ACUTE LEUKEMIA

• Acute leukemia is a progressive, malignant

disease characterized by large numbers of
immature white blood cells that resemble blast
cells.

• These cells can be found in the blood, the bone

marrow, the lymph nodes, the spleen, and
other organs causing infiltration of organs.
 Etiology
• Viral infections (virus Epshtteina-Barr caused
limphoma Berkitta, Hodgkina,
• Mutation – The incidence of leukaemia is increased
in identical twins and in syndromes of chromosomal
abnormality, e.g. Down's syndrome, Klinefelter's
syndrome. The Down syndrome increases risk of
development acute leucemia at 20 times
• Radiation - nuclear, x-ray, chemotheraphy, nuclear
radiations.
• Toxic agents – smoking, benzane
• Prior blood disorders – chronic myeloblastic leukemia,
myelodysplastic syndrome, refractory anemia.
 PATHOGENESIS

• Proliferation of tumor cells with metastatic

process to different organs.
• Disappearances of normal haemopoises due to
hyperproduction of blast cells.
• Leucopenia leads to massive infections, with
bacteria, viruses and fungi.
• Anemia leads to with pallor and weakness.
• Thrombocytopenia lead to easy bruising and
internal bleeding.
 Acute Leukemias
(AML/ALL)

Block in differentiation–“blasts” with

prolonged generation time
↓
Accumulation of “blasts’
(Result from a clonal expansion & Failure of
maturation)
↓
Suppress normal hematopoiesis
(↓ in normal RBCs, WBCs and PLTs)
 Name the different cells.
Platelet

Neutrophil (Band Cell) Eosinophil

Mature
Neutrophil

Basophil

Monocyte

Lymphocyte Red Blood Cell

(Mature Erythrocyte)
 ALL
naïve

B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes

AML
Hematopoietic Myeloid Neutrophils
stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
 Acute Leukemia
• accumulation of blasts in the marrow
 Classification

• leukemia can be divided on the basis of the speed

of evolution of the disease into:
– Acute or chronic.

• Each of these is then further subdivided into

– myeloid or lymphoid, according to the cell type
involved.
 Classification of Leukemia

Acute Chronic

Myeloid Acute Myeloid Chronic Myeloid Leukaemia

Leukaemia (AML) (CML)
origin

Lymphoid Acute Lymphoblastic Chronic Lymphocytic

origin Leukaemia (ALL) Leukaemia (CLL)
 According to stages :
• Acute period
• Complete(Incomplete) remission
• Recovering
• Recurrence (first or repeated)
• Terminal stage
 FAB’S CLASSIFICATION
NON – LYMPHOBLASTIC (AML) LYMPHOBLASTIC (ALL)
• M0 - Undifferentiated leukemia
• M1 - Myeloblastic without • L1 - Small cells with
differentiation
homogeneous chromatin,
• M2 - Myeloblastic with regular nuclear shape without
differentiation
growing.
• M3 - Promyelocytic
• M4 - Myelomonocytic
– M4eo - Myelomonocytic with • L2 - Large and heterogeneous
eosinophilia cells, heterogeneous
• M5 - Monoblastic leukemia chromatin, irregular nuclear
shape with growing.
– M5a - Monoblastic without
differentiation
– M5b - Monocytic with • L3 - Large and homogeneous
differentiation cells and cytoplasmic
• M6 - Erythroleukemia vacuolization ( Brikets
• M7 - Megakaryoblastic leukemia leukemia).
 Lymphocytic Myeloid
Acute Chronic Acute Chronic myeloid
lymphocytic lymphocytic myeloid leukemia (CML)
leukemia (ALL) leukemia (CLL) leukemia
(AML)

Uncontrolled Lymphoproliferation Uncontrolled A malignant clonal

proliferation of disorder proliferation of disorder of hemopoietic
abnormal, proliferation and primitive myeloid stem cells
immature accumulation of cells (blasts) -abnormal proliferation,
lymphocyte and mature-appearing accumulation of
their progenitors neoblastic immature granulocytes
lymphocytes
-enlarged lymph node
& lymphocytosis
common type of most often affects adults Common adults and mainly in adults
leukemia in young over 55 age of 55 and children Small # of children
children and over 65 younger adults
age. No children
 Differentiation of leukaemia

Acute Chronic
Onset Rapid Gradual
(Rapidly progressive) (Slowly progressive)
Patient Children - 3 – 7y Older people – 60y
Cell type Immature (blasts) More mature

Survival Fatal if not treated Long survival

Treatment Responds well to May be resistant

chemotherapy
 Distinguishing Characteristics
Acute Lymphoid Chronic Acute Myeloid Chronic Myeloid
Lymphoid
Exam Lymphadenopathy Splenomegaly (Not Found) Lymphadenopathy
Splenomegaly Splenomegaly
Hepatomegaly Hepatomegaly
Imaging Mediastinal No Mass No Mass No Mass
Mass
Marrow Blasts No blasts Blasts No blasts
Tdt Tdt (5% cases) Fibrotic
(95% cases) BCR-ABL gene Tdt in end stage
PML/RAR gene
Markers CD 2,5,7 (T cell) CD 19 (B cells) N/A N/A
CD 10, 19 (B cell) (95% cases)
Spinal Blasts No blasts Blasts No blasts
Tap (Not as common as (5% cases)
AML)
Other Bleeding Associated with Associated with Fever, night sweats,
Pain chromosome trisomies & weight loss
CNS symptoms abnormalities translocations At end stage
2:1 male to female becomes ALL
Age Children (2-7 yrs) Adults 50+ Adults (15-39) Adults
Young Adults Children
Adults (50+, 65)
Common symptoms of leukemia
• Fever, chills, and other flu-like symptoms
• Weakness and fatigue
• Frequent infections
• Loss of appetite and/or weight
• Swollen or tender lymph nodes, liver, or spleen
• Easy bleeding or bruising
• Tiny red spots (called petechiae) under the skin
• Swollen or bleeding gums
• Sweating, especially at night
• Bone or joint pain
• Spenomegaly and Hepatomegaly
 CLINICAL SYNDROMES
1. HYPERPLASTIC: due to blast cells infiltration.
• lymphoadenopathy, hepatospenomegaly, leukemic
infiltration of gums
• Skin :- non tender infiltration, rose to brown
• Joint :- osteoalgia and arthralgia
• Lung :- pneumonia, pleurisy with dyspnoe, cyanosis,
auscultive changes and intoxication
• GIT :- ulceration
• Brain : neuroleukemia , vision loss , meningitis
Cervical lymphadenopathy
SKIN LEUKEMYTES
Leukemic Infiltrate of eye
Leukemic Infiltrate of tonque
 Mediastinal Involvement

Leukemic Infiltrate of lung

There is a large mediastinal mass caused by thymic enlargement atpresentation, (b)
After 1 weekof therapy with prednisolone,vincristine and daunorubicin the mass has
resolved.
linik manifistation- dyspnoe, cyanosis, cough, intoxication.
Treatment with use antibiotic of a wide spectrum of action. If this therapy is
Gum Hypertrophy
Other more severe symptoms related to
decreased platelet counts that occur less
commonly are gastrointestinal or genitourinary
tract and central nervous system (CNS)
bleeding.
CNS infiltration with high numbers of leukemic
cells has been reported in 5% to 20% of children
and approximately 15% of adults with AML.
Headache, blindness, and other neurological
complications are indications of meningeal
involvement. Leukemic blast cells circulate
through the peripheral blood and may invade
any tissue.
 2. ANEMIC SYNDROME
• Pale skin and mucus
• Dizziness (Головокружение)
• Fatigue and weakness (усталость и слабость)

• Dyspnoe and palpitation

• Tachycardia, soft systolic murmur
Pallor
 3. Haemorrhgic syndrome
• Thrombocytopenia
• Skin bleeding
• Ecchymosis
• Recurrent bleeding from gums
• GIT and lung bleedings, nose bleeds
• Petechia
• Abnormal menstruation
Petechia
Purpura
ACUTE LEUKAEMIA - HAEMORRHAGE
 4. Intoxication and infections
complications
• Fever
• Anorexia and weight loss
• Infections due to neutropenia
Infections in ALL
 DIAGNOSIS

• Non specific : physical

examination, complete blood
count, biochemical, urine analysis,
x-ray, ECG, etc
• Specific : bone marrow puncture
(sternal/hip), cytogenic test
(immunatyping)
PHYSICAL EXAMINATION
– skin is pale
– Non-palpable rash with
red dots on the skin
called petechiae
(leukemytes)
– Enarged liver
– Enlarged spleen
– Enlarged lymph nodes
– Bone tenderness
– Systolic Murmurs
– Fever and signs of
infections
 Diagnosis
Acute leukemias-laboratory findings
1. Blood examination
- ANEMIA – normochromic, normocytic
- THROMBOCYTOPENIA
- LEUCOPENIA
- BLAST CELLS – hiatus leukemic present
- Basophil-Eosinophil –absent/ dissociation
- ESR – increased
 ALL

• This peripheral blood sample shows high numbers of the lymphoblasts that are
characteristic of acute lymphoblastic leukemia. A nucleated red blood cell is present
in the center (arrow).
AML
2. Bone marrow morphology
• Necessary for diagnosis
• Useful for determining type
• Useful for prognosis

- Acute leukemias are defined by the

presence of > 20% blasts in bone marrow
(% of nucleated marrow cells - Presence
of blast cells,
- Suppression of normal hematopoiesis
NORMAL BONE MARROW
 BONE MARROW BIOPSY
Trocar is stuck into the hip
bone, just above the buttock,
and some marrow sucked
out for examination. This is
usually done on each side,
since two samples are more
accurate than one. It is done
under local anesthesia and
takes about 15 minutes. The
bone marrow is placed
under Wright or Giemsa
stain made upon a
microscope slide.
• Bone marrow biopsy This involves taking a
sample of bone marrow from the back of the hip
bone (pelvis). The sample is then looked at
under a microscope to see if it contains any
abnormal cells.

• The bone marrow sample is taken under a local

anaesthetic. You are given a small injection to
numb the area, and a needle is passed gently
through the skin and into the bone. A tiny
sample of the marrow is then drawn (aspirated)
into a syringe (a bone-marrow aspirate).
Sometimes a small core of marrow is also
needed (a trephine biopsy) and this takes a few
minutes longer. This procedure can be painful
for a few seconds, and you may feel some
discomfort for a few hours afterwards.
 RESULT OF B.M PUNCTURE
ALL AML

granules in blast cells. • presence of more than

Cell marker called TdT 30% blasts in bone
in 95 % of cases. It is marrow.
subtyped to either B- • AUER rods in the blast
cell or T-cell type. cells
Negative reaction • myeloid markers,
myeloperoxidase & such as CD13
natrii esterase • Platelet precursors
Lymphoid markers evaluating degree of
Positive reaction in dysplasia
glycogen & phosphatase • Base on the
cytochemical stains
AML classified into 7
subtypes (M1-M2)
ACUTE MYELOID LEUKAEMIA
ACUTE LYMPHOBLASTIC LEUKAEMIA
 ACUTE LEUKEMIAS
FAB CLASSIFICATION

ALL AML
M0
L1
M1 M7
M2 M6
L2
M5
M3
M4
L3
ACUTE MYELOID LEUKEMIA
FAB CLASSIFICATION

AML M0
M1 M7
M2 M6
M5
M3
M4
 FAB Classification of AML
Class Morphology Comments
Blasts lack cytologic markers 2-3%
M0
Very immature myeloblasts 20% (Ph chromosome worsens prognosis)
M1
Myeloblasts & promyelocytes 30%, t,(8;21) good prognosis
M2
Hypergranular promyelocytes 5-10% DIC, t(15,17)
M3 “many auer rods” Responds to ATRA
Myelocytic & monocytic diff. 20-30%, inv16/del16q better
M4 prognosis
Monoblasts & promonocytes 10%, pediatric age-young adults, 11q23
M5 abnormalities
Erythroblasts > myeloblasts 5%, older adults
M6
Megakaryocytic blasts Myelofibrosis
M7
 Myeloid maturation

myeloblast promyelocyte myelocyte metamyelocyte band neutrophil

MATURATION
M M1
2

M3 M4 M5

M M7
6
AML
 Auer rods in AML (M3)

Hypergranular promyelocytes,“many auer

rods”
5-10% DIC, t(15,17), Responds to ATRA
ACUTE LYMPHOBLASTIC LEUKEMIAS

FAB
CLASSIFICATION
ALL
L1

L2

L3
 FAB CLASSIFICATION
Lymphoblasts:
Small & Monomorphic L1

ALL

ACUTE LYMPHOBLASTIC LEUKEMIAS

 FAB CLASSIFICATION
Lymphoblasts:
Large & Heterogeneous

ALL
L2

ACUTE LYMPHOBLASTIC LEUKEMIAS

 FAB CLASSIFICATION
Burkitt ALL

ALL

L3

ACUTE LYMPHOBLASTIC LEUKEMIAS

3. Cytochemical stains
4. Immunophenotyping
5. Cytogenetics
6. Molecular studies
 Biochemical and urine analysis

• Elevated LDH SIGNS OF INFECTION

• Elevated Uric acid
• Pyuria
• Hypokalemia,
hypocalcemia, • Heamaturia
hypomagnesemia due to
renal failure (M5 & M4)
• Leucocyturia
• Signs of DIC – elevated • Glucosuria
prothrombin and • Protienuria
fibrinogen (M3)
• Signs of • Casturia
hepatodepression • Bacteriuria
 Cytogenetics

• Chromosomal abnormalities are found in

the blasts in 70% of cases of AML and
90% of ALL
• Important in the pathogenesis of the
disease
• Important for diagnosis
• Prognostic implications
• Eg t(15;17) and M3 AML
 Acute Leukemia

• Treatment
– Untreated acute leukemia is invariably fatal, most
often within months

– Treatment of leukemia may be divided into

• Supportive treatments

• Specific treatments
 Treatment
– Specific therapy
• Chemotherapy
• Sometimes radiotherapy
• Treatment: Specific therapy
– Principles of cytotoxic drugs
• Most of cytotoxic drugs used in leukaemia therapy damage
the capacity of cell for reproduction.

• Combination of at least three drugs are now usually used to

– Increase cytotoxic effect
– Improve remission rate
– Reduce the frequency of emergence of drug resistance
Typical treatment regime

Induction

Consolidation
Possible
SCT
Cranial prophylaxis

Maintenance

Late intensification

Maintenance
• Remission induction
– To kill rapidly most of the tumor cells and get the
patient into a state of remission (defined as)
• Less than 5% blasts in bone marrow
• Normal peripheral blood
• No other symptoms or signs of disease
– Prednisolone or dexamethasone, vincristine and
asparagenase – are the usual drugs used.
– > 90% of children and 80 – 90% of adults achieve
remission
• Consolidation / intensification blocks
– These courses use high dose of several chemotherapy
drugs in order to reduce the tumor burden to very low
levels.
• Vincristine
• Cyclophosphamide
• Cytosine arabinoside
• Etiposide
• Cranial prophylaxis
– High dose systemic methotrexate
– Intrathecal methotrexate (or cytosine arabinoside)
– Cranial irradiation
Prophylaxis of neuroleukemia;
• Intrathecal chemotheraphy – (CVAD) cyclophosphamide,
vincristine, doxorubicin (Adriamycin), and dexamethasone.
• Low risk – 4 intrathecal
High risk – 16 intrathecal
• Maintenance therapy
– This given for two years in girls and adults and for
three years in boys
– Daily oral mercaptopurine
– Once weekly oral methotrexate
– There is a high of varicella or measles infections in
children
 Remission criteria in acute leukemia
Complete remission in AML has been defined using the following criteria
developed by an International Working Group

• Normal values for absolute neutrophil count (>1000/microL) and platelet

count (>100,000/microL), and independence from red cell transfusion.
• A bone marrow biopsy that reveals no clusters or collections of blast cells.
Extramedullary leukemia (eg, central nervous system or soft tissue
involvement) must be absent.
• A bone marrow aspiration reveals normal maturation of all cellular
components (ie, erythrocytic, granulocytic, and megakaryocytic series).
There is no requirement for bone marrow cellularity.
• Less than 5 percent blast cells are present in the bone marrow, and none
can have a leukemic phenotype (eg, Auer rods). The persistence of
dysplasia is worrisome as an indicator of residual AML but has not been
validated as a criterion for remission status.
• The absence of a previously detected clonal cytogenetic abnormality (ie,
complete cytogenetic remission, CRc) confirms the morphologic diagnosis
of CR but is not currently a required criterion. However, in a report from the
CALGB, conversion from an abnormal to a normal karyotype at the time of
first CR was an important prognostic indicator, supporting the use of CRc as
a criterion for CR in AML [2,4].
Chronic Myelogenius
Leukemia
• It’s clonal myeloproliferative disease
arising from emmatural cells of a
myelopoiesis which morphological
substrate are mainly maturing and mature
granulocytes, basically neutrophils
 Possible etiological factors
• Ionising radiation.
• Small doses of radiation.
• Weak electromagnetic radiances.
• Herbicides, insecticides etc.
• Chemical agents - benzene
 Chronic myelogenous leukemia
(CML)

• Adults, usually 40-50

• Philadelphia chromosome
• Clinical: slow onset, nonspecific symptoms, marked splenomegaly
• Lab: leukocytosis (>100,000)
– PMNs, myelocytes, eosinophils, basophils, <5% “blasts”
• BM: hypercellular (granulocytic/megakaryocytic)
• D/D: leukemoid reaction (↑LAP)
• Course: 50% accelerated phase
– ↑ anemia, ↓ PLTs, ++ cytogenetic abn, blastic crisis
CML
In 95% of cases, CML shows a specific chromosome
aberration (Philadelphia chromosome with a specific BCR-
ABL translocation) and may make the transition into a blast
crisis. The formation of the Philadelphia chromosome plays a
significantrole in the understanding of the pathogenesis of
CML. The main portion of the long arm of chromosome 22is
deleted and translocated to the distal end of the long arm of
chromosome 9. This results in an elongated chromosome 9 or
9q. A small part of chromosome 9 is then reciprocally
translocated to the broken end of22 or 22. This now forms the
BCR-ABL hybrid gene, which codes for a 210-kDa protein, or
p210, which has increased tyrosine kinase activity.5,8
Tyrosine kinase activity provides an important mediator to
regulate metabolic pathways causing abnormal cell cycling.
The activation of tyrosine kinase activity may suppress
apoptosis (natural cell death) in hematopoietic cells and
provide the mechanism for excess cell production
The Philadelphia (Ph) Chromosome Leads to CML

BCR ABL

Ph chromosome

BCR-ABL
(activated
tyrosine kinase)

CML
 fusion 22
bcr/abl

abl
bcr

fusion 9
abl/bcr
 CML

Chronic Accelerated Blast

Phase Phase Crisis
 STAGING OF CML

Three main stages, determined by percentage of blast cells in the blood

- Chronic Phase
- Patient usually diagnosed
- Fewer than 10% of cells in blood and bone marrow are blast
- Prognosis: (with imatinib) 5yr: 70%, 10yr: 30-40%

- Accelerated Phase
- 10-19% of cells in blood or bone marrow are blast, Basophilia ≥ 20%

- Blastic Phase, aka “blast crisis”

- Fulminant symptoms of disease, multiple organ involvement
- 20-30% or more blasts in bone marrow and blood
- Prognosis: UNPROMISING, 2 months, may extend survival with
newer drugs or chemotherapy
 Chronic myeloid leukemia

• Laboratory finding
– Blood count
• Hb low, WBC raised, platelets low, normal or raised
– Blood film.
• Neutrophilia with the whole spectrum of myeloid
precursors including occasional blasts
– Bone marrow aspirate.
• Increased cellularity, increased myeloid precursors
– Cytogenetics reveals
• t(9;22) translocation (the Philadelphia chromosome)
Numerous granulocytic forms seen here, including
immature myeloid cells and bands – CML
Diagnostic criterias of chronical
phase CML
• Combined or isolated increasing of a lien and-
or a liver.
• The maintenance of leucocytes in peripheric
blood more than 80x109/l.
• Alteration in the leukocytic formula to the left
with total of myeloblasts and promyelocytes
more than 4 %.
• Total of blasts and promyelocytes in an bone
marrow more than 8 %..
 Unfavorable signs for forecasting of
survival rate of patients in chronic
phase CML
- The lien dimensions ≥ 5 sm from under edge of a
costal arch;
- Percent of blast cells in blood ≥ 3 % and-or bone
marrow ≥ 5 %;
- Haemoglobin level ≤ 100 g/l;
- Percent of eosinocytes in blood ≥ 4 %..
 DIAGNOSTIC CRITERIA OF THE
PHASE OF THE ACCELERATION.
• Presence in peripheric blood / a bone marrow of blast
cells to 10-29 %
• The sum of blasts and promyelocytes of ≥30 %
• Quantity of basophils in blood of ≥20 %
• Thrombocytopenia <100 *109/l, not bound to therapy
• Augmentation of the sizes of a lien in the course of
therapy (more than on 10 sm)
• Additional chromosomal anomalies (an additional Ph-
chromosome, a trisomy of 8th pair, an isochromosome
17, etc.).
 Diagnostic criteria blast crisis
• The diagnosis of a blast crisis (BC) is established at
presence in peripheric blood or in a bone marrow of
blast cells more than 30 % or at appearance of the
extramedullary locuses of a hemopoiesis (except a liver
and a lien).
• Average duration БК of 3-6 months.
 Methods of diagnostics CML.
• Morphological blood analysis and a bone
marrow punctate.
• Karyological research of a bone marrow
(standard cytogenetic research and a method
fluorescent hybridisation in situ-FISH)
• PCR - for diagnostics and monitoring of the
minimum residual illness in the course of
therapy (revealing chimer BCR-AB α a
transcript).
 Methods of diagnostics CML.
• Morphological blood analysis and a bone
marrow punctate.
• Karyological research of a bone marrow
(standard cytogenetic research and a method
fluorescent hybridisation in situ-FISH)
• PCR - for diagnostics and monitoring of the
minimum residual illness in the course of
therapy (revealing chimer BCR-AB α a
transcript).
 Laboratory findings
1 Leucocytosis is usually >50 x 109/L and sometimes>500 x 109/L (Fig.
13.2). A complete spectrumof myeloid cells is seen in the peripheral
blood. The levels of neutrophils and myelocytes exceed those of
blast cells and promyelocytes.
2 Increased circulating basophils.
3 Normochromic, normocytic anaemia is usual.
4 Platelet count may be increased (m.ost frequently), normal or
decreased.
5. Neutrophil alkaline phosphatase score is invariably low. It is raised in
the myeloproliferative diseases and infections.
• 6 Bone marrow is hypercellular with granulopoietic
• predominance.
• 7 Ph chromosome on cytogenetic analysis (conventional
• or FISH) of blood or bone marrow (Fig. 13.1).
• 8 Serum uric acid is usually raised.
 Clinical FeaturesSigns and Symptoms

• People with CML may not have any symptoms at the time of
diagnosis. They may be diagnosed following a medical examination
for another condition or as part of a periodic checkup. CML signs
and symptoms tend to develop gradually. Some signs and
symptoms of CML are:
• shortness of breath due to anaemia
• abdominal discomfort due to splenomegaly
• weight loss
• fever, sweats, NOT due to infection
• headache (occasionally) due to hyperleucocytosis
• bruising, epistaxis, menorrhagea, bleeding (uncommon).
• Gout
• Many of the signs and symptoms for CML are common to other
illnesses. Most people with these signs and symptoms do not have
CML
 The symptoms of chronic phase
CML
• can depend on how high the person's white
blood cell count is. Often, people do not notice
any symptoms at all. Their CML is found during
a routine doctor's visit. Others may have
symptoms such as:
• Fatigue (tiredness)
• Headache
• Pain or a feeling of fullness on the left side of the
abdomen (caused by an enlarged spleen)
 Accelerated phase can include

• Fever
• Night sweats
• Weight loss
• Shortness of breath and pale skin caused
by anemia (too few red blood cells)
 Blast phase

In the blast phase, the number of blasts in the

bloodstream grow rapidly. As a result, there are
fewer normal blood cells (white blood cells, red
blood cells and platelets), and the symptoms
listed above become severe. Patients often have
problems with bruises, bleeding and infection.
When CML is in the blast phase, the disease
resembles acute myelogenous leukemia, or in a
minority of cases, acute lymphocytic leukemia.
Splenomegaly
At the expressed
splenomegaly the
liver, but always
to a lesser
degree is usually
enlarged also)
The patient in a myelosis
terminal-stage.
Imatinib (Gleevec)
 Normal Bcr-Abl Signaling

• The kinase domain

activates a substrate Substrate
protein, eg, PI3 kinase, by
phosphorylation
• This activated substrate Effector
initiates a signaling Bcr-Abl
cascade culminating in cell
proliferation and survival
ADP P
PPP
ATP
PPP
ADP = adenosine diphosphate; ATP = adenosine triphosphate; SIGNALING
P = phosphate.
Savage and Antman. N Engl J Med. 2002;346:683
Scheijen and Griffin. Oncogene. 2002;21:3314.
 Imatinib Mesylate
Mechanism of Action

• Imatinib mesylate occupies

the ATP binding pocket of the Bcr-Abl
Abl kinase domain
• This prevents substrate
phosphorylation and signaling
• A lack of signaling inhibits P
proliferation and survival
ATP
PPP
Imatinib
mesylate SIGNALING

Savage and Antman. N Engl J Med. 2002;346:683.

 Chronic myeloid leukemia

• Treatment
– Chemotherapy
• hydroxyurea
– Tyrosine kinase inhibitors
– Interferone α
– Stem cell transplantation
 Common Treatments
• Usage of Tasigna • Usage of Sprycel • The usage of Gleevec
– Too few white – Too few red cells, during the beginning
cells and/or white cells and/or of CML
platelets platelets – Swelling from too
– Changes in liver much fluid in the
– Too much fluid in body
enzymes the chest
– Changes in – Puffiness around
– Too much fluid in the eyes
pancreatic
other tissues – Nausea
enzymes
(edema) – Vomiting
– Nausea
– Diarrhea – Muscle cramps
– Constipation
– Diarrhea – Headache – Diarrhea
– Itching – Low calcium levels – Rash
– Rash in the blood
– Slight changes in
liver function.
Chronic lymphogenic
leukemia
Chronic lymphocytic leukemia (CLL) is a
monoclonal disorder characterized by a progressive
accumulation of functionally incompetent
lymphocytes.
 causes

- As in the case of most malignancies, the

exact cause of CLL is uncertain.
- The protooncogene bcl2 is known to be
overexpressed, which leads to
suppression of apoptosis (programmed
cell death) in the affected lymphoid cells.
- CLL is an acquired disorder, and reports of
truly familial cases are exceedingly rare.
 Signs and symptoms
Patients with CLL present with a wide range of symptoms and
signs at presentation. Onset is insidious, and it is not unusual for
this disorder to be discovered incidentally after a blood cell count is
performed for another reason.
Predisposition to repeated infections such as pneumonia, herpes
simplex labialis, and herpes zoster
Enlarged lymph nodes
Early satiety and/or abdominal discomfort related to an enlarged
spleen
Mucocutaneous bleeding and/or petechiae secondary to
thrombocytopenia
Tiredness and fatigue secondary to anemia
• Physical:
Localized or generalized lymphadenopathy
-Splenomegaly (30-40% of cases)
-Hepatomegaly (20% of cases)
-Petechiae
-Pallor
 Staging
• Two staging systems are in common use, the Rai-Sawitsky in the
United States and the Binet in Europe.
The Rai-Sawitsky staging system divides CLL into 5 Stages, 0-IV.
 Stage 0 is lymphocytosis in the blood and marrow only, with a
survival of longer than 120 months.
 Stage I is lymphocytosis and adenopathy, with a survival of 95
months.
 Stage II is lymphocytosis plus splenomegaly and/or hepatomegaly,
with a survival of 72 months.
 Stage III is lymphocytosis plus anemia (hemoglobin <10 g), with a
survival of 30 months.
 Stage IV is lymphocytosis plus thrombocytopenia (platelets
<100,000), with a survival of 30 months.
Chronic lymphocytic leukemia, autoimmune hemolytic anemia, Kaposi's
sarcoma
A 70 year old man with a 6-year history of generalized lymphadenopathy,
hepatosplenomegaly, hypogammaglobulinemia and recurrent pulmonary
infections, undergoing chemotherapy with monthly courses of chlorambucil-
methylprednisolone. Four months earlier he became anemic (Ht 24%,
reticulocytes 185.000/μL). In the last 3 months he developed a confluent
palpable rash on the interior surface of the leg ranging from purple patches in
the early lesions to red-brown-blue macules or nodules in the older lesions, with
rapid extension. The nodules had a large base and bled easily. The lesions
were non-pruritic and painful and the adjacent skin was red and swollen.
 Chronic Lymphocytic Leukemia
(CLL)

• Indolent clinical course

• Median survival : 4-6 yrs
• Occasional transformation to large non-Hodgkin’s lymphoma (Richter’s
syndrome) --- 3 to 5 %
CLL:
CLL

lymphocytes

‘smudge’ cells
 Diagnostic criteria of CLL
• Absolute lymphocytosis in blood
• More than 30 Treatment
• At the time of diagnosis, most patients do not need to be treated with chemotherapy unless they have weight
loss of more than 10%, extreme fatigue, fever related to leukemia, night sweats, progressive marrow failure,
autoimmune anemia or thrombocytopenia not responding to prednisone, progressive splenomegaly, massive
lymphadenopathy, or progressive lymphocytosis. Progressive lymphocytosis is defined as an increase of
greater than 50% in 2 months or a doubling time of less than 6 months.
• Patients at stage 0 whose disease is stable require only periodic follow-up. Early treatment has not been
demonstrated to be advantageous. Prednisolone alone, usually in a dose of 20-60 mg daily initially, with
subsequent gradual dose reduction, may be useful in patients with autoimmune manifestations of the disease.
Nucleoside analogs (ie, fludarabine, cladribine, and pentostatin) include a new group of drugs
with major activity against indolent lymphoid malignancies, including CLL.
- Fludarabine is the most extensively studied and currently is the most commonly used second-line
therapy in CLL.
- Responses to treatment with chlorambucil and prednisone are observed in 38-47% of patients.
- Patients treated with fludarabine have much higher rates (80%) of overall responses and a 37%
complete remission rate.
• Studies using purine analogs, especially fludarabine, compared to alkylator-based therapies
have shown that the response rates are superior and the progression-free interval is longer, but
evidence to show prolonged overall survival is premature
• % of lymphocytes in a bone marrow punctate
• Immunologic acknowledgement of presence V-kleto-chnogo of a clone of leukemic lymphocytes
• Lien and liver augmentation - a facultative sign
• Auxiliary diagnostic character of a lymphatic tumoral proliferation - Botkin-Gumprehta cells in a
blood smear (leukolysis cells represent an artefact: in their liquid blood is not present, they are
formed in the course of smear preparation)
• Immunophenotypingе, for CLL presence CD - 19, 22, 23 is characteristic
Investigation:
Blood film:
70-99% of white cells mature
• CBC: lymphocyte.
– WBC:. Smudge or smear cells also present.
– Diff:lymphocytosis ,the Immunophenotyping:
absolute lymphocyte Shows that the lymphocyte are B cells
count is>5x109/l and
(CD19) expressing one form of light
may be up to 300x109/l
chain
or.
( or  only) cells are also CD5 &
CD23+ve.
• Bone marrow aspiration:
Lymphocytic replacement of normal marrow.
• Immunoglobulinelectrophoresis:
 of Ig, more marker with advance disease.
• Cytogenetic :
The 4 most common abnormalities are; deletion of13q14,trisomy 12,
deletion of 11q23 & structural abnormality of 17p involving the p53 gene.
 Rai
Staging

CLL
 Abdomen

Hb.
MARROW

BLOOD

Platelet
L. N.

Marrow No Normal Normal

Lymphocyte No
Palpable Hb Platelets
<20% 1,500 to 4,000 Palpable
/uL L.N. Disease
Lymph-
ocytes
SURVIVAL
CLL GOK
 CLL
Stage “0”

Marrow No Normal Normal

LC No
Palpable Hb Platelets
>40% > Palpable
15,000 L.N. Disease
LC /uL SURVIVAL
150
months
 CLL
Stage “I”

Marrow No Normal Normal

LC Palpable
Palpable Hb Platelets
>40% > L.N.
15,000 Disease
LC /uL SURVIVAL
101
months
 CLL
Stage “II”

Marrow Hepato- Normal Normal

LC
Hb Platelets
>40% > Palpable Spleno-
15,000 L.N. megaly
LC /uL SURVIVAL
71
months
 CLL
Stage “III”

Marrow Hepato- Anemia Normal

LC
Spleno- Platelets
>40% > Palpable
megaly
15,000 L.N.
LC /uL SURVIVAL
19
months
 CLL
Stage “IV”

Marrow LC Hepato- Anemia Thrombo-

> Palpable Spleno- cytopenia
>40% megaly
15,000 L.N.
LC /uL
SURVIVAL
19
months
Binet
Staging

CLL
 CLL
Group A
No anemia or thrombocytopenia, Axillary
< three of five lymph node areas L.N.

Inguinal
Group B
L.N.
No anemia or thrombocytopenia,
Three or more lymph node areas Cervical
L.N.
Group C
Anemia (Hb <10 g/dL) or Liver
Thrombocytopenia (Platelets <100 x 109/L)

Spleen
Binet Staging of CLL
 Complications

- Hypogammaglobinemia and impaired T-cell function associated with

CLL predispose patients to potentially serious infections. Patients
who demonstrate a pattern of repeated infections, such as
pneumonia and septicemia, should be treated monthly with
prophylactic parenteral gamma globulin.
- Anemia secondary to bone marrow involvement with CLL, splenic
sequestration of red blood cells, and autoimmune hemolytic anemia
associated with a positive Coombs test are included in the
differential diagnosis of a patient with anemia who has CLL.
- Thrombocytopenia: The causes of low platelets in patients with CLL
are very similar to the causes of anemia in patients with CLL and
include bone marrow involvement, splenic sequestration, and
immune thrombocytopenia.
•
Treatment
At the time of diagnosis, most patients do not need to be treated with chemotherapy
unless they have weight loss of more than 10%, extreme fatigue, fever related to
leukemia, night sweats, progressive marrow failure, autoimmune anemia or
thrombocytopenia not responding to prednisone, progressive splenomegaly, massive
lymphadenopathy, or progressive lymphocytosis. Progressive lymphocytosis is defined as
an increase of greater than 50% in 2 months or a doubling time of less than 6 months.
• Patients at stage 0 whose disease is stable require only periodic follow-up. Early
treatment has not been demonstrated to be advantageous. Prednisolone alone, usually in
a dose of 20-60 mg daily initially, with subsequent gradual dose reduction, may be useful
in patients with autoimmune manifestations of the disease.
Nucleoside analogs (ie, fludarabine, cladribine, and pentostatin) include a new group of
drugs with major activity against indolent lymphoid malignancies, including CLL.
 Fludarabine is the most extensively studied and currently is the most commonly used
second-line therapy in CLL.
 Responses to treatment with chlorambucil and prednisone are observed in 38-47% of
patients.
 Patients treated with fludarabine have much higher rates (80%) of overall responses and
a 37% complete remission rate.
• Studies using purine analogs, especially fludarabine, compared to alkylator-based
therapies have shown that the response rates are superior and the progression-free
interval is longer, but evidence to show prolonged overall survival is premature
The combination of fludarabine and cyclophosphamide has shown higher
response rates, but direct comparative trials of fludarabine and
cyclophosphamide to fludarabine alone are lacking.
oThe combination of fludarabine and chlorambucil recently has been shown to
result in more infections than either single agent alone.
•Various combination regimens have shown improved response rates in several
randomized trials but failed to show any survival advantage. Common
combination regimens include chlorambucil and corticosteroids;
cyclophosphamide, doxorubicin, and prednisone (CAP); cyclophosphamide,
vincristine, and prednisone (CVP); and cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP).
•Therapy with monoclonal antibodies has been evaluated in patients with CLL.
The most useful agent in clinical trials so far appears to be CAMPATH-1H, an
antibody directed at CD52. Rituxan (rituximab) also is effective as a second-line
or third-line treatment and may assume a more prominent role in the future.
Patients with CLL demonstrate autoimmune anemia and or thrombocytopenia
up to 25% of the time, and, at the same time, immune incompetence is present,
characterized by a progressive profound hypogammaglobulinemia
Department of Internal Medicine№1
KSMU
CLASSES OF RECOMMENDATIONS
CLASSES OF RECOMMENDATIONS
 SUPRAVENTRICULAR TACHYCARDIA
Supraventricular tachycardia
(SVT) literally indicates
tachycardia (atrial rates >100
beats per minute at rest), the
mechanism of which involves
tissue from the His bundle or
above.
Traditionally, SVT has been used
to describe all kinds of
tachycardias apart from
ventricular tachycardias (VTs)
and AF.
 CONVENTIONAL CLASSIFICATION OF SVT

ATRIAL TACHYCARDIAS
Sinus tachycardia
Focal AT
Multifocal AT
Macro−re-entrant atrial tachycardia (MRAT)
•Cavotricuspid isthmus-dependent MRAT
• – Typical atrial flutter, counter-clockwise (common) or
clockwise (reverse)
• – Other cavotricuspid isthmus-dependent MRAT
•Non-cavotricuspid isthmus-dependent MRAT
• – RA MRAT
• – LA MRAT
AF
 CONVENTIONAL CLASSIFICATION OF SVT

AV junctional tachycardias
Atrioventricular nodal re-entrant tachycardia (AVNRT)
•Typical
•Atypical
Non-re-entrant junctional tachycardia
•JET (junctional ectopic or focal junctional tachycardia)
•Other non-re-entrant variants
 CONVENTIONAL CLASSIFICATION OF SVT

Atrioventricular re-entrant tachycardia (AVRT)

•Orthodromic (including permanent junctional reciprocating
tachycardia)
•Antidromic (with retrograde conduction through the
atrioventricular node or, rarely, over another pathway)
Differential diagnosis of narrow and wide QRS tachycardias
Narrow QRS (≤120 ms) tachycardias

Regular Atrial Irregular Atrial

 Sinus tachycardia  Multifocal AT
 Atrial tachycardia  Atrial fibrillation
 Atrial flutter with  Atrial flutter (variable
fixed AV conduction block)
Regular ventricular
Idiopathic VT (especially
high septal VT)

Regular Atrioventricular
 AV Nodal Re-entry Tachycardia (AVNRT)
 AV re-entry tachycardia (AVRT).
Differential diagnosis of narrow and wide QRS tachycardias
Wide QRS (>120 ms) tachycardias

Regular Irregular
 VT / flutter
 Antidromic AVRT
 SVTs with  Polymorphic VT
aberration/BBB (pre-  Torsade de pointes
existing or rate-  Ventricular fibrillation
dependent during
tachycardia)
 EPIDEMIOLOGY OF SVT
Women have a risk of developing SVT that is two
times greater than that of men, and persons aged
≥65 years or have more than five times the risk of
developing SVT than younger individuals.
 EPIDEMIOLOGY OF SVT
Women are more likely to be affected by AVNRT than
men (ratio ∼70:30), while the converse is true for AVRT
(ratio 45:55).
A relationship with the monthly cycle has been
suggested.
The proportion of patients with AVRT decreases with
age, whereas the proportion of those with AVNRT and AT
increases with age.
 EPIDEMIOLOGY OF SVT
The epidemiology of atrial flutter is not known with
certainty.
The incidence of atrial flutter in men is >2.5 times
that of women and increases exponentially with
age.
Patients with atrial flutter are more likely to have
been smokers, have a longer PR interval, history of
myocardial infarction , and history of heart failure.
 Clinical presentation

The impact of SVT on an individual is based on a

range of factors and may result in palpitations,
fatigue, light-headedness, chest discomfort,
dyspnoea, and altered consciousness.
Rapid rhythms are more likely to present with a
clear history and acutely than less-rapid rhythms,
but SVT usually produces symptoms
 Clinical presentation

• Light-headedness in association with SVT is not

infrequen.
• Presyncope and syncope are less common, and
tend to be associated with presentation in older
individuals.
 Clinical presentation

• In older patients, symptoms may be more extreme—with

dizziness, presyncope, and syncope—in view of the less-
accommodating characteristics of the circulation; drops in
blood pressure are usually immediate and tend to recover.
• In some patients, a description of polyuria (possibly due to
atrial stretch-induced atrial natriuretic peptide activity) can
be elucidated, although this is infrequent
 Clinical presentation

• A sudden onset more likely points to AVNRT or AVRT,

although an AT may also present in this way.
• Characteristics in terms of the regularity or
irregularity are helpful.
• The duration of individual episodes may help in terms
of differentiation. Re-entrant tachycardias tend to last
longer than AT episodes, which may occur in a series
of repetitive runs.
 Clinical presentation

• Clear descriptions of pounding in the neck (the so-

called ‘frog sign’) or ‘shirt flapping’ would point to the
possible competing influences of atrial and ventricular
contraction on the tricuspid valve, and to AVNRT as a
likely cause
• SVT may be unrecognized at initial medical evaluation
and the clinical characteristics can mimic panic
disorder
 Initial evaluation of patients with
supraventricular tachycardia

Standard
•History, physical examination, and 12 lead ECG
•Full blood counts, biochemistry profile, and thyroid
function
•An ECG during tachycardia should be sought
•Transthoracic echocardiography
 Initial evaluation of patients with
supraventricular tachycardia
Optional
•Exercise tolerance testing
•24 h ECG monitoring, transtelephonic monitoring, or an
implantable loop recorder
•Myocardial ischaemia testing in patients with risk factors for
coronary artery disease (including men aged >40 years and
post-menopausal women)
 Sinus tachycardia

Sinus tachycardia is defined as a sinus rate >100

b.p.m. On the ECG, the P wave is positive in leads I,
II, and aVF, and biphasic/negative in lead V1.
 CAUSES OF PHYSIOLOGICAL SINUS TACHYCARDIA
Physiological Emotion, physical exercise, pain, pregnancy
causes
Pathological Anxiety, panic attack, anaemia, fever, dehydration,
causes infection, malignancies, hyperthyroidism, hypoglycaemia,
pheochromocytoma, Cushing’s disease, diabetes mellitus
with evidence of autonomic dysfunction, pulmonary
embolus, myocardial infarction, pericarditis, valve
disease, congestive heart failure, shock
Drugs Epinephrine, norepinephrine, dopamine, dobutamine,
atropine, beta-2 adrenergic receptor agonists
(salbutamol), methylxanthines, doxorubicin, daunorubicin,
beta-blocker withdrawal
Illicit drugs Amphetamines, cocaine, lysergic acid diethylamide,
psilocybin, ecstasy, crack, cocaine
Other Caffeine, alcohol
 SINUS TACHYCARDIA
Type Р wave PR/RP QRS Other
of symptoms
tachyarrhythmia

Sinus tachycardia Identical to the PR<RP Normal Gradual the

P wave sinus configurations, beginning and
rhythm's rеgular the end
arrhythmias

Sinus rhythm with a resting heart rate of > 100 bpm

 SINUS TACHYCARDIA

Rate around 108. Regular sinus rhythm - there is a P wave before

each QRS and the P waves are up in II and down in aVR.
HR 114 b/p/min
 TREATMENT
Sinus tachycardia is usually not treated.
Treatment should eliminate the causes of
arrhythmia
CLASSIFICATION OF ANTIARRHYTHMIC AGENTS
TREATMENT
 ATRIAL TACHYCARDIA

Atrial tachycardia is a form

of supraventricular
tachycardia, originating
within the atria but
outside of the sinus node
 ETIOLOGY

• diseases of the cardiovascular system (hypertension, IHD,

myocarditis, heart defects, etc.)
• chronic bronchopulmonary diseases
• iatrogenic (surgical/catheter surgery for atrial fibrillation)
• alcohol and drug intoxication
• endocrine diseases (thyrotoxicosis, pheochromocytoma,
etc.)
• excess body weight
• apnea
• violations of the electrolyte and acid-base composition of
the blood
 PATHOPHYSIOLOGY OF ATRIAL
TACHYCARDIA

• Usually due to single ectopic focus.

• The underlying mechanism can involve reentry,
triggered activity or increased automaticity.
• The arrhythmia may be sustained or
incessant.
 CLINICAL MANIFESTATIONS
Symptoms may include:
palpitations
shortness of breath
hest pain
rarely syncope or presyncope
 ECG Features of Atrial
Tachycardia
• Atrial rate 150-200 bpm.
• P wave morphology is abnormal when compared with
sinus P wave due to ectopic origin.
• There is usually an abnormal P-wave axis (e.g. inverted in
the inferior leads II, III and aVF)
• At least three consecutive identical ectopic P waves.
• QRS complexes usually normal morphology.
 ATRIAL TACHYCARDIA

FOCAL ATRIAL TACHYCARDIA

The morphology of the P

wave on the ECG differs
R-P > P-R
from the sinus waves
Wave P is located in
front of the QRS complex
(narrow)
>
R-P > P-R P-R R-P
FOCAL ATRIAL TACHYCARDIA
Acute therapy
CHRONIC THERAPY OF FOCAL ATRIAL
TACHYCARDIA.
 MULTIFOCAL ATRIAL TACHYCARDIA

Multifocal AT is defined as a rapid,

irregular rhythm with at least three
distinct morphologies of P waves on the
surface ECG.
 MULTIFOCAL ATRIAL TACHYCARDIA

Multifocal AT is commonly associated with

underlying conditions, including pulmonary
disease, pulmonary hypertension, coronary
disease, and valvular heart disease, as well
as hypomagnesaemia and theophylline
therapy.
 ATRIAL TACHYCARDIA

MULTIFOCAL ATRIAL TACHYCARDIA

The presence of three or more P waves of different etiology in one

ECG lead
The presence of an isoline between the P waves

Irregular intervals of PR, PPи RP

 MULTIFOCAL ATRIAL TACHYCARDIA

Note the varying morphology of the P waves and the PR intervals.

 MULTIFOCAL ATRIAL TACHYCARDIA

Note the varying morphology of the P waves and the PR intervals.

THERAPY OF MULTIFOCAL ATRIAL TACHYCARDIA
THERAPY OF MULTIFOCAL ATRIAL TACHYCARDIA
 AV NODAL RE-ENTRY TACHYCARDIA (AVNRT)

AVNRT s a steady circulation of impulses (re-entry) in the

AV node and the adjacent septal region of the atrial
myocardium.
 AV NODAL RE-ENTRY TACHYCARDIA (AVNRT)

Onset of AVNRT seems to occur bimodally over time. In many

patients, attacks indeed manifest early in life, whereas in a
substantial proportion of patients AVNRT starts later, e.g. in
the fourth or fifth decade of life.
One-half of the patients with minimal symptoms and short-
lived, infrequent episodes of tachycardia may become
asymptomatic within the next 13 years.
AVNRT may result in AF that usually, although not invariably,
is eliminated following catheter ablation of AVNRT.
Familial AVNRT should be considered.
 AV Nodal Re-entry Tachycardia
• This is the commonest cause of palpitations in patients
with structurally normal hearts.
• AVNRT is typically paroxysmal and may occur
spontaneously or upon provocation with exertion,
caffeine, alcohol, beta-agonists (salbutamol) or
sympathomimetics (amphetamines).
• It is more common in women than men (~ 75% of
cases occurring in women) and may occur in young and
healthy patients as well as those suffering chronic
heart disease.
 AV NODAL RE-ENTRY TACHYCARDIA
CLINICAL MANIFESTATIONS
• Patients describe sensations of "shirt flapping " or "neck pulsation",
which may be associated with backflow of blood from contractions
of the right atrium with the tricuspid valve closed.
• AVNRT is characterized by polyuria associated with higher pressure
in the right atrium, increased levels of atrial natriuretic peptide.
• Syncope is rare, but complaints of dizziness are widespread enough.
• The heart rate at AVRT is higher when this arrhythmia is induced
during physical exertion.
• Blood pressure, especially with a high heart rate, decreases to the
greatest extent in the first 10-30 seconds from the start of LVT and
tends to recover within the next 30-60 seconds, despite minimal
changes in heart rate.
 AVNRT: electrocardiogram during tachycardia
 Suddenly starting and just as suddenly ending an attack of
increased heart rate to 140-250 beats per minute while
maintaining the regular rhythm.
 Absence of P' waves in leads II, III and aVF, which merge
with the ventricular QRS complex
 Normal unchanged (not widened and deformed) ventricular
complexes QRS', similar to QRS, recorded before the onset
of paroxysm.
AVNRT: electrocardiogram during tachycardia
AVNRT is a narrow complex tachycardia, i.e. QRS duration
<120 ms.
ST-segment depression may be seen during or after the
tachycardia.
 AVNRT: electrocardiogram during tachycardia

In the typical form of AVNRT (also called slow–fast AVNRT),

retrograde P waves are constantly related to the QRS and, in
the majority of cases, are indiscernible or very close to the
QRS complex. Thus, P waves are either masked by the QRS
complex or seen as a small terminal P' wave that is not
present during sinus rhythm.
 AV NODAL RE-ENTRY TACHYCARDIA

P R > RP

Prolongation of the P-R interval at the time of paroxysm development, usually

atrial extrasystole
The value of the R-P interval is usually ≤ 90 ms
AVNRT: ACUTE THERAPY

Adenosine 6–18 mg i.v. bolus

AVNRT: ACUTE THERAPY
AVNRT:CHRONIC THERAPY
ATRIOVENTRICULAR RE-ENTRY TACHYCARDIA (AVRT)
AVRT is a form of paroxysmal supraventricular tachycardia
that occurs in patients with accessory pathways, usually due
to formation of a re-entry circuit between the AV node and
accessory pathway.

ECG features depend on

the direction of
conduction, which can
be orthodromic or
antidromic.

Orthodromic AVRT: Anterograde conduction through AV node

Antidromic AVRT: Retrograde conduction through AV node
ECG features of AVRT with orthodromic conduction:

• Rate usually 150-250 bpm

• Retrograde P waves are usually visible, with a long RP
interval
• Interval PR>RP
• QRS < 120ms unless pre-existing bundle branch block, or
rate-related aberrant conduction
• QRS alternans: phasic variation in QRS amplitude
associated with AVRT, distinguished from еlectrical
alternans by a normal QRS amplitude
• Rate-related ischemia is common
 ORTHODROMIC AVRT

Regular, narrow complex tachycardia

 ORTHODROMIC AVRT

Regular, narrow complex tachycardia at 180 bpm

The QRS complexes are narrow because impulses are being transmitted in an orthodromic
direction (A -> V) via the AV node
Retrograde P waves are visible in V1 (see first beat), and quite clearly in lead III (notch at
beginning of T wave), with a long RP interval
 ANTIDROMIC AVRT

Antidromic AVRT is rare, and makes up only 5% of

tachyarrhythmias in patients with WPW. As the name
suggests, it involves anterograde conduction via the accessory
pathway.
Retrograde conduction is usually via the AV node, but can also
be via another accessory pathway.
The abnormal direction of ventricular depolarisation results in
a broad complex tachycardia, which can be easily mistaken for
VT.
 ANTIDROMIC AVRT

ECG FEATURES OF AVRT WITH ANTIDROMIC CONDUCTION:

 Rate usually 140–280 bpm
 Wide QRS complexes due to abnormal ventricular
depolarisation via accessory pathway
 ANTIDROMIC AVRT
AVRT: Regular broad complex tachycardia
 ANTIDROMIC AVRT

Antidromic AVRT in a 5-year old boy with WPW:

Regular, broad complex tachycardia at ~280 bpm; this would be very difficult to distinguish from
VT
However, given the child’s age, VT is very unlikely: > 95% of broad complex tachycardias in
children are actually some form of SVT with aberrancy
This rhythm resolved with vagal manoeuvres
AVRT: ACUTE THERAPY
AVRT: CHRONIC THERAPY
 INDICATIONS FOR HOSPITALIZATION

• Unstable hemodynamics
• High risk of proarrhythmic effects of
antiarrhythmic drugs
 Acute management in the
absence of an established
diagnosis
Regular tachycardias
Narrow QRS (≤120 ms)
tachycardias

Adenosine, an endogenous purine nucleoside

(6–18 mg i.v. bolus) is the first drug of choice

Verapamil [0.075 − 0.15 mg/kg i.v. (average

5 − 10 mg) over 2 min] or i.v. diltiazem [0.25
mg/kg (average 20 mg) over 2 min]

Beta-blockers (i.v.), such as short-acting

esmolol (0.5 mg/kg i.v. bolus or 0.05 − 0.3
mg/kg/min infusion) or metoprolol (2.5–15 mg
given i.v. in 2.5 mg boluses),
Acute management in the
absence of an established
diagnosis

Wide QRS (>120 ms)

tachycardias
 CONVENTIONAL CLASSIFICATION OF SVT

ATRIAL TACHYCARDIAS
Sinus tachycardia
Focal AT
Multifocal AT
Macro−re-entrant atrial tachycardia (MRAT)
•Cavotricuspid isthmus-dependent MRAT
• – Typical atrial flutter, counter-clockwise (common) or
clockwise (reverse)
• – Other cavotricuspid isthmus-dependent MRAT
•Non-cavotricuspid isthmus-dependent MRAT
• – RA MRAT
• – LA MRAT
AF
 ATRIAL FLUTTER
Atrial flutter is a type of supraventricular tachycardia caused by a re-
entry circuit within the right atrium. The length of the re-entry circuit
corresponds to the size of the right atrium, resulting in a fairly
predictable atrial rate of around 300 bpm (range 200-400).
 EPIDEMIOLOGY

Atrial flutter (TP) is diagnosed in approximately 7-

10% of all supraventricular tachyarrhythmias.
In men, it is found about 4-5 times more often than
in women. With age, the frequency of atrial flutter
increases.
 ETIOLOGY

• diseases of the cardiovascular system (hypertension, IHD,

myocarditis, heart defects, etc.)
• chronic bronchopulmonary diseases
• iatrogenic (surgical/catheter surgery for atrial fibrillation)
• alcohol and drug intoxication
• endocrine diseases (thyrotoxicosis, pheochromocytoma,
etc.)
• excess body weight
• apnea
• violations of the electrolyte and acid-base composition of
the blood
 ATRIAL FLUTTER

ECG FEATURES OF ATRIAL FLUTTER

• Narrow complex tachycardia
• Regular atrial activity at ~ 300 bpm
• Flutter waves (“saw-tooth” pattern) best seen in leads II, III, aVF
— may be more easily spotted by turning the ECG upside down!
• Flutter waves in V1 may resemble P waves
• Loss of the isoelectric baseline
 ANTICLOCKWISE ATRIAL FLUTTER

There are inverted flutter waves in II, III + aVF at a rate of 300 bpm (one per big square)
There are upright flutter waves in V1 simulating P waves
There is a 2:1 AV block resulting in a ventricular rate of 150 bpm
ANTICLOCKWISE ATRIAL FLUTTER
 CLOCKWISE ATRIAL FLUTTER

The block varies between 2:1 and 4:1

The presence of positive flutter waves in lead II suggests a clockwise re-
entry circuit.
CLOCKWISE ATRIAL FLUTTER
ATRIAL FIBRILLATION
ATRIAL FIBRILLATION
ATRIAL FIBRILLATION
ATRIAL FIBRILLATION
EPIDEMIOLOGY
RISK FACTORS FOR INCIDENT AF
AF-RELATED OUTCOMES.
AF-RELATED OUTCOMES.
CLINICAL FEATURES OF ATRIAL FIBRILLATION
Classification: Atrial Fibrillation
 4S-AF scheme as an example of
structured characterization of AF
SYSTEMS USED FOR AF SCREENING
SYSTEMS USED FOR AF SCREENING
DIAGNOSTIC ASSESSMENT IN ATRIAL FIBRILLATION
EHRA SYMPTOM SCALE
 Clinical symptoms

Typical symptoms of AF are: increased, usually

irregular heartbeat, heart failure, shortness of breath,
fatigue, poor exercise tolerance and sweating.
At objective examination: heart tones are irregular,
pulse deficiency.
 Clinical symptoms

In patients with AF, the quality of life ↓, tolerance to physical

activity decreases, and left ventricular dysfunction often
appears and/or progresses with the development of heart
failure.
In about a quarter of cases, arrhythmia may be asymptomatic
and is detected during a medical examination.
MULTIDISCIPLINARY ATRIAL FIBRILLATION TEAMS

Fi
In
m
(a

©ESC
“А” ANTICOAGULATION/AVOID STROKE
 CHA
Table 8 CHA2DS2-VASc DS2-VASc
score2(1) score
CHA2DS2-VASc score
Risk factors and definitions Points Comment
awarded
C Congestive heart failure 1 Recent decompensated HF irrespective of LVEF (thus incorporating
Clinical HF, or objective HFrEF or HFpEF), or the presence (even if asymptomatic) of moderate-
evidence of moderate to severe LV systolic impairment on cardiac imaging; HCM confers a high
severe LV dysfunction, or HCM stroke risk and OAC is beneficial for stroke reduction.
H Hypertension 1 History of hypertension may result in vascular changes that predispose
or on antihypertensive therapy to stroke, and a well-controlled BP today may not be well-controlled
over time. Uncontrolled BP − the optimal BP target associated with the
lowest risk of ischaemic stroke, death, and other cardiovascular
outcomes is 120−129/<80 mmHg.
A Age 75 years or older 2 Age is a powerful driver of stroke risk, and most population cohorts
show that the risk rises from age 65 years upwards. Age-related risk is
a continuum, but for reasons of simplicity and practicality, 1 point is
given for age 65−74 years and 2 points for age ≥75 years.

www.escardio.org/guidelines 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation
(European Heart Journal 2020-doi/10.1093/eurheartj/ehaa612)
CHA2DS2-VASc score
CLINICAL RISK FACTORS IN THE HAS-BLED SCORE
 CLINICAL RISK FACTORS IN THE HAS-BLED SCORE
Table 10 Clinical risk factors in the HAS-BLED score (2)

Risk factors and definitions Points

awarded
L Labile INRb 1
TTR <60% in patient receiving VKA
E Elderly 1
Aged >65 years or extreme frailty
D Drugs or excessive alcohol drinking 1 point
Concomitant use of antiplatelet or non-steroidal anti-inflammatory for each
drugs; and/or excessivec alcohol per week
Maximum score 9
bOnly relevant if patient receiving a VKA.
cAlcohol excess or abuse refers to a high intake (e.g. >14 units per week), where the clinician assesses there would be an impact on health or bleeding risk.

2020 ESC Guidelines for the diagnosis and management of atrial fibrillati
 ASSESSMENT OF THE RISK OF BLEEDING

An assessment of the risk of bleeding is recommended in all

AF patients before starting anticoagulant therapy.
HAS-BLED ≥ 3 indicates a high risk of bleeding.
This does not mean that anticoagulant therapy is not
necessary
NON-VITAMIN K ANTAGONIST ORAL
ANTICOAGULANTS
 ANTITHROMBOTIC DRUGS
The main antithrombotic drugs for the prevention of
stroke and systemic embolism in AF patients are VKA
and non–vitamin K oral anticoagulant (NOAK)
ATRIAL FIBRILLATION: THERAPEUTIC WINDOW OF
WARFARIN
“B” Better symptom control
 Rate control
Тarget heart rate <80 beats per minute (bpm) at rest and
<110 bpm during moderate exercise
CHOICE OF RATE CONTROL DRUGS.
 DRUGS FOR RATE CONTROL IN AF
Table 13 Drugs for rate control in AFa (1)
Intravenous administration Usual oral maintenance dose Contraindicated
Beta-blockersb
Metoprolol tartrate 2.5−5 mg i.v. bolus; up to 4 doses 25−100 mg b.i.d. In case of asthma use
Metoprolol XL N/A 50−400 mg o.d. beta-1-blockers
(succinate) Contraindicated in acute
HF and history of severe
Bisoprolol N/A 1.25−20 mg o.d. bronchospasm
Atenololc N/A 25−100 mg o.d.

Esmolol 500 µg/kg i.v. bolus over 1 min, N/A

followed by 50−300 µg/kg/min
Landiolol 100 µg/kg i.v. bolus over 1 min, N/A
followed by 10−40 µg/kg/min; in
patients with cardiac dysfunction:
1-10 µg/kg/min
Nebivolol N/A 2.5−10 mg o.d.

Carvedilol N/A 3.125−50 mg b.i.d.

aAll
rate control drugs are contraindicated in Wolff−Parkinson−White syndrome, also i.v. amiodarone. bOther beta-blockers are available but not recommended as
specific rate control therapy in AF and therefore not mentioned here (e.g. propranolol and labetalol). cNo data on atenolol; should not be used in HFrEF.

www.escardio.org/guidelines 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation
(European Heart Journal 2020-doi/10.1093/eurheartj/ehaa612)
 DRUGS FOR RATE CONTROL IN AF
Table 13 Drugs for rate control in AFa (2)
Intravenous administration Usual oral maintenance dose Contraindicated
Non-dihydropyridine calcium channel antagonists
Verapamil 2.5−10 mg i.v. bolus 40 mg b.i.d. to 480 mg Contraindicated in HFrEF
over 5 min (extended release) o.d. Adapt doses in hepatic and
Diltiazem 0.25 mg/kg i.v. bolus over 5 min, then 60 mg t.i.d. to 360 mg renal impairment
5−15 mg/h (extended release) o.d.
Digitalis glycosides
Digoxin 0.5 mg i.v. bolus (0.75−1.5 mg over 0.0625−0.25 mg o.d. High plasma levels
24 hours in divided doses) associated with increased
mortality
Check renal function
before starting and adapt
dose in CKD patients
Digitoxin 0.4−0.6 mg 0.05−0.1 mg o.d. High plasma levels
associated with increased
mortality
aAll rate control drugs are contraindicated in Wolff−Parkinson−White syndrome, also i.v. amiodarone.
DRUGS FOR RATE CONTROL IN AF
 RHYTHM CONTROL

The ‘rhythm control strategy’ refers to attempts to

restore and maintain sinus rhythm
RHYTHM CONTROL

cardioversion

antiarrhythmics

catheter ablation
 ANTIARRHYTHMIC
Table 14 Antiarrhythmic drugs used forDRUGS USED
restoration of sinusFOR
rhythm (1) RESTORATION OF SINUS RHYTHM
Antiarrhythmic drugs for restoration of sinus rhythm (pharmacological cardioversion)
Drug Administration Initial dose Further dosing Acute success rate Contraindications/
route For For and expected time to Precautions/
cardioversion cardioversion sinus rhythm comments
Flecainidea Oralb 200−300 mg - Overall: 59−78% • Should not be used in
i.v. 2 mg/kg over (51% at 3 h, ischaemic heart disease
10 min 72% at 8 h) and/or significant structural
Propafenonea Oralb 450−600 mg - Oral: 45−55% at 3 h, heart disease
i.v. 1.5−2 mg/kg 69−78% at 8 h; • May induce hypotension, AFL
over 10 min i.v.: 43−89% with 1:1 conduction (in
Up to 6 h 3.5−5.0% of patients)
• Flecainide may induce mild
QRS complex widening
• Do NOT use for
pharmacological
cardioversion of AFL
aMost frequently used for cardioversion of AF, available in most countries. bMay be self-administered by selected outpatients as a ‘pill-in-the-pocket’ treatment
strategy. For more details regarding pharmacokinetic or pharmacodynamic properties refer to EHRA AADs–clinical use and clinical decision making: a consensus
document.

www.escardio.org/guidelines 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation
(European Heart Journal 2020-doi/10.1093/eurheartj/ehaa612)
 INDICATIONS FOR CATHETER ABLATION OF
re 17 Indications forSYMPTOMATIC
catheter ablationAF
of symptomatic AF

©ESC
b
LONG-TERM RHYTHM CONTROL THERAPY
 “C” — Cardiovascular risk factors and
concomitant diseases — detection and
management
Lifestyle interventions and cardiovascular
risk factors/comorbidities
 AF Treatment : Interventional Procedures
LEFT ATRIAL APPENDAGE OCCLUSION
Left atrial appendage closure is a
minimally invasive cardiac
procedure that is used to reduce
stroke risk in certain individuals
with atrial fibrillation. The
procedure involves the delivery of
an implant device that seals off
the left atrial appendage, thereby
preventing clots from escaping
the appendage and traveling to
the brain.
The Watchman implant device is
the new ‘gold standard’ in left
atrial appendage closure. The
device is a parachute-shaped
device that expands to cover the
passageway between the left
atrial appendage and the left
atrium.
Management of AF
 VT IN THE ETIOLOGY OF ARRHYTHMOGENIC SUDDEN
CARDIAC DEATH
BRADYCARDIAS

POLYMORPHIC VT
VT

VF
 VENTRICULAR TACHYCARDIA

these are 3 QRS complexes or more with

localization of the arrhythmogenic substrate below
the level of the Gis bundle and a frequency of over
100 per minute.
VENTRICULAR TACHYCARDIA

ischemic zone

reentry wave
 VENTRICULAR TACHYCARDIA

The pathogenic electrical event leading to sudden cardiac

death is likely VT followed by VF and eventually asystole
VENTRICULAR TACHYCARDIA

HEMODYNAMICS

STABLE UNSTABLE
 SYNCOPE

The two main dangers of VT are the transition to ventricular

fibrillation and syncope due to a high pulse and reduced
ejection fraction
 VENTRICULAR TACHYCARDIA

Non-sustained Sustained

Three or more consecutive Duration > 30 seconds,

ventricular complexes, or requiring
terminating spontaneously intervention due to
in < 30 seconds haemodynamic
compromise
VENTRICULAR TACHYCARDIA

Monomorphic Polymorphic
 ETIOLOGY

STRUCTURAL CARDIOLOGICAL DISEASES:

Coronary heart disease, heart failure, valvular heart defects, CMP.

HEREDITARY
(LONG QT SYNDROME, SHORT QT SYNDROME, BRUGADA SYNDROME,
ETC.)

IDIOPATHIC VT (about 10%)

 CLINICAL PICTURE

The clinic is various. From absolute asymptomatic

to palpitations, chest discomfort, chest pain,
asthma , dizziness, presyncopal and syncopal states,
complete circulatory arrest.
Palpitations, presyncope and syncope are the
three most important symptoms.
 STANDARD RESEARCH METHODS
• Anamnesis, family history
• Exclusion of taking medications that prolong QT
interval, sodium channel blockers,
proarrhythmogenic drug combinations
• General and biochemical blood analysis (to
exclude concomitant diseases)
• ECG in 12 leads
• Holter Monitor ECG in 12 leads
• Echo-cardiography
MODERN HEART RATE MONITORING SYSTEMS
 MONOMORPHIC VT: ECG FEATURES

• usually the regular rhythm with a frequency of

110-250 per minute;
• the duration of the QRS complex is more than 120
ms, and more often - more than 140 ms;
• in 50% of cases, AV dissociation is observed;
• can be "captures"
MONOMORPHIC VT: ECG FEATURES
 WHAT IS THE RHYTHM?

VT – broad complex tachycardia: regular ventricular rhythm, broad QRS complexes, no

visible P waves.
Acute therapy of wide complex tachycardia in the
absence of an established diagnosis

an initial energy of 100 J

is recommended
 Ventricular tachycardia
• Long-term anti-arrhythmic therapy may be indicated to
prevent recurrence of VT; beta-blockers and a number of
class III antiarrhythmics are commonly used.
• Catheter ablation is a possible treatment for those with
recurrent VT; remote magnetic navigation is one effective
method to do the procedure.
An implantable
cardioverter defibrillator
(ICVD) is more effective
than drug therapy for
prevention of sudden
cardiac death due to VT
and VF, but may be
constrained by cost issues.
 Ventricular Flutter
• Extreme form of ventricular tachycardia (VT) with loss of
organised electrical activity
• Associated with rapid and profound hemodynamic compromise
• Usually short lived due to progression to ventricular fibrillation
• As with ventricular fibrillation rapid initiation of advanced life
support is required

How to Recognise VF
 Continuous Sine Wave
 No identifiable P waves, QRS
complexes, or T waves
 Rate usually > 200 beats / min

Typical appearance of ventricular flutter:

Monomorphic sine wave at >200bpm.
ECG looks identical when turned upside down.
12-lead ECG example of ventricular flutter

Extremely rapid monomorphic sine wave at

around 300 bpm
 Ventricular Fibrillation (VF)
Ventricular fibrillation (VF) is the tmost important shockable
cardiac arrest rhythm.
ECG Findings
Chaotic irregular deflections of varying amplitude
No identifiable P waves, QRS complexes, or T waves
Rate 150 to 500 per minute
Amplitude decreases with duration (coarse VF -> fine VF)

Typical rhythm strip of ventricular fibrillation

•Appearance of fine VF
 TREATMENT
150-360 Joules

300 mg
THE END
 Department of Internal Medicine №1

Acute coronary
syndrome Company name

Lecture: ass.-prof. Khardikova E.M.

 Acute coronary syndrome –
any combination of clinical
signs or symptoms that make
you suspect a unstable
angina or myocardial
infarction.
ACS is rather not a diagnosis, but a "label" that
orients the doctor to a certain algorithm of
actions, a strategy for early active or even
aggressive treatment.
 CLASSIFICATION

At the stage of preliminary diagnosis

or early hospital stages:

1. ACS with ST segment elevation

Myocardial infarction with ST segment elevation
(acute blockade of LBBB is also included in this
group).
2. ACS without ST segment elevation
 ACS WITH ST-SEGMENT ELEVATION

ACS with ST segment elevation - recent clinical signs or

symptoms of myocardial ischemia in combination with the
presence of persistent (lasting more than 20 minutes) ST
segment elevation in at least two adjacent ECG leads

Includes:
 MI with persistent
ST segment
elevation
 unstable angina.
 ACS WITHOUT PERSISTENT ST-
SEGMENT ELEVATION

ACS without persistent ST segment elevation -

recent clinical signs or symptoms of myocardial
ischemia, when there are no persistent (lasting more
than 20 minutes) ST segment elevation on the ECG.

Includes:
 MI without persistent ST
segment elevation
 unstable angina.
 UNSTABLE ANGINA

Unstable angina is a type of ACS that is defined as one or more

of the following in patients whose cardiac biomarker levels do not
meet criteria for MI:
 Rest angina that is prolonged (usually > 20 minutes)
 New-onset angina of at least class 3 severity in the Canadian
Cardiovascular Society (CCS) classification
 Increasing angina, ie, previously diagnosed angina that has
become distinctly more frequent, more severe, longer in
duration, or lower in threshold (eg, increased by ≥ 1 CCS class
or to at least CCS class 3)
 ACUTE MYOCARDIAL INFARCTION

AMI defines cardiomyocyte necrosis in a clinical setting consistent

with acute myocardial ischaemia.
A combination of criteria is required to meet the diagnosis of AMI,
namely the detection of an increase and/or decrease of a cardiac
biomarker, preferably high-sensitivity cardiac troponin T or I, with
at least one value above the 99th percentile of the upper reference
limit and at least one of the following:
• Symptoms of myocardial ischaemia.
• New ischaemic ECG changes.
• Development of pathological Q waves on ECG.
• Imaging evidence of loss of viable myocardium or new regional
wall motion abnormality in a pattern consistent with an ischaemic
aetiology.
• Intracoronary thrombus detected on angiography or autopsy.
 CLINICAL DIAGNOSIS AFTER
CONFIRMATION/EXCLUSION OF MI:

1. ST segment elevation MI (this group also

includes acute blockade of LBBB) - STEMI
2. Non-ST segment elevation MI - NSTEMI
3. Unstable angina
DIFFERENTIAL DIAGNOSTICS
 Diagnostic algorithm in
acute coronary syndrome
CLASSIFICATION OF MI IN TERMS
OF LESION

Q WAVE MI (large focal or transmural)

NON–Q WAVE MI (small focal)
 CLASSIFICATION OF MI BY
LOCALIZATION

• left ventricular myocardial infarction

(anterior, lateral, lower, posterior);
• isolated apex myocardial infarction;
• interventricular septal myocardial
infarction (septal);
• right ventricular myocardial infarction;
• combined localization: posterior-lower,
anterolateral, etc.
 CLASSIFICATION OF MI
ACCORDING TO THE ANATOMY OF
THE LESION
• transmural
• intramural
• subendocardial
• subepicardial
 CLASSIFICATION
CLINICAL DIAGNOSIS AFTER
CONFIRMATION/EXCLUSION OF MI:
1. Q WAVE MI
2. NON–Q WAVE MI
3. UNSTABLE ANGINA
 CLASSIFICATION

Recurrent myocardial infarction

Incident MI is defined as the
individual’s first MI.
When features of MI occur in the
first 28 days after an incident
event, the second event is not
counted as a new MI for
epidemiological purposes.
If characteristics of MI occur after
28 days following an incident MI, it
is considered to be a recurrent MI
 CLASSIFICATION
Re-infarction

The term re-infarction is used clinically for an acute MI that

occurs within 28 days of an incident or recurrent MI.
 DEFINITION

The term acute myocardial infarction (AMI)

should be used when there is evidence of
myocardial injury (defined as an elevation of
cardiac troponin values with at least one value
above the 99th percentile upper reference limit)
with necrosis in a clinical setting consistent
with myocardial ischaemia
Spectrum of myocardial injury, ranging
from no injury to myocardial infarction
MYOCARDIAL INFARCTION TYPE 1

Criteria for type 1 MI

Detection of a rise and/or fall of cTn values with at least one
value above the 99th percentile URL and with at least one of
the following:
• Symptoms of acute myocardial ischaemia;
• New ischaemic ECG changes;
• Development of pathological Q waves;
• Imaging evidence of new loss of viable myocardium or new
regional wall motion abnormality in a pattern consistent with an
ischaemic aetiology;
• Identification of a coronary thrombus by angiography including
intracoronary imaging or by autopsy.
MYOCARDIAL INFARCTION TYPE 1
 MYOCARDIAL INFARCTION TYPE 2

Detection of a rise and/or fall of cTn values with at least one

value above the 99th percentile URL, and evidence of an
imbalance between myocardial oxygen supply and demand
unrelated to acute coronary athero-thrombosis, requiring at
least one of the following:

•Symptoms of acute myocardial ischaemia;

•New ischaemic ECG changes;
•Development of pathological Q waves;
•Imaging evidence of new loss of viable myocardium or new
regional wall motion abnormality in a pattern consistent with an
ischaemic aetiology
MYOCARDIAL INFARCTION TYPE 2
MYOCARDIAL INFARCTION TYPE 2
A MODEL FOR INTERPRETING
MYOCARDIAL INJURY
MYOCARDIAL INFARCTION TYPE 3

Patients who suffer cardiac death,

with symptoms suggestive of
myocardial ischaemia
accompanied by presumed new
ischaemic ECG changes or
ventricular fibrillation, but die
before blood samples for
biomarkers can be obtained, or
before increases in cardiac
biomarkers can be identified, or MI
is detected by autopsy
examination.
 MYOCARDIAL INFARCTION TYPE 4
TYPE 4A MYOCARDIAL INFARCTION
Myocardial infarction associated with
percutaneous coronary intervention
Criteria for PCI-related MI ≤ 48 h after the
index procedure:
- New ischaemic ECG changes;
- Development of new pathological Q waves;
- Imaging evidence of new loss of viable
myocardium or new regional wall motion
abnormality in a pattern consistent with an
ischaemic aetiology;
- Angiographic findings consistent with a procedural flow-
limiting complication such as coronary dissection, occlusion of
a major epicardial artery or a side branch occlusion/thrombus,
disruption of collateral flow, or distal embolization
 MYOCARDIAL INFARCTION TYPE 4
TYPE 4В MYOCARDIAL INFARCTION

Stent/scaffold thrombosis
associated with percutaneous
coronary intervention.
A subcategory of PCI-related MI is
stent/scaffold thrombosis, type 4b MI,
as documented by angiography or
autopsy using the same criteria
utilized for type 1 MI.
The following temporal categories
are suggested: acute, 0–24 h;
subacute, > 24 h to 30 days; late, >
30 days to 1 year; and very late > 1
year after stent/scaffold implantation
 MYOCARDIAL INFARCTION TYPE 4
TYPE 4C MYOCARDIAL INFARCTION
Restenosis associated with percutaneous coronary
intervention
MYOCARDIAL INFARCTION
TYPE 5

Myocardial infarction associated

with coronary artery bypass
grafting (CABG)
CABG-related MI is arbitrarily defined as
elevation of cTn values > 10 times the 99th
percentile URL in patients with normal
baseline cTn values.
• Development of new pathological Q waves;
• Angiographic documented new graft
occlusion or new native coronary artery
occlusion;
• Imaging evidence of new loss of viable
myocardium or new regional wall motion
abnormality in a pattern consistent with an
ischaemic aetiology.
 DIAGNOSIS
The formulation of the diagnosis includes:
• a form of coronary heart disease (unstable angina or
MI)
• with or without ST segment elevation on the ECG
• localization
• the date of the onset of the disease.
• the date of the coronarography and its results
• in the case of PCI: characteristics of the stent, number
and the date of intervention
 DIAGNOSIS
In any variant of ACS, to assess the prognosis,
the diagnosis should indicate the class of acute
HF according to the Killip classification.

Class I: No evidence of heart failure (mortality 6%)

Class II: Findings of mild to moderate heart failure (S3 gallop,
rales < half-way up lung fields or elevated jugular venous
pressure (mortality 17%)
Class III: Pulmonary edema (mortality 38%)
Class IV: Cardiogenic shock defined as systolic blood
pressure < 90 and signs of hypoperfusion such as oliguria,
cyanosis, and sweating (mortality 67%)
 EXAMPLES OF DIAGNOSES.
• Non-ST segment elevation MI of the anterior left
ventricle wall from 19/04/2022. Acute heart failure I
class by Killip.
• Unstable angina. Acute heart failure I class by Killip.
• ST segment elevation MI of the inferior LV wall from
12.12.2021. Postinfarction cardiosclerosis (STEMI in
August 2020). Coronary angiography from 19.04.2022.
Stenosing atherosclerosis of the coronary arteries:
acute subocclusion of the right coronary artery,
stenosis of the anterior interventricular branch -80%.
PCI (19.04.2022): balloon angioplasty and XYZ stent
implantation in the right coronary artery. Acute HF II
Class by Killip.
 EPIDEMIOLOGY

Acute coronary syndrome

(ACS) occurs three to four
times more often in men
than in women below the
age of 60 years, but after
the age of 75, women
represent the majority of
patients.
Women tend to present more often with atypical
symptoms, up to 30%
 EPIDEMIOLOGY
Women also have a higher
risk of bleeding complications
with PCI. There is an ongoing
debate regarding whether
outcomes are poorer in
women, with several studies
indicating that a poorer
outcome is related to older
age and more comorbidities
among women suffering MI.
 RISK FACTORS FOR MI

 Age: men after 55 years; women after

65 years.
 The presence of coronary heart disease
in the anamnesis
 Drug use
 Obesity, physical inactivity
 Hypercholesterolemia
 Previous MI, stroke, angina pectoris.
 Concomitant pathology (DM, AH II, III
stages, high and very high risk)
 Chronic renal failure
 Obesity
PROVOKING FACTORS OF IM
• intense physical activity;
• psychoemotional stressful situation;
• depression;
• surgical intervention;
• injury;
• overeating;
• pronounced cooling or overheating;
• smoking;
• low social and educational status
CLINICAL FORMS OF MI
ATYPICAL
TYPICAL
FORMS

ABDOMINAL ARRHYTHMIC

ASTHMATIC
CEREBRAL

PAIN-FREE
CHARACTERISTICS OF CHEST PAIN IN
MYOCARDIAL ISCHEMIA

Сhest discomfort, which

resembles classic angina
pectoris but occurs at rest or
with less activity than usual, is
the most common symptom.
The intensity of MI pain is
variable, usually severe, and in
some instances intolerable.
Pain is prolonged, usually
lasts >20 minutes, and
frequently lasts for hours.
CHARACTERISTICS OF CHEST PAIN IN
MYOCARDIAL ISCHEMIA

The discomfort is
typically described as
constricting,
crushing, oppressing,
or compressing.
The pain is usually
retrosternal, frequently
spreading to both sides
of the anterior chest,
with predilection for the
left side.
CHARACTERISTICS OF CHEST PAIN IN
MYOCARDIAL ISCHEMIA

Often there is
irradiation of
pain to the left
shoulder, left
scapula,
interscapular
area, neck, lower
jaw, ear, pharynx.
In rare cases,
the pain radiates
only to the right
arm, right
shoulder, right
scapula.
CHARACTERISTICS OF CHEST PAIN IN
MYOCARDIAL ISCHEMIA

There is pallor of the skin, weakness, cold sweat.

Such pain is not associated with movement and
change of body position, the act of breathing, is
not stopped by taking nitrates
 ATYPICAL FORMS

ABDOMINAL TYPE
Pain of an acute MI may begin
in the epigastric area and
simulate a variety of abdominal
disorders.
It is manifested by nausea,
vomiting, which does not bring
relief, belching, bloating. Pain
can radiate to the lumbar
region, there is pain during
palpation in the epigastric
region.
 ATYPICAL FORMS

ASTHMATIC TYPE
The leading symptom is
shortness of breath. The
clinical picture of cardiac
asthma or pulmonary edema
develops.
 ATYPICAL FORMS

Arrhythmic.
It is manifested by various
rhythm disturbances.
 ATYPICAL FORMS

Cerebral form.
It is represented by
dizziness, impaired
consciousness,
neurological symptoms
ATYPICAL FORMS

Pain-free (low-symptomatic).
 Physical examination

The results of a physical examination may vary from a

variant of the norm to the following manifestations:
 systolic murmur at the apex of the heart;
 pathological III heart tone;
 pulsation of the neck veins;
 arterial hypertension due to sympathetic activation;
 hypotension due to LV systolic dysfunction or
development acute mitral regurgitation;
 acute pulmonary edema (shortness of breath, wet
wheezing during lung auscultation);
 cardiogenic shock (hypotension, acute pulmonary edema,
signs of hypoperfusion of organs)
 INSTRUMENTAL RESEARCH

In all patients with suspected

ACS, it is recommended for 10
minutes after the first contact
with a medical professional
(usually pre-hospitally), register
and interpret the ECG at rest as
in at least 12 standard leads for
the diagnosis of STEMI, the
exclusion of ACS with ST
segment elevation and other
causes of symptoms.
 STAGES OF MYOCARDIAL INFARCTION

Acute period: during the first hour from the beginning of the pain
attack. During this period, unfortunately, patients rarely get
medical help.

ST-segment elevation (measured at the J-point) is considered suggestive of

ongoing coronary artery acute occlusion in the following cases: at least two
contiguous leads with ST-segment elevation ≥ 2.5 mm in men < 40 years,
≥2 mm in men ≥ 40 years, or ≥ 1.5 mm in women in leads V2–V3 and/or ≥
1 mm in the other leads [in the absence of left ventricular (LV) hypertrophy or
left bundle branch block LBBB)]
 STAGES OF MYOCARDIAL INFARCTION

Prolonged new convex ST-segment elevation, particularly

when associated with reciprocal ST-segment depression, usually
reflects acute coronary occlusion and results in myocardial injury
with necrosis. Reciprocal changes can help to differentiate STEMI
from pericarditis or early repolarization changes.
STAGES OF MYOCARDIAL INFARCTION
STAGES OF MYOCARDIAL INFARCTION

Subacute period: lasts up to 1-3 weeks. During this

period, potassium ions gradually leave the necrosis
zone, the damage becomes smaller and the ST
segment gradually approaches the isoline, the negative
T wave begins to be visualized.
STAGES OF MYOCARDIAL INFARCTION

On the 5th day of MI, pathological Q waves in II, III, aVF with
negative T waves were formed
STAGES OF MYOCARDIAL INFARCTION

Scarring period: from 1-3 weeks to 3 months. Potassium ions

have long since left the necrosis zone, there are no damage
currents, dead myocardiocytes are replaced by connective tissue,
a scar forms, its neovascularization occurs, etc.
The marker of the scarring stage is the pathological Q wave,
which in most patients remains forever.
STAGES OF MYOCARDIAL INFARCTION

Scarring in the area of the LV anterior wall, apex, IVS with transition to the LV
lateral wall after myocardial infarction
Anterior MI
ANTEROLATERAL MI
TRUE POSTERIOR MI
Inferior MI

Significant Q waves and T-wave

inversions in leads II, III, and aVF. With
lateral damage, changes also may be
seen in leads V5 and V6
 TOPICAL DIAGNOSIS OF
MYOCARDIAL INFARCTION
TOPICAL DIAGNOSIS OF
MYOCARDIAL INFARCTION
Electrocardiographic localization
of infarct related coronary artery

Inferior wall MI: ECG showing ST elevation in inferior leads with

ST elevation in lead III>II and ST depression in L I and aVL
suggestive of RCA occlusion.
Right coronary angiogram of the same patient showing total
occlusion (arrow) of RCA in the distal part
Electrocardiographic localization
of infarct related coronary artery

Anterior wall MI. ECG showing ST elevation in leads V2, V3, I,aVL and
ST depression in inferior leads suggestive of proximal left anterior
descending arteryocclusion. Left coronary angiogram of the same
patient confirming the site of occlusion in the proximal LAD
 SERUM CARDIAC MARKERS

Myocardial injury is defined

cTnI and cTnT are the as being present when blood
preferred biomarkers for levels of cTn are increased
the evaluation of above the 99th percentile
myocardial injury, and upper reference limit.
high-sensitivity (hs)- The injury may be acute, as
cTn assays are evidenced by a newly
recommended for detected dynamic rising
routine clinical use. and/or falling pattern of cTn
values above the 99th
percentile URL, or chronic, in
the setting of persistently
elevated cTn levels.
 Imaging techniques
ECHOCARDIOGRAPHY

The strength of
echocardiography is the
combined assessment of
cardiac structure and
function, in particular
myocardial thickness,
thickening/thinning, and
motion.
Regional wall motion abnormalities induced by ischaemia can be
detected by echocardiography almost immediately after onset
when > 20% transmural myocardial thickness is affected.
 Imaging techniques
ECHOCARDIOGRAPHY

The technique is useful in

diagnosing mechanical
complications in patients with
MI and haemodynamic
compromise (shock), or other
potentially fatal entities such as
acute aortic dissection or
massive pulmonary embolism
where the clinical presentation
might be similar to that seen with
acute MI.
 IMAGING TECHNIQUES

CARDIAC MAGNETIC RESONANCE IMAGING

The high tissue contrast and resolution of CMR provides an
accurate assessment of myocardial structure and function.
Although less commonly used in the acute setting, it has similar
capabilities to echocardiography in suspected MI.
CMR also has the ability to identify the presence and extent of
myocardial oedema/inflammation, allowing the distinction of
acute vs. chronic myocardial injury
DIFFERENTIAL DIAGNOSES OF ACS IN THE
SETTING OF ACUTE CHEST PAIN
 PRE-HOSPITAL LOGISTICS OF CARE

First Medical Contact

If the pain syndrome persists, the patient should be given a tablet
of nitroglycerin (or spray) 0.4 -0.5 mg for resorption under the
tongue, if necessary, twice again with an interval of 5 minutes
 PRE-HOSPITAL LOGISTICS OF CARE

First Medical Contact

If the clinical manifestations of myocardial ischemia persist after
taking nitroglycerin three times under the tongue, its intravenous
infusion (nitrates) should be started.
 PRE-HOSPITAL LOGISTICS OF CARE

Patients whose symptoms are not relieved after three serial

sublingual nitroglycerin tablets or whose symptoms recur with
adequate anti-ischemic therapy, intravenous administration of
the narcotic analgesic morphine is indicated (10 mg of the drug
is diluted in 10 ml of 0.9% sodium chloride solution,
administered intravenously slowly 2-4 mg, then, if necessary, 2-8
mg at intervals of 5-15 minutes until the effect is achieved).
PRE-HOSPITAL LOGISTICS OF CARE
STEMI
PRE-HOSPITAL AND HOSPITAL
LOGISTICS OF CARE
STEMI
 PRE-HOSPITAL LOGISTICS OF CARE

Periprocedural pharmacotherapy
First Medical Contact
P2Y12 inhibitors Unfractionated heparin
Platelet inhibition Prasugrel (60 mg loading
initial bolus 70–100 U/kg or
dose and 10 mg maintenance
dose once daily per os) Enoxaparin
0,5 mg/kg i.v. bolus
Ticagrelor (180 mg p.o.
loading dose and 90 mg
Acetylsalicylic acid maintenance dose twice daily).
150–300 mg. Clopidogrel 600 mg Anticoagulation
 PRIMARY MECHANISMS O BALLOON
ANGIOPLASTY AND STENTING

 A balloon angioplasty catheter is positioned into the stenosis over a

guidewire under fluoroscopic guidance.
 The balloon is inflated temporarily occluding the vessel.
 The lumen is enlarged primarily by stretching the vessel
 A stent mounted on a deflated balloon is placed into the lesion and
pressed against the vessel wall with balloon inflation The balloon is
deflated and removed, leaving the stent permanently against the wall
acting as a scaffold to hold the dissections against the wall and prevent
vessel recoil.
PCI
PRE-HOSPITAL LOGISTICS OF CARE
STEMI
 THROMBOLYTIC THERAPY
Acetylsalicylic acid Enoxaparin
P2Y12 inhibitors 30 mg i.v. bolus after 15 minutes
150–300 mg. Clopidogrel 600 mg subcutaneously 1 mg / kg 2 times
a day (maximum - 100 mg) 2
times a day

Platelet inhibition Anticoagulation

THROMBOLYTICS
Fibrinolytic therapy is
Single-bolus weight-
recommended within 12 h of
symptom onset if primary PCI
adjusted tenecteplase
cannot be performed within tissue plasminogen
120 min from STEMI diagnosis activator
Contra-indications to
fibrinolytic therapy
Contra-indications to
fibrinolytic therapy
CORONARY ARTERY BYPASS GRAFT
SURGERY

Coronary artery bypass graft

surgery (CABG) should be
considered for patients with a
patent infarct-related artery
but with unsuitable
anatomy for PCI, and either
a large myocardial area at
jeopardy or with cardiogenic
shock
HOSPITAL LOGISTICS OF CARE
NSTEMI
 GRACE RISK SCORE
Global Registry of Acute Coronary Events
https://www.outcomes-umassmed.org/grace/acs_risk2/index.html
GRACE RISK SCORE
 Selection of non-ST-segment
elevation ACS treatment strategy
PHARMACOLOGICAL TREATMENTS

Algorithm for antithrombotic therapy

REVASCULARIZATION MODALITIES

DES = drug-eluting stent

coronary artery bypass

grafting
 Management strategy for
NSTE-ACS patients.

Dual antiplatelet therapy consisting of a potent P2Y12

receptor inhibitor in addition to aspirin is generally
recommended for 12 months, irrespective of the stent type,
unless there are contraindications.
 Management during hospitalization

Beta-blockers

Early intravenous Mid- and long-term

beta-blocker administration beta-blocker treatment

 reduces the incidence of  mortality reduction

acute malignant ventricular  oral BB initiation
arrhythmias should be considered
 reduction in infarct size within the first 24 h.
 Management during hospitalization

Calcium antagonists
Routine use of calcium antagonists in the acute phase
is not indicated.
In patients with contraindications to beta-blockers,
particularly in the presence of obstructive airway
disease, calcium antagonists are a reasonable option
for patients without heart failure or impaired LV
function.
Management during hospitalization

Lipid-lowering therapy

The treatment goal is an LDL-C concentration

of < 1.8 mmol/L or at least 50% reduction in
LDL-C if the baseline LDL-C level is 1.8–
3.5 mmol/L
 Management during hospitalization

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND

ANGIOTENSIN II RECEPTOR BLOCKERS

Treatment with ACE inhibitors is recommended in patients

with systolic LV dysfunction or heart failure,
hypertension, or diabetes, and should be considered in all
MI patients.
Patients who do not tolerate an ACE inhibitor should be
given an angiotensin II receptor blocker (ARB).
 Management during hospitalization

Mineralocorticoid/aldosterone receptor
antagonists
MRA therapy is recommended in patients with LV
dysfunction (LVEF ≤40%) and heart failure after MI
Thank you for your attention
 Kursk State Medical University
The Department of Internal Disease № 1

Lecture on the topic

«Pneumonia»

Associate Professor
N.A.Borisova
 Pneumonia is an infection of the
lung parenchyma which can be viral
or bacterial. Immunocompromised
patients are also at risk of
“opportunistic” infections which do
not normally affect healthy
individuals.
Aspiration of gastric content and
lipoid material can also result in a
pneumonia.
 Smoking causes inflammation and decreased mucociliary
function in the respiratory tract. It predisposes to any of the infections
listed below, and smoking cessation contributes to speedier recovery
from these infections.
 Pneumonia is a group of acute infectious
(mainly bacterial, in recent times often viral) diseases
of different etiology, pathogenesis, morphological
characteristics, which are characterized by focal
lesions of the respiratory sections of the lungs with
the formation of intraalveolar exudation, which is
detected by physical and X-ray examination.
Timely diagnosis of pneumonia, assessment of
the severity of the course of the disease, taking into
account concomitant diseases, the correct using of
antibiotic therapy will lead to complete recovery,
reduction of complications and mortality.
Clinical Classification of Pneumonia
• Community-acquired (acquired outside the hospital)
pneumonia (synonyms: home, outpatient).

• Nosocomial (hospital, nosocomial) pneumonia.

• Aspiration pneumonia

• Pneumonia in persons with severe immune defects

(congenital immunodeficiency, HIV infection,
immunosuppression).

Practically significant is the division of pneumonia

into community-acquired and nosocomial.
 The most common causes
1. Community-acquired pneumonia
- mostly gram-positive flora:
➢ Streptococcus pneumoniae (20-60%)
➢ Haemophilus influenzae (3-10%)
➢ Mycoplasma pneumoniae (1-6%)
➢ Chlamydia pneumoniae (4-6%)
➢ Staphylococcus aureus (3-5%)
In young people, the cause of
pneumoniae are - atypical pathogens
(Mycoplasma pneumoniae, Legionella
pneumoniae
and Chlamydia pneumoniae),
Gram-negative flora - rare,
 The most common causes

2. Nosocomial pneumonia -
mostly
gram-negative flora:
➢ Klebsiella pneumoniae (11,5%)
➢ Pseudomonas aeruginoza (17%)
➢ Escherichia coli (6,5%)
➢ Others (up to 14%)
➢ Gram-positive flora: Staphylococcus
aureus
 Complaints

Main: Addisional:
1. The onset of the disease is acute 1. Unmotivated weakness
with an increase body 2. Fatigue
temperature or gradual on the
background of acute respiratory 3. Heavy sweating at night
disease or bronchitis 4. Drowsiness or restlessness
2. Chills 5. Anorexia
3. Cough dry or with sputum (assess 6. Nausea, vomiting
the nature sputum), possibly
hemoptysis
4. Dyspnea, mainly inspiratory
5. Chest pain associated with
breathing or cough
 Typical chest examination findings
Condition Percussion Vocal Fremitus Breath Sounds Bronhophonia Adventitious
Sounds

Norma Resonant Normal Vesicular Normal Absent

Pneumonia Dull Increased Bronchial Increased Crackles or

breathing moist rales

Exudative Dull Decreased or Breath Sounds Decreased or Absent or

pleurisy absent are decreased absent pleural
or absent friction rub
What other syndromes will be
present?
 Pneumonia

Uncomplicated Complicated

Pulmonary: Extrapulmonary:
- Infectious-toxic syndrome
- Pleurisy
- DIC syndrome
- Pulmonary distraction
- Cardio-vascular
- Pulmonary abscess
insufficiency (myocarditis)
- Pneumothorax
- Respiratory distress
- Pyopneumothorax
syndrome of adult
 Diagnosis of pneumonia
Diagnostic studies in CAP are aimed at clarifying the
diagnosis, determining the pathogen, assessing the severity
of the course and prognosis of the disease, as well as
detecting complications.
The diagnostic algorithm for suspected CAP includes:
➢ detailed history taking;
➢ analysis of patient complaints;
➢ physical examination;
➢ laboratory and instrumental
examinations.
 The diagnostic examination of patient
with pneumonia includes:
➢ pulse oximetry with SpO2 measurement to detect RI and the
severity of hypoxemia;

➢ X-ray of the chest in two projections;

➢ complete blood count: leukocytosis more than 10-12x109/l with

a shift of the leukocyte formula to the left and leukopenia below
3x109/l or leukocytosis above 25x109/l are unfavorable prognostic
signs;

➢ biochemical blood test - urea, creatinine, electrolytes, liver

enzymes;
 The diagnostic examination of patient with
pneumonia includes:
➢ microbiological diagnostics: microscopy of a Gram-stained
smear, sputum culture to isolate the pathogen and determine
its sensitivity to antibiotics, blood culture study (it is
optimal to take two samples of venous blood from
different veins with an interval of 30-60 minutes before
antibiotic therapy is prescribed);
➢ study of arterial blood gases (PaO2, PaCO2) to clarify the
need for mechanical ventilation;
➢ ECG in standard leads;
➢ in the presence of pleural effusion and conditions for safe
pleural puncture.
 Criteria for the diagnosis of pneumonia
The diagnosis of Pneumonia is definite if the
patient has:
➢ a radiologically confirmed focal infiltration of the lung tissue and at
least two of the following clinical signs:

➢ acute fever at the onset of the disease (more > 38,0°C);

➢ cough with sputum;

➢ objective signs (shortening of percussion sound, focus of crepitus

and/or fine bubbling rales, hard bronchial breathing);

➢ leukocytosis > 10x109/l and/or shift to the left (band neutrop. >10%).
 X-ray changes
The main radiological sign of pneumonia is an
infiltration due to the accumulation of inflammatory exudate in
the respiratory regions.
Changes are more often unilateral, extending to one or
two bronchopulmonary segments. The X-ray picture of
pneumonia is determined by the type of infiltration of the lung
tissue and the stage of the inflammatory process.
 Computed tomography is performed with:
1. Viral pneumonia.

2. On radiographs no typical changes for pneumonia.

3. Recurrent pneumonia or prolonged pneumonia, in which the

duration of the existence of infiltrative changes in the lung
tissue exceeds one month (in both cases, the cause of the
recurrence or long-term preservation of changes in the lung
tissue may be stenosis of the large bronchus, caused, among
other things, by a malignant neoplasm) .

Fibrobronchoscopy is not a mandatory research method

for CAP; it is performed only if there are certain indications
and when conducting differential diagnosis.
 Criteria of severe CAP
Clinical signs: Laboratory signs:

➢ acute respiratory failure: respiratory ➢ leukopenia: leukocyte level < 4x109/l

rate > 30 per minute
➢ hypoxemia: SaO2 < 90%;
➢ hypotension: systolic blood pressure
< 90 mm Hg, diastolic blood pressure ➢ PaO2< 60 mm Hg
< 60 mm Hg
➢ hemoglobin < 100 g/l
➢ two- or multi-lobar lesion
➢ hematocrit < 30%
➢ disturbance of consciousness
➢ acute renal failure (anuria, blood
➢ extrapulmonary focus of infection creatinine > 176 µmol/L, urea
(meningitis, pericarditis, etc.) nitrogen ≥ 7,0 mg/dL).
 Therapy of pneumonia
Antibiotics are recommended for all patients with a
definite diagnosis of CAP. Antibiotics must be done as soon as
possible (optimally in first 8 hours from the moment of
diagnosis) to improve the prognosis.
Patients with CAP without comorbides and other risk
factors as the drug of choice:
protected penicillins (amoxicillin + clavulanic acid, ampicillin
+sulbactam) ± macrolides (azithromycin, clarithromycin)
Аlternatives are respiratory fluoroquinolones
 Therapy of pneumonia
For all patients with CAP, after the start of treatment in
48-72 hours, it is recommended to evaluate the effectiveness
and safety of the starting ABT regimen for a timely review of
treatment tactics and assess the feasibility of hospitalization.
The main criteria for the effectiveness of ABT are:
➢ decrease in temperature,
➢ decrease in the severity of the intoxication syndrome and
➢ decrease in the main clinical symptoms and signs of
CAP.
If the patient persists with fever and intoxication, or
progression signs of CAP are present, or complications
develop, antibiotic therapy should be regarded as ineffective.
 Therapy of pneumonia
Criteria for the sufficiency of antibiotic
therapy (all must be present):
➢ persistent decrease in body temperature <37,2ºС at least 48
hours;
➢ absence of intoxication syndrome;
➢ respiratory rate <20/min (in patients without chronic DN);
➢ absence of purulent sputum;
➢ the number of leukocytes in the blood <10x109/l,
neutrophils < 80%, young forms < 6%.
 COVID-19 - Pathogenesis
➢ The initial stage of infection is
penetration of SARS-CoV-2 into target
cells, having angiotensin-converting
enzyme type II (ACE2) receptors;
➢ ACE2 receptors are present on the cells
of the respiratory tract, kidneys,
esophagus, gold bladder, ileum, heart,
central nervous system;
➢ However, the main and quickly
achievable target is the alveolar cells of
type II (AT2) of the lungs, which
determines the development of
pneumonia.
➢ The role of CD147 in SARS-CoV-2 cell
invasion is also discussed.
 COVID-19 - Pathological picture
Morphological changes are connected
with the stage of the disease.
➢ The exudative (early) stage is dominated
by signs of intra-alveolar edema - diffuse
alveolar damage, acute bronchiolitis,
alveolo-hemorrhagic syndrome (intra-
alveolar hemorrhages).
➢ Macroscopically - a picture of “shock
lungs”: the mass of the lungs is increased,
the lungs are dense consistency, from the
surface – “dark cherry” color, lacquered
appearance, on the cut – air less, “dark
cherry”. Ander pressing with cut surfaces
dripping dark red liquid that is difficult to
squeeze out of the tissue.
 COVID-19 - Pneumonia

The clinical picture of the disease consists of

manifestations of a viral infection and its complications.
Features of symptoms:
➢ patients complaints include: viral intoxication, cough
and dyspnea are appear, body temperature rises to
subfebrile or febrile figures;
➢ objective examination: the symptoms of respiratory
failure are determined in patients - a forced posture,
acrocyanosis, tachypnea. There is a dry (very rarely
productive cough) and fever;
➢ percussion: over the lungs - dullness is noted, and on
auscultation - breathing is weakened.
 Laboratory studies for pneumonia
caused by SARS-CoV-2

➢ general blood analysis - level of

erythrocytes, hematocrit,
leukocytes, platelets, leukocyte
formula;
➢ biochemical analysis (urea,
creatinine, electrolytes, liver
enzymes, bilirubin, glucose,
albumin).
 Laboratory studies for pneumonia
caused by SARS-CoV-2
➢ pulse oximetry - SpO2 to detect
respiratory failure and assess the
severity of hypoxemia;

➢ patients with signs of acute

respiratory failure (ARF) (SpO2 less
than 90% according to pulse oximetry)
- an examination of arterial blood gases
with the determination of PaO2,PaCO2,
pH, bicarbonate, lactate;
 Specific laboratory diagnosis

➢ Detection of SARS-CoV-2 RNA by

PCR must be done to patients with
clinical symptoms of respiratory disease
suspected of being an infection caused
bySARS-CoV-2.
 Identification of indicators of the
inflammatory response
Must be done:
➢ Tests for C-reactive protein,
➢ procalcitonin,
➢ ferritin,
➢ D-dimer,
➢ total and subpopulations of lymphocytes,
➢ interleukins IL-4, IL-6, IL-10, TNF-α, INF-γ
➢ and other indicators of inflammation and immune status
 Chest X-ray
➢ Chest X-ray reveals bilateral confluent infiltrative shadows.
➢ Most sevear changes are localized in the basal parts of the lungs.
➢A small pleural effusion may also be present.

Fig. Symmetric central foci of hyperdensity in the form of "butterfly wings",

hydrothorax - CT picture of alveolar pulmonary edema
Fig. 1, Fig. 2: focal subpleural foci of “ground glass”;
Fig. 3: nodes and focal exudation;
Fig. 4, Fig. 5: multifocal seals on the affected areas;
Fig. 6: diffuse seals, "white lung".
 COVID-19
Classification by the volume of the
lesion according to CT:
CT - 1 (< 25% of the volume)
CT - 2 (25-50% of the volume)
CT - 3 (50-75% of the volume)
CT - 4 (> 75% of the volume)
 Thank you for your
attention and participation
in the discussion
of the issues under study!
Polycythaemia Vera
 Defenition

Chronic myeloproliferative diseases with

defeat of stem cell, proliferation
hematopoiesis, characterized by
excessive erythrocyte, leukocyte,
thrombocyte production.
 INTRODUCTION
• The different types of myeloproliferative disorders
include idiopathic myelofibrosis, essential
thrombocythemia and polycythemia vera.
• Primary polycythemia, often called polycythemia
vera (PCV), polycythemia rubra vera (PRV), or
erythremia, occurs when excess red blood cells are
produced as a result of an abnormality of the bone
marrow. In polycythemia vera, blood cell production,
notably red cells, is increased as a result of an
acquired stem cell mutation.
• Another type of polycythemia is called secondary
polycythemia. Secondary polycythemia is caused by
lower blood oxygen saturation
 Etiology

• Its etiology is not fully established, but

hypersensitivity to interleukin-3 may play a
role in the sustained erythrocytosis
observed in this disease.
• This can be due to a failure of apoptosis as
result of deregulation of the Bcl-xl gene which
is known to oppose programmed cell death.
• Polycythemia vera usually occurs within the
age range of 20-80, with 60 being the mean
age of onset. The disease is slightly more
common in males than in females.
 Risk Factors

• The cause of polycythemia vera is unknown.

• Polycythemia vera is called a clonal disorder

because it begins with a change to the DNA
in a single cell: all the cells that will dominate
blood cell production are the offspring of the
one mutant cell.
 Risk Factors
• The gene that causes the acquired genetic
mutation responsible for PV has not been
identified. The change to the DNA in the
cell has not been linked to any
environmental cause.
• Most patients with polycythemia vera do
not have a family history of the disorder.
However, there are reports of familial
incidence.
Pathogenesis
Eritropoetina (EPO)
 Polycythaemia Rubra Vera
• The red cell volume increase is caused by a
clonal malignancy of a marrow stem cell.

• Increase in the RBC’s is accampannied by an

increase of granulocytes and plts

• Some chromosomal changes, deletion of 20q

(most frequent)
 Clinical features
• Older subjects with an equal sex incidence

• Headaches, dyspnoea, blurred vision and night sweats

• Plethoric appearance
• Splenomegaly
• Haemorrage or thrombosis
• Hypertension
• Gout
• Peptic ulcer
 Symptoms
• Thrombotic episodes (blood clots).
During the first 10 years after diagnosis, 40 to
60% of polycythemia vera patients have blood
clots. The clots may cause serious or fatal
problems, such as stroke, heart attack, deep vein
thrombosis or pulmonary embolism.
• Skin. The skin may appear reddened or purplish,
especially, palms, ear lobes, and cheeks.
 Symptoms

• Neurologic symptoms. These may

include visual disturbances, such as
double vision or blind spots and vertigo (a
spinning feeling.)
• The deep veins of the leg – this can cause
symptoms such as pain, swelling, heat, and
redness in the calf (known as deep vein
thrombosis or DVT).
• The brain – this may cause mild symptoms such
as headaches, sight disturbances, or dizziness.
Blood clots in the brain may also cause
symptoms that are more serious, such as a
stroke or TIAs (transient ischaemic attacks [mini-
strokes]).
• The heart – a blood clot in the heart may cause
chest pain, and in severe cases, can result in a
heart attack.
• The lungs – a blood clot in the lung may cause
breathlessness and chest pain. This is known as
pulmonary embolism.
 SYNDROMS

Plethoric
syndrome

Thrombotic ore
hemorrhagic
complication

Anemic
syndrome
 Criteria for diagnosis of
polycythaemia rubra vera
1. Category A
• Total red cell mass (>35ml/kg, >32ml/kg)
• Splenomegaly

2. Category B

• Plts>400x109/l
• WBC>12x109/l
• Raised NAP score
• Raised serum vitamin B12 level
Investigation of Polycythemia Vera

• From Physical exam

• From Blood tests

• Bone marrow analysis

• Biochemical analysis
 Physical examination

• Enlarged liver and spleen

• Reddened (or purplish) appearance

of the skin
 Plethora vera
Pseudoconjunctivitis
 Lab findings
• HB, Hct, RBC count are increased
• Total red cell volume is increased
• Neutrophil leucocytosis
• Plts increased
• NAP is increased
• Serum vitamin B12 is increased
• B.M is hypercellular (megakaryocytes)
• Blood viscosity is increased
• Plasma urate is increased
• Circulationg erythroid progenitors (CFUE)
are increased
Blood analysis
 Bone marrow analysis
• Moderate to marked hypercellularity

• Trilineage hyperplasia

• Megakaryocytes increased; hyperlobulated

• Dilated sinusoids with intravascular hematopoiesis

• Decreased or absent iron stores

• Increased reticulin (only in a minority of patients)

• Bone marrow biopsy This involves taking a
sample of bone marrow from the back of the hip
bone (pelvis). The sample is then looked at
under a microscope to see if it contains any
abnormal cells.

• The bone marrow sample is taken under a local

anaesthetic. You are given a small injection to
numb the area, and a needle is passed gently
through the skin and into the bone. A tiny
sample of the marrow is then drawn (aspirated)
into a syringe (a bone-marrow aspirate).
Sometimes a small core of marrow is also
needed (a trephine biopsy) and this takes a few
minutes longer. This procedure can be painful
for a few seconds, and you may feel some
discomfort for a few hours afterwards.
Bone marrow analysis
 Biochemical analysis
Elevated serum B12 level.

Elevated serum uric acid level.

Normal or near-normal arterial oxygen saturation.

An erythropoietin (EPO) assay, to measure of the

blood level of EPO.
 DIAGNOSIS OF POLYCYTHEMIA
Major Criteria VERA
- total RBC vol men > 36 mg/kg;
women > 32 mg/kg
- arterial 02 saturation > 92%
- Splenomegaly
Minor Criteria
- Platelet count > 400 x 109/L
- Leukocytosis > 12 x 109/L
- LAP > 100 (no infection)
- Serum B12 > 900 pg/ml or
UB12 BC > 2200 pg/ml
 DIAGNOSIS OF POLYCYTHEMIA
VERA

A diagnosis of is made when a patent fulfills all

three of the major criteria, or any two major
and any two minor criteria.
 Complications
Complications of polycythemia vera result mainly from the
increase in red cells and platelets:

• Too many red blood cells make it difficult for the blood to flow
smoothly.

• Too many platelets can lead to the formation of clots.

 Complications
• Underlying vascular disease, commonly found in
older persons with the disease, can increase the risk
of clotting complications, such strokes or heart
attacks.

• Peptic ulcers may be associated with polycythemia

vera; angina or congestive heart failure; gout and
bleeding or bruising.
 Aims and Goals of Treatment
• To control symptoms.

• To decrease the risk of complications.

• Lowering the number of red cells to normal or near

normal levels.

• Lowering the platelet count if it is high or becomes

high over time
 Treatment

Phlebotomy

Chemotherapy

Radiation Therapy
 Phlebotomy
• Phlebotomy is the usual starting point of
treatment for most patients. A volume of blood
is drawn at regular intervals to decrease the
number of red cells to normal red cell counts
within a period of weeks or months.

• The immediate effect of phlebotomy is to

reduce the hematocrit, which results in the
improvement of certain symptoms, such as
headaches. The usual consequence of
phlebotomy is iron deficiency.
 Chemotherapy

• The most commonly used myelosuppressive

agent for polycythemia vera, hydroxyurea is
given in pill form. It has few side effects, and
helps to reduce both the red cell and platelet
counts.

• Hydroxyurea is thought to have much less

potential for causing leukemic changes than
other myelosuppressive agents.
 Radiation Therapy
• Radioactive phosphorus (32p) is an option for
patients who are unable to have frequent follow-up
because longer-lasting control is possible with one or
two doses given intravenously.
• Anagrelide is another drug that can be used if platelet
numbers are too high. The drug can blunt the rate of
platelet formation in the marrow.
• Interferon-alpha and other chemotherapy agents are
available in special cases but are not used in most
patients because they are not as effective, are
inconvenient to administer, or may have more severe
effects
 Prognosis for Polycythemia Vera

• Polycythemia vera is a chronic disease; it is not

curable. The median survival of patients treated
for polycythemia vera exceeds 10 years.
• Careful medical supervision and therapy to keep
the red count near normal are important. People
with polycythemia vera who receive treatment
often have a normal or near-normal quality of
life.
Prognosis for Polycythemia Vera

• Some patients may have disability from blood

clots or other symptoms. People with
polycythemia vera are at slightly greater risk
for developing leukemia than the general
population.