BLOOD DISORDERS - MODULE 4

What is anemia?

• a decrease in oxygen carrying capacity of blood

• most common

How is oxygen carrying capacity determined?

1. number of RBCs

2. amount of hemoglobin in RBCs

reduction in either or both causes anemia

What is hypoxemia?

• reduction in oxygen content of the blood

• caused by anemia

What is hypoxia?

• abnormally low oxygen in tissues

• caused by hypoxemia

What are the general signs and symptoms of anemia?

• fatigue

• dizziness + headaches

• shortness of breath

• increased breathing rate and depth

• rapid and pounding heart beat

• vasodilation

• decrease in blood viscosity

• pale lips, nail beds, and mucous membranes

Why is fatigue a sign / symptom of anemia?

• low aerobic respiration = low ATP

Why is dizziness and headache a sign / symptom of anemia?

• low ATP in CNS

  • nerve tissues are sensitive

Why is shortness of breath a sign / symptom of anemia?

• no sufficient O2 to tissues for their demands

• worse on exertion

Why is increased breathing rate and depth a sign / symptom of anemia?

• body’s attempt to correct hypoxemia

  • respiratory center response is to increase diffusion rate of O2 in the lungs

Why is rapid and pounding heart beat a sign / symptom of anemia?

• body’s attempt to correct hypoxemia

  • cardiac center response increases HR and SV

    • increases blood flow to lungs and hypoxic tissues

Why is vasodilation a sign and symptom of anemia?

• increases demands on heart

• hypoxia causes release of signaling mlcs like nitric oxide

  • leads to local vasodilation of tissue capillaries

  • total peripheral resistance decreases

  • venous return increases

Why is a decrease in blood viscosity a sign / symptom of anemia?

• reduction in blood cells

• body maintains total blood volume

• decrease TPR

  • increases venous return to heart

Why are pale lips, nail beds, and mucous membranes a sign / symptom of anemia?

• less oxygenated blood = less bright red

What are other clinical manifestations of anemia?

• impaired healing

• numbness

• nausea

• GI symptoms

  • constipation, diarrhea, loss of appetite, etc)

• low grade fever

What are some etiologies of anemia?

• chronic blood loss

• iron deficiency (often from hemorrhage)

• pernicious (B12 deficiency)

• folate anemia (B9 deficiency)

• red bone marrow disorders (e.g. leukemia)

• sickle cell, thalassemia, etc

What is anemia through blood loss?

• is either through:

  • slow / chronic blood loss secondary to other illness

  • acute bleeding

• results in iron deficiency

• 2-4 ml blood loss a day sufficient = 1-2 mg iron

What is anemia through blood secondary to?

• menorrhagia

• ulcerative colitis

• bleeding gastric ulcers

• hemorrhoids

• medications (aspirin)

• cancer bleeding

• excess blood loss in childbirth

What is hemoglobin production dependent on?

• iron availability

Where is iron stored and when is it toxic?

• 80% bound to hemoglobin in RBCs

• 20% bound to:

  • ferritin in cells

  • transferrin in plasma

• free iron is toxic

What is iron deficiency anemia?

• most common world wide

• results from:

  • chronic blood loss

  • lack of sufficient iron in diet

  • reduced iron absorption ability (genetic predisposition, type of diet, inflammatory bowel disease

Who is at risk with iron deficiency anemia and how is it treated?

• poverty, women, children, and elderly are at risk

• treated by:

  • replacing lost iron

  • identify + treat the condition causing the loss

What is the pathogenesis of iron deficiency anemia?

1. iron depletes

2. lower hematocrit + reduced cell volume (MCV) + low hemoglobin content per cell (MCHC) produced

3. anemic blood cells gradually replace older blood cells

What is the histology of iron deficiency anemia?

• distinctive blood cells

• microcytic cells (small)

• hypochromic cells (pale)

What is vitamin B12 essential for?

• DNA synthesis / mitosis in RBC

• myelination of nerves / nerve function

• B12 comes from a meat, fish, and dairy diet

• intrinsic factor from gastric mucosa allows B12 absorption in the small intestine

What is the etiology of B12 deficiency anemia?

• diet

• autoimmune destruction of gastric mucosa

• heavy alcohol ingestion

• cigarette smoking

• gastrectomy

• malabsorption

• aging

What is the pathogenesis of B12 deficiency anemia?

• slow (20-30 years)

• undetected gastritis progression

• slow depletion of B12 in liver

How is B12 deficiency anemia diagnosed?

• megaloblastic RBCs

  • macrocytic (large)

  • normochromic (normal colour)

What are the signs / symptoms of B12 deficiency anemia and how is it treated?

• anemia symptoms

• low serum B12 levels

• neurologic complications like parasthesias in hands / feet (tingling + numbness), depression, sometimes dementia

• treated by B12 injections

What is folic acid (B9) essential for?

• nucleic acid synthesis within RBC

• cell growth and mitosis

What is folate deficiency anemia?

• similar to pernicious anemia

• neurological manifestations include peripheral neuropathies and neural tube defects in the fetus

• other symptoms include mouth ulcers and watery diarrhea

• common in malnutrition, low green veg and meat diets

• elderly, children, alcoholism, and pregnancy are at risk

What is polycythemia?

• excessive erythrocyte presence

• relative polycythemia is from dehydration, is a minor consequence and can be fixed

• absolute polycythemia can be primary or secondary

What is primary absolute polycythemia?

• polycythemia vera

• rare non malignant condition

• overabundance of bone marrow stem cells

What is secondary absolute polycythemia?

• due to hypoxia

• common in those living at higher altitudes, smokers, and people with COPD and / or coronary heart failure

• results in overproduction of erythropoetin to replace low oxygen levels

What are the polycythemia manifestations?

• are related to increased RBCs, hemoglobin level, and hematocrit with increased blood viscosity and volume

• includes:

  • splenomegaly

  • depletion of iron

  • hypertension

  • disrupted cardiac output

  • decreased cerebral blood flow

  • venous stasis

  • thromboembolism

How is leukocyte function affected?

• if there are too few / too many cells (quantitative changes)

• cells are functionally defective (qualitative changes)

What is leukocytosis?

• normal response to stressors such as infection, surgery, pregnancy, and hormones

• pathological when caused by malignancies or blood disorders

What is leukocytopenia?

• never a normal response

• when count falls to < 1000/mm3, infection risk increases a lot

• results from radiation, chemotherapy, and autoimmune disease (e.g. SLE)

How do granulocyte counts change during infections?

• increase due to infection

• decreases can be due to production falling behind its need

• most often seen in neutrophils

  • it is the most numerous granulocyte with a primary role against infection

What is neutrophilia?

• an early response to infection

• shift to left

What is neutropenia?

• where production cannot keep up with demand

• other causes include:

  • starvation

  • autoimmune disorders

  • HIV

  • chemotherapy

What is agranulocytosis?

• granulocytopenia

• extremely low counts of neutrophils

• can be caused by chemotherapy and aplastic anemia

What is lymphocytosis?

• usually produced through viral infection

What is lymphocytopenia?

• immune deficiencies

• neoplasia

• drugs

• no known cause

What is infectious mononucleosis?

• acute viral infection of B lymphocytes (epstein barr virus)

• transmitted through saliva and other body fluids

• increased number of abnormal lyphocytes

  • atypical cells produce heterophile antibodies for diagnosis

Who is most commonly observed for mononucleosis?

• people aged 150 - 19 years old

• asymptomatic EBV infection is common in children

  • provides immunity against reinfection

What is the pathophysiology of infectios mononucleosis

• EBV invades oropahrynx, nasopharynx, and salivary epithelial cells

  • to lymphoid tissues and B cells

• usually self limiting

What are the symptoms of infectious mononucleosis?

• fever

• sore throat

• cervical lymph node enlargement

• may progress to more serious symtpoms

  • splenomegaly

What is leukemia?

• a malignant disorder of the blood and blood forming organs

• does pancytopenia which is a reduction in the celllar components of the blood

What are leukemic cells?

• immature and poorly differentiated

• proliferate rapidly and have a long life span

• dont function normally

• interferes with the maturation of normal blood cells

• circulate in the bloodstream

• crosses the blood brain barrier

• infiltrates many body organs

What are the risk factors for leukemia?

• can reappear in families

• associated with other genetic conditions like down syndrome

• increased risk has been linked to cigarette smoke, ionizing radiation, infections with HIV or HCV, some drugs (chloramphenicol), and some chemotherapies

What are the 4 classes of leukemias?

• type of cell line affected

  • lymphocytic or myeloid

• progression of the disease

  • acute or chronic

What are acute leukemias?

• rapid growth of immature blood cells

• has an abrupt onset

• short survival time if untreated

What is acute lymphocytic?

• ALL

• lymphocytes (85% B cell line)

• least common type overall

• most common in children

• accounts for ¾ cases of childhood cancer

What is acute myeloid?

• AML

• concerns any cells except lymphocytes (e.g. neutrophils, platelets, and erythrocytes)

• tends to occur in older adults

• also seen in children and younger adults

What are the clinical manifestations of acute leukemias?

• fatigue from anemia

• shortness of breath

• tachycardia

• bleeding from thrombocytopenia

• infections and fever

• anorexia

• weight loss

• liver, spleen, and lymph node enlargement

• bone pain

• neurological / CNA manifestations

How are acute leukemias evaluated?

• difficult to detect early as symptoms are very general

• blood tests and bone marrow biopsy

  • many imature WBC (60% to 100% of cells)

How is acute leukemia is treated?

• chemotherapy

• blood transfusion and antimicrobial agents

What are chronic leukemias?

• slow growth of mature cells which dont function normally

• onset is gradual with longer survival time

• symptoms appear very slowly

What are the clinical manifestations of chronic leukemias?

• fatigue

• weight loss

• low grade fever

• splenomegaly

What are CLL clinical manifestations?

• accounts for half of all leukemias (generally in older people)

• CLL involves mostly B cell transformation

  • they refuse apoptosis and accumulate while becoming inactive + no AB production

• increase in infection due to low AB

• causes anemia, thrombocytopenia, and neutropenia

• can be slow or aggressive

What are the CML clinical manifestations?

• average age affected is 67

• affects stem cells meaning there are excessive amounts of marrow granulocytes, RBC precursors, and megakaryocytes

What is chronic CML?

• 2.5 years

• may be asymptomatic

What is accelerated CML?

• 6-18 months

• primary symptoms develop

• more immature cells in bone marrow and blow

• infections, weight loss, fever, enlargement of spleen and liver

What is terminal blast CML?

• 3-6 months

• more blast cells in blood

• increase in severity of symptoms

• resembles AML

• prognosis poor at this point

How are chronic leukemias treated?

• bone marrow transplant

• biological repsonse modifiers which increase immune response (e.g. interferon alpha)

• combination chemotherapy

What are the survival rates and cause of death for chronic leukemias?

• CLL survival rate is variable

• 90% live 5 years or longer for CML

• death is caused by infection or hemorrhage from metastatic infiltration of tissues

How are platelets altered in function?

• by number or quality of platelets

• too few platelets which is thrombocytopenia

  • hemorrhage risk

  • spontaneous bleeding can occur without trauma

    • petechiae, purpuric spots, ecchymosis

  • bleeding can be fatal if in the GI tract, respiratory tract, or CNS

What is thrombocytopenia?

• results from decreased platelet production, increased consumption, or both

• may occur primary or secondary to other conditions

What is heparin induced thrombocytopenia?

• most common drug induced condition

• can occur when heparin is given with surgery

• IgG antibodies are produced against a heparin / platelet factor complex

  • causes platelet aggregation + increased clot formation, leading to stroke, pulmonary embolism, myocardial infarction, etc

What is immune thrombocytopenic purpura?

• antibodies complex with compounds in the platelet membrane

  • makes them more susceptibel to phagocytosis in the spleen

• levels of thrombopoetin do not rise in response to lowered platelets

What is primary thrombocythemia?

• platelet production increases due to defects in thrombopoetin receptors on platelets

• the receptor cant bind and remove thrombopoietin from the blood

  • keeps hormones high in blood, resulting in more platelet production

What is secondary thrombocythemia?

• occurs with any disease state that stimulates thrombopoietin production

  • including surgery, infection, cancer, and chronic inflammation

• people are at high risk of large vessel thrombosis

What is the function of impaired platelets?

• characterized by increasing bleeding time in the presence of a normal platelet count

• inherited by von willebrand disease (rare)

• acquired by:

  • drugs (aspirin + NSAIDs) which decrease platelet aggregation

  • secondary to leukemia where low quality platelets are produced