AP Exam 2

Capillary dynamics

• BP=HP→ NFP→ volume of fluid pushed out (volume of interstitial fluid)→ volume of fluid returned to blood from movement through tissue (rate of return)

• NFP= HP-OP

  • + NFP, fluid pushed out in tissues

  • -NFP, fluid drawn back into blood capillaries 

• HP= hydrostatic pressure of the blood capillary (always trying to leave the blood capillary)

• OP= osmotic pressure drawing H20 into blood capillary (remains constant always trying to go into blood capillary)

Lymphatic system

• no pump

• relies on pressure gradient (starts with BP)

• lymph=interstitial fluid

Lymph fluid movement ensured by

• changes in thoracic pressure 

• mini valves

• muscle contraction

• vibrations of major arteries 

Lymphatic drainage

• BP→ HP(C)→ NFP→ volume of fluid pushed out (vol. of interstitial fluid)→ HP(IF)-→ force on minivalve→ vol. lymph in capillary (when vol. of excess IF to be drained more than capacity than it leads to edema)-→ speed of drainage 

Lymphatic drainage (at the minvalve)

• HP (IF) pushes on valve→ excess IF goes in lymphatic capillary

• Lymph inside lymphatic capillaries pushes on underside on minivalve (HPIF)-→ control fluid entry into vessel

• At vessel capacity valve shuts

Types of edema

• Hypertensive edema due to increased BP, which leads to increased HP, etc

• Inflammatory edema- cytokines induce capillary endothelial cells to separate -→ increased NFP, so increased vol. fluid into tissue etc

• Lymphedema- trauma, removal, blockage of lymph vessels = excess IF cannot be collected properly so not drained and accumulates

Lymph nodes

• more afferent than efferent vessels so fluid stagnates

• Germinal centers: B cells and macrophages

• Medulla-T cells (can migrate)

• collections- cervical, inguinal, axillary

• sentinels- mediastinum, GI/abdomen

Lymph organs

Thymus: T-lymphocytes (T-cell) mature/educate here 

Spleen: white pulp (lymphocytes), red pulp (RBC)

Tonsils: palatine, sublingual, pharyngeal (crypts to trap bacteria, mucus, and particulates)

MALT (Mucosa Associated Lymphoid Tissue)

• peyers patches and ileo-cecal valve aggregates (ileum)

• Appendix

• Bronchi nodes

Cells of Immune system

Innate:

• Phagocytes (macrophages,neutrophils)

• NK cells

• Dendritic cells

• Reticular cells

Adaptive

• B-cells

• T-cells

Innate defenses (1st defense)

Surface barriers (1st defense to prevent initial injury or infection)

• skin: waterproof, colonizing bacteria

• mucosa: thick mucus 

• nasal hairs; traps particles

• chemical secretions: sebum, stomach acid, earwax, tears, saliva, vaginal fluid 

• mucus: trap pathogen & particles, expel or ingest

Innate defenses (2nd defense)

Internal defense (2nd defense when trauma first comes)

• phagocytes: remove cell debris, bacteria, parasites, activity enhanced by C3b, macrophages, neutrophils

• NK cells: perforin (lyse cell), cancer cel (no MHC I), infected cell (Non-self MHC I)

• Inflammation: edema/swelling, redness and heat (blood to area), pain. Prostaglandins cytokines (IL-1, TNFx, IL-6, etc)

• Fever: pyrogen resets thermostat, increased metabolic rate, sequester Zn and Fe, increased tissue repair, decreases pathogen replication

• Antimicrobial proteins

  • Interferon:

    • prevent viral entry into healthy neighboring cells, PKR protein

  • Complement

    • enhance phagocytosis (C3B)

    • MAC complex→ (C5-9) hole in cell membrane → Lysis

2nd defense pt.2 

• inflammation present for any drama 

  • proportional to extent of trauma

  • not dependent on pathogen present

• Macrophages phagocytose necrosed/destroyed cells and pathogen. Activity exists without pathogen present

• Neutrophils, NK cells, fever, antimicrobial proteins act in presence of pathogen

Inflammation

• Injury-→ trauma→ cells release cytokines (which cause/allow chemotaxis)→ endothelium express CAMs→ grab passing WBC (roll &stop)=margination→endothelium separate→ WBC migrate through gap (diapedesis)-→ chemotaxis→ WBC to injury site→ phagocytosis of debris and pathogen

4 Cardinal Signs of inflammation

• Heat/redness

  • function: increased WBC and platelets to area → decreased infection and hemorrhage.

  • increased nutrients and oxygen to tissues→ increased healing and metabolism

  • increased blood flow (histamine-→ vasodilation)

• Edema

  • function: stabilize injury, contain pathogen

  • cytokines increased vascular permeability

• Pain

  • bradykinin (free nerve endings)

  • kinins and prostaglandins- traumatized tissue

  • function; indicate presence of injury

• NSAIDS- non steroidal anti-inflammatory drug (ibuprofen, aspirin, acetaminophen)

  • inhibit COX-1→ housekeeping →maintain base prostaglandin levels

  • COX-2→ induce increase in prostaglandins with trauma and infection

Anitgens

Immunogenicity- ability to be recognized by the immune cells

Immunoreactivity : ability to provoke an immune response

Determinants- complexity of the protein/DNA/polysaccharide —> more antigens possible-→ increased immunoreactivity 

Antigen presentation and processing

MHC- Major Hisocompatability complex

• MHC 1

  • on all cells expect RBC

  • ID self from nonself

• presence of pathogen antigen in MHC 1 on cell surface

  • → target for destruction by NK cells and Tc Cells (both release perforins—> cell lysis)

• Macrophages phagocytose cell debris → debris fragments (self and pathogen Ags) presented on MHC II for ID by B and T cells

• MHC II = ID unknown Ag

  • 1. engulf debris

  • phagocytose

  • Add Ag to MHC II

  • transfer

  • present Ag on surface via MHC II

B cells

• mature in bone marrow (receptor editing)

• BCR= unique receptor on each cell (gene shuffling)

• receptor same structure as antibody cell makes on activation

• Activated by Ag in lymph, APC, or Th cells

• Has MHC II so can be APC itself 

B cell clonal selection 

• Ag challenge and activation of B-cell clone 

• B cell proliferates→ differentiates into either memory cells or plasma cells

• Memory cells→ same selection and activation with repeat pathogen exposure→ increased # of memory cells→increased number of Ab titer in blood

• Plasma cells→travel in ECF to remove fluid bound pathogen/Ag. 

Antibodies remove fluid borne antigens by (most of these are IgG or IgM):

• Precipitation

• Lysis

• Agglutination (RBC only)

• Neutralization

5 Antibody Classes

• IgA

• IgD

• IgE

• IgG- made during infection and retained

• IgM-most made and used during infection

Different kinds of T cells 

• Educated in thymus

• No recognition of MHC ± peptide (can’t recognize self) -→ death by neglect 

• strong recognition of MHC I, MHC II ± peptide (respond/kill self)→ apoptosis

• Weak recognition of MHC II + peptide (better recognition using MHC II) → mature CD4 cell 

• Weak recognition of MHC I + peptide (better at self-recognition on MHC I) → mature CD8 cell 

CD 4/TH Cells

• co-ordinate humoral (antibody) and cellular (T-cells/other immune cells)

• required for full activation of Tc and B cells

• Uses MHC II

• releases co-stimulators (IL-2, IL-13, IL-4, IL-1)

CD8/Tc Cells

• effectors

• use perforin to lyse cells

• activated by TH cells

• Must have costimulation for full activation

Immune response

• Trauma

• Innate defenses

  • inflammation

  • mucus (phagocytes, macrophages)

  • fever, antimicrobial proteins, neutrophils (phagocytes), NK cells-perforins

• Makes cell debris

  • Free floating Ag→ B-cell selection & activation→ proliferate→ memory cells→or differentiate→ plasma cells→ antibodies

  • Antigen presenting cell (macrophage) engulfs and display antigen on either

    • MHC II or MHC I

      • MHC I make CD8/TC cell activation, which returns to infection site and destroys infected cells using MHC I identification and perforins

      • MHC II makes CD 4/helper cells which activates TC cells, and costimulates/enhances NK cells and macrophages

• Non-memory cells apoptose 7-30 days post-infection

• Ab not used remains in blood 

Upper respiratory 

nasopharynx→ oropharynx→ laryngealpharynx 

Lower respiratory

Trachea→ bronchi (branching 1-17, cartilage rings→ slabs) → bronchioles (branching 18-23, smooth muscle only)→ terminal bronchiole→ respiratory bronchiole (elastin fibers)→alveolar sacs&ducts→alveoli

Conduction zone→ anatomical dead space (VD)

Lower+upper 

Respiratory zone

• respiratory bronchiole (elastin fibers)→ alveolar sacs & ducts→ alveoli

Alveolar cells

Type 1 alveolar cell:

• Respiratory membrane

• angiotensin converting enzyme (ACE)

Macrophage/dust cell- remove particulate

Type II alveolar cell:

• secretes surfactant

Pleura

• visceral - encase lungs

• parietal: line ribcage, mediastinum, contacts with pericardium diaphragm

• cavity: serous membrane→ pleural fluid→ adhere lungs to ribcage

• Holds lungs so always slightly inflated and helps pull open lungs on inhale

Volumes

• VT= tidal volume, air in and out of system/breath

• f= frequency of breaths/min

• Ve= fxVt= minute volume 

• Va (alveolar ventilation)= f x (Vt- Vd)

Mechanics of breathing (Boyles Law)

• Boyles Law → P=1/V

  • Inhale: diaphragm contracts down, pec minor & scalenes contract pulling ribcage up

  • V increases, P decreases, air sucked into lungs

  • Exhale: diaphragm relaxes, elastic recoil of lungs (quiet breathing) with contract rectus abdominus and seratus anterior and internal intercostals (forced breathing)

  • P=intrathoracic pressure and discussed in relation to atmospheric pressure

Henry’s Law

• Gas can be forced into liquid when under pressure 

• Inhale→ Volume increases, Pressure decreases, so gas goes liquid-→ gas → CO2 release into lungs, maximum CO2 exchange into alveoli

• Exhale: V decreases, P increases, so gas goes gas → liquid→O2 forced into blood, maximum O2 exchange into blood

Gas Exchange Efficiency dependent on:

• availability of air in lungs (airway and thoracic wall compliance)

• concentration gradients of gases (steeper the gradient=more rapid the exchange) Dalton’s Law

• surface area (more surface area=more potential energy)

• perfusion (more blood flow to area= more potential exchange)

  • ventilation: perfusion coupling→ blood goes where air is

Gas transport 

• Begins in the alveoli-→ 100 mmHg of oxygen in lung—> O2 entering the lung starts at 40 mmHg and leaving the lung is at 100 mmHg-→ this oxygen dissolves in plasma and binds to Hb—> systemic circulation (arteries) to the tissues→ oxygen (100) goes into the tissues-→ usual tissue O2 concentration is 40 mmHG→ in the tissues the CO2 is 45 mmHg—> goes down gradient to capillary (40 mmHg)→ CO 2 dissolves in plasma, binds to Hb, dissolves in cytoplasm of RBC→ Co2+H2O→H2CO3→H+ + HCO-3-→ H buffered by binding amino end of globin chains, HCO-3 is exchanged with Cl- so Cl inside RBC and HCO-3 is in plasma -→ systemic circulation(veins)→ CO2=45 in blood and CO2=40 in lung, gradient goes into lung→ CO2 on Hb is replaced with oxygen, CO2 released from plasma, Put HCO3 back into RBC and Cl out and reverse equation → Co2 + H2O 

O2 concentration, pH, and temperature

• O2 concentration:

  • how much oxygen you’ll need for full saturation of Hb

  • Tissue= based on rate of metabolism/ATP, constant drop off of O2, increased metabolism uses more oxygen so its important to drop off oxygen continuously to maintain ATP production and cellular respiration.

• PH

  • low pH increases hydrogen, O2 prefers to bind to H than Fe (acidotic)

  • when H and Co2 binds to HB it makes the bond looser, and causes O2 to be easier to remove

  • if acidotic it also releases more CO2

  • if alkaline, makes it tighter and harder to let go of oxygen

• Temperature

  • increased heat, provides energy, and makes bond easier to break

  • decreased heat, electrons slow down, become more stable, and wants to hold onto oxygen and not let go

BPG

• regulates glycolysis in RBC

• used by RBC to make ATP

• As BPG decreases, ATP production decreases, and decreases Hb: O2 release→ RBC degrade

• No BPG=harder to carry oxygen/decreased oxygen capacity