modules 8 & 9 learning objecitves

reticulocytes?

baby blood cells

increase in reticulocytes?

make about 1% of those a day
increase in reticulocytes indicative of some bleeding/breaking down of RBCs prematurely

lymph nodes in cancer

lymph nodes fixed, hard, NOT painful

lymph nodes in infection

lymph nodes mobile, tender, painful, maybe red

normal leukocyte (WBC) count

4500 - 10,500 cells uL

neutropenia

circulating neutrophil count of less than 1500 ul

congenital: some disease conditions can cause neutropenia right at birth

acquired:

• - autoimmune

• - secondary (lupus)

• - virus (secondary infection)

• - some drugs

• - cancers (hematologic malignancies)

infectious mononucleosis

causative agent = Epstein Barr Virus(lymphoproliferative disorder)

mostly found in young adults (kissing disease)

infectious mononucleosis causes

infected oral secretions; EBV infected saliva

infectious mononucleosis what happens

infect the B cells --> kills the cell or incorporates itself in the cells genome (abnormal proteins made)

body produces abnormal antibodies (heterophils) against the infected B cells (used for the diagnosis)

what plays role in infectious mononucleosis?

CD8 & NK cells play the pivotal role in controlling the disease

healthy immune system is important to control disease

do all infected b cells get killed

not all infected B cells are killed; virus lives and shed itself in the saliva for life (flare up when immunosuppressed)

infectious mononucleosis s/s

onset of symptoms between 4-8 weeks
prodromal period: malaise, anorexia, chills (nonspecifc)
fever, pharyngitis, lymphadenopathy (cervical, axillary, groin lymph nodes)
hepatitis (anorexia, jaundice) and spleenomegaly (reservoir of all immune cells)

infectious mononucleosis s/s in CNS(if advances)

cranial nerve palsies, encephalitis, meningitis, transverse myelitis, Guillain-Barre syndrome

immunosuppressed individuals

non-hodgkin lymphoma

why should you avoid contact sports

- spleen is swollen & heavily vascularized (lots of blood)
- can rupture if hit

limited space in bone marrow

one type of cell in overproduction --> space filled

- space filled --> pressure increases (volume cannot change)

- increased pressure --> patient complains of pain

limited resources in bone marrow

- one type of cell takes up majority of resources --> other cells go down

- overproduction of WBCs --> decreased production of RBCs, platelets, etc.

leukemia/lymphoma

lymphomas & leukemias are both tumors of the hematopoietic and lymphoid tissues
they are both lymphoproliferative disorders
closely related
both cancers and lead to high WBCs in circulation (15,000+)

an early clinical manifestation of lymphoma

night sweats

acute lymphoblastic leukemia/lymphoma (ALL)

acute
lympho-blasts-big cells
nucleus not condensed
immature cells (less differentiated)
precursor (early) B cell neoplasia
mostly in children 3-4 years (80% curable)

chronic lymphocytic leukemia/lymphoma (CLL)

chronic
lympho-cytes-small cells
nucleus condensed
mature cells (more differentiated)
peripheral (later) B cell neoplasia
WBC count very high with 75-90% lymphocytes
more common in older men

leukemia/lymphoma/blood cancer s/s

general symptoms
localized non-tender, painless lymph nodes
infiltrate and overwhelm spleen --> spleenomegaly
- patient complains of abdominal pain (left)
hepatic infiltration --> hepatomegaly
- patient complains of abdominal pain (right upper quadrant)

leukemia/lymphoma/blood cancer s/s what happens

BM starts to produce only one type of abnormal cells
- leukemic cells increase (lymphoid line)
- decreased RBC --> anemia
- WBC increased (normal healthy leukocytes decreased)
- platelets decrease --> bleeding

bone pain
arthralgia (hot, swollen, NOT red)
can hide in brain and testes --> get cancer again
recurrent infections, fevers
- high WBCs, but abnormal (no protection)
SOB/DOE
fatigue

lymphoma (B symptoms)

on top of all generalized symptoms....

fever

excessive night sweats

unexplained weight loss

thrombocytopenia classifications

low platelets

petechiae = (less than)<3mm bleeding

purpura = >3mm (less than )<10mm bleeding

ecchymosis = (greater than)>10mm bleeding

bleeding gums, easily bruised

acute myeloid leukemia

quick & aggressive

affecting myeloid line (mostly WBCs)

risk factors:

- radiation exposure

- previous chemo

- blood disorders (polycythemia vera, myelodysplastic syndrome)

- chemical exposure (benzene)

- genetic (translocation of chromosomes --> formation of abnormal protein)

- older age

- males

chronic myeloid leukemia

not as aggressive as acute
Philadelphia chromosome
(translocation 9:22)

leukemia milk

don't stick to each other in BMH

- leave BMH --> go into circulation --> can stay in circulation for long time

- leukemia --> change characteristic --> move out of bloodstream --> find a place to house themselves in body --> lymphoma

lymphoma: (cheese)

- move out with others into circulation --> don't like to be in circulation too long --> find some place in body

- sometimes change their characteristics --> become individual cells --> go into circulation --> become leukemia

acute

curable, can kill you fast

chronic

manage over time, die with it/not of it

precursor B cell leukemia/lymphoma

same thing/different presentation

pre B acute lymphoblastic leukemia/lymphoma (ALL)

B cells affected, immature, left side, short lasting (curable)

early on B cell line, early in stages of differentiation (blast), very aggressive (acute)

non-Hodgkin's lymphoma

• Involves lymphocytes, but it doesn't specify B or T cells.

• Not limited to a particular side of the body.

• Variable prognosis, depending on the subtype.

peripheral B cell neoplasia

chronic lymphocytic leukemia/lymphoma (CLL)

small cell leukemia/lymphoma (SCL)

small (mature, function a little better), chronic (less aggressive)

non-Hodgkin's lymphoma

precursor T cell/NK cell neoplasia

pre T/NK ALL

non-Hodgkin's lymphoma

peripheral T cell/NK cell neoplasia

type of hematologic cancer

presence of Reed-Steinberg cells in cohesive mass

^^good prognosis

Hodgkin's lymphoma

Reed-Steinberg cells are found in:

Reed-Steinberg cells are found in:

B cells

surface markers in normal B cells CD 19, 20

leukemic B cells:

markers change

CD 19, CD5

CD5 found in T cells

what happens to b cells?

1. B cells, which should fight off antigens, become abnormal.

2. They don't react to antigens like they should.

3. They don't self-destruct like they should (similar to cancer cells).

4. They multiply rapidly and excessively.

5. This overwhelms your bone marrow, hogs nutrients, and disrupts other cell populations.

monoclonal antibodies

1. remove CD5 marker from the patient.

2. Inject it into a rat to create specific antibodies.

3. Give these antibodies to the patient.

4. They target and destroy cancerous B cells with CD5, sparing healthy cells.

shape of RBC

• biconcave disc shape helps them flow smoothly through blood vessels.

• This shape provides a larger surface area for carrying hemoglobin, which can bind to four oxygen molecules.

• Red blood cells are essential for oxygen and carbon dioxide diffusion in the body.

RBC shape memory

RBC change shape as it moves through the small capillaries and regains its shape back

between aorta and capillaries

mature RBCs and Hg

no organelles
packed with hemoglobin (280 million Hg molecules in each RBC)
Hg carries 97% of O2

binding of hemoglobin to oxygen

tightly or loosely is determined by the shape of the Hg molecule
change in shape of the Hg molecule/how tightly they bind is effected by:
- increased level CO2
- decrease in pH
- temperature
- CO (latches on much faster than CO2)

products of hemoglobin

macrophages phagocytose old deformed RBCs
hemoglobin in RBCs broken down into globin & heme
globin (proteins) broken down into amino acids (body uses them)
heme is broken down into iron & bilirubin

liver & bilirubin

bilirubin broken down into unconjugated form --> sent to liver --> liver converts it to the conjugated form --> excreted with bile in the GI tract (gives color to urine & feces)
liver not functioning properly --> high levels of unconjugated bilirubin in blood (diagnosis of liver problem)
liver fine --> many RBCs breaking down --> more conjugated bilirubin in blood
blood draw high conjugated --> assume more RBCs broken down
jaundice = elevated bilirubin

free iron, transferrin, ferritin

free iron is toxic --> body does not like it freely floating

free iron floating around --> body produces transferrin --> attaches to free iron --> takes it to BM (stimulates BM to produce more erythrocytes)
body stores free iron as ferritin (deficiency of ferritin indicates iron storages are low)
body does not do well excreting extra iron

males: mostly loose through fecal matter
females: fecal + menstruation

where iron from

FOOD

animal products = heme-Fe

vegetables and fruit = non-heme Fe

absorption of heme-fe is better

vegetarians at risk of iron deficiency

absorption of iron what helps/hurts it

adequate pH of gastric acid (1.1) is important

PPI/antacids increase pH reduces iron abdorption

iron supplementation and Vit C helps with absorption

what leads to Fe deficiencies

decreased intake of Fe

decreased absorption of Fe

increased demand for Fe (children, infants, pregnant, periods)

increased loss:
- bleeding
- menstruation
- kidneys
- GI loss
- hookworm (#1 underdeveloped)
- peptic ulcer disease (#1 developed)/ulcerative colitis
- long term use of NSAIDs
- blood donation

who is at risk for Fe deficiency anemia:

people who take antiacids & proton pump inhibitors

compostion of blood

1. Plasma (55%): A watery liquid with proteins, electrolytes, and nutrients.

2. Red Blood Cells (45%): Carry oxygen and have hemoglobin.

3. White Blood Cells: Part of the immune system.

4. Platelets: Aid in blood clotting.

anemia

less amount of RBCs

polycythemia

body produces excessive amount of RBCs --> more hematocrit

changes in hematocrit in anemia and polycythemia

marathon runner = end of marathon seems polycythemic (super dehydrated)

marathon runner = infuse LOTS of water appears anemic

hematocrit tells you about hydration status as well

normal hemoglobin hematocrit 1:3

functions of the hematologic system direct roles

carry nutrients to cells

carry away waste from cells

carry O2 to inside cell (every molecule of hemoglobin carries 4 molecules of oxygen)

functions of the hematologic system supportive role:

intracellular communication

- endocrine = produced in a particular region of the body/effect far away (insulin)

- exocrine = effect close to where made (lipase)

- paracrine = within organ itself

protection/defense

self-repair mechanism (clotting cascade)

how you get anemia

blood loss

iron deficiency anemia

- malnutrition (diet)

- GI blood loss

- menorrhagia

decreased RBC production anemia

- Vit B-12/folate deficiency

- aplastic anemia

increased RBC destruction anemia

- RBC malformation

sickle cell anemia

anemia s/s

• low amount of iron/hemoglobin

• pale (less color)

• hypotension

• fatigue (less oxygen)

• DOE/SOB (physical activity causes tiredness)

• weakness (less oxygen)

• tachycardia (less oxygen --> HR goes up)

• increased flow of circulation (less sticky)

• - rapid bounding pulse

• - low viscosity, high velocity

• tinnitus (blood flowing faster)

• vertigo

• cheilosis (cracked lips_

• atrophic glossitis (tongue inflammation)

• nails spoon shaped (less keratin)

MCV / MCHC

what are they used for?

diagnosing different types of anemia

MCV = mean corpuscular volume

MCHC = mean corpuscular hemoglobin concentration

types of anemia are classified by:

cell size & hemoglobin concentration

anemia labs

Hg (M: 14-16.5 g/dL; W 12-15 g/dL)

hematocrit to hemoglobin 1:3

MCV/mean size of RBCs 80-100 fL

production of RBCs

• mmature cells are larger.

• As they mature, they can't reproduce as much.

• The nucleus starts open and loose but becomes condensed and eventually disappears, making the cell smaller.

• The cytoplasm turns red as it matures, and smaller cells appear redder.

• Less red cells are bigger and less mature.

what is needed for DNA replication & proliferation

Vit-B12 & folic acid

pregnant woman required to make more RBCs --> need more folic acid

in the absence of Vit-B12 and folic acid --> chromatin is NOT condensed but replication is continued

- production of defective RBCs

- become big

folic acid

needed for DNA maturation

affects all cells that are rapidly proliferating (GI, hair, neurons in fetus (NTD), tongue)

deficiency in folic acid can result in pancytopenia

sources: green leafy vegetables

celiac disease, ETOH, IBS patients can have folic acid deficiency

deficiency s/s:

- anemia s/s

- smooth tongue

- irritability

- diarrhea

Vit B-12

required for production of myelin (myelin sheaths cover nerve cells)

sources: meat

vegetarians may need supplementation

intrinsic factors produced by the liver required for absorption of Vit B-12 (carry Vit B-12 to jejunum where absorbed)

liver problems --> not enough intrinsic factor --> Vit B-12 deficiency

pernicious anemia

deficiency of intrinsic factors

deficiency more dangerous than folic acid (maintenance of nervous system, production of RBCs, can cause damage to the brain and spinal cord)

Vit B-12 & folic acid anemia

macrocytic megaloblastic anemia

bigger cell, abnormal cell (broken down quickly), more anemic

MCV > 100 fL (normal 80-100)

Vit B-12 deficiency s/s

tied to nervous system

low grade fevers

difficulty in proprioception, concentrating and sluggish responses, brain fog

neuropathic pain

unsteady gait, clumsy, loss of sensation in feet

pins and needles sensations or numbness in fingers or toes

glossitis (swollen beefy red tongue)

personality or memory changes

heartburn, nausea, diarrhea, impaired urination, weight loss

long term complications may include gastric cancer and carcinoids

Vit B-12 deficiency can present with decreased proprioception

chronic bleeding:

something going on in the patient for long time, iron levels low

anemia caused by chronic bleeding

iron levels decrease --> decreased ferritin levels --> decreased serum iron levels

body wants to transfer more Fe to BM (needed for production of RBCs)

body goes into mode where it produces more transferrin

cells stay in BM longer awaiting Fe --> microcytic (small) and hypochromic (faded) --> microcytic hypochromic anemia

chronic bleeding --> anemia (low hemoglobin), low ferratin, high transferrin

iron deficiency anemia

blood loss/chronic blood loss over time (most common anemia)

microcytic hypochromic anemia

diet, GI bleeding (#1), meds, PUD, hemorrhoids, gastritis, menstruation, stomach cancer, IBD, lead toxicity

labs: low Hg, low ferratin, high transferrin

questions to ask pale patient:

do you think you are able to do what you did a month or two ago? does what you did two months ago make you really tired now?

hemolytic anemia

RBCs broken down before 120 days

defect in RBC itself or some extrinsic factor

- mononucleosis

- mechanical heart valve (hit metal)

- any metal object implanted in body

hemolytic anemia evidence

- anemia s/s

- splenomegaly (working harder than it needs)

- jaundice (unconjugated bilirubin goes up --> liver --> conjugated bilirubin)

- stool color

- urobilinogen (breakdown of bilirubin by gut bacteria)

- accelerated erythropoiesis (overproduction for loss)

- increase in reticulocytes (rather than erythrocytes)

- MCV higher (bigger cells)

- hypochromic (reticulocytes less red)

- BM biopsy indicate hypercellular BM (more RBCs within BM)

globin chain synthesis (qualitative & quantitative defects)

qualitative defect (sickle cell disease) = have all globin chains, not functioning properly

quantitative defect (thalassemia) = don't have enough globin chains

sickle cell disease

• Autosomal recessive disease.

• Abnormal, sickled-shaped cells cause hemolysis (cell breakdown) and block small blood vessels, leading to pain, numbness, and oxygen deficiency (ischemia).

• Can be reversible or not.

• Can occur anywhere in the body, causing generalized pain.

• Caused by a mutation on the 11th chromosome.

sickle cell crisis

not everyone that has sickle cell disease will go into a crisis

causes:

- exposed to too much cold (vasoconstriction), dehydration, hypoxemia, low pH

can lead to sickle cell anemia

acute sickle cell disease

severe anemia (if gets to the point where lost of sickle cells being destroyed)
not everyone who has sickle cell disease has anemia

vaso-occlusive phenomena:
- pain (mostly generalized)
- stroke/transient ischemic attack
- acute kidney injury
- bone infarction
- venous thrombo embolism
- mesenteric ischemia
- local tissue hypoxia
- priapism
infection
splenic sequestration = large amount of blood pooling in spleen --> not enough in circulation

chronic sickle cell disease s/s

pain
anemia
neurological defects/seizure disorders
renal impairments (CKD)
osteoporosis
chronic leg ulcers
proliferative retinopathy

aplastic anemia

myeloid stem line (not allowing for production of cells in that category (RBCs))

labs: anemia + leukopenia + thrombocytopenia --> pancytopenia

idiopathic (65%), chemical, radiation, virus (cytomegalovirus)

genetic alteration --> hyper-proliferative myeloid stem cell

anemia s/s:

- progressive weakness

- pallor

- dyspnea

- tachycardia

thrombocytopenia s/s:

- petechiae, purpura, ecchymosis

- risk of bleeding goes up

leukopenia s/s

- recurrent and frequent infections

role of kidney in anemia

produce erythropoietin (hormone stimulates RBC production)

decrease in RBCs (anemic) --> reduction O2 carrying capacity --> perfusion to kidneys decreased --> stimulate erythropoietin production --> erythropoietin goes to BM --> tells BM to increase RBC production

kidneys sense decrease in perfusion (low amount of oxygen to kidneys) --> need more RBCs

in the presence of adequate amount of Vit B-12 and folate and healthy BM, production can be increased to 10x

chronic kidney disease:

- kidneys cannot stimulate erythropoietin

- should be worried about them having anemia

benign

normal cells growing in wrong place/time (don't harm)

- freckles

- skin tags

- moles

- cherry angioma

- uterine fibroids

benign tumor = incase in fibrous capsule, resembles tissue of origin

malignant

cancerous cell (abnormal, no important function and harmful to normal body function)

- abnormal chromosomes

- ability to migrate

- loose adherence

- invade other tissues

- rapid cell division

- promotes self growth

- loss of apoptosis

neoplasm

abnormal growth in some part of a tissue or organ; tumor with cancerous growth

can grow becuase of loss of apoptosis

neoplasia

abnormal growth and proliferation of abnormal cells or due to a benign or malignant process

multiple myeloma

plasma cells responsible for producing immunoglobulins --> abnormal antibodies formed

protein electrophoresis: plasma cells secreting abnormal antibody fragments

blood draw --> find M protein --> suspect multiple myeloma

Bence Jones protein in urine

multiple myeloma s/s

- recurrent infections

- bone lesions/pain (1st symptoms unlike other cancers)

- hypercalcemia

- renal insufficiency/failure

- anemia

- neutropenia

- thrombocytopenia

carcinoma in-situ

group of cancerous cells that are still localized to its place of origin
has not metastasized
cancerous cell that has not spread

coagulation

no involvement of RBCs & WBCs
property of plasma (involves platelets and clotting factors)
process by which soluble fibrinogen converts into insoluble fibrin
liquid blood --> becomes solid when clotted

mechanisms that prevent the formation of a blood clot
endothelial cells

- tightly connected (don't let anything escape)

- prevent leak

- keep coagulation system under check (prevents platelets from sticking with each others)

healthy endothelial cells release:

- NO, PGI2 (prostaglandins), ADP diphosphate (vasodilators prevent platelets from sticking to each other)

- antithrombin 3 (prevents clots)

- heparin sulfate (blood thinner)

- tissue plasminogen activator (tPA) helps break down plasminogen --> plasmin

- thrombomodulin

injured endothelium

1. Injury causes a hole in the endothelium (inner blood vessel lining).

2. Nearby healthy endothelial cells release von Willebrand factor (vWf).

3. vWf captures and pulls platelets to the injury site.

4. Platelets attach via GP1b receptors on vWf.

5. Platelet adhesion activates them.

6. Activated platelets release granules (delta & alpha).

7. Granules help platelets stick together, forming the primary, loose platelet plug.

8. To secure it, the body creates a fibrin mesh, forming the secondary, tight platelet plug or thrombus, preventing dislodging and complications like pulmonary embolism or stroke.

platelet adhesion

ability of platelets to stick to a non-platelet layer (VW)

GP1b deficiency

platelet adhesion difficult