PATHOLOGY AND MICROBIOLOGY UNIT II NOTES STAFF NAME: Mrs.T.

PRIYA, AP/BME
1) Describe the various hematological disorders and  Leukemic cells do not die normally causing an
the mechanisms of its pathogenesis. increase in no of WBCs.
Hematology is the study of blood in health and disease.  Based on type of cell line, 2 types
It includes problems with the red blood cells, white blood Myeloid leukemia Lymphoid leukemia.
cells, platelets, blood vessels, bone marrow, lymph nodes,  Myeloid stem cells  Lymphoid stem cells
spleen, and the proteins involved in bleeding and clotting differentiate in to differentiate into T-
(hemostasis and thrombosis). RBC, Platelets, lymphocytes , B-
Function Granulocytes , lymphocytes and NK
 Transportation Monocytes. cells
o Oxygen  Cancer condition  Cancer condition
o Nutrients occurs in myeloid occurs in the
o Hormones stem cells lymphoid stem cells
o Waste Products It is further classified into
 Regulation of pH & osmosis Acute chronic
 Protection  Acute forms the  Chronic forms of
o Coagulation leukemia have leukemia have cells
o Fight Infections cells that that do not die
 Maintenance of body temperature proliferate normally
RBC disorder (Erythrocyte Disorder) quickly and  Chronic leukemia
Anemia donot develop is common in elder
 Anemia is a reduction in the number of RBCs, the properly people
quantity of hemoglobin, or the volume of RBCs  Acute leukemia
 The main function of RBCs is oxygenation, is common in
anemia results in varying degrees of hypoxia childrens
Causes 4 types:
1) An insufficient number of RBC  Acute myeloblastic leukemia-common in adults
 Blood loss- hemorrhagic anemia- due to injury  Acute lymphoblastic leukemia-common in young
 Decreased production of erythrocytes- aplastic childrens
anemia- bone marrow defect  Chronic myeloblastic leukemia-common in adults
 Increased destruction of erythrocytes- hemolytic  Chronic lymphoblastic leukemia-affected in adults
anemia-due to infection, abnormal blood transfusion in age of 55
2) Low hemoglobin content  In all leukemias, bone marrow becomes almost
 Iron-deficiency anemia-inadequate intake of totally occupied by cancerous leukocytes and
Iron-essential for Hb production immature WBC flood into blood stream.
 Pernicious anemia-deficiency of vitamin B12 Symptoms include
3) Abnormal hemoglobin Fever,weight loss,bone pain,frequent infection,
 Due to genetic abnormalities headache, sore throat, night sweats etc
a) Thalassemia-defect in globin part of Hb LYMPHOMA
b) Sickle-cell anemia- defect in Hb gene o Group of blood cell tumour developed from
(HbA)-sickle shape lymphatic cells
Polycythemia Signs and Symptoms
 Excess of RBC that increase blood viscosity o Enlarged lymph nodes o Weight loss
WBC DISORDERS o Fever o Itching
More common WBC disorder are 1) Lymphoma 2) o Drenching sweats o Feeling tired
Leukemia  Cancer of lymphocytes consisting of about 35
Patient has increased risk of infection due to malfunction different subtyupes.
or absence of certain types of WBC.  2 categories
LEUKEMIA  Hodgkin lymphoma(HL) eg.EB virus
 Leukemia -cancer of blood forming cells or stem  Non-hodgkin lymphoma(NHL).eg auto immune
cells, located in the bone marrow. disease,HIV/AIDS
 These cancer cells have exaggerated proliferation or  hodgkin lymphoma affets a specific subtype of B-
development problem causing immature cells to be lymphocytes
released from the bone marrow.  Non-hodgkin lymphoma affects other B-
 Over production of abnormal leukocytes occur in the lymphopcytes or T-lymphocytes.
leukemia.
1
PATHOLOGY AND MICROBIOLOGY UNIT II NOTES STAFF NAME: Mrs.T.PRIYA, AP/BME
 There are 5 subtytes of HL& 30 30 subtytes of  It is the first stage of wound healing. This involves
NHL blood changing from a liquid to a gel.
 HL is marked by presence of a type of cell called
Reed-Sternberg cell(RS cell)
 RS cells are large cancerous cell.
 HL is one of the curable form of cancer
 NHL do not have RS cell
 Fast growing NHL can be cured
 Slow growing NHL can be cured slowly
BLEEDING DISORDER
 Anything that interfers with clotting mechanism
result in
 Abnormal bleeding.
 Bleeding disorder occurs due to platelet
Steps:
deficiency or deficits of some procoagulants which
1) Vessel Spasm
can results from impaired liver function.
 When arteries are damaged the smooth muscles
1) THROMBOCYTOPENIA:
surrounding the vessels immediately constrict,
 Thrombocytopenia is a decrease in the no. of
reducing blood flow from several minutes to
platelets caused by decreased platelet production.
several hours.
 Sequentration iof platelet in spleen
 triggered by factors such as a direct injury to
 Destruction of platelet by immune system
vascular smooth muscle, chemicals released
 Decreased in no of platelets causes spontaneous
by endothelial cells and platelets, and reflexes
bleeding from small blood vessels all over the
initiated by local pain receptors
body
 *Seratonin and Thromboxane A2 are activated.
 It arises from condition that suppress or destroy
2) Formation of Platelet Plug ( primary hemostasis)
bone marrow ,exposure to ionising radiation of
 If a vessel is damaged, the COLLAGEN is
certain drugs.
exposed and platelets bind to it, vWF(Von
2) IMPAIRED LIVER FUNCTION
Willebrand factor) allows this binding to
 When liver unsble to synthesize its usual supply of
occur.
procoagulants ,its results in bleeding.
 The platelets become activated through this
 Vit-k deficiency causes impaired liver function.
adhesion and DEGRANULATE in process
 Vit-k is required by liver cells for production of
called platelet release reaction.
clotting factors.
 These granules contain ADP, SERATONIN &
 Vit-k deficiency can occur if fat absorption is
THROMBOXANE A2.
impaired,because vit-k is a fat soluable
 Net result is the formation of an aggregate
vitamin.that is absorbed into blood with fats.
layer of activated platelets at the site of the
 In liver disease ,liver cell to produce bile which is
injury, eventually forming a platelet plug full
required for fat and vit-k absorption.
of ACTIVATED PLATELETS.
3) HEMOPHILIA:
 vWF : Produced from endothelial cells to
 It is a type of bleeding disorder due to defiecency
allow binding to platelets so they can become
of clotting factor responsible for clotting.
activated.
 TYPES:
3) Blood Coagulation( Secondary hemostasis)
 Hemophilia –A- due to defieciency of factor VIII
 FIBRIN formation begins through either
 Hemophilia-B-due to defieciency of factor IX
INTRINSIC/EXTRINSIC PATHWAY, which
 Hemophilia-C - due to defieciency of factor XI
converges on Factor X.
 Minor tissue trauma causes prolonged bleeding
 This begins the COMMON PATHWAY which
into tissue that is life threatening.
is when Factor X combines with Factor V
2) Write short notes on Hemostasis.
(together they are prothrombinase) and
 Hemostasis is the physiologic mechanism that
converts PROTHROMBIN into THROMBIN.
stems bleeding after injury to the vasculature.
 Thrombin then turns FIBRINOGEN into a
 Normal hemostasis depends on both cellular
loose FIBRIN network. Factor XII stabalizes
components and soluble plasma proteins.
the fibrin by making it resistant to proteolytic
 Circulating platelets adhere and aggregate at sites
cleavage.
of blood vessel injury.
*VITAMIN K plays important role -Used as a

2
PATHOLOGY AND MICROBIOLOGY UNIT II NOTES STAFF NAME: Mrs.T.PRIYA, AP/BME
cofactor for the production of Factors II, VII,  A larger thrombus causing a much greater
IX & X in the liver. obstruction to the blood flow may result in anoxia,
4) Clot Retraction the complete deprivation of oxygen , infarction&
 After clot formation actin and myosin ischaemia
(cytoskeletal proteins) contract to pull the Causes:
clot together and squeeze out any serum/fluid o changes in the vessel wall
from injured site. o changes in blood flow
5) Clot Dissolution (Lysis) o changes in the blood constituents
 Plasmin is produced from plasminogen Changes in the vessel wall
(proteolytic enzyme) and this enzyme breaks • Primarily damage to endothelium surface
down the clot once healing has begun. • Causes of endothelial cell injury: -radiation,
cigarette smoke, cholesterol/lipids
• Results of endothelial cell injury:
– exposed subendothelial
extracellular matrix
– platelet activation
– activation of coagulation
cascade
– depletion of antiplatelet,
anticoagulant and
fibrinolytic functions
Changes in blood flow
– Normal flow is laminar-
cells in centre of blood
stream
• Disrupted flow is static or turbulent
Stasis Turbulence
1) Arteriolar vasoconstriction
 Platelets in contact • Eddy currents with
2) Primary haemostasis ® temporary platelet plug
with endothelium local pockets of
a) Platelet adhesion
 Prevent dilution of stasis
b) Platelet activation (shape change & granule
clotting factors • Promote endothelial
release)
 Retard inflow of cell injury
c) Platelet aggregation
clotting factor • e.g. ulcerated
3. Secondary haemostasis ® solid permanent plug
inhibitors atherosclerotic
a) Activation of coagulation cascade
e.g.myocardial infarct, plaque
b) Conversion of fibrinogen to insoluble fibrin
aneurysm,
c) Aggregates of polymerized fibrin & platelets
Changes in blood constituents
4. Counter-regulatory mechanisms ® restrict plug to
• Hypercoagulability - Leads to recurrent venous
site of injury
thrombosis, arterial thrombosis, recurrent abortion
3) Discuss the mechanism of pathogenesis of
and stillbirths
Thrombosis.
• Hyperviscosity - predisposes to stasis in small
 Thrombosis is the formation of a blood clot
vessels
(thrombus) inside a blood vessel, obstructing the
• polycythaemia) / deformed RBC’s
flow of blood through the circulatory system
• Presence of endothelial cell toxins in cigarette
causing tissue hypoxia.
smoke, high levels of lipid or cholesterol
 When a blood vessel is injured, the body uses
– predispose to endothelial cell injury
platelets and fibrin to form a blood clot to prevent
Arterial Thrombi
blood loss.
• occurs in Large vessels (aorta, heart) Smaller
 A clot that breaks free and begins to travel around
vessels (coronary arteries, leg arteries) - often
the body is known as an embolus.
occlusive
 When a thrombus is significantly large enough to
• Classically have alternating white and red layers
reduce the blood flow to a tissue, hypoxia (oxygen
called lines of Zahn
deprivation) can occur and metabolic products
– alternating layers of pale platelets and
such as lactic acid can accumulate.
darker RBC’s

3
PATHOLOGY AND MICROBIOLOGY UNIT II NOTES STAFF NAME: Mrs.T.PRIYA, AP/BME
• e.g. infarcted left ventricle, damaged heart valves, arterioles of pulmonary artery
atherosclerotic plaques < 20μm in diameter: pass through the pulmonary
• Consequences: circulation and enter left heart, and consequently cause
– Ischaemia in tissues distal to thrombus embolism of cerebral microvasculature
with possible necrosis (infarction) （3） Air embolism--embolism caused by entry of air
– May embolize due to rapid flow bubbles into circulation
Venous Thrombi Gas bubbles with the circulation can obstruct cardio-
• Occurs at sites of stasis, commonly veins of lower vascular flow.
extremity  The gas bubbles may form masses with blood in
• Red - More enmeshed erythrocytes, less platelets right heart, and then act like physical obstructions
• Predisposing factors- Bed rest, immobilization, to occlude major vessels
heart failure, surgery, trauma, pregnancy,  Eg : Decompression sickness - Occurs when
hypercoagulable states individuals are exposed to sudden change in
• Consequences: atmospheric pressure. If the diver rise to the
– Rarely cause ischaemia if affect arterial surface too rapidly, the nitrogen dissolves in blood
supply & expands in the tissues and bubbles out to form
– More commonly embolize gas emboli.
Fate of Thrombi 4） Amniotic fluid embolism
1. Dissolution by fibrinolysis Amniotic fluid surrounds and protects a baby inside
2. Propagation along length of vessel ® complete the womb.
vessel occlusion  complication with entry of amniotic fluid into
3. Embolization uterine venous circulation
4. Recanalization - capillaries invade thrombus to re-  The amniotic fluid and its component are leaked
establish blood flow into the maternal circulation via a tear in the
5. Organization - Inflammation and fibrosis ® placental membranes and rupture of the uterine
replacement by scar, may obliterate vessel lumen veins.
4) Describe about various types of embolism and  Characterized by sudden severe DIC and shock,
its pathological features. followed by seizures and coma.
Any intravascular mass (solid, liquid or gas) carried by 5) Write notes on infarction
blood to site distant from point of origin An infarct is an area of ischemic necrosis caused by
• Most derived from thrombi (thromboembolism) occlusion of either the arterial supply or the venous
• Lodge in vessels too small to permit further drainage in a particular tissue.
passage Morphological Classification of infarcts
1) Pulmonary Thromboembolism 1) White Infarct
 Arise from thrombi in systemic venous circulation  arterial occlusion- Ischemia following obstruction
mostly leg veins (95%), pelvic veins of nutrient artery or hypoperfusion of tissue
 Embolus migrates from deep leg veins through  Seen in Solid organs with end-arterial circulation
venous system to pulmonary circulation such as kidney, heart, spleen
 Saddle embolus in branching main pulmonary  Wedge shaped. occluded vessel at the apex,base at
artery the serosal surface
 Small emboli may lodge in the branching  Better defined with time, paler, hyperemic margins
arterioles of pulmonary artery ,and usually be 2) Red (hemorrhagic) Infarct
clinical silent  venous occlusion of organ with single venous
 Large emboli often occlude the main pulmonary outflow e.g. testicular torsion
artery and cause sudden death  Seen in Loose tissues- e.g. lung
（2）Fat embolism - embolism caused by fat in the  Tissues with dual circulations: lung and gut
circulation 3) Septic infarct
Fat globules in the circulation after fractures of long  Following fragmentation of bacterial vegetation
bone, trauma of soft tissue and a liver with fatty change. from a heart valve or following microbes seeding a
 Release of fatty acids from fat globules cause local necrotic area.
injury to endothelium and thereby activate  Converted into an abscess
thrombosis.  Greater inflammatory response
 Effect depends on the size and the number of fat  scarring
globules Event Sequence
>20μm in diameter: occlusion of the branching 1. Coagulative necrosis
4
PATHOLOGY AND MICROBIOLOGY UNIT II NOTES STAFF NAME: Mrs.T.PRIYA, AP/BME
2. Infiltration by neutrophils  Causes arteriolar dilatation and peripheral
3. Infiltration by macrophages pooling of blood
4. Phagocytosis of debris  Worsens hypotension and exacerbates tissue
5. Granulation tissue formation ischaemia
6. Scar formation  Irreversible phase
6) Write notes on Shock (Cardiovascular  Irreversible cellular and tissue injury
Collapse)  No response even if haemodynamic defects
 Circulatory failure resulting in inadequate tissue corrected
perfusion (systemic hypoperfusion) 7) Write notes on Intra vascular coagulation
 Results in: • DIC is a rare, life threatening condition that
 hypotension prevents a person’s blood from clotting normally.
 impaired tissue perfusion • cause excessive clotting (thrombosis) or
 cellular hypoxia bleeding(hemorrhage) and lead to shock, organ
 reversible cellular injury failure and death.
 irreversible cell injury and cell death • In DIC, blood clotting does not function properly.
Types of Shock • Causing blood clotting cell (platelets) to clump
 Cardiogenic - due to myocardial pump failure together and clots small blood vessels throughout.
 Outflow obstruction (e.g. pulmonary embolism) Thrombotic disorder
 e.g. myocardial infarction, ventricular rupture, – Sudden / insidious onset of widespread fibrin
ventricular arrhythmia, cardiac tamponade, thrombi in microcirculation
pulmonary embolism – Consumption of platelets and coagulation factors
 Hypovolaemic - due to loss of blood or plasma – Activation of fibrinolytic pathways
volume – Severe bleeding disorder
 e.g. haemorrhage, trauma, burns, vomiting, CAUSES:
diarrhoea • Bacterial,viral or fungal infection
 Neurogenic shock • Some cancers
 peripheral pooling of blood due to loss of • Complication during pregnancy
vascular tone • Snake bite
 e.g. anaesthetic accident / spinal cord
injury
 Anaphylactic shock
 systemic IgE-mediated hypersensitivity
reaction to allergens
 release of mast cell mediators
 systemic vasodilation and increased vascular
permeability
 Septic shock
 overwhelming microbial infection
 gram negative sepsis- due to lipopolysaccharide
in walls of gram negative bacteria
 results in endothelial damage, complement
activation & activation of macrophages with
cytokine release SYMPTOMS:
Stages of Shock • Blood platelets and clotting factor depleted
 Nonprogressive phase causing excesive bleeding ( haemorrhage)
 Reflex compensatory mechanisms • Organ damage
maintain perfusion of vital organs • Shortness of breath from lung damage, low urine
 Tachycardia, peripheral vasoconstriction output from kidney damage, stroke from damage
(pale cold clammy skin), renal to brain.
conservation of fluid (anuria) Pathogenesis of DIC
 Progressive phase • Increased thrombin generation
 Tissue hypoperfusion & metabolic imbalance • Depression of physiologic anticoagulation
 Development of acidosis mechanism
 Due to anaerobic glycolysis and renal failure • Delayed removal of fibrin due to impaired
fibrinolysis
5
PATHOLOGY AND MICROBIOLOGY UNIT II NOTES STAFF NAME: Mrs.T.PRIYA, AP/BME
Results in:
2 MARKS  hypotension
1) List the pathophysiology of edema  impaired tissue perfusion
Edema results from increased movement of fluid  cellular hypoxia
from the intravascular to the interstitial space or 10) Define anaphylactic shock.
decreased movement of water from the  systemic IgE-mediated hypersensitivity reaction
interstitium into the capillaries or lymphatic to allergens cause this
vessels.Increased hydrostatic pressure; reduced  release of mast cell mediators
colloidal or oncotic pressure within blood vessels  systemic vasodilation and increased vascular
cause edema. permeability resulting in inadequate tissue
Raised hydrostatic pressure often reflects retention perfusion
of water and sodium by the kidney. 11) List out the causes of excessive bleeding.
2) Define edema.  Bacterial,viral or fungal infection
Edema is the abnormal accumulation of fluid in certain  Some cancers
tissues within the body. The accumulation of fluid may  Complication during pregnancy
be under the skin (peripheral edema), or it may  Snake bite
accumulate in the lungs (pulmonary edema). 12) What is the symptom for Leukemia?
3) What is hematoma?  Fever,weight loss, bone pain, frequent infection
A hematoma is a collection of blood outside of a blood  headache
vessel. A hematoma is initially in liquid form spread  sore throat
among the tissues where it may coagulate and solidify  night sweats etc
4) Define thrombosis. 13) What is a lymphome?
Thrombosis is the formation of a blood clot Group of blood cell tumour developed from
(thrombus) inside a blood vessel, obstructing the flow lymphatic cells is called Lymphoma.
of blood through the circulatory system causing tissue 2 categories
hypoxia.  Hodgkin lymphoma(HL) eg.EB virus
5) What is the need for vascular coagulation?  Non-hodgkin lymphoma(NHL).eg auto immune
 To prevent bleeding, disease,HIV/AIDS
 To maintain hemostasis ,vascular 14) Write notes on Hodgkin’s lymphoma.
coagulation is needed. o Hodgkin lymphoma affects a specific
Clotting factors and platelets are used. subtype of B-lymphocytes.
6) Why sudden deaths occur during pulmonary o There are 5 subtytes of HL
embolism?
 HL is marked by presence of a type of cell called
Pulmonary embolism is caused by a sudden
Reed-Sternberg cell(RS cell)
blockage of a major blood vessel — the artery.
 RS cells are large cancerous cell.
The pulmonary artery is the blood vessel that
 HL is one of the curable form of cancer
carries blood from the heart to the lungs. When the
clot travels to the lungs, it blocks the lung artery,
stopping blood flow to the lungs causing death.
7) Define embolism.
Any intravascular mass (solid, liquid or gas) carried by
blood to site distant from point of origin is called
Embolism
• Most derived from thrombi (thromboembolism)
• Lodge in vessels too small to permit further
passage
8) What is air embolism?
Embolism caused by entry of air bubbles into
circulation.The gas bubbles may form masses with blood
in right heart, and then act like physical obstructions to
occlude major vessels
Eg : Decompression sickness
9) What is meant by shock?
Circulatory failure resulting in inadequate tissue
perfusion (systemic hypoperfusion) is shock
6