Haematology PATHO Flashcards
What is the composition of blood after centrifuge separation
45% Cellular (RBC)
1% Buffy coat (leukocytes (WBC), platelets)
55% Plasma (90% water,
10% solutes (albumin, globulins, clotting factors, electrolytes)
List the functions of blood
Gas exchange (Co2, O2)
nutrient and waste transport
acid-base balance
thermoregulation
haemodynamic stability
hemostasis (blood clotting)
immune system
Endocrine system
Most abundant blood cell and function
Erythrocytes (RBC)
45% of blood
oxygen, carbon dioxide
iron store
acid-base balance
Most abundant blood protein and function
Albumin
oncotic pressure
drug transportation
Types of blood proteins and function
Albumin
- oncotic pressure
- drug transport
Immunoglobulins
- IgM (innate), IgG (adaptive), IgE (parasite/hypersensitivity), IgA (secretory)
Clotting factors
- Fibrinogen - cross link platelet plug
Anuclear blood cell
RBC
- no nucleus
- no organelles
- no mitochondrea
- heme ring
- flexible disc shape
- lifespan 120 days
Cellular fragments in blood
Platelets
- cellular fragments
- originate from megakaryocytes in the bone marrow
Two types of leukocytes
- Granular (Granulocytes)
- eosinophils (parasitic, hypersensitivity reactions)
- basophils (allergic reactions)
- neutrophils (first responders innate immunity)
- granules of histamine, degranulate during immune response
- Agranulocytes
- B cells (plasma cells, produce immunoglobulins, adaptive humoral immunity)
- T Cells (helper T cells, killer T cells, adaptive cellular immunity)
- NK Cells (innate immune response)
Immature blood cells are called
BLASTS
myeloblasts
erythroblasts
megakaryoblasts
lymphoblasts
- not usually found in circulation, unless pathology exists
Ex. immature neutrophils, neutroblasts will be released by bone marrow if system is overwhelmed by infection or inflammation, left shift
Mature blood cells are called
Cytes
erythrocytes
thrombocytes
megakaryocytes
lymphocytes
Function of cytokines
Cytokines are signal molecules, promote cellular development
Types of cytokine signals
autocrine - same cell
paracrine - neighbour cell
endocrine - far away organ/cell
Haematopoetic cytokines
Granulocyte colony stimulating factor (G-CSF)
- platelets
- neutrophils
Granulocyte macrophage colony stimulating factor (GM-CSF)
Myeloblasts (neutrophils, basophils, eosinophils, monocytes)
erythropoetin (EPO)
erythrocytes
thrombopoetin (TPO)
thrombocytes
IL-11
platelets
IL3,9, G-CSF, GM-CSF
myeloid stem cells (precursor of both myeloblasts, lymphoblasts)
IL1
Erythroblasts
IL3
myeloblasts - granulocytes
IL5,6
lymphoblasts - B cells
IL7
lymphoblasts - T Cells
Differential diagnosis elevated WBC?
Neutrophils
- acute inflammation
- acute infection
basophils
- type I hypersensitivity reaction (asthma, allergies)
- release cytokines IL which activate plasma cells to secrete IgE
eosinophils
- phagocytize IgE-antigen complexes
- parasite reaction
- type I hypersensitivity reaction
Elevated BLASTS
- cancer?
Neutropenia
Low neutrophil
< 500
immunocompromised
Prevention platelet activation
Prostaglandins released by endothelial cells prevent platelet activation
PGI2
Promotion platelet activation
- collagen
- ADP
- PAF, platelet activating factor
- thrombin
- activaiton of IIb/IIIa receptor
- binds to fibrinogen creating cross links and platelet plug
- also binds clotting factors VWF, IX, V
Activated platelet form
- sticky
- flat
- adhere to ECM
- release 1. dense bodies (ADP, calcium, serotonin), 2. alpha granules (fibrinogen, V)
- promotes cross linking
- attracts more platelets
RBC structure
2 alpha, 2 beta polypeptides
4 protoporphyrin rings
4 heme groups
4 iron (Fe2+ unbound by oxygen)
Where is majority of the bodies iron stored?
Erythrocytes 70%
ferritin stores liver
Where is heme broken down?
heme broken down to bilirubin
recycled in liver
glucuronate attached and excreted in urine or feces
Function of folate
purine DNA/RNA synthesis
closure of neural tube during pregnancy
Types of anemia
- macrocytic anemia
- microcytic anemia
- anemia chronic disease (normocytic anemia)
Function of vitamin B12
myelination of nerves
low vitamin B12 - demyelination and spasticity
Function of Iron
carrier of oxygen in the RBC
GI malabsorption can lead to anemia
Examples
alcoholism
drugs
crohn’s disease
UC disease
short bowel
etc.
Laboratory findings of iron deficiency anemia
low RBC
low hemoglobin
low serum iron
low ferritin
high transferrin binding capacity
low MCV < 80
low MCHC (hypochromic)
laboratory findings of folic acid deficient anemia
low RBC
low hemoglobin
high MCV > 100 (macrocytic)
normal MCHC (normochromic)
low serum folate
high homocysteine
low or normal Vitamin B12 (needed for folate activation)
Laboratory findings of vitamin B12 deficient anemia
low RBC
low hemoglobin
high MCV > 100
normal MCHC
low serum vitamin B12
high methylmalonic acid level
normal or low folate
normal, low, or no intrinsic factor
laboratory findings of anemia of chronic disease
low RBC
low hemoglobin
normal or high iron
normal MCV
normal MCHC
or low MCV, low MCHC
Cause of anemia for chronic disease
low RBC production
low RBC lifespan
increase demand RBC
3 systems involved in hemostasis
- vasculature - vasoconstriction
- platelets - platelet activation, adhesion, aggregation, platelet plug
- coagulation factors - coagulation cascade (intrinsic, extrinsic, common), and fibrin clot formation
4 events of hemostasis
PRIMARY HEMOSTASIS
1. vasoconstriction VSM - serotonin, histamine, calcium
- platelet plug formation
- activation, adhesion, aggregation
SECONDARY HEMOSTASIS
3. coagulation cascade and fibrin clot formation
- intrinsic, extrinsic, common
- prothrombinase complex
- clot dissolution
- TPA (Tissue plasminogen activator)
- APC (activated protein C) and protein S
- Anti-thrombin and endogenous heparin
Platelet activation
ADP
TXA2
Collagen
thrombin (IIa)
PAF
Inhibition of platelet activation
PGI2
prostaglandin I2
Platelet adhesion
“glue” = von willebrand factor VWF
binds GPIb receptor
activates platelets
results in expression of IIb/IIIa receptors
leads to platelet release reaction
alpha granules - fibrinogen, V (VWF)
dense bodies - serotonin, calcium, ADP
Platelet aggregation
cross linking of platelets via fibrinogen mesh
VWF + GPIIa/IIIb + Fibrinogen
3 phases of Secondary hemostasis
formation fibrin through intrinsic/extrinsic coagulation cascade
- initiation
- amplification
- propagation
Fibrin clot formation
Common pathway
X –> Xa
II –> IIa (thrombin)
Fibrinogen –> Fibrin
XIII stabilizes fibrin
Coagulation cascade extrinsic pathway
Tissue factor VII –> VIIa
X –> Xa
IX –> IXa
Xa
II –> IIa
Fibrinogen –> FIbrin
*Tissue factor activates both the X and the IX
Coagulation cascade intrinsic pathway
XII –> XIIa
XI –> XIa
IX –> IXa
X –> Xa
II -> IIa
fibrinogen –> Fibrin
endogenous to the blood vessels
Propagation and amplification
IIa
activates IX
activates V
activates VIII
VII
activates IX
Drug that inhibits intrinsic pathway
Heparin
binds and activates anti-thrombin
anti-thrombin binds clotting factors
X, II (thrombin) - common pathway
XII, XI, IX - intrinsic pathway
measure aPTT
activated partial thromboplastin time
Drug that inhibits extrinsic pathway
warfarin
inhibits formation of vitamin K dependent coagulation factors - IX , X, VII, II
extrinsic pathway
measured with INR (prothrombin time)
Inhibition of coagulation
natural physiology
anti-thrombin
- made by liver
- circulation 2-3 days
- binds heparin
- binds to coagulation factors XII, IX, IX, X, II
Thrombomodulin + Activated protein C + protein S
- binds and inactivates V, VIII
TPA
- tissue plasminogen activator
- breakdown of fibrin to D Dimers
Virchows Triad
- injury - endothelial
- hypercoagulation state
- stasis - blood flow
Why does inflammation promote coagulation?
CK
creatine kinase
blocks anti-thrombin, thrombomodulin, activated protein C and protein S
results in decrease in fibrinolysis
