Blood, Circulatory &

Lymphatic Disorders
Gould Chapters
10 & 11

Week 13
Outline
• Blood dyscrasias
• Compare & distinguish between types of anemias
• Understand pathophysiology of clotting disorders
• Define the major types of leukemias & their systemic effects

• Lymphatic disorders: compare between lymphomas &

myeloma
Blood & Circulatory
Disorders
Gould Chapter 10
Blood: Functions

• Transport oxygen and nutrients to all

tissues
• Remove waste products of cellular
metabolism
• Play a critical role in the body’s
defenses/immune system, and serve in
maintaining body homeostasis
Blood Vessels
Two separate circulations (both begin and
end in the heart:
1. Pulmonary circulation
• Gas exchange in lungs
2. Systemic circulation
• Exchange of gases, nutrients,
and wastes in tissues
• Arteries: arterioles
• Transport blood away from heart
• Veins: venules
• Return blood back to the heart
• Capillaries
• Microcirculation within tissues
Blood: Diagnostics
• CBC: complete blood count
• Includes total RBC’s, WBC’s & platelets
•Differential count for WBC’s
• Leukocytosis (increased WBCs)
• Associated with inflammation or infection
• Leukopenia (decreased WBCs)
• Associated with some viral infections,
radiation, chemotherapy
• Increased eosinophils
• Common in allergic responses
Blood: Diagnostics
• CBC: complete blood count
• Hematocrit:
• % by volume of cellular elements in blood
• Mean corpuscular volume (MCV)
• Indicates the oxygen-carrying capacity of blood

• Amount of hemoglobin (Hb) per unit volume of blood

Blood: Diagnostics

• Morphology
• Observe with blood smears
• Shows size, shape, uniformity, maturity of cells
• Different types of anemias can be distinguished
Blood: Diagnostics
• Reticulocyte count
• assess bone marrow function
• Chemical analysis
• determine serum levels of components (Fe, Vitamin
B12, folic acid etc.)
• Bleeding time
• measures platelet function
• Prothrombin time (PT) & partial thromboplastin time (PTT)
• Measure function of various factors in coagulation process
• INR is standardized version of PT
Blood: Therapies

• Whole blood, packed red blood cells, packed

platelets
• For severe anemia or thrombocytopenia
• Plasma or colloid volume: expanding solutions
• To maintain blood volume
• Artificial blood products
• Compatible with all blood types
• None of them can perform all the complex
functions of normal whole blood
Blood: Therapies
• Epoetin alfa: artificial form of erythropoietin
• Before certain surgical procedures (e.g. hip
replacement)
• Anemia related to cancer or chronic renal failure
• Bone marrow transplants
• Close tissue match necessary
• Treatment of some cancers
• Severe immune deficiency
• Severe blood cell diseases
 Blood Dyscrasias
Anemia:
• Decrease in Hgb causing reduction in oxygen transport in the
blood
• Oxygen deficit leads to sequence of events:
• Less energy production in all cells
• Cell metabolism and reproduction diminished
• Compensation mechanisms
• Tachycardia and peripheral vasoconstriction
• General signs of anemia
• Fatigue, pallor (pale face), dyspnea, tachycardia
• Decreased regeneration of epithelial cells
• Digestive tract becomes inflamed. ulcerated, leading to
stomatitis
• Inflamed, cracked lips
• Dysphasia
• Hair, skin may show degenerative changes
• Severe anemia may lead to angina or congestive heart failure (CHF)
Blood Dyscrasias: Anemia
Types of anemia

A. Iron deficiency anemia

B. Pernicious anemia: Vitamin B12 deficiency
C. Aplastic anemia
D. Sickle cell anemia
E. Thalassemia
 A. Iron Deficiency Anemia
• Insufficient iron impairs Hgb
synthesis
• Microcytic, hypochromic RBCs
• Result of low hemoglobin
concentration in cells
• Very common
• Ranges from mild to severe
• Occurs in all age groups, but more
common in women of childbearing age
• Estimated that one in five women is
affected
• Proportion increases for pregnant
women
• Frequently sign of an underlying
problem
A. Iron Deficiency Anemia
Etiology
• Dietary intake of iron below minimum
requirement
• Chronic blood loss
• As from bleeding, ulcer, hemorrhoids, cancer
• Impaired duodenal absorption of iron
• In many disorders, malabsorption syndromes
• Severe liver disease
• May affect iron absorption as well as storage
A. Iron Deficiency Anemia due to blood loss

Normal Abnormal
A. Iron Deficiency Anemia
Signs and Symptoms
• Pallor of skin and mucous membranes
• Fatigue, lethargy, cold intolerance
• Irritability
• Degenerative changes
• Stomatitis and glossitis
• Menstrual irregularities
• Delayed healing
• Tachycardia, heart palpitations, dyspnea, syncope
A. Iron Deficiency Anemia
Diagnostic Tests
• Lab tests will show lower values for:
• Hgb, HCT, MCV, mean corpuscular
Hgb, serum ferritin, serum iron, and
transferrin saturation
Treatment
• Depends on underlying etiology but could
include iron-rich foods, iron supplements
 B. Pernicious Anemia
• Also called Megaloblastic
Anemia
• Lack of absorption of vitamin B12
because of lack of intrinsic factor
• Intrinsic factor secreted by
gastric mucosa
• Required for intestinal
absorption of vitamin B12
• Characterized by very large,
immature, nucleated
erythrocytes
• Carry less hemoglobin
• Shorter life span
B. Pernicious Anemia
• Deficit of B12 leads to impaired maturation of erythrocytes;
affects DNA synthesis
• Destroyed prematurely è have low RBC & Hbg count
(anemia)
• Also causes demyelination of peripheral nerves, eventually
spinal cord impacted
• Loss of myelin interferes with nerve conduction which may
irreversible.
B. Pernicious Anemia
Etiology

• Dietary insufficiency is very rarely a cause

• Genetic factors have been implicated
• More common in light-skinned women of
northern European ancestry
• Often accompanies chronic gastritis
• May also be an outcome of gastric surgery
 B. Pernicious Anemia
Signs and Symptoms
• Tongue is typically enlarged, red, sore, and shiny
• Digestive discomfort, often with nausea and
diarrhea
• Feeling of pins and needles, tingling in limbs
Diagnostic Test
• Microscopic examination (erythrocytes)
• Bone marrow examination (hyperactive)
• Vitamin B12 serum levels below normal
• Presence of hypochlorhydria or achlorhydria
• Presence of gastric atrophy
Treatment
• Prophylaxis oral supplements
• B12 injections
 C. Aplastic Anemia

• Impairment or failure of bone marrow leading to

lost of stem cells & pancytopenia (decreased
erythrocytes, leukocytes, platelets)
• May be temporary or permanent
C. Aplastic Anemia
Etiology
• Often idiopathic but possible causes include:
• Myelotoxins
• Radiation, industrial chemicals, drugs
• Viruses
• Particularly hepatitis C
• Genetic abnormalities
• Myelodysplastic syndrome
• Fanconi’s anemia
C. Aplastic Anemia
Signs & symptoms
• Onset is insidious for most cases
• Because all blood cells can be affected, will observe:
• Leukopenia: recurrent/multiple infections
• Thrombocytopenia: tendency to bleed excessively (mouth),
petechiae on skin
• Uncontrollable infection and hemorrhage are likely

Normal bone marrow Aplastic anemia

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C. Aplastic Anemia
Diagnostic Tests
• Blood counts indicate pancytopenia.
• Anemia, leukopenia, thrombocytopenia
• Bone marrow biopsy may be required
• Erythrocytes often appear normal
Treatment
• Identification of cause and prompt treatment
needed for bone marrow recovery
• Removal of any bone marrow suppressants
• Blood transfusion
• Bone marrow transplantation

Failure to identify cause and treat effectively is

life-threatening!
Hemolytic Anemias
• result from excessive destruction of RBCs, or hemolysis
• leads to low erythrocyte count, low total hemoglobin
• Many causes including:
• genetic defects affecting structure
• immune reactions
• changes in blood chemistry
• presence of toxins in the blood, infections such as malaria
• Antigen-antibody reactions
• transfusion reactions
• blood incompatibility in neonates (erythroblastosis
fetalis)
 D. Sickle Cell Anemia
a chain b chain
• Inherited characteristic:
abnormal hemoglobin S (HbS)
created from single aa
mutation
• Sickle cell crisis occurs whenever
oxygen levels are lowered
• Altered hemoglobin is unstable
b chain a chain
and changes shape in hypoxemia heme
• Sickle-shaped cells are too large
to pass through the
microcirculation
• Obstruction leads to multiple
infarctions and areas of necrosis

http://library.med.utah.edu/WebPath/HEMEHTML/HEME015.html
 D. Sickle Cell Anemia

Sickle cell anemia:

effects of sickling
 D. Sickle Cell Anemia
• Genetic condition
• Autosomal
• Incomplete dominance
• Anemia occurs in homozygous recessive
• Diagnostic testing is available
• More common in individuals of African ancestry
• Heterozygous condition is somewhat protective
against malaria

• 50% of sickle cell trait

Inheritance of sickle cell anemia

D. Sickle Cell Anemia
Signs and Symptoms:
• Severe pain because of ischemia of tissues and infarction
• Pallor, weakness, tachycardia, dyspnea
• Hyperbilirubinemia: jaundice
• Splenomegaly
• Vascular occlusions and infarctions
• In lungs
• Acute chest syndrome
• Smaller blood vessels
• Hand-foot syndrome
• Delay of growth and development
• Congestive heart failure
• Frequent infections (pneumonia common cause of death
in children
D. Sickle Cell Anemia
Signs and Symptoms:
• Severe pain because of ischemia of tissues and infarction
• Pallor, weakness, tachycardia, dyspnea
• Hyperbilirubinemia: jaundice
• Splenomegaly
• Vascular occlusions and infarctions
• In lungs
• Acute chest syndrome
• Smaller blood vessels
• Hand-foot syndrome
• Delay of growth and development
• Congestive heart failure
• Frequent infections (pneumonia common cause of death
in children
 D. Sickle Cell Anemia
Diagnostic Tests
• Blood test: determine abnormal RBC morphology
• Hemoglobin electrophoresis
• Prenatal DNA analysis
Treatment
• Hydroxyurea has reduced the frequency of this crisis
• Dietary supplementation with folic acid
• Prevention: avoidance of strenuous activity or high
altitudes, dehydration, infection, exposure to cold
• Bone marrow transplantation
• Immunization in children
• Against pneumonia, influenza, meningitis
E. Thalassemia
• Hemolytic anemia due to
genetic defect: missing one or a chain b chain
more genes for Hb

• a-thalassemias: missing one

or both alpha chains
• b-thalassemias: missing one
or both beta chains
b chain a chain
• Two types of thalassemia heme

• Minor: person is a carrier of

trait
• Major (Cooley’s anemia):
inherit from both parents
E. Thalassemia
Etiology
• Most common genetic disorder in the world
• Thalassemia beta (autosomal dominant inheritance)
• Occurs frequently in Mediterranean countries
• More common form
• Thalassemia alpha
• Found in those of Indian, Chinese, Southeast Asian
descent

Signs & Symptoms

• Child’s growth, development impaired directly by hypoxia and
indirectly by fatigue, inactivity
• Hyperactivity in bone marrow leads to invasion of bone, impairs
normal skeletal development
• Heart failure as a result of compensation mechanism increasing
cardiac workload
E. Thalassemia
Diagnostic Tests
• RBCs are microcytic, often varying in size, and
hypochromic (less color)
• Increase in erythropoietin levels
• Often iron overload exists
• Prenatal diagnosis can be done by chorionic villus assay
at 12 weeks or by amniocentesis at 16 weeks

Treatment
• Blood transfusions
• Iron chelation therapy may be necessary to remove the
excess iron
• Administration of folate is also recommended
• Bone marrow transplants have been curative in some
children and are in clinical research trials
Anemias
Blood Clotting Disorders: Causes
• Thrombocytopenia: due to acute viral infections (children),
autoimmune reactions (adults), HIV infection,
hepatomegaly, splenomegaly & some medications
• Chemotherapy, radiation, leukemia & other cancers è ¯
platelet count
• Defective platelet function associated with uremia (end-
stage kidney failure), ASA, NSAID

• Vitamin K deficiency è ¯ production of prothrombin &

fibrinogen
• Inherited defects: deficiency of one clotting factor
• Hemorrhagic fever viruses e.g.?
• Anticoagulant medications: warfarin (Coumadin)
 Blood Clotting Disorders
Warning Signs of Excessive Bleeding and Possible Blood-Clotting
Disorders

• Persistent bleeding from the gums (around the teeth) or

repeated nosebleeds
• Petechiae: pinpoint flat red spots on skin or mucous membranes
(like a rash); result from bleeding from a capillary or small arteriole
• Frequent purpura and ecchymoses: large purplish red or greenish
areas on the skin (bruises)
• More persistent bleeding than warranted by a trauma
• Bleeding into a joint: hemarthroses; swollen, red, and painful
• Coughing up blood: hemoptysis; bright red flecks in sputum
• Vomiting blood: hematemesis; often coarse brown particles
(coffee grounds); may be red
• Blood in feces: often black (tarry) or occult (hidden)
• Anemia
• Feeling faint and anxious, low blood pressure, rapid pulse
Blood Clotting Disorders: Hemophilia A
• Classic hemophilia
• Deficit or abnormality of factor VIII
• Most common inherited clotting disorder
• X-linked recessive trait
• Manifested in men, carried by women
• Varying degrees of severity
• Prolonged bleeding after minor tissue
trauma
• Spontaneous bleeding into joints
• Possible hematuria or blood in feces
Blood Clotting Disorders: Hemophilia A
• Classic hemophilia
• Deficit or abnormality of factor VIII
• Most common inherited clotting disorder
• X-linked recessive trait
• Manifested in men, carried by women
• Varying degrees of severity

Inheritance of hemophilia A
Blood Clotting Disorders: Hemophilia A
Signs and symptoms
• Prolonged bleeding after minor tissue
trauma including hematomas
• Spontaneous bleeding into joints
(hemarthrosis), can cause deformities with
recurrent inflammations
• Possible hematuria (kidneys) or blood in
feces (digestive tract)
Blood Clotting Disorders: Hemophilia A

• Diagnostic tests
• Bleeding time and PT normal
• PTT, activated PTT (aPTT), coagulation
time prolonged
• Serum levels of factor VIII are low
• Treatment
• Desmopressin (DDAVP)
• Replacement therapy for factor VIII
 Blood Clotting Disorders: DIC
Disseminated Intravascular Coagulation (DIC)

• Involves both excessive bleeding and clotting

• Excessive clotting in circulation
• Thrombi and infarcts occur
• Clotting factors are reduced to a dangerous level
• Widespread, uncontrollable hemorrhage results
• Very poor prognosis, with high fatality rate
Blood Clotting Disorders: DIC
Etiology
• Complication of many primary problems
• Obstetrical complications, such as abruptio placentae
• Infections
• Carcinomas
• Major trauma
Blood Clotting Disorders: DIC
 Blood Clotting Disorders: DIC
Signs and symptoms
• Reduced fibrinogen level
• Thrombocytopenia
• Prolonged bleeding time, PT, APTT, and thrombin time
• Hypotension, hypovolemic shock
• Multiple bleeding sites are common.
• Petechiae or ecchymoses
• Mucosal bleeding and hematuria
• Vascular occlusions resulting in infarctions
• SOB, cyanosis
• Neurologic effects including seizures, decrease LOC.
• ARF with oliguria

Treatment
• Difficult, depends on what is most dominant
• Focused on treating underlying cause
Neoplastic Blood Disorders
• group of diseases that originate in the
bone marrow and cause imbalances
with the number red blood cells, white
blood cells, or platelets
Neoplastic Disorder: Polycythemia
• Primary (polycythemia vera): ­ production of
erythrocytes & other cells in bone marrow
• Often seen in 40-60 yrs;
• Etiology: idiopathic
• ­ blood volume & viscosity
• Blood vessels distended, blood flow sluggish è frequent
thromboses, tissue infarctions, elevated BP
• Spleen & liver can become congested & enlarge

• Secondary (erythrocytosis): ­ production of RBCs due to

prolonged hypoxia & ­ erythropoietin secretion
• Increase in RBCs not as high as primary: more reticulocytes
• Etiology: May be compensation mechanism due to
chronic lung or heart disease or high altitudes
Neoplastic Disorder: Polycythemia
• Distended blood vessels, sluggish blood
flow
• Increased blood pressure
• Hypertrophied heart
• Hepatomegaly
• Splenomegaly
• Dyspnea
• Headaches
• Visual disturbances
• Thromboses and infarctions
Neoplastic Disorder: Polycythemia
Diagnostic tests
• Increased cell counts
• Increased hemoglobin and hematocrit values
• Hypercellular bone marrow
• Hyperuricemia

Treatment
• Identify specific cause
• Drugs or radiation
• Suppression of bone marrow activity
• Periodic phlebotomy
Comparing Hematocrit Conditions
 Leukemia
• Group neoplastic disorders involving WBCs
• 5 - year net survival: 61% (CCS 2023 summary)
• Most commonly diagnosed cancer for children 0 -14 years (35%),
account for 23% of cancer deaths for this age group
• Pathophysiology: (acute lymphocytic leukemia)

https://cdn.cancer.ca/-/media/files/cancer-information/resources/publications/canadian-cancer-statistics-
2023/2023pdfen.pdf?rev=43c8cc8f34b547d4ad227000bd8df9dc&hash=68C12E2EE9AA7308C14C3065BDFED5B0&_gl=1*6yl46p*_gcl_
au*OTcwOTg5MzEuMTcwMTAyMDQ2Nw..
 Leukemia
Acute Leukemia
• High proportion of very immature, nonfunctional cells in bone
marrow & peripheral circulation
• usually abrupt onset: marked signs & complications
• Seen more often in younger population or younger adult
• Etiology: unknown but possible association with chromosomal
abnormalities (increased incidence in children with Down
Syndrome)
Chronic Leukemia
• Higher proportion mature cells
• Insidious onset, mild signs: better prognosis
• Seen more often in older population
• Often due to exposure to radiation, benzene, viruses

• Both can further differentiate depending on the type of

stem cell that is affected
Leukemia

• Diagnostic tests
• Peripheral blood smears
• Immature leukocytes and altered numbers of WBCs
• Numbers of RBCs and platelets decreased
• Bone marrow biopsy for confirmation
• Treatment
• Chemotherapy
• ALL in young children responds well to drugs
• Biological therapy (interferon)
• May be used to stimulate the immune system
Leukemia Types

Acute lymphocytic leukemia, common in young children. Blood smear

shows small lymphocytes and normocytic anemia
Leukemia
Signs and symptoms
Acute leukemia:
• Multiple infections
• Severe hemorrhage because of thrombocytopenia
• Signs of anemia
• Bone pain
• Weight loss (anorexia), fatigue
• Fever
• Enlargement of lymph nodes, spleen, and liver
• If leukemic cells infiltrate CNS: headache, visual
disturbances, drowsiness, or vomiting follows
• Pain

Chronic leukemia: insidious, early signs fatigue, weakness,

frequent infections
Lymphatic Disorders
Gould Chapter 11
Lymph capillaries in tissue spaces
Lymphatic System: Structures
• Lymphatic vessels
• Lymphoid tissue
• Lymphatic nodules
• Tonsils
• Lymph nodes
• Spleen
• Thymus gland
• Red bone marrow
Function
• Return of excess interstitial fluid to
the cardiovascular system
• Vessels empty into the subclavian
veins
• Filter and destroy foreign material
• Initiate the immune response
• Absorb lipids from the GI tract
 Function
1. Excess interstitial fluid flows as pressure builds up
in the tissues via capillaries containing one-way
minivalves at the terminus
2. The lymphatic capillaries join to form larger
vessels with valves to ensure a one-way flow of
fluid.
3. Lymphatic vessels are interrupted periodically by
lymph nodes, at which point the lymph is filtered,
more lymphocytes may enter the lymph en-route Structure of a typical lymphatic capillary

to general circulation
4. Vessels of URQ of body empty into right
lymphatic duct, which returns lymph into general
circulation via right subclavian vein
5. Remainder of lymphatic vessels drain into the
thoracic duct in upper abdomen, thoracic cavity
then drains into left subclavian vein
6. Lymphatic capillaries in intestinal villi absorb and
transport most lipids as chylomicrons

Principal organs of the lymphatic system

Lymphomas
• Malignant neoplasms involving lymphocyte proliferation in
lymph nodes
• Specific causes not identified
• Higher risk in adults who received radiation during childhood

• Two main disorders

A. Hodgkin’s lymphoma
B. Non-Hodgkin’s lymphoma
• Differentiated by lymph node biopsy
A. Hodgkin’s Lymphoma
http://library.med.utah.edu/WebPath/HEMEHTML/HEME043.html

• Onset: adults 20-30 yrs (men &

women)
• Second peak: over 50 yrs (mainly
men)
• Prognosis: excellent when
malignancy is localized in early
stages
• >80% net survival (CCS ‘06-’08)
• Initially involves a single lymph node Go11.8

è cancer spreads to adjacent nodes

• To organs via lymphatics
• T-lymphocytes seem to be defective
& lymphocyte count ¯
• Presence of Reed-Sternberg cell
• Giant cell present in lymph node
A. Hodgkin’s Lymphoma: Staging

Go11.9
A. Hodgkin’s Lymphoma: Staging
Signs and symptoms:
• Enlarged lymph node, often cervical
• Splenomegaly, enlarged lymph nodes at other locations, e.g.
enlarged mediastinal nodes which may compress esophagus
• Weight loss, anemia, low-grade fever/night sweats, fatigue
• Pruritus
• Recurrent infection

Treatment
• Radiation
• Chemotherapy
• Stem cell transplant
B. Non-Hodgkin’s Lymphoma
• Often associated with HIV infections
• Will have one lymph node involved, but will spread in non-
organized pattern, scattered throughout body
• Intestinal nodes & organs frequently involved in early stage
• More difficult to treat, but increased survival rate (~65% net
survival CCS ‘06-’08)

• Often involve B-lymphocytes

Treatment:
• Chemotherapy
• Radiation
Multiple Myeloma (Plasma Cell Myeloma)
• Neoplastic disease of unknown
etiology: older adults
• Involves plasma cells è
mature B cells that produce Ab
• ­ number of malignant plasma
cells replace the bone marrow &
erode bone
• Blood cell production impaired
& production of Ab
• Vertebrae, ribs, pelvis, skull
have multiple tumors
Go11.10

• Pathologic fractures occur at

weakened bone sites
• Hypercalcemia: as bone is
broken down
• Tumor cells spread throughout;
into lymph nodes, organs
http://library.med.utah.edu/WebPath/HEMEHTML/HEME040.html
Multiple Myeloma (Plasma Cell Myeloma)
Sign & Symptoms
• Well advanced before diagnosis: insidious
• Bone pain: present at rest
• Frequent infections
• Anemia, bleeding tendencies
• Pathological fractures
• Kidney function affected è kidney failure
Treatment
• Chemo: median survival 2-5 yrs
• Symptom management
• Blood transfusion in end stages