Week 10: Hematology Flashcards
What are Erythrocytes?
RBCs (Red Blood Cells)
What are Leukocytes?
WBCs (White Blood Cells)
What are Platelets?
Small cell fragments in blood that form CLOTS & stop/prevent BLEEDING
- Made in bone marrow (sponge-like tissue inside bones!)
HbS stands for…
Hemoglobin
HbC means…
hemoglobin C
What is sickle cell disease?
group of autosomal RECESSIVE disorders
What are the 3 types of sickle cell diseases (covered in class)?
- sickle cell anemia (HbS) MOST SEVERE
- sickle cell-thalassemia disease
- sickle cell-HbC disease
What is the MOST SEVERE type of sickle cell disease?
Sickle Cell Anemia
What is sickling?
Hemoglobin is abnormal, which causes the RBCs to become HARD & STICKY and look like a C-shaped farm tool called a “sickle.”
The sickle cells die early, which causes a constant shortage of RBCs.
When a cell turns from a regular circular shape to a crescent-looking shape…
What goes on in the sickling process? (3)
an occasional, intermitt. phenomenon…
- low PO2 in blood (hypoxemia)
- high H+ conc. in blood (low pH)
- high plasma osmolality; low plasma V; low temp.
“How does sickling cause damage to erythrocytes?” (3)
- MEMBRANE DERANGEMENTS occur b/c as HbS units grow, they PROTRUDE through membrane skeleton…causing changes in membrane structure!
- Membrane derangement = changes in ionic flow…
—–> influx in Ca++
—–> efflux of K+ & H2O - Damaged cells = end stage, non-deformable/STIFF & irreversible sickled cells :(
How can sickled erythrocytes regain normal shape? (3)
- reoxygenation
- return of PO2 –> normal
- rehydration
When is are sickled cells irreversible?
When there is permanent plasma membrane damage…b/c of sickling :(
**Hemoglobin structural alterations observed with sickle cell disease:
a) are irreversible
b) increase flexibility of erythrocytes
c) are stimulated by deoxygenation
d) are stimulated by alkalosis
C
**d would be correct if it said ACIDOSIS
What are the 4 general manifestations of sickling?
- pallor
- irritability
- fatigue
- jaundice
“pif-j”
Regarding sickling, what are the 4 Types of Crises?
- Vaso-occlusive crises
- Aplastic crisis
- Sequestration crisis
- Hyperhemolytic crisis
In terms of ACUTE manifestations of sickle cell disease, what are some things seen in the BRAIN? (4)
- thrombosis/hemorrhage
—-> causing paralysis, sensory deficits, or death :0
In terms of ACUTE manifestations of sickle cell disease, what are some things seen in the LUNGS? (3)
- Atelectasis (incomplete lung expansion)
- Infarction
- Pneumonia
In terms of ACUTE manifestations of sickle cell disease, what are some things seen in the ABDOMINAL ORGANS? (5)
- Acute hepatomegaly (enlarged liver b/c of underlying disease)
- gallstones
- splenic sequestration (too many blood cells get stuck in the spleen; EMERGENCY!!! usually w/ ppl who what sickle cell disease)
- splenomegaly (enlarged spleen)
- Infarction (tissue death or necrosis due to inadequate blood supply to the affected area)
In terms of ACUTE manifestations of sickle cell disease, what are some things seen in the BONES & JOINTS? (1)**
- Hand-foot syndrome (painful swelling of hands and feet)
In terms of ACUTE manifestations of sickle cell disease, what are some things seen in the KIDNEYS? (1)
- Hematuria (blood in urine)
What is the MOST PROFOUND ISSUE when it comes to sickle cell disease?
Sticky RBCs get stuck in vasculature
Vasoocclusive crisis is also called:
pain crisis
What is vasooclusive crisis?
- sickling is in microcirculation
- EXTREMELY PAINFUL
- and symmetric
What are the 2 syndromes seen in vasooclusive crisis?
- Hand-foot syndrome
——-> (hands & feet have PAINFUL swelling) - Acute chest syndrome
——-> (sickled RBCs attach to the lung, which is INJURED, UNDERVENTILATED, AND INFLAMED…fail to be reoxygenated :( )
Aplastic crisis is:
Transient cessation in RBC production occurs b/c viral infection
**RBCs are temporarily not made b/c of viral infection
Sequestration crisis is:
Large amounts of blood pool in SPLEEN :0
Hyperhemolytic crisis is:
Rate of RBC destruction is accelerated :(
In sickle cell disease, what is the most common cause of death?
Infection
(spleen doesn’t work as well, so immune system is weaker :( )
More manifestations of sickle cell disease include: (3)
- Infection
- Glomerular disease
——- Hyposthenuria: the inability of tubules of kidneys to concentrate urine; leads to bed wetting, proteinuria - Gallstones / cholecystitis
Treatment for sickle cell disease include:
- immediate correction of ACIDOSIS & DEHYDRATION
- Antibiotics (for infections)
- Oxygen (to reverse hypoxia)
- Pain management (pain is complex…sooo multimodal management)
- Hydroxyurea (causes increase in HbF conc. ; anti-inflamm. effect)
- Transfusion therapy (can decrease morbidity and mortality)
- Curative treatments (hematopoietic stem cell transplantation & gene therapy)
In terms of pharmacotherapy of sickle cell disease/sickle cell crises, what is the main goal?
Control pain
From what was learned in class, what are the drugs used to treat sickle cell disease/sickle cell crises? (7)
Opioids
—–> 1. Morphine
—–> 2. Hydromorphone
NSAIDs
—–> 3. Ibuprofen
—–> 4. Naproxen
Tricyclic Antidepressants
—–> 5. Amitriptyline
Antiepileptics
—–> 6. Gabapentin
Antisickling agents
—–> 7. Hydroxyurea
What is Morphine’s use?
For acute / severe chronic pain
What is the mechanism of action of morphine? (2)*******
- Binds with MU and KAPPA receptors in the brain and dorsal horn of the spinal cord
- Mimics endogenous opioids (ex. endorphins & enkephalins) …also stimulates opioid receptors
What are the adverse effects of morphine? (6)
- Dysphoria (restlessness, depression, anxiety)
- Hallucinations
- Nausea, constipation
- Orthostatic HYPOtension, dizziness
- Pruritus (itchy skin)
- RESP. DEPRESSION , cardiac arrest
What is the mech. of action of hydromorphone?*****
- inhibits ascending pain pathways in CNS
- increases pain threshold
- alters pain perception
What are the adverse effects of hydromorphone? (5)
- Life-threatening resp. depression!!!
- HYPOtension
- Drowsiness, dizziness, confusion
- Pruritus (itchy skin)
- Nausea, constipation
**HYDROMORPHONE IS x5 MORE POTENT THAN MORPHINE!!!!!
What is the mech of action of ibuprofen? **
Inhibition of prostaglandin synthesis
What are the adverse effects of ibuprofen? (5)
- Nausea
- Heartburn
- Epigastric pain
- Dizziness
- GI ulcers w/ bleeding
What is naproxen used for?
Relief of minor aches and pains in muscles, bones, joints
What is the mech of action of naproxen?
Inhibits COX-1 , COX-2
What are the adverse effects of naproxen? (4)
- Nausea, vomiting
- Peptic ulcer
- GI ulcers
- Bleeding
What is amitriptyline used for?
Neuropathic pain (+depression)
What is the mech of action of amitriptyline?
Inhibits the reuptake of norepinephrine and serotonin (and to lesser extent dopamine) into presynaptic nerve terminals
What are the adverse effects of amitriptyline?
- orthostatic HYPOtension
- anticholinergic effects
When is gabapentin used?
Treats seizures; neuropathic pain
What is the mech of action of gabapentin?
Stimulates influx of chloride ions that interact with the GABA receptor-chloride channel complex —> more GABA in synapse
What are the adverse effects of gabapentin? (7)
- Somnolence** (sleepy, drowsy)
- Dizziness*****
- Ataxia*****
- Fatigue
- Nystagmus
- Weight gain
- Headache
What is the use of hydroxyurea?
for recurrent vaso-occlusive events; frequent painful episodes :(
What is the mech of action of hydroxyurea?
- causes production of RBCs containing fetal hemoglobin. By increasing fetal HbS, RBC sickling & destruction is reduced, and O2 transport throughout body is improved :)
Adverse effects of hydroxyurea include: (6)
- bone marrow suppression (neutropenia, anemia, thrombocytopenia)
- elevation of hepatic enzymes (liver damage)**
- anorexia
- nausea/vomiting**
- hair thin
- darkened nailbeds
What is leukemia?
blood cell cancers; undiff./immature cells…ABRUPT & RAPID!
What is the patho of leukemia? (4) *know general
- Leukemic blasts populate bone marrow
- enter bloodstream
- overcrowd bone marrow
- impede/halt proliferation of other cell lines
*abnormal WBCs (leukemic blasts) fill bone marrow & can spill into blood :0; they “crowd out” bone marrow, & cause cell. proliferation…
What is the difference between leukemia vs lymphoma?
Leukemia: bone marrow
Lymphoma: mainly lumps and bumps in lymph nodes
What is the “Philadelphia Chromosome”? *****
- common genetic abnormality; mitotic error…abnormal 9 & 22 chromosomes
- promotes cell proliferation, decreases sensitivity to apoptosis (cell death)
- leukemic cells pool in blood, liver, spleen, lymph nodes, etc. :(
What are the 2 types of ACUTE Leukemias?*****
ALL: (Acute Lymphocytic Leukemia)
- “L”….”Little ones”….kids.
bone marrow finding: increase in Lymphoblasts
- good survival rate
AML: (Acute Myelogenous Leukemia)
- “M”….grandMa….older folks.
bone marrow finding: increase in Myeloblasts
- low survival rate :(
What are the manifestations seen in AML & ALL?
- BONE PAIN
- fatigue, pallor (anemic)
- bleeding
——> petechiae (pinpoint, round spots that form on skin…caused by bleeding)
——> purpura (small blood vessels leak blood under the skin)
——> ecchymosis (bruises;…blood pools under skin; caused by blood vessel breakage) - infection (b/c less glucosites)
——> mouth, throat, resp. tract, lower colon, UT, skin
——> fever, chills - anorexia, weight loss, can’t really taste sour/sweet things, muscle atrophy, difficulty swallowing
- CNS
——> papilledema (eye swelling), facial palsy (drooping face…weakness/paralysis to one side of face), auditory disturb, meningeal irritation
What is the treatment for AML & ALL?
Bone marrow transplant
chemo/radiation
What is myelosuppression?
- bone marrow suppression;
- consequence of leukemia and treatments! :0
To treat Anemia:
—–> blood products
To treat Neutropenia (lack of neutrophils, a type of WBC):
—–> G-CSF
—–> GM-CSF
A nurse recalls that acute lymphocytic leukemia:
a) is most common in adults
b) has a higher mortality rate in children compared with adults
c) is defined as greater than 30% lymphoblasts in bone marrow
d) is caused by abnormal proliferation of myeloid precursor cells
C
Thrombocythemia is also known as:
Thrombocytosis
The normal platelet range is:
150-400 x 10^9 / L
High or low platelets: Thrombocytopenia?
LOW; decreased platelet production, increased destruction, or both :(
“penia” = LOWWW
Definition: What is thrombocytopenia?
Low platelets; decreased platelet production, increased destruction, or both
may be congenital OR acquired
ex. DIC (disseminated intravascular coagulation)
What are the MAJOR concerns of thrombocytopenia? ***
- more bleeding
- can be fatal if platelets too low/ happens in GI tract, resp tract, or CNS :0
What is thrombocythemia? (thrombocytosis)
HIGH platelet count; because of accelerated platelet production in bone marrow
What is the patho of AML / ALL?
AML:
- malignancy of stem cell precursors of myeloid lineage (RBCs, platelets, & WBCs) (except B and T cells)
- Bone marrow crowding by blast cells produces marrow failure and complications, including
—–> anemia, thrombocytopenia, & neutropenia
ALL:
- bone marrow becomes dense with lymphoblast that replace normal marrow and disrupt normal function
What are the causes of thrombocythemia (thrombocytosis)?
- Primary (essential)
—–> Too many platelets being made b/c of bone marrow defect (genetic defect) - Secondary (reactive)
——> After splenectomy (spleen removal)
no more spleen =no more regulation of blood cells :0
What are the manifestations of thrombocythemia?
Symptoms of microvasculature thrombosis:
—-> warm, congested, RED hands & feet w/ painful burning sensations (erythromelalgia)
———> extreme cases: (acrocyanosis) blue/purple coloured hands/feet; gangrene (turns green/black) maybe :0
- hemorrhage (bleeding and clotting may occur simultaneously) —>DIC!!!
An individual has disseminated intravascular coagulation (DIC). Which pathophysiologic mechanism is occurring?
a) platelet consumption results in thrombocytosis
b) tissue factor is decreased
c) clotting is abnormally widespread and ongoing
d) natural anticoagulants
C
What are the manifestations of DIC?
- Bleeding EVERYWHERE…wounds, eyes, nose, gums, arterial lines, etc.
- SHOCK (hemorrhage)
- Cyanosis in fingers, toes….infarction!
What is DIC?
Disseminated Intravascular Coagulation;
- increase in thrombin —> imbalance between coagulation + fibrinolytic system
