Test 3

Hemoglobin concentration in blood

mean corpuscular hemoglobin concentration. Hypochromic(low Hb) or normochromic

Pale (PBJTDF)
Breathlessness
Jaundice
Tachycardia
Dizziness
Fatigue

1. Lose Blood
2. Destroy too much blood
3. Make too little blood

At first, Hb is normal
After 2-3 days=see lots of reticulocytes (bigger than normal RBCs)

-Intracorpuscular vs. extracorpuscular
AND chronic vs acute

-Signs of destruction= INCREASED bilirubin and LDH BUT DECREASED hepatoglobin

-Signs of production= INCREASED reticulocytes, nucleated RBCs in blood

-Microangiopathic Hemolytic anemia
-Caused by physical trauma to RBCs ---> results in schistocytes =fragments AND triangulocytes (very specific for MAHA)

-usually due to coag pathways and RBCs getting caught in fibrin strands

(AMOST)
-Artificial heart valve
-Malignancy
-Obstetric complications
-Sepsis
-Tauma

EXTRACORPUSCULAR
1. Warm AIHA
-Main Ab: IgG coats cells
-Spleen destroys
-Spherocytes (sphere RBCs) bite cells

2. Cold AIHA
-Main Ab= IgM, complement coat cells
-Intravascular hemolysis
-Agglutination (IgM is big=forms clumps)

DAT for diagnosis

-Sickle Cell Anemia
-Hemoglobinopathy (qualitative defect)
-caused by single AA sub in beta chain
-sickle RBCs are fragile and easily get stuck in vessels (especially in spleen and cause infarct-->scar

-chronic hemolysis
-INCREASE infections due to autosplenectomy
-Tx= vaccinate, transfuse

-INTRACORPUSCULAR
-quantitative defect in Hb
-Cant make enough alpha or beta chains
-causes hypochromic, microcytic anemia w/ INCREASED RBCs and target cells
-some PTs present w/ medullary expansion due to marrow compensation

-INTRACORPUSCULAR
-TONS of spherocytes
-SPECTRIN defects (cytoskeleton prot)
-Splenctomy is curative

INTRACORPUSCULAR
-Decrease G6PD---> INCREASED peroxides----> cell lysis
-oxidant exposure
-bite cells(removal of Heinz bodies)
-self limiting
-Triggers are broad beans (favism), drungs (antiBs, aspirin)

-RBCS cant reduce nasty stuff--> attack Hb bonds --> heme dissociates from globin---> GLOBIN sticks to RBC membrane (HEINZ BODY) ---> spleen bites out heinz body

-Most imp cause=GI Bleed

-RBCs are microcytic, hypochromic
-Atrophic glossitis (no papilla) and Koilonychia (concave nail bed)
-Most common type of anemia

-Infections, inflammation, malignancy
- Fe metabolism disturbed
-normochromic, normocytic (but Hb is decreased in lab test)


-Defective DNA synthesis (NOT RNA) =BIG CELLS
-Nuclear/cytoplasmic asynchrony
- DECREASED B12/folate
-MACROCYTIC & hypersegmented neutrophils
-atrophic glossitis
-DECREASE B12 causes atherosclerosis/thrombosis & neurological damage

-Pancytopenia (reduction of all cells RBCs, WBCs, platlets)
-empty marrow
-asymp

idiopathic, drugs, virus, pregnancy

-Most Neutrophils live in marrow (all maturation stages) and only 5% live in the blood (only segmented)
-Half of blood neutrophils are stuck on vessel walls

-Inflammation and Infection (both in mature and immature)
-Physiologic changes (stress/hormones)

-only in infection
-toxic granulation, dohle bodies, and cytoplasmic vacuolization(BAD)

-Infection (bacterial), inflammation
-severe anemia
-something filling up marrow

TOXIC CHANGES TOO!

-LEFT SHIFT in blood smear

-TCells=80%
-BCells=15
-NK cells=5


Mature & Reactive (funny looking lymphocytes)
-MATURE=
---infectious lymphcytosis
---bordetella pertussis
---trasient stress

REACTIVE
--mono
--ped viral infections
--viral hep
--immune disorders

DOWNEY CELLS

Chronic myeloid leukemia



Drugs, asthma, skin disease, parasites


Infection, autoimmune disease and malignancy

Leukemias
-hematopoietic cells
-starts in marrow-->blood-->nodes
-myeloid or lymphoid
-acute or chronic

Lymphoma
-hematopoietic cells
-starts in LN-->blood-->marrow
-lymphoid only
-hodgkin or non-hodgkin

Acute lymphoblastic leukemia
chromic lymphocytic leukemia
hodgkin lymphoma
non-hodgkin lymphoma
multiple myeloma (plasma cell disorder)

Acute
--sudden onset
--adults or children
--rapidly fatal w/o tx
--immature blast cells

Chronic
--slow onset
--only adults
--longer course
--mature cells

malignant proliferation of imature myeloid or lumphoid cells in the bone marrow

-caused by
---clonal expansion
---maturation failure

what it does?
--crowds out normal cells
--inhibits normal cell fxn
--infiltrates other organs

Clinic findings
--symptoms of bone marrow failure
--fatugue, infection, bleeding
--bone pain (marrow expanding)
--organ infliltration

Lab
--blasts
-leukocytosis (TON of imm WBCs)
-anemia
-thrombocytopenia

-Malignant prolif of myeloid blasts in blood, bone marrow
-dx=20% cells are blasts, AUER RODS (M1-M4)
-MANY Subtypes
-BAD prog.

-acute monoblastic leukemia (can move to oral cavity and brain)


-TX
-chemo & bone marrow xplant

Myelodysplastic syndrome
-dysmyelopoiesis +/- blast cell (pre-cancer predictor)
-MACROCYTIC ANEMIA

Malignant proliferation of LYMPHOID blasts in blood, bone marrow
-classified as B vs T
-Children
-Good prog


T-lineage ALL=bad prog

B-lineage ALL
-- 'B-cell precursor ALL'=better prog
-- B-cell ALL- BAD prog
--Burketts
-- STARRY SKY blood smear


Tx= chemo +/- marrow xplant


Age (1-10)=GOOD
Cytogenetics= hyperdiploidy is GOOD

Malignant proliferation of myeloid cells (not blasts, but maturing cells) in blood, bone marrow

4 disorders:
----Chronic myeloid leukemia-most common and in neutrophils
----polycythemia vera---RBCs
----Essential thrombocythemia-platlet
----myelofibrosis

1. ONLY IN ADULTS
2. long course
3. INCREASED WBC w/ left shift
4. hypercellular marrow
5. big spleen

1. Neutrophilic leukocytosis
2. Basophilia
3. philly chromosome (dyfxnl tyrosine kinase)
4. three phases

Chronic phase
stable counts
easily controlled
3-4 years (w/o therapy)
Accelerated phase
unstable counts
fatal w/in months
Blast crisis
lots of blasts
fatal w/in weeks

tx- imatinib

1. Panmyelosis- ALL myeloid cells proliferate like CRAZY
2. marrow fibrosis
3. extramedullary hematopoiesis
4. teardrop RBCs

1. HIGH RBCs (blood sludge)
2. Different from secondary polycythemia

VERY HIGH platlet count
---LOTS of MEGAKARYOCYTES
2. dift from secondary thrombocythemia

1. Malignant proliferation of lymphocytes in blood, bone marrow
2. CLL most importatnt
3. ONLY ADULTS
4. long course, lingers and incurable

1. Lymphocyte are small, and mature
2. B Cells display CD5+
3. long and relentless

Death usually due to infections

Moss common cause overall= benign reaction to infection
Most common malignant cause= metastic carcinoma

-malignant proliferation of lymphoid cells (blasts or mature) in lymph nodes
-skips around-->metastisis
-MOST ARE B CELLS

-Painless, firm lymphadenopathy
-extranodal manifestations
-'B' symptoms: weight loss, night sweats, fever
-CAN PRESENT IN GINGIVA

Low Grade NHL
-older PTs
-Incurable
-small, mature cells
-non-destructive

HIGH-GRADE NHL
-can occur in children
-Aggresive
-BIG, UGLY cells
-DESTRUCTIVE

LOW-GRADE
-small lymphocytic lymphoma
-malt lymphoma
-follicular lymphoma
-mycosis fungoides

HIGH-GRADE
-large cell lymphoma
-lymphoblastic lymphoma
-burkitt lymphoma

1. Small mature lymphocytes
2. Same thing as CLL
3. CD5+ on B cells
4. Long course, death by infection

-no germinal centers

1. Associated with H. pylori
2. early on can be cured by Antibiotics

1. small cleaved cells, mixed or large
2. t(14;18) - IgH and bcl-2
IgH regulates apoptosis-cell dont die
3. Grade 1, 2 or 3
1=single node 2=2 nodes or more on same side of diaphragm 3=LN on both sides diaphragm 4=extranodal

1. Skin lesions
2. Blood involvement
3. Cerebriform lymphocytes
4. T-CELL IMMUNOPHENOTYPE

1. Large B CELLS
2. Extranodal involvement
3. GRows rapidly=bad prognosis

-typically PTs are Teenage males w/ mediastinal mass
--T=TCell/thymus
-DIFFUSE
-Same as ALL(B-cell lineage)

1. Children and yound adults (blacks)
2. fast growing, extranodal mass
3. STARRY SKY PATTERN
4. SAME AS B-CELL ALL

1. Younger PTs=good prog
2.Reed-sternberg cells!!!


1.Young PTs
2/localized
3. DANGER=Second malignancies --> harder to treat

1. Monoclonal gammopathy-- EXCESS of single Ab
2.Decreased normal Abs
3. osteolytic lesions
4. poker chip plasma cells
Clin features
Weakness, infections, RENAL FAILURE, BONE PAIN, hypercalcemia

Tx=
chemo/radiation
bone marrow xplant

1. Proteins in subendothelium are exposed
2. platelets ahere to to protein
3. Granules release contents
4. Platelets aggregate
5. Phospholipids are exposed
6. TF exposed
7. cascade begins=FIBRIN MADE
8. FIBRIN=solidified plug


FIBRIN

Tissue factor protein 1 (TF1)
Antithrombin 3 (AT3)
Protein C, S


tissue plasminogen activator (t-PA)
plasmin

Intrinsic=
12, 11, 8, 9

Extrinsic= 7


cascade always starts with extrinsic side of cascade and tissue factor (TF)
-turned off immediately by factor Xa



Thrombin is the activator of intrinsic


factor 10

-Hidden in cells
-microparticles floating in blood
-endothelial cells and monocytes (during inflammation)

Factors 8 and 5 are co-factors

factor 8 acts on factor 9 to accelerate response

factor 5 acts on factor 10 to accelerate response

thrombin

activated factor 11

exposed tissue factor

acivated factors 7 -->from extrinsic
AND
activated factor 9-->from intrinsic

activated factor 10

thrombin which leads to CLOT

Plasmin cutting up fibrin protein leaving FDPs

t-PA (tissue plasminogen activator (protein and a drug))

turns off cascade by inactivating cofactors

inactivates factor 7

GOES EVERYWHERE---> inactivates enzymes

HERAPIN potentiates

150-450x10^9

30=thrombocytopenia

granulomere=contains granules

hyalomere=no granules

1.inflate blood pressure cuff
2.make incision
3.time bleeding

1. blood drawn into citrate tube
2. spin, decant plasma,
3. add reagent
4. watch for fibrin formation

Plasma + thromboplastin

MEASURES EXTRINSIC PATHWAY

Increased by
1. decreased in factors 7,10, 5, 2, 1
2. coumadin (affects both sides)
3. heparin
4. disseminated intravascular coag

PT are never ordered, INR instead (corrected PT)

1. To asses liver fxn
2. monitor coumadin therapy
3. diagnose DIC

Plasma + phospholipid
MEASURES INTRISIC (11, 9, 8)

Increased by
Hemophilia A & B
DIC
heparin

1.to investigate history of abnormal bleeding
2. monitor heparin therapy
3. diagnose DIC

Measures FDPs (including D-dimers=specific for clot break down)
VERY VERY sensitive


oder to rule out a clot

factor 13

thrombi and minor clotting

Platelet Bleeding
-Superficial (skin)
-Petechiae
-Spontaneous

Factor Bleeding
-Deep (joints)
- big bleeds
-TRAUMA

Most common HEREDITARY bleeding disorder
-AUTOSOMAL DOMINANT
- vW factor decreased
-made by megs and endo cells
-sticks platlets down on subendothelium
-factor 8 carrier molecule

Symptoms-
Mucosal bleeding
deep joint bleeding in severe cases

Lab tests
prolonged bleeding time
PTT=prolonged
PT-normal

Tx
DDAVP (raises factor 8 and vWF levels)
cryoppt (contains factor 8 and vWF)
factor 8

Hemophilia A= factor 8
" " B= factor 9

-most common hereditary MISSING FACTOR disease
-X-linked recessive (some are spontaneous mutations)

deep joint bleeding/joint deformity

PTT prolonged
Factor 8 levels low

Tx w/ DDAVP
Factor 8 admin

-much less common than A
-x-linked recessive w/ some spontaneous
-same clinical and lab findings as A

-arises from another disease
MOST
malignancy, OB complications, sepsis, trauma
-Widespread activation of coagulation which cause a microthrombi in the circulation
-see a DECREASE in clotting factors AND platelets
-INCREASE in FDPs

Pentad of symptoms:
1. MAHA-microangiopathic hemolytic anemia (causes hematuria/jaundice)
2. thrombocytopenia (bleeding/bruising)
3. fever
4. neurologic defects (thrombi in CNS)
5. renal failure (thrombi in kidney)
DEFICIENCY of ADAMTS13
-vWF multimers trap platlets

Tx: plasmapheresis (in acquired TTP)
plasma infusion (in hereditary TTP)

-caused by MAHA and thrombocytopeia
-related to e. coli infections
-toxins damage endothelium

-Pts make antiplatelet Abs
-SPLENIC MACROPHAGES eat platelets
-dx by exclusion-NO GOOD TESTS
-tx w/ steroids or splenectomy

1. Endothelial damage
-atherosclerosis
2.Stasis
-immobilization
-varicose veins
-cardiac dysfxn
3. Hypercoagulability
-surgery
-carcinoma
-estrogen/postpartum
-thrombotic disorders

1. no obvious cause
2. family hx
3. weird location
4. recurrent
5. pt is young
6. miscarriages

-most common cause of UNEXPLAINED MUTATIONS (point mutation in factor 5 gene)
-FACTOr 5 cant be turned off (cant be cleaved by protein C)
-prot C works to modulate factor 5 & 8

dx: PTT and INR NOT HELPFUL (NEED GENETIC TESTING)
tx: DONT (unless thrombosis-->anticoags)