Histology

Question 1

Plasma proteins

Answer 1

7% plasma
1. Albumin: most abundant
A. Retain fluid in micro vasculature
B. Binds molecules for transport
2. Globulins: large family (alpha and beta)
A. Transport lipids and metals
B. Involved in coagulation
3. Fibrinogen: non-active precursor of fibrin
4. Immunoglobulins (gamma-globulins): antibodies secreted by plasma cells
5. Complement proteins: part of innate immune system
6. Regulatory proteins: enzymes, pro enzymes, and hormones

Question 2

Plasma solutes

Answer 2

1. Proteins
2. Nutrients and metabolites
3. Minerals and electrolytes
   A. Establish and maintain membrane potentials
   B. pH balance
   C. Regulate osmosis
4. Dissolved respiratory gases
   A. O2 - 98% on hemoglobin
   B. CO2
   
   1. 66% bicarbonate
   2. 27% on hemoglobin
5. Waste

Question 3

Serum

Answer 3

Plasma after blood clots

Question 4

Erythrocytes

Answer 4

44% of whole blood
1. Transport O2 and CO2
2. No mito => only anaerobic glycolysis
3. Anuclear
4. Plasmolemma
  A. 40% lipids, 10% carbs, 50% proteins
  B. Peripheral and integral proteins anchor cytoskeleton proteins
  C. Blood type antigens on extracellular surface
5. Hemoglobin

Question 5

Hemoglobin

Answer 5

Tetrameric protein

1. Carries O2 and CO2 at different binding sites
2. Low pO2 and high pCO2 -> high carbonic acid => low pH
3. High pO2 and low pCO2 -> inc pH
4. CO competes for O2 site and has higher affinity

Question 6

Platelets

Answer 6

Promote clotting and healing
1. Anucleate 
2. From megakaryocytes in red marrow (fragments)
3. Circulate ~10 days
4. Sparse mitochondria
5. Granules in inner cytoplasm
6. Outer cytoplasm facilitates rapid degranulation
  A. Marginal bundles (MB)
  B. Open canalicular system (OCS)

Question 7

Platelet granules

Answer 7

In inner cytoplasm

1. Alpha granules: platelet specific proteins (PDGF, PF-4)
2. Delta granules: contain ADP, ATP, and serotonin taken up from plasma
3. Glycogen granules

Question 8

Clotting

Answer 8

1. Primary aggregation: glycocalx allows platelets to adhere damaged endothelium/CT -> platelet plug
2. Secondary aggregation: platelets in plug -> adhesive glycoprotein and ADP -> more aggregation
3. Blood coagulation: proteins from endothelium and PF-4 from alpha granules -> cascade plasma proteins
4. Clot retraction: clot contracts due to platelet-derived actin and myosin
5. Clot removal: plasminogen (proteolytic enzyme)

Question 9

Granulocytes

Answer 9

Innate immune cells
1. All
  A. Lysosome (azurophilic) granules
  B. Polymorphic nuclei (lobed)
  C. Poorly developed golgi and RER
  D. Few mito
  E. Short life span
2. Neutrophils (50-70% circ. WBCs)
3. Eosinophils (1-4% WBCs)
4. Basophils (least common WBC)

Question 10

Neutrophils

Answer 10

Granulocyte
1. 50-70% WBCs
2. 1st line of defense
3. Nucleus 2-5 lobes
4. Specific granules - stain light pink
  A. ECM-degrading enzymes and bacteriocidal
  B. Glycogen granules used in anaerobic glycolysis
5. Form pus at wound/infection sites

Question 11

Eosinophils

Answer 11

Granulocyte
1. 1-4% WBCs
2. Allergies and parasites
3. Bi-lobed nucleus
4. Specific granules pink/red
  A. Major basic proteins (MBP)
  B. Eosinophilic peroxidase
  C. Antiparasitic enzymes and toxins
5. Functional characteristics
  A. Modulate inflammatory response (allergies)
  B. Parasitic infections

Question 12

Basophils

Answer 12

Granulocyte
1. Least common WBC
2. Bi-lobed/S-shaped nuclei
  A. Often obscured by granules
3. Specific granules - stain purple
  A. Heparin
  B. GAGs
  C. Histamines
  D. PAF
4. Fxn
  A. Mediate inflammation
  B. Allergies (type I hypersensitivity - acquired)

Question 13

Agranulocytes

Answer 13

Adaptive immune cells
1. All
  A. Lysosome (azurophilic) granules
  B. No specific granules
  C. Nuclei not lobed
  D. Circulate undifferentiated 
  E. Life span hours to years
2. Lymphocytes (20-40% WBCs)
3. Monocytes (2-8% WBCs)

Question 14

Lymphocytes

Answer 14

Agranulocytes
1. 20-40% WBCs
2. Smallest WBCs
3. Cluster of differentiation (CD markers)
A. B lymphocytes
B. T lymphocytes
C. NK cells (innate)
4. Nucleus spherical (sometimes dented if large)
5. Thin ring of cytoplasm
6. Can’t differentiate B/T on smear w/o special staining

Question 15

Monocytes

Answer 15

Agranulocytes
1. 2-8% WBCs
2. Antigen presenting cells (APCs)
3. Give rise to cells outside circulatory system
  A. Macrophages
  B. Osteoclasts
  C. Microglia
  D. Mononuclear phagocyte system
4. Nucleus indented or C-shaped 
5. Basophils cytoplasm
6. Very small azurophilic granules

Question 16

Leukocyte extravasion (diapedesis)

Answer 16

1. In post-capillary venules
2. Activated macrophages -> IL-1/TNF-alpha -> endothelial cells in venules insert glycoprotein selectins in cell surface
3. Neutrophils w/ correct glycoprotein stick to selectins as they pass and roll to slow down
4. Cytokines. -> integrins on neutrophils and integrin ligand ICAM-1 on endothelial cells inhibit junction always complexes between endothelial cells => loosened
5. Integrins stop neutrophils on endothelial surface -> receive more signals
6. Mobile neutrophils probe endothelium w/ pseudopodia and follow chemokines to work to wound/infected site
7. Activated in ECM outside of circulation

Question 17

Hematopoiesis

Answer 17

Formation of all blood cells

Question 18

Hematopoiesis sites

Answer 18

1. First trimester: mesodermal yolk sac
2. Second trimester: mostly liver, some spleen
3. Third trimester thru life: red bone marrow
4. Childhood thru early adulthood: most bones
5. 30+: mostly vertebral bodies, sternum, and ribs
6. Ileum/iliac crests: common for collecting samples

Question 19

Red bone marrow

Answer 19

1. Hematopoietic cords: hematopoietic cell lines, maturing cells, and more
2. Reticular tissue: supportive mesh work for hemopoeitic cords
3. Sinusoid always capillaries: bid gaps lined by discontinuous endothelium
4. Adipocytes: amount varies, inc w/ age

Question 20

Hemopoietic stem cell

Answer 20

1. Rare w/in red marrow
2. Proliferate slowly
3. Pluripotent stem cell
4. Randomly differentiate -> progenitor cells
   A. Common myeloid progenitor (CMP)
   B. Common lymphoid progenitor (CLP)

Question 21

Pluripotent stem cell

Answer 21

Can differentiate into any blood cell or contribute to cellular regeneration

Question 22

Erythorporesis

Answer 22

1. MEP (or CMP) -> proerythroblast
  A. Driven by EPO
  B. Large nucleus w/ mottled staining
  C. Cytoplasm stains basophilic (blue)
  D. Fxn: make mRNA and polyribosomes -> Hb
2. Maturation
  A. Dec nucleus as mRNA production dec
  B. Cytoplasm -> eosinophilic as inc Hb and dec polyribosomes
3. Reticulocytes: immature but functional
  A. Form when pyknotic nucleus ejected
  B. Still some polyribosomes
4. RBCs pushed -> sinusoidal capillaries

Question 23

Thrombopoiesis

Answer 23

1. MEP (or CMP) -> megakaryoblast
  A. Driven by TPO
  B. Large, ovoid nucleus w/ mottoes staining
  C. Cytoplasm stains basophilic
  D. Fxn: inc mRNA -> protein synthesis
2. Promegakaryoblast = megakaryoblast often multiple rounds endomitosis
  A. Polyploid (8N to 64N)
  B. Lobular nuclei
  C. Larger than megakaryoblast
  D. Cytoplasm less intensely basophilic
3. Megakaryocyte
  A. Irregularly lobed nucleus
  B. Well-dev golgi and RER needed to produce specific granules and platelets
  C. Near sinusoidal capillaries
  D. Fragment -> platelets into circ

Question 24

Granulooiesis

Answer 24

1. Granulocytic progenitor cell and myeloblast
   A. Driven by G-CSF
   B. Uniformly stained nucleus w/ faint nucleoli
   C. Cytoplasm slightly basophilic
   D. No granules
   E. Type granulocyte indistinguishable
2. Promyelocyte
   A. Golgi and RER active
   B. Azurophilic granules accumulate
3. Myelocyte -> metamyelocyte
   A. Specific granules produced and accumulate
   B. Specific granulocytes distinguishable
4. Band stage: intermediate stage
   A. Nucleus not in polymorphic shape

Question 25

Neutrophils compartments

Answer 25

``` 1. Bone marrow A. Mitosis 1. Stem cell 2. Myeloblast 3. Promyelocyte 4. Myelocyte B. Maturation 1. Metamyelocyte 2. Band cell 3. Mature granulocyte C. Storage 2. Blood A. Marginal cells: bind to endothelium B. Circulating cells ```

Question 26

Monocytopoiesis

Answer 26

1. Monocytes progenitor (MoP) and monoblasts A. Driven by M-CSF B. Indistinguishable from granulocytic myeloblast 2. Promonocyte: difficult to find and distinguish A. Nucleus slightly indented B. Cytoplasm slightly basophilic 3. Monocyte A. Nucleus more indented/C-shaped B. Azurophilic granules accumulate C. Enter sinusoidal sinuses -> body D. Differentiate further to be tissue specific

Question 27

Lymphopoiesis

Answer 27

1. CLP -> lymphoblast A. Several specific transcription factors B. Slightly larger than lymphocyte 2. Immature lymphocyte A. Nucleus condensed B. Thin ring basophilic cytoplasm C. Can’t distinguish different lymphocytes w/o special staining 1. Immature T cells -> thymus 2. Immature B cells -> marrow 3. Immature NK cells -> marrow or secondary lymphoid organs

Question 28

APCs

Answer 28

1. Monocyte derives: transient residents in tissues 2. Dendritic cells: permanent residents in non-lymphoid tissues 3. Follicular dendritic cells A. In lymphoid organs B. Present antigens to B cells C. Derived from mesenchyme D. Don’t express MHC 4. Thymus epithelial cells: endoderm derived epithelium in thymus A. Express MHC I and/or II

Question 29

Primary lymphoid organs

Answer 29

Sites of adult lymphocyte production, differentiation, and maturation (not activation) 1. Bone marrow 2. Thymus

Question 30

Thymus

Answer 30

Primary lymphoid organ 1. T cells 2. From 3rd pharyngeal pouch 3. Fxnal at birth, dec w/ age 4. Histological characteristics A. Outer capsule = vascularized CT separated into lobes B. Cortex: many lymphocytes/blasts 1. Thymic epithelial cells A. Type I: squamous, lines CT and contributes blood-thymus barrier B. Type II: act as APCs (T cells that bind -> medulla) C. Type III: squamous 1. Separate cortex and medulla 2. Express MHC I and II C. Medulla- lighter staining 1. Type IV: similar type III in cortex 2. Type V: cytoreticular framework to support T cells, DC, and macrophages (if attack self -> apoptosis) 3. Type VI: Hassall corpuscles (secrete cytokines)

Question 31

Secondary lymphoid organs

Answer 31

Where B/T cells activated 1. MALT (mucosa associated lymphoid tissues) 2. Lymph nodes 3. Spleen

Question 32

MALT

Answer 32

1. Mucosa of GI, resp, and UG systems 2. Lymphoid nodule (LN): localized concentrations lymphatic tissue, mostly T and B cells A. Primary nodule: no immune response B. Secondary nodule: 1. Germinal center: active B cell response 2. Mantle zone (corona): mostly T cells

Question 33

Lymph nodes

Answer 33

1. Capsule w/ trabeculae 2. Cortex (superficial) A. Subcapsular and cortical sinuses B. Lymphoid nodules 3. Paracortex (deep) A. Cortical sinuses B. High endothelial venules (HEVs) 4. Medulla A. Medullary sinuses B. Medullary cords 5. Fxn: A. APCs/active lymphocytes -> lymph nodes 1. Blood stream via HEV (90% all cells) 2. Lymph via afferent vessels (10% cells) B. Migrate -> lymphoid nodules in cortex C. Initiate immune response D. Lymph fluid and cells excite lymph nodes thru medullary sinuses that drain -> efferent lymphatic vessels

Question 34

Spleen

Answer 34

``` 1. Fxn: A. Filter effete RBCs B. Site immune response C. Reservoir blood D. Fetal hematopoiesis 2. Histological characteristics A. Capsule w/ trabeculae B. Splenic pulp 1. White (20%) A. Central arteriole B. Periarteriolar lymphoid sheath (PAL) C. Transient lymphoid nodules 2. Red (80%) A. Penicillar arterioles B. Splenic sinuses C. Splenic cords ```