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Human Organs and Tissues > Peripheral Blood > Flashcards

Peripheral Blood Flashcards

1
Q

What are some (of 9) functions of blood

A
  • Oxygen delivery via RBCs (haemoglobin).
  • Carbon dioxide removal via RBCs and HCO3-
  • Distribute nutrients to cells of the body.
  • Removal of metabolic wastes from cell metabolism.
  • Distribution hormones, signalling molecules, etc.
  • Regulation of body temperature.
  • Buffer body fluids and osmotic balance.
  • Hemostasis (clotting)
  • Immune cell circulation, diapedesis, inflammation and protection.
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2
Q

What is the rough composition of blood

A

about 60:40 plasma to RBCs with some leukocytes also

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3
Q

What are 8 protein factors that are present in the plasma? Which is the most abundant?

A
  1. Albumin (most abundant
  2. a and b globulin
  3. gamma globulin
  4. clotting factors
  5. complement factors
  6. chilomicrons
  7. VLDL
  8. LDL
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4
Q

Which of the protein plasma factors originate in the liver?

A

Albumin, alpha and beta globulin, clotting factors, complement factors, VLDL and LDL

(6/8)

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5
Q

Which of the protein plasma factors originate in the intestinal epithelium?

A

chilomicrons

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6
Q

where does gamma globulin come from?

A

plasma cells

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7
Q

What are the 2 functions of albumin in the plasma?

A

maintenance of osmotic pressure

transport of metabolites and medication

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8
Q

what is function of alpha and beta globulin?

A

transporting metal ions and vitamins

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9
Q

What is the function of chilomicrons in the plasma?

A

Transport of triglycerides from intestine to liver

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10
Q

What is the function of VLDL in the plasma?

A

Transport of triglycerides from liver to body cells

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11
Q

What is the function of LDL in the plasma?

A

transport of cholesterol from the liver to the body cells

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12
Q

what are the 3 cellular blood components ?

A
  • Red cells (most abundant)
  • Platelets
  • White cells
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13
Q

What are the 5 types of white blood cells present in the blood?

A 
– Neutrophils
– Monocytes
– Lymphocytes 
– Eosinophils 
– Basophils
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14
Q

What are the two components that are common to all forms of blood staining? What do they bind to?

A
  1. Azure B (blue) binds to anionic molecules like DNA, RNA and histamine
  2. Eosin Y (pink) and binds to cationic sites of proteins
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15
Q

What is the normal physiology of a red blood cell? (shape, size, normal numbers..)

A
  1. anucleate
  2. biconcave
  3. 6.5 – 8.0 µm in diameter
  4. 3.9 – 6.0 x1012/L normally
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16
Q

What does the diameter of the central pallor of the RBC tell you about the health of a patient?

A

Increase diameter = decreased hemoglobin

- can be important in diagnosing some types of anemia

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17
Q

Why is hemoglobin sequestered in RBCs?

A

because free hemoglobin is toxic to tissues and quickly degraded

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18
Q

What’s the general structure of hemoglobin

A

2 alpha and 2 beta chains, each with a heme group

- each heme group has iron in it

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19
Q

What is the difference in % saturation vs. O2 pressure between myoglobin and hemoglobin?

A

myoglobin is hyperbolic where hemoglobin is sigmoidal

- hemoglobin allows oxygen to be offloaded in tissues where there is a low pressure of O2

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20
Q

What is iron deficiency anemia? what do the RBCs look like?

A

Hemoglobin cannot be made w/o iron so a lack of iron = decreased capacity to carry oxygen

RBCs appear pale and small

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21
Q

What is hereditary spherocytosis?

A

a cytoskeleton structure defect that results in defective attachment of cytoskeleton to cel membrane

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22
Q

What is the results of hereditary spherocytosis?

A

production of spherocytes that get trapped in the spleen and degraded by macrophages to produce further microspherocytes etc.

End up with anemic symptoms

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23
Q

What causes sickle cell anemia?

A

single AA substitution in the ß chain of hemoglobin

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24
Q

What is the pathology of sickle cell anemia?

A

If affected cells stay too long in low O2 area, the hemoglobin will form irreversible long chains

The RBCs then cannot squeeze through the capillaries and start sticking to the vessel walls and to each other and clogging up blood vessels. This is called a sickle cell crisis

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25
Q

Where do platelets come from?

A

cytoplasmic fragments of megakaryocytes

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26
Q

How big are platelets? How many do we normally have?

A
  • Number in health: 150-400x109/L

* Size 2-4 mm

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27
Q

What are the 5 platelet receptors used for activation?

A
  1. GPIbIX receptors, attachment to vWF
  2. GPIIbIIIa receptors, attachment to fibrin
  3. ADP receptors (P2Y12)
  4. Thrombin receptors (PAR1/4)
  5. Thromboxane A2 receptor
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28
Q

What is in the electron dense delta granules of the platelets?

A

nucleotides (ADP) and Ca++

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29
Q

What is the in specific alpha granules of the platelets?

A

fibrinogen, factor V, and von Willebrand Factor

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30
Q

What receptor does von Willebrand Factor bind to on the platelet? why is this functionally useful?

A

GPIbIX

allows the platelet to adhere to the site of vessel injury by binding both the vWF and sub-endothelial collagen to start clot formation

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31
Q

What happens after the platelet binds vWf and sub-endothelial collagen?

A

Platelets become activated and aggregate to seal the site of vessel injury.

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32
Q

What structural feature of the surface of platelets allows for activation of clot forming factors and formation of fibrin clot?

A

phospholipids

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33
Q

What do the platelets bind to form a stable clot? with what receptor?

A

Bind fibrin via the GPIIbIIIa receptor to form a stable clot

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34
Q

What is present in high levels in a normal blood vessel that prevents clotting?

A

cAMP/GMP

PGI2, NO (produced by endothelial cells)

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35
Q

What happens when there is damage to the endothelium?

A

collagen and vWf are exposed and bind to thrombin which is a platelet activator

TxA2 and ADP are produced
- activates platelets?

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36
Q

What 2 drugs prevent platelet aggregation? How?

A

Asprin blocks TxA2 production

Plavix blocks P2Y12 receptor activation by ADP

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37
Q

What does the coagulation cascade result in?

A

generation of a fibrin clot

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38
Q

What is the amplification step in the coagulation cascade?

A

FII (thrombin) acts to amplify factors in the pathway before it
- increases FXa, itself, and ultimately Fibrin

39
Q

Hemophilia is what kind of disorder?

A

X linked recessive

- mainly affects men

40
Q

What are the two types of hemophilia? what is each one a deficiency in?

A

Hemophilia A - FVIII (8) deficiency

Hemophilia B - FIX deficiency

41
Q

Which of the types of hemophilia is more common?

A

Hemophilia A (85%)

42
Q

What is the incidence of hemophilia?

A

1/5000 males

43
Q

what is the correlation between level of factor and disease prognosis

A

strong association

the more factor you have, the less sever the hemophilia

44
Q

What are the 3 granulocytes?

A

Neutrophils
Eosinophils
Basophils

45
Q

How do you differentiate between granulocytes?

A

Based on staining pattern of granules

46
Q

Which are the most abundant granulocytes?

A

Neutrophils

47
Q

Where are neutrophils produced? How long do they circulate? how long do they last in tissues?

A
  • Produced in the bone marrow.
  • Circulate for 7-10 hours.
  • Migrate into tissues (die within 48h).
48
Q

What are 4 morphological features of neutrophils?

A
  1. Segmented nucleus (3-4 generally)
  2. Barr body present sometimes (inactivated X chromosome in females)
  3. Primary (dark, purple) granules
  4. Secondary (small, orange/pink) granules
49
Q

How big are neutrophils approx?

A

13 µm

50
Q

How abundant are neutrophils?

A

Most abundant WBC
- 50-70%

2.0 – 8.0 x109/L

51
Q

What are 3 things in the 1º granules of neutrophils?

A

Lysozyme
Hydrolytic enzymes
Myeloperoxidase

52
Q

What are 2 things in 2º granules of neutrophils?

A

Defensins

Lysozyme

53
Q

What are defensins?

A

Short cationic peptides that insert into bacterial cell membranes and create pores

54
Q

What type of killing occurs in 2º granules?

A

oxygen independent

55
Q

What are 3 mediators of oxygen dependent killing in neutrophils? what do they produce?

A
  1. NADPH oxidase - produces superoxide (O2-)
  2. Myeloperoxidase - produces ClO-
  3. Nitric oxide synthase - produces NO
56
Q

What causes chronic granulomatous diseases (CGD) ?

A

deficiency in phagocyte NADPH oxidase

57
Q

What is the pathology of CGD?

A

dysfunctional killing of bacterial and fungal organisms by neutrophils.

• Patients suffer from recurrent bacterial and fungal infections.

58
Q

What is the main treatment for CGD?

A

bone marrow transplant

59
Q

What integrin on the surface of neutrophils interacts with Ig-superfamily CAMs to mediate arrest during migration?

A

LFA-1

60
Q

What 2 things mediate rolling during neutrophil migration?

A

Mucin like CAMs on the neutrophil that interact with E-selectin on the endothelium of blood vessels

61
Q

What is the cause of Leukocyte Adhesion Deficiency (LAD)?

A

deficiency of Leukocyte Function- Associated Antigen (LFA)-1 integrin.

inability of neutrophils to transmigrate from blood to tissues.

62
Q

what is the prognosis for someone with LAD? why?

A

Most patients with severe LAD die when younger than 1 year. Bacterial infections are responsible for most deaths.

63
Q

What are 2 morphological features of Eosinophils?

A
  1. Segmented nucleus (2 lobes)

2. Spherical pink/orange granules (eosinophilic granules).

64
Q

What is the approximate size/number/% of Eosinophils

A

• Size: approximately 12-17 mm in diameter.
• Number: 0.1 – 1.0 x109/L
-<1% of white cells

65
Q

What are 2 functions of Eosinophils?

A
  1. Antiparasitic function

2. Allergic response

66
Q

What protein is unique to Eosinophils?

A

anti-parasite protein called eosinophil cationic protein (ECP)

67
Q

What kinds of enzymes do Eosinophils have?

A

lysosomal and oxygen-radical generation enzymes similar to neutrophils and monocytes

68
Q

What are two morphological features of Basophils?

A

– segmented nucleus (2 nuclear lobes).

– Spherical purple granules (basophilic granules).

69
Q

What is the approximate size/number/% of Basophils

A

• Size: approximately 12-17 mm in diameter.
• Number: 0.1 – 0.2 x109/L
-<1% of white cells

70
Q

What are 2 functions of Basophils?

A
  • Back up mast cell responses during inflammation

* Also involved in allergic reactions

71
Q

What are 3 morphological features of Monocytes?

A
  1. Horse shoe nucleus
  2. Bluish grey cytoplasm often vacuolated.
  3. Variable number of fine reddish granules.
72
Q

How long do monocytes circulate in the blood for

A

around 8 hours

73
Q

What are 4 functions o monocytes/macrophages?

A

• Phagocytosis of microorganisms
• Killing of ingested microorganisms – Oxygen dependent
– Oxygen independent

Macrophage only:
• Recruitment of immune system cells into inflammatory site
– Secrete cytokines and chemokines
• Present antigen to T cells

74
Q

What 4 changes occur when a monocyte differentiates into a macrophage?

A
  1. Increase in size (5-10 fold)
  2. Increased numbers and complexity of organelles
  3. Increased phagocytic activity
  4. Increased levels of hydrolytic enzymes
75
Q

What are the 2 anaphylatoxins generated by the complement cascade?

A

C3a and C5a

76
Q

What is the main opsonin of the complement pathway?

A

C3b

77
Q

What forms pores in bacterial cell membranes?

A

the MAC, (C5-C9)

78
Q

What 3 features prevent host cells from being destroyed by the complement cascade?

A
  1. Complement activation and effector function is inactivated by host cell receptors.
  2. decay accelerating factor (DAF; CD55), inhibits formation of C3 convertase.
  3. membrane inhibitor of reactive lysis (MIRL; CD59), inhibits MAC assembly.
79
Q

the classical pathway is activated by..?

A

antigen antibody complexes

80
Q

the lectin pathway is activated by?

A

microbial cell wall binding mannose binding lectin

81
Q

the alternative pathway is activated by?

A

microbial cell surfaces

82
Q

What do C3 and C5 convertase do?

A

split C3 into C3a and C3b and C5 into C5a and C5b

83
Q

What is Paroxysmal Nocturnal Hemoglobinuria?

A

Intravascular hemolysis due to CD55 and CD59 being absent on RBCs, leaving them susceptible to complement

84
Q

What are some symptoms of PNH?

A

blood in urine and renal failure

↓ NO endothelium, thrombosis and pulmonary hypertension –> ultimately leading to heart failure

acute leukemia

85
Q

What are the 2 drugs used to treat Paroxysmal Nocturnal Hemoglobinuria (PNH)?

A

anti-C5 mAb, Eculizumab

86
Q

What is the approximate CD4 to CD8 ratio?

A

CD4:CD8 = 2:1

87
Q

T cells make up __% of lymphocytes?

A

70-80

88
Q

B cells make up __ % of lymphocytes?

A

10-20

89
Q

NK cells make up __ % of lymphocytes

A

5-10

90
Q

What is the morphology of naive (quiescent) lymphocytes?

A
  • Round nucleus (size of red cells)
  • Small rim of blue cytoplasm
  • Size: 9 mm in diameter
91
Q

What is the morphology of large granular lymphocytes?

A
  • Larger cell
  • More abundant cytoplasm
  • Large granules containing perforin and grenzyme
92
Q

What is the % of WBCs that are lymphocytes?

A

20-40 %

93
Q

What are 2 areas where a defect can result in SCID?

A

– IL-2g receptor subunit

– recombination activating gene, RAG-1 or RAG-2.

Human Organs and Tissues (16 decks)

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