - beer * red wine).
3. Vanilla (in foods or fluids)
4. Licorice
5. Nicotine (4 hours before collection of urine and during the urine collection),
6. Alcohol (ethanol) & cocaine.
7. These analytes are sensitive to drugs (azathloprine).
330
331
Def of **Autoimmunity**
- The process where the host immune system ceases to recognize one or more of the body's normal constituents as self, creates autoantibodies that starts to attack its own (Cells - Tissues - Organs) causing inflammation & damage.
332
Examples of **Autoimmunity**
- Systemic Lupus Erythematosus (SLE).
- Rheumatoid Arthritis.
333
Causes of **Autoimmunity**
Mostly Unknown
334
Def of **Autoantibodies**
- Proteins created by the immune system when it fails to distinguish between self-antigens & non-self-antigens (foreign antigens) e.g. bacterial or viral.
335
what are **Autoantibodies** directed against?
These autoantibodies may be directed against a variety of substrates including:
- Intra-cellular antigens.
- Cell surface antigens.
- Extracellular antigens.
336
SLE
337
Immunological testing for **SLE**
- Antinuclear antibodies (ANA)
- SLE specific antibodies
- Complement proteins
- Anti-platelet antibodies & Anti-erythrocyte antibodies
- Anti-histone antibodies
- RF (Rheumatoid factors)
338
Antinuclear antibodies (ANA) in Testing for **SLE**
- Highly sensitive (Seen in large proportion of patients).
- But not specific (Seen in other autoimmune diseases).
339
SLE specific antibodies in Testing for **SLE**
340
Complement proteins in Testing for **SLE**
- Decrease Serum complement (C3-C4)
- Due to its consumption.
341
Anti-platelet antibodies & Anti-erythrocyte antibodies in Testing for **SLE**
- Present in about 70% of patients.
- Responsible for hemolytic anemia & thrombocytopenia.
342
Anti-histone antibodies in Testing for **SLE**
- Present in drug induces lupus.
343
RF (Rheumatoid factors) in Testing for **SLE**
+ve in 30% of patients.
344
Def of **Rheumatoid Arthritis**
- Chronic systemic inflammatory auto immune disease that affect the joints.
345
Immunological testing for **Rheumatoid Arthritis**
- Specific tests
- Others
346
Specific tests for **Rheumatoid Arthritis**
- Rheumatoid factors (RF): Positive in 75% of patients.
- Anti-CCP autoantibodies (Anti-Cyclic Citrulinated Peptide)
347
Charaters of Anti-CCP autoantibodies (Anti-Cyclic Citrulinated Peptide) in testing for RA
- Highly specific for RA (96%).
- They appear before the onset of RA symptoms.
348
Other tests for RA
- Serum complement: Decrease in presence of vasculitis.
- Antinuclear antibodies (ANA): May be positive.
- Hypergammaglobulinemia & Cryoglobulinemia.
349
Def of **Immunodeficiency disorders**
- Deficiency of one or more of the 4 major components of the immune system (B lymphocytes - T lymphocytes - phagocytic cells - complement system).
- Which protect the individual against different viral, bacterial, fungal and protozoal infections.
350
what are **Primary Immunodeficiency disorders**?
- B cell Immunodeficiency Disorders.
- T cell Immunodeficiency Disorders.
351
Classification of **Immunodeficiency disorders**
- Primary immunodeficiency diseases (Presented from birth)
- Secondary immunodeficiency diseases (Acquired due to infection as AIDS).
352
Examples of **B-Cell Immunodeficiency disorders**
353
Examples of **T-Cell Immunodeficiency disorders**
DIGEORGE'S SYNDROME
(CONGENITAL THYMIC APLASIA)
354
Clinical Features of **T-Cell Immunodeficiency disorders**
355
Laboratory assessment of immune competence
- Complement assay
- Evaluation of Humoral (B cells) mediated immunity
- Evaluation of Cellular (T cells) mediated immunity
- Assessment of phagocytic function
356
Methods of Complement assay
- Immunoassay "Assay of C3 & C4 levels"
- Functional "Hemolytic assay CH50"
357
Methods of Immunoassay "Assay of C3 & C4 levels"
* Electro immunodiffusion
* Rate nephelometry
* ELISA
* Single radial diffusion
358
Methods for Evaluation of Humoral (B cells) mediated immunity
- Protein electrophoresis
- Quantitative immunoglobulins level
- IgG subclasses level
- Total B cell count
- Specific antibody response after immunization in vivo
- Stimulation of B cells in vitro
359
Methods of Quantitative assessment of immunoglobulins level
* Radial immunodiffusion
* Nephelometry
* ELISA
360
Methods of assessment of IgG subclasses level
ELISA
361
Methods of assessment of Total B cell count
- Using Flow cytometry
- Normally 10 - 20% of total circulating lymphocytes
362
Specific antibody response after
immunization in vivo
**Principle:** Immunization with tetanus or pneumococcal polysaccharide Antigens
363
Stimulation of B cells in vitro
- By Mitogen or Antigen, and assessment of immunoglobulin release
364
Evaluation of Cellular (T cells)
mediated immunity
- Total Lymphocytes count
- Monoclonal antibodies to T cell subsets
- Total T cell count
- Delayed cutaneous hypersensitivity skin test in vivo
- Lymphocyte response in vitro
365
# MOAs = Method of assessment
MOAs of Total Lymphocytes count
Normally > 1200/ul "At any age"
366
MOAs of Monoclonal antibodies to T cell subsets
Using Flow cytometry
367
MOAs of Total T cell count
- Using Flow cytometry
- Normally >60% of total circulating lymphocytes
368
MOAs of Delayed cutaneous hypersensitivity skin test in vivo
- Using PPD
- Used to evaluate specific cellular immunity to antigen
369
MOAs of Lymphocyte response in vitro
- By Mitogen or Antigen
370
Assessment of phagocytic function
- Nitro-blue tetrazolium test
- Chemiluminescence
- Chemotaxis
- Assessment of superoxide production
- Enzyme tests
- Genetic analysis
371
what is Nitro-blue tetrazolium test used in?
Used lo diagnosis of CGD
372
Chemiluminescence
Albnormal in...
* CGD
* Myeloperoxidase deficiency
373
MOAs of Chemotaxis
- **Principle:** Measure ability of neutrophils to move in a directed, migratory pattern toward chemotactic substance
374
when is Chemotaxis abnormal?
- Abnormal in various disorders "Not specific"
375
Superoxide production in CGD
- Absenl in CGD
- Defective in other syndromes
376
Genetic analysis
Available for
* CGD
* LAD
* Chediak Higashi syndrome
377
Indication of Enzyme tests
* e.g., G6PD - Myeloperoxidase
378
Intro To Nucleic Acids
379
Def of **PCR**
An enzymatic method, Used for making multiple copies of a pre-selected segment of DNA /RNA.
380
RNA Extraction
381
what are The primary materials (reagents) used in PCR?
382
what should happen before **PCR**?
We need to extract the nucleic acid from the cell at first.
383
DNA Extraction
384
Cyclic reactions
- There are 3 major phases, which are repeated for 20 to 40 cycles.
- This is done on an automated Thermal Cycler.
385
Phases of Cyclic reactions
386
Verification of PCR products
- Agarose gel electrophoresis.
- Hybridized with a labelled probe.
387
Clinical applications of PCR
388
Def of **Infectious Diseases**
- Clinically evident diseases resulted from the presence of pathogenic microorganisms with the potential of transmission from a person to another.]
- Infectious Diseases are many but limited by our knowledge, facilities, & ignorance.
389
what are causes of **Infectious Diseases**?
- Bacterial.
- Viral.
- Fungal.
- Parasitic.
390
Samples will be subjected to:
- Phenotypic microbiological analyses.
- Immunological-serological analyses.
- Genotypic-Molecular biological analyses.
391
Types of samples
* Blood.
* Sputum.
* Urine.
* CSF.
* Stool.
* Pus.
392
Phases of diagnosis
393
Preanalytical phase of diagnosis
394
Importance of **Sampling**
**(good sample = true result)**
- The successful identification of microbe depends on sampling.
- The specimen is the beginning:
As all diagnostic information from the laboratory depends upon the knowledge by which specimens are chosen & the care with which they are collected & transported.
395
Proper selection of type of sample
Collect the appropriate type of specimen for diagnosis of the infectious disease.
396
what does the quality of the sample Depend on?
- Proper Selection
- Proper Collection
- Proper Transport
397
Proper collection of sample
Avoid harming the patient & causing discomfort
**Site:**
- Collected from: site of pathogen is most likely to be found
- collected into: sterile containers
**Time:**
- The acute stage is the best.
- Before antimicrobial therapy has begun.
**Quanlity:**
- Sufficient quantity.
398
proper transport of sample
- Specimens should be protected from heat & cold.
- Specimen transported promptly Within 2 hours.
- Use of transport media especially for anaerobic culture.
399
Def of **Direct methods of diagnosis**
- Detection of organisms, their structural components & their products.
400
Clinical specimens from various organs
- Circulatory System.
- (Skin- Abscess - Wound) Specimens.
- Eyes & Ears.
- Respiratory System.
- Central Nervous System.
- Urinary Tract.
- Genital Tract.
- Oral Cavity.
- Gastrointestinal Tract.
- Body Fluids.
401
Examples of **Direct methods of diagnosis**
- Macroscopic evaluation.
- Microscopy (Unstained & Stained).
- Culture & biochemical reactions.
- Detection of microbial antigens & products.
- Molecular identification of nucleic acids (PCR & DNA probe technology).
402
Def of **InDirect methods of diagnosis**
- Detection of antibodies against the microorganism in the patient's serum.
403
Examples of **InDirect methods of diagnosis**
- Serologic method
404
Macroscopic examination of samples
405
Microscopic examination of samples
406
Def of **Culture**
The process of growing & propagating organisms in a media that is conducive for their growth.
407
Importance of **Culture**
It Reproduce the organism for use for additional testing
408
Types of **Culture**
409
Identification of bacteria
1. Morphology.
2. Growth requirements.
3. Biochemistry.
4. Enzymes.
5. Antigens.
410
Rapid identification of bacteria
Automated bacterial identification & Antimicrobial susceptibility systems.
411
Example of **Automated bacterial identification and antimicrobial susceptibility systems**
VITEK system.
412
Principle of **Automated bacterial identification and antimicrobial susceptibility systems**
413
Time of results of **Automated bacterial identification and antimicrobial susceptibility systems**
Available within 6-8 hours.
414
Drawbacks of Culture of Pathogenic Microbes
415
Diagnosis of infection with slow-growing or non-culturable bacteria tends to rely on....
**Direct:** by molecular methods (PCR).
**Indirect:** by serodiagnosis (antibody detection).
416
Diagnostic Methods through time
417
Def of **Direct Antigen detection**
Assays are available for rapid detection of
- Bacterial Antigens (surface antigen - soluble antigen).
- Or toxin in biological fluids e.g. (CSF - blood - urine).
418
When are **Direct Antigen detection** useful?
- Prior antibiotic therapy has been initiated & cultures are negative after 24 hours of incubation.
- Rapid results in critical ill patients e.g. meningitis.
419
Principle & Types of **Direct Antigen detection**
420
Def of **Molecular biology Techniques**
Molecular detection techniques for bacterial, viral and fungal DNA.
421
Importance of **Molecular biology Techniques**
422
Disadvantages of **Molecular biology Techniques**
423
Def of **MULTIPLEX PCR**
Simultaneous detection of dozens of targets from one patient sample
424
Characters of **MULTIPLEX PCR**
425
Def of **Indirect tests (serodiagnosis & Immune status tests)**
Tests for detection of specific antibody for infectious agents including (IgM - IgG - IgA).
426
What is diagnostic in **Indirect tests (serodiagnosis & Immune status tests)**?
Rising antibody titer (at least 4 folds) is diagnostic.
427
Time of sample collection in **Indirect tests (serodiagnosis & Immune status tests)**
Samples are withdrawn at acute & convalescent stages (within 14 days).
428
Techniques of **Indirect tests (serodiagnosis & Immune status tests)**
429
Advantages of **Indirect tests (serodiagnosis & Immune status tests)**
- Inexpensive.
- Easy to perform.
——-
- Allows identification of:
* Acute infection → IgM.
* Past infection → IgG.
430
Disadvantages of **Indirect tests (serodiagnosis & Immune status tests)**
- Delayed response.
- False negative results during sero-conversion window.
- Time of infection not always clear.
431
Sampling for mycological examination
- Clean the site with alcohol 70%.
- Sterile scalpel is used for scrapping.
- Sterile scissor is used for trimming the nails.
- Scales are transferred in clean dark paper.
432
Inoculation of fungal infections
433
Sampling for viral examination
**Time:** Sample should be collected during the most active stage of the disease.
**Transport:**
* Samples as (urine - stool - sputum - CSF) are transported directly to the lab.
* Swaps from (throat - nose - vesicles - cervix) are transported in viral transport medium.
434
Biohazard label should be used for containers of .....
(HBV - HCV - HIV)
435
Methods of viral detection
436
Def of **MIC (minimum inhibitory concentration**
The lowest concentration of antimicrobials that will inhibit the growth of organisms.
437
importance of **MIC (minimum inhibitory concentration**
Confirm resistance of organisms to an antimicrobial agent.
438
Methods of **MIC (minimum inhibitory concentration**
439
Post-Analytical phase of diagnosis
- Reporting of:
* Identification.
* Antibiotic sensitivity.
- Treatment
440
Def of **Rapid Detection Tests**
Tests that give results in minutes to 1-2 hours.
441
Characters of **Rapid Detection Tests**
- Accurate.
- Simple to use.
- Low cost.
- Stable under extreme conditions.
- Little or no processing.
- Culturally acceptable "Give the same result of the culture".
- Easy to interpret.
442
Revolution in Direct Detection of Infections
- Direct antigens.
- Direct antibody.
- Nucleic Acid (NA) based technology.
443
Check conclusion
..
444
Check take home messages
..
