FPP-Week 1

Question 1

Plasma vs Serum

Answer 1

Plasma is fluid phase after centrifuge W HEPARIN

Serum is AFTER COAGULATION (removes clotting factors)

Question 2

Complete Blood Count (CBC)

Answer 2

Erythrocyte/RBCs: 4.6-6.1 million/ul (mcl)
varies w/ altitude
Male: 4.6-6.1
Female: 4.2-5.4

Leukocyte/WBCs: 4-10 thousand/ul

Question 3

Differential Count

Answer 3

Granulocytes:
neutrophils: 34-71%
eosinophils: 0-7
basophils: 0-1
Agranulocytes:
monocytes: 5-12
lymphocytes: 19-53

Question 4

Erythrocytes

Answer 4

RBCs
7.5um diameter
no organelles or nucleus, biconcave
Hb causes eosinophilia, makes 33%
Also CA (carbonic anhydrase)
  -Band 3: binds ankyrin which binds spectrins which maintains biconcave shape (mutations cause spherocytosis)
ABO and Rh
Lifespan=120days
hematocrit>55%: polycythemia (more RBCs) or erythrocytosis (bigger RBCs)

Question 5

Neutrophils

Answer 5

polymorphonuclear, polys (PMN), lobulated nucleus
Anti-bacterial
granules: lysosomes and “specific” (don’t stain)
PMN to fit between cells (caspase)
1. release granules (degrade bacteria)
2. phagocytosis
3. respiratory burst (NADPH oxidase) superoxides
Lifespan=few days

Question 6

Eosinophils

Answer 6

bi-lobed nucleus
anti-parasitic (also allergies)
large red (eosin) granules, crystalloid center
kills parasites via major basic protein (MBP)
phagocytize antigen-antibody complex
secrete leukotrienes, LTC4 (asthma), and PAF
lifespan=few weeks
If activated: Neoplasia, Asthma, Allergy, Connective tissue disease, Parasitic disease (NAACP)
Have CCR3 (Eotaxin and RANTES receptor)
Steroids cause apoptosis

Question 7

Basophils

Answer 7

Nucleus obscured by blue granules
heparin and histamine
like mast cells
1. antigen invades system
2. plasma cell makes IgE
3. IgE binds basophil
4. Later on, antigen binds IgE on mast cell, causes granule release, allergic response
lifespan=years

Question 8

Monocytes

Answer 8

Largest WBC, indented/horseshoe nucleus

in tissues, become APCs or macrophages

Question 9

Lymphocytes

Answer 9

B (bone marrow) and T (thymus)
T predominates in blood
cart-wheel nucleus

Question 10

Megakaryocytes

Answer 10

Usually only in bone marrow

buds off platelets

Question 11

Platelets

Answer 11

2um, 300,000/ul
granulomere - clotting factors and PDGF
hyalomere - microtubules (outside edge)

Question 12

Hypertrophy

Answer 12

increase in size of cells

physiologic: functional demand or hormonal (skeletal muscle, uterus in pregnancy)
pathologic: cardiac muscle in hypertension

Question 13

Hyperplasia

Answer 13

Increase in cell number
laile and stable cells
physiologic: hormonal in breast tissue and of liver post-resection, wound healing
pathologic: excessive growth factors (e.g. endometrial or prostatic), increased risk on cancer
BPH-no increased cancer risk, nodules
also skin warts from viral infxns (papilloma)

Question 14

Atrophy

Answer 14

Decrease in cell size

physiologic: loss of hormone stimulation
pathologic: decreased functional demand, loss of innervation, malnutrition

Question 15

Metaplasia

Answer 15

One cell type replaced by another
adaptive to chronic stress, reversible, risk of cancer
Epithelial: ciliated columnar->squamous (smokers), squamous->gastric (distal esophagus (Barrett) reflux)
Mesenchymal: bone formation in soft tissue at injury sites

Question 16

Necrosis

Answer 16

enlarged cell
karyolysis
disrupted plasma membrane (blebs)
Enzymatic digestion of cell contents (may leak)
Causes adjacent inflammation
Always pathologic
increased eosinophilia

Question 17

Apoptosis

Answer 17

reduced cell size
nucleus fragmentation into nucleosome-size 
Intact plasma membrane (blebs)
cell components released in apoptotic bodies
NO inflammation
Often physiologic, sometimes pathologic
increased eosinophilia
chromatin condensation
Regulated by Bcl-2, Cyt-C, Caspase

Question 18

Reversible cell injury

Answer 18

fatty change (lipid vacuoles) e.g fatty liver
cell swelling, blebs, distended ER
clumped chromatin, swollen mitochondria

Question 19

Coagulative necrosis

Answer 19

hypoxic or anoxic injury due to ischemia
persistence of dead cell outlines, loss of cell details
occurs in all solid organs (not brain)

Question 20

Liquefactive necrosis

Answer 20

complete digestion of dead cells
common with bacterial or fungal infxns
also brain infarcts

Question 21

Caseous necrosis

Answer 21

characteristic of TB
resembles cheese, crumbly
fragmented cells with loss of cell outlines
usually surrounded by border of inflammation (granuloma)

Question 22

Gangrenous necrosis

Answer 22

ischemic coagulative necrosis of extremity
wet: when bacteria also present
also used for severe necrosis of other organs

Question 23

Fat necrosis

Answer 23

Typical in pancreas
chalky white (fatty acids with Ca)
also when trauma to fatty tissue

Question 24

Fibrinoid necrosis

Answer 24

Deposition of immune complexes in vascular wall
bright pink, amorphous
vasculitis syndromes

Question 25

Pathologic calcification

Answer 25

Dystrophic: damaged or dying tissues, normal serum levels, basophilic Metastatic: hypercalcemia, normal tissue (e.g. renal failure, increased PTH), interstitial tissues

Question 26

Chronic Granulomatous Disease (CGD)

Answer 26

Functional absence of respiratory burst in neutrophils and monocytes (impaired bacterial killing) NADPH oxidase, usually X-linked, can be auto recessive Onset by age 2, infxn with S epidermidis, S marcescens, aspergillus Tx: TM-sulfa, itraconazole,, bone marrow transplant Dx test: DHR test, flow for superoxide production Lack of superoxide-> lack of eat me signal on dead cells-> disordered inflammation

Question 27

Leukocyte Adhesion Deficiency-1 (LAD-1)

Answer 27

Autosomal recessive deficiency of many adhesion molecules, shared beta chain (CD18) bc lack adhesion molecules, leukocytes can't adhere to endothelium to reach infxns recurrent pyogenic infxns, delayed umbilical detachment, leukocytosis, no pus, decreased wound healing, impaired phagocytosis, chemotaxis, etc Tx: aggressive infxn tx, bone marrow if severe Dx: flow cytometry for CD18

Question 28

Toll-Like Receptor (TLR) signaling

Answer 28

Most: MyD88, IRAK-> NFkB, Erk, Jnk, p38-> inflammatory cytokines TLR3-> TRIF->IRF-3, IFN-B TLR4-> both pathways

Question 29

MyD88/IRAK4 deficiency

Answer 29

Primary immunodeficiency in innate immunity S pneumoniae, S aureus, P aeruginosa early onset, high mortality, but if make it to 8yo, then good TxL IVIG/Abx prophylaxis

Question 30

TLR3/TRIF pathway deficiency

Answer 30

Early onset herpes virus encephalitis | incomplete penetrance

Question 31

Late Complement Deficiency

Answer 31

C5-C9 (form membrane attack complex) | recurrent meningococcal disease (N meningitidis)

Question 32

Early Complement Deficiency

Answer 32

C2 most common, autosomal recessive Screening test: CH50 (if 0, then individual complement deficiency, if low but >0, then consumption of complement problem)

Question 33

Severe Combined Immunodeficiency (SCID)

Answer 33

Profound defect in cellular and humoral immunity early onset, lots of infxns, failure to thrive 100% mortality w/o bone marrow transplant screening: CBC, lymphopenia confirmatory: lymphocyte enumeration (Tcells=0) Also newborn screening-- TREC (T cell receptor excision circles) are marker for normal naive T cells, low in SCID, qPCR

Question 34

22q11.2 Deletion Syndrome (DiGeorge Syndrome)

Answer 34

Wide clinical spectrum, CATCH22 (cardiac defects, abnormal faces, Thymic hypoplasia, cleft palate, hypocalcemia) recurrent infxns, autoimmunity, some require IVIG low set ears Dx: DNA microarray, FISH confirm: qPCR for haploinsufficiency TBX1 (CHW)

Question 35

X-Linked Agammaglobulinemia (XLA)

Answer 35

No antibodies (85% of cases are XLA) Recurrent otitis, sinsusitis, pneumonia brinchiectasis if not dx early Screening: IgG, IgA, IgM Defecit in Btk, which leads to lack of "live" signal in B-cell development Don't use serological assays for dx (bc no antibodies), use direct methods only

Question 36

Common Variable Immunodeficiency (CVID)

Answer 36

Decrease in IgG and low IgA or IgM onset >4yo clinical course is variable Bronchiectasis (widening of bronchi) and interstitial lung disease are common -treat similar to cystic fibrosis also cancer Don't use serological assays for dx (bc no antibodies), use direct methods only

Question 37

Type I hypersensitivity

Answer 37

anaphylaxis, asthma, allergies IgE antibody-> mast cells, histamine, tryptase Allergies: allergen->APC->Th2->B-cell->IgE->>>allergen->mast cell->histamine, tryptase, [leukotrienes, IL-3,4,5, MIP-1a, RANTES, Eotaxin, PAF, TNF] Real bad real quick, then again 4hrs later when more cells get recruited (cytokines->T-cells and eosinophils)

Question 38

Type II hypersensitivity

Answer 38

Cell, matrix-bound antigens autoimmune hemolytic anemia, erythroblastosis fetalis, Goodpasture syndrome IgG/IgM-> binds to antigen on cell surface-> phagocytosis or lysis of target cell (macrophages, NK cells (Fc receptor))

Question 39

Type III hypersensitivity

Answer 39

Soluble antigens serum sickness, systemic lupus erythematosis, arthus rxn, rheumatoid arthritis, farmer's lung antigen-antibody complexes (IgG)-> activated complement-neutrophils->deposit (vessel walls) and release toxic stuff Kidneys, vessels, joints, skin destruction

Question 40

Type IV hypersensitivity

Answer 40

Cell-mediated TB, contact dermatitis (poison ivy), transplant rejection antigen (haptin-carrier)-> APCs-> sensitized T-cells (CD4 Th1 and CD8 CTL)-> release cytokines (INF-g, TNF-a,b, IL-3), lymphokines, cytotoxicity -> macrophages-> destruction 24-72 hour delay

Question 41

Goodpasture syndrome

Answer 41

Type II hypersensitivity nephritis and lung hemorrhages auto-immune to Type IV collagen in basement membranes of glomeruli and lung aveoli

Question 42

Acute Rheumatic fever

Answer 42

Type II hypersensitivity Antibodies against Strep cross-react with heart Carditis

Question 43

Serum Sickness

Answer 43

Type III hypersensitivity rxn to large quantities of foreign protein occurs 7-10 days after exposure (switch from IgM to IgG) flu-like, urticarial rash, arthritis, glomerulonephritis Complexes form most when antigen is no longer in extreme excess, closer to equilibrium only.

Question 44

Systemic Lupus Erythematosus (SLE)

Answer 44

Type III hypersensitivity antibodies against DNA or other nuclear things arthritis, glomerulonephritis, skin disease Lumpy deposition of complexes in these areas

Question 45

Acute Inflammation

Answer 45

Infxns, trauma, chemical agents, necrosis, foreign bodies, hypersensitivities TLR->cytokines, TNF->leukocytes / Inflammasome(dead cells)->caspase->IL-1->leukocytes Vascular: histamine, NO-> stasis, leukocytes / histamine,bradykinin->endothelial cell contraction -->edema Morphology: lots of neutrophils

Question 46

Leukocyte Recruitment

Answer 46

Margination: accumulation at vessel periphery Rolling: weak adhesion to endothelium (integrins, selectins) Adhesion: firmer (integrins) Transmigration (diapedesis): move through endothelium (PECAM, CD31) Chemotaxis: move toward injury site (chemokines, ECM) Leukocytes recognize opsonins, phagocytose-> ROS-> release degridative enzymes

Question 47

Mediators of Inflammation

Answer 47

Histamine- vasodilation, vascular permeability- mast cells, basophils, platelets NO- vasodilation, tissue damage- endothelium, macrophages Bradykinin- vascular permeability, pain- plasma (liver) IL1, TNF- chemotaxis, leukocyte recruitment, fever- macrophages, endothelial cells, mast cells ROS- tissue damage- leukocytes

Question 48

Serous Inflammation

Answer 48

Mildest acute inflammation thin (protein poor) fluid (blister) effusions, blisters

Question 49

Fibrinous Inflammation

Answer 49

More severe larger vascular leaks-> fibrin affects linings (meninges, pericardium, pleura) may resolve or lead to scarring

Question 50

Suppurative Inflammation

Answer 50

``` purulent large # of neutrophils liquefied=pus pyogenic bacteria (Staph) Abscess ```

Question 51

Ulcer

Answer 51

Local defect | sloughing of surface covering and necrotic inflammatory tissue

Question 52

Chronic Inflammation

Answer 52

Persistent infxns (TB), prolonged toxin exposure, autoimmune disease, foreign bodies (silica) Macrophages persist Cytokines, IFN-g Adaptive immune response is activated Morphology: mononuclear cells (macrophages, lymphocytes, plasma cells),, tissue destruction, angiogenesis, fibrosis

Question 53

Granulomatous Inflammation

Answer 53

``` Chronic inflammation TB, syphilis, silica, sarcoidosis inert foreign bodies,, immune rxn Multinucleated giant cells (INF-g) surrounded by fibrosis TB: central caseous necrosis ```

Question 54

Systemic Effects of Inflammation

Answer 54

Acute phase rxn / SIRS fever (pyrogens (LPS, IL1, TNF, PGE2) elevated acute-phase proteins (via IL6,, C-reactive protein, fibrinogen--> elevated ESR, erythrocyte sedimentation rate) leukocytosis (via TNF,IL1,, increased WBC --Neutrophilia: bacterial (left-shift) --Lymphocytosis: viral --Eosinophilia: allergies, asthma, parasites

Question 55

Extracellular Matrix

Answer 55

Interstitial matrix: 3D amorphous gel Basement membrane: highly organized around epithelial, endothelial, smooth muscle cells Provides scaffold for healing, stores growth factors, creates microenvironment Collagen and elastin,, proteoglycans and hyaluronan,, adhesive glycoproteins and receptors

Question 56

Ehlers-Danlos Syndrome

Answer 56

Genetic defect in collagen synthesis or structure | tissues lack tensile strength, hyperextensible, fragile

Question 57

Tissue repair / scar formation

Answer 57

Angiogenesis (VEGF, NO, FGF) fibroblast migration and proliferation (TGF-B, PDGF, FGF) ECM deposition maturation/remodelng of fibrous tissue Granulation tissue= present by 3-5 days, contains new vessels, inflammatory cells, fibroblasts, collagen

Question 58

Healing by First Intention (Primary union)

Answer 58

uninfected surgical incisions | clotting, then neutrophils, then macrophages and granulation tissue, then collagen, then scar w/o inflammation

Question 59

Healing by Secondary Intention (Secondary Union)

Answer 59

More extensive damage, abscesses, ulcers Large fibrin clot, more necrosis, large granulation tissue Wound contraction= myofibroblasts Substantial scar with thinned epidermis

Question 60

Wound healing complications

Answer 60

Dehiscence: re-opening of the wound Ulceration: lack of closure (often due to lack of angiogenesis) Keloid: excessive collagen Exuberant Granulation: open wound Desmoid: Excessive fibroblasts (low-grade neoplasm) Contractures: Scar gets too tight

Question 61

Alcoholic cirrhosis

Answer 61

Lots of collagen with nodules of regenerating hepatocytes, loss of normal structure and function ECM damage

Question 62

Allograft rejection

Answer 62

major target= MHC (HLA: 6xClass I, 6xClass II) MHC matching less important for solid organ, more important for hematopoietic stem cell Minor HCs also important sometimes Direct: T-cell recognizes unprocessed allogenic MHC Indirect: T-cell recognizes processed peptide of allogenic MHC bound in host MHC Hyperacute: due to pre-formed antibodies (xenotransplantation),, complement activation, endothelial damage, inflammation Acute: Mostly T-cell mediated,, endothelialitis, interstitial damage Chronic: months or years, macrophages, smooth muscle proliferation, vessel occlusion

Question 63

Hematopoietic Stem Cell Transplan (HSCT)

Answer 63

therapy for malignancies, aplastic anemia, and immune deficiencies First, chemo or radiation to eliminate bad HSCs, then new ones delivered IV Graft rejection: Graft vs Host: Graft vs Tumor: donor T-cells kill residual tumor cells

Question 64

Mixed Lymphocyte reaction

Answer 64

Assay for T-cell reactivity for transplant | Mix blood mononuclear cells from two donors in tissue culture, see if they react

Question 65

HIV Transmission

Answer 65

Enters through open cuts, direct injection, mucus membranes (rectum, vagina, mouth) via blood, semen, vaginal secretion, breast milk Highest risk via blood, then semen, then vaginal, none by saliva Receptive anal intercourse the most risk bc rectum only one cell thick (after needle sharing and mom-baby) HSV and syphilis increase risk (bc activated t-cells) genetic factors like CCR5 decrease risk Uncircumsized=higher risk

Question 66

Acute HIV infxn

Answer 66

symptoms begin 1-4 weeks following exposure, last for 2 weeks test + for HIV RNA, but can be - for HIV antibodies fairly non-specific symptoms, fever, sore throat, diarrhea, rash

Question 67

Immune Reconstitution Inflammatory Syndrome (IRIS)

Answer 67

paradoxical deterioration in clinical status after initiating antiretroviral therapy due to the recovery of immune response to latent or sub-clinical infxns AKA IRD or immune rebound illness develops within 8 weeks of starting ART happens with rapid improvement in immunologic or virologic parameters

Question 68

HIV pathogenesis

Answer 68

Increases risk of many other things, incl heart disease GALT is where most T-cells lost GI disturbances due to gut permeability increase chronic immune activation, even with long-term suppression Prognosis dependent on viral load "set point" and CTL response Uses conformational masking to evade immune antibody response