CCNM: Physiology 1: hematology and CBC Flashcards Preview

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Intercellular connections:

1. Connections that are STRUCTURAL
Refer to figure2-8

Cellular Adhesion Molecules (CAMs): allow cells to bind to BM and each other

Integrins - cell to cell & cell to BM (basal membrane), bind to receptors
IgG superfamily - membrane bound immunoglobins
Cadherins - calcium dependent molecules that mediate cell to cell adhesion
Selectins - lectin-like binding domains that bind carbs


Note - pages 35 - 42 description of basic cell molecule (i.e. mitochondria)

Molecular motors: (some basic info)

Kinesin - move to (+) end of microtubule

Dynein - move to (-) end of microtubule

Myosin - binds to actin in muscle production motion



Tight Junctions

Aka zonula occludens
Surround APICAL margin of epithelial cells
Permit passage of some small molecules and ions between cells: Paracellular pathway
Prevent movement of cellular proteins
Ridges composed mostly of: occludin, claudin, and JAMs (junctional adhesion molecule)

Disruption is associated with changes in intercellular permeability of tight junction
i.e. infectious diarrhea, renal disorders, dermatological disorders, BBB disruption


Zonula Adherens

Located basal to tight junctions
Aka belt desmosome
Function: Associate cell skeletons of adjacent cells, therefore structurally link cells for stability



Function: anchor basal surface of cells to basal lamina (like sticky shoes)
Focal adhesions are similar but, but much more dynamic
-assist in cellular movement
-provide info to cell about extra cellular matrix (ECM)
-proteins assemble/disassemble regularly


Gap Junction

Dodecameric channels
-6 from each cell
Each unit called a connexin, 6 connexins = connexon
Function: Allows for intercellular communication (yay), and passage of ions/small molecules between cells without having to enter ECM (like living in residence... You can go from home to school without even stepping outside)


Leukocyte Extravasation
(leukocyte rolling)

-RBCs are fast flowing and WBCs (leukocytes) roll along the endothelial cells nice and slow

-P-selectins on endothelial cells interact with PSGL -1on leukocyte
* leukocytes are able to roll because existing interactions are broken and new ones form
-Oh no, inflammation!
-Inflamed endothelial cells: 1 upregulate P-selectins (increases p-selectin-PGSL-1 interactions therefore neutrophil slows even more) and 2 secrete IL-8 which remain at the periphery of these cells
-IL-8 on endothelial cell binds with chemokine receptor (Rc) on leukocyte. This causes a cascade of signalling, initaiated by a G-protein associated with chemokine Rc, within the leukocyte.
-This activates the integrin - conformational change in integrin allows for binding with iCAM on inflamed endothelial cell. These strong interactions allow leukocyte to fully adhere to cell surface.
-integrin signalling and chemokine exposure cause a reorganization of leukocyte cytoskeleton and a change in cell morphology.
The leukocyte can now insert itself between two endothelial cells and squeeze through to the surrounding inflamed connective tissue. This is called Transendothelial Migration.


1. Message transmission, 2. local or general and 3. specificity depends on:

GAP JUNCTION: cell to cell, local and anatomical location
SYNAPTIC: across synaptic cleft, local, and anatomical location AND Rc
AUTOCRINE/PARACRINE: by diffusion in interstitial tissue, local, and Rc
ENDOCRINE: by circulating body fluids, general and Rc

Describe the four main types of Receptors:

A) Channel-linked Rc - signal binds and causes conformational change that allows it to open/close
B) Enzyme-linked Rc - same as above but instead of open/close, it activates enzyme and generates a product
C) G-protein coupled Rc -signal binds to Rc and g-protein binds to Rc, g- protein gets activated
D) intercellular Rc - signal diffuses through cell membrane and binds to Rc, and activates it


Describe the our main ways that receptors are regulated:
Regulation of gating in ion channels:

A) Ligand-gated channels open in response to ligand binding
B) Phosphorylation-gated channels: protein phosphorylation or dephosphorylation regulate opening/closing
C) Voltage-gated: changes in membrane potential alter channel openings
D) Stretch or pressure-gated: mechanical stretch of the membranes result in channel openings

Na, K ATPase:
Catalyzes the hydrolysis of ATP to ADP and uses the energy to extrude 3 Na+ from the cell and take two K+ in the cell for each ATP molecule hydrolyzed.
An electrogenic pump: Three (+) charges out of the cell for two (+) charges that go in the cell
A coupling ratio of 3:2


Calcium Handling in Mammalian Cells

Where is Calcium stored in the cell?
How does it enter the cell?
How is it transported out of the cell?

Stored in the endoplasmic reticulum and to a lesser extent the mitochondria
Enters the cell via LIGAND-GATED channels, VOLTAGE-GATED channels, and store operated calcium channels (SOCCs)
Exits the cell via Ca, Mg ATPases, Ca,H ATPases and Na,Ca antiport

Note: in the cell, Calcium binds to Calcium binding proteins (CaBP) that bring about various effects


G-Protein - common way to translate a signal to a biological effect
Heterotrimeric G Protein.... A summary

Ligand binds to G protein coupled receptor (on membrane) -->
GTP replaces GDP on alpha subunit-->
GTP-Alpha separates from beta-gamma and both subunits activate various effectors-->
Produce physiological effects
Intrinsic GTPase activity of GTP-alpha then converts GTP to GDP and then alpha, beta and gamma all reunite.

Figure 2-26 - release of IP3 and DAG as secondary messengers

-Ligand binds to G-protein coupled Rc and activates phospholipase C (PLC) or activation of intracellular protein kinases will activate PLC
-activated PLC will result in hydrolysis of PIP2 --> this produces DAG and IP3
-IP3 releases Calcium from ER where it will bind to CaBP and cause physiological effects
-DAG activates protein kinase C (PKC) which will cause physiological effects


Adenylyl cyclase:
- a membrane bound protein
- converts ATP to cAMP

-stimulatory ligands bind to stimulatory Rc and activates adenylyl cyclase via Gs G-protein
-inhibitory ligands Bind inhibitory Rc and inhibit adenylyl cyclase via Gi G-protein

- made from ATP by Adenylyl cyclase
- broken down into AMP (inactive form) by phosphodiesterase
-cAMP activates PKA
-PKA phosphorylates proteins --> producing physiological effects



92% - Water
7% - Proteins
1% - Nutrient and waste products (amino acids, vitamins, glucose, oxygen, carbon dioxide, nitrogenous waste and trace elements - note these are not bound to anything, just dissolved in plasma fluid

Interstitial fluid = plasma - proteins

Plasma Proteins
- albumin - carrier protein - good indicator of liver function
- Fibrinogen - clotting material
- Transferrin - transfers ions
- Ferritin - iron storage (mostly in liver)
- globulins - ie immunoglobulins (IgG)


Name the plasma proteins and their function.

(Note most are made in the liver)

Albumin - carrier protein - best indicator of liver function
Fibrinogen - clotting material
Transferrin - transfers ions
Ferritin - storages iron (mainly in liver)
Globulins - ie immunoglobulins (IgG)


What is oncotic pressure?

Oncotic pressure - water pulled out of interstitial fluid into capillaries due to the presence of plasma proteins.

Clinical significance! Liver/kidney disease and malnutrition result in decreased plasma proteins therefore less water is being pulled into vessels (decrease in oncotic pressure) --> leads to edema (too much water in interstitial fluid)


What produces platelets? And what regulates its production?

Megakaryocytes, they are regulated by thrombopoetin (TPO) - which is made in liver and kidney

Megakaryocytes shed fragments of their extensions - which are platelets


Thrombocytopenia. What is this?

Decreased number of platelets!
-decreased production (cancer, chemo, viral infection of marrow)
-increased destruction (autoimmune, inflammation, rxn to meds)


Look over clotting process and platelet activation diagrams

Refer to front


NSAIDS inhibit what?

Inhibit cox enzyme that promotes synthesis of thromboxane A2

Note - thromboxane A2 has a role in platelet aggregation


Describe physiological role of cellular elements of blood: (WBC, RBC, platelet)
White blood cells:

White blood cells (leukocytes):
-Produced in bone marrow, respond to infection (viral bacterial and parasitic) and damage (tumors).
-75% of all hematopoiesis is WBC (25% is RBC)
-Consists of:
Neutrophils (50-60%) (phagocytose bacteria and destroy via lysosomes and H2O2)
Lymphocytes (20-40%) (activates immune system: produce B cells (antibodies) and T cells (cell lysis)
Eosinophils (1-6%) (major basic protein - cytotoxic to parasites; involved in allergies (histamine, leukotrienes))
Basophils (<1%) (NOT SAME AS MAST CELLS, but similar), (heparin, histamine, IgE Rc (type 1 hypersensitivity rxn))
Monocytes (2-10%) (become macrophage when enter tissue; antigen presenting cell - phagocytose bacteria/debris like neutrophil)


Describe physiological role of cellular elements of blood: (WBC, RBC, platelets)
Red blood cells:

Red blood cells (erythrocytes):
- Biconcave disks that carry hemoglobin which carries oxygen to cells.
- Have flexible cytoskeleton - can change in shape in response to osmotic changes (within limits; if swell too much will lyse)
- pass through narrow capillaries
- health of RBC can be derived from its shape ( ie sickle cell, spherocyte)
- Note - sickle cell anemia: genetic mutation within the amino acids of Hb. Sickle Hb crystallizes causing cell to sickle.
- hematocrit = percentage of blood by volume that is occupied by erythrocytes


Describe physiological role of cellular elements of blood: (WBC, RBC, platelet)

- small granulated bodies that aggregate at sites of vascular injury


Describe the processes that can activate platelets and the coagulation cascade and the factors that promote and inhibit these processes:

Platelets circulate in an inactive state (smooth discoid shape). Healthy endothelium releases PROSTACYCLIN which keeps platelets inactive.
A break in the endothelium that exposes the collagen is the INITIAL platelet activation.
The initial event is constriction of the vessel and formation of a TEMPORARY HEMOSTATIC PLUG of platelets that is triggered when platelets bind to collagen and aggregate.
Collagen and Tissue Factor 3 (released from damaged endothelial cells) activate the coagulation cascade.

Inhibit clotting process - prostacyclin, NSAIDS
Promote clotting process - thromboxane A2, ADP, thrombin
Inhibit coagulation - heparin, antithrombin 3, warfarin
Promote coagulation - tissue factor 3


Describe how ADP, TXA2 and thrombin participate in the coagulation cascade and platelet activation.

ADP, thromboxane A2 (TXA2), and thrombin all further activate platelets. They are released from already activated platelets.

Thrombin - converts fibrinogen into fibrin in the coagulation cascade.


Describe the physiological process of fibrinolysis and the factors that promote it.

Plasminogen gets converted to Plasmin. Plasmin, which is also embedded within the clots with fibrin and platelets, is the active enzyme that dissolves fibrin and fibrinogen. It is slowly secreted by endothelium to restore integrity of blood vessel.

Both thrombin and t-PA (tissue type plasminogen activator) promote the formation of Plasmin.

Note: t-PA is given in ER for hear attack or stroke


Describe the importance of colony stimulating factors, EPO and TPO within the context of hematopoiesis.

Erythropoietin (EPO) is produced in the kidneys (10-15% also from liver) in response to hypoxia. It stimulates production of RBC's in the bone marrow.
(Note - hypoxia is from sustained low oxygen environment I.e. training for marathon at higher elevation)

Thrombopoetin (TPO) is produced in liver and kidney. It stimulates development of megakaryocytes. Megakaryocytes extend into the capillaries and shed fragments of their extensions which become platelets. (Therefore TPO stimulates platelet production).


Describe the process of erythropoiesis and RBC maturation.

Process from progenitor cells (stem cells) to the release of reticulocytes into circulation takes about 7 days.

Hypoxia -> kidney (or little in liver) secrete erythropoietin -> it stimulates differentiation of progenitor stem cells into erythrocyte lineage -> increased rate of mitosis of RBC precursors -> will first form an ERYTHROBLAST -> it will lose its nucleus & mitochondrias (phagocytosed by WBC) to become an immature RETICULOCYTE -> will then enter circulation and mature in 24 hours to become an ERYTHROCYTE (touchdown :) )


Describe how RBCs are degraded and how hemoglobin is metabolized in the human body

Erythrocytes live for about 120 days.

Damaged RBCs have difficulty passing through capillaries -> phagocytosed by macrophages within the SPLEEN -> iron and amino acids are recycled & waste gets converted to bilirubin and transported to liver by albumin where it is excreted via bile or by kidneys
Hemoglobin components recycled:
- amino acids incorporated into new proteins
- some iron from heme is used in new heme (and remnants of heme converted to bilirubin)


Iron metabolism in human body. Go.

Absorbed from diet through small intestine wall via active transport -> transported to bone marrow while bound to transferrin in the plasma -> in bone marrow it will be incorporated into Hb within newly formed RBC and released into circulation -> when RBC damaged, spleen degrades Hb into bilirubin which is excreted via bile or kidney ** BUT iron and amino acids are recycled

Note - liver stores excess iron within ferritin protein (ferritin is what we measure when we measure iron status)

Prof emphasized that it is VERY hard for our bodies to excrete iron, other than blood donation.


Differentiate between anemias caused by accelerated blood loss vs. decreased red blood cell production.

Blood loss:
- cells are normal in size and Hb content but LOW in number
- hemolytic anemias - cells rupture at abnormally high rate (could be hereditary or acquired)

Decreased blood cell production:
- Defective RBC or Hb production in the bone marrow
- aplastic anemia - can be caused by certain drugs or radiation
- inadequate dietary intake of essential nutrients (iron - required for heme & B12 and folate - required for DNA synthesis)
- inadequate production of EPO