Flashcards
Immunity + Nutrition + Bodily processes
Cards in this deck (93)
- 1Vit A- constituent of visual pigment
- for epithelial cell differentiation (pancreatic cells, mucus-secreting cells)
- If deficient: night blindness, bitot spot, dry scaly skin, corneal degeneration
- acute overdose: nausea/vertigo/vomiting/blurred vision
- chronic overdose: liver toxicity, alopecia, dry skin, pseudo tumor cerebri
- teratogenic - 2Vit B1- thiamine --> TPP (thiamine pyrophosphate)
- cofactor for: pyruvate dehydrogenase (pyruvate --> TCA cycle)
: a-ketoglutarate dehydrogenase (TCA)
: transketolase (HMP shunt)
: branched-chain ketoacid dehydrogenase
- deficiency (alcohol, malnutrition) --> high aerobic tissues affected first
- Wernicke-Korsakoff Syndrome: confusion/ataxia/ophthalmoplegia + memory loss
- Dry beriberi: polyneuritis + symmetrical muscle wasting
- Wet beriberi: dilated cardiomyopathy + edema - 3Vit B2-riboflavin (FAD, FMN)
- cofactors in redox reactions (succinate dehydrogenase)
- Cheilosis (lip inflammation + mouth corner fissure)
- Corneal vascularization - 4Vit B3-Niacin (NAD, NADP), from Trp
- lowers [VLDL], raises [HDL] (dyslipidemia)
- If deficient: Glossitis
: Pellagra (dermatitis, dementia, diarrhea)
- Hartnup disease: no neutral amino acid transporters in proximal renal tubule --> no tryptophan --> deficient Niacin
- If excess: hyperuricemia, hyperglycemia - 5Vit B5-Pantothenic acid
- component of CoA
- DEA if deficient: dermatitis/enteritis/alopecia - 6Vit B6- Pyridoxine --> PLP --> cofactor for:
1. transamination (ALT, AST)
2. glycogen phosphorylase
3. decarboxylation reactions
4. synthesis - heme + niacin
5. synthesis - histamine + neurotransmitter
- If deficient:
convulsions/peripheral neuropathy - 7Vit B7- Biotin
- Cofactor for carboxylation enzymes (adds one carbon group):
1. pyruvate carboxylase (pyruvate --> oxaloacetate)
2. acetyl-CoA carboxylase (acetyl-CoA --> malonyl CoA)
3. Propionyl-CoA carboxylase (propionyl-CoA --> methylmalonyl-CoA)
- If deficient: DEA (dermatitis/enteritis/alopecia) - 8Vit B9- Folate --> jejunal absorption --> THF
- Cofactor for methylations --> DNA/RNA synthesis
- If deficient:
1. macrocytic megaloblastic anemia
2. glossitis
- These causes deficiencies:
1. malnutrition
2. phenytoin
3. sulfonamide
4. methotrexate (inhibits dUMP --> dTMP) - 9Vit B12- Cobalamin (methionine synthase cofactor)
- large reserve pool in liver
- deficiency:
1. macrocytic megaloblastic anemia
2. paresthesias
3. subacute combined degeneration (abnormal myelin)
- Deficiency due to:
1. malabsorption/insufficient intake
2. pernicious anemia (no intrinsic factor)
3. no terminal ileum - 10Vit C- Ascorbic acid
- Facilitates iron absorption
- Hydroxylation of proline + lysine
- Conversion of dopamine to NE
- If deficient:
1. Scurvy (swollen gum, bruising, petechiae, poor wound healing, dental problems)
2. Weakened immune response
- if excess:
1. calcium oxalate nephrolithiasis
2. nausea/vomiting/diarrhea - 11Vit DD2 = ergocalciferol = plants
D3 = cholecalciferol = animals/skin
25-OH D3 = storage form
1,25-(OH)2D3 (calcitriol) = active form
- low [Vit D] --> bone mineralization
- high [Vit D] --> bone resorption
- If deficient:
1. Rickets in children (bone pain/deformity)
2. osteomalacia in adults
- If excess:
1. Hypercalcemia + hypercalciuria - 12Vit E- tocopherol
- Antioxidant to protect RBCs
- If deficient:
1. hemolytic anemia
2. subacute combined degeneration
(like Vit B12 deficiency w/o megaloblastic macrocytic anemia) - 13Vit KPhylloquinone, Phytomenadione --> come from intestinal flora
- cofactor for g-carboxylation of glutamic acid --> required for factors II, VII, IX, X
- if deficient:
1. neonatal hemorrhage w/ prothrombin time - 14Zinc- important for formation of zinc fingers (transcription factor motif)
- If deficient:
1. delayed wound healing
2. hypogonadism
Due to acrodematitis enteropathica (recessive metabolic disorder) - 15Purely Glucogenic Essential Amino Acids-Met
-Val
-His - 16Glucogenic and Ketogenic Essential Amino Acids-Ile
-Phe
-Thr
-Trp - 17Ketogenic Essential Amino Acids- Leu
- Lys - 18Derivatives of PheThyroxine
Melanin
Dopamine
NE
Epi - 19Derivatives of TrpSerotonin
Melatonin
Niacin --> NAD/NADP - 20Derivatives of HistidineHistamine
- 21Derivatives of GlycineHeme
- 22Derivatives of GlutamateGABA
Glutathione - 23Derivatives of ArginineCreatine
Urea
NO - 24Glycogen regulation - InsulinInsulin --> RTK -->
1. --> + Glycogen synthase
2. --> + protein phosphatase --> + glycogen synthase
2a. protein phosphatase --> - glycogen phosphorylase - 25Glycogen regulation - GlucagonGlucagon --> Adenylate cyclase --> + cAMP
--> + PK-A -->
1. + Glycogen phosphorylase kinase --> + glycogen phosphorylase
2. - glycogen synthase - 26Glycogen regulation - Epinephrine1. Epi --> B-receptor --> Adenylate cyclase --> + cAMP --> + PK-A --> + glycogen phosphorylase kinase --> + glycogen phosphorylase
2. Epi --> a-receptor --> ER release Ca --> + glycogen phosphorylase kinase --> + glycogen phosphorylase - 27Ketone bodiesIn liver: fatty acids/amino acids --> acetoacetate + B-hydroxybutyrate
1. Prolonged starvation/diabetic ketoacidosis --> oxaloacetate depleted for gluconeogenesis.
2. Alcoholism --> NADH shunts oxaloacetate --> malate
- Both processes --> acetyl-CoA buildup --> ketone bodies buildup
- Urine test can only detect acetoacetate but not B-hydroxybutyrate - 28Innate ImmunityNeutrophils, macrophages, monocytes, dendritic cells, natural killer (NK) cells, complement
- nonspecific rapid response
- Secretes lysozyme, complement, CRP, defensins
- TLRs recognize pathogen-associated molecular patterns (PAMPs) (i.e. LPS, flagellin, nucleic acids) - 29Adaptive ImmunityT cells, B cells, circulating antibodies
- Highly specific, refined over time
- Memory response is faster and stronger - 30MHC I- HLA-A, B, and C
- Binds T-cell receptors and CD8
- Expressed on ALL nucleated cells
- Present endogenously synthesized antigens to CD8+ cytotoxic T cells (viral or cytosolic proteins)
- Antigen peptide loaded onto MHC I in RER
- Assoc. w/ B2-microglobulin - 31MHC II- HLA-DP, DQ, DR
- Binds T-cell receptor and CD4
- Expressed on APCs
- Presents exogenously synthesized antigens to CD4+ helper T cells
- Composed for an a and B chain - 32Natural Killer Cell- Lymphocyte member of innate immunity
- IL-2, IL-12, IFN-a, IFN-B activates this
- Induced to kill via perforin and granzyme:
1. Exposed to signal on target cell
2. Absence of MHC I on target cell
3. Its CD16 binds to Fc region of Ig (antibody-dependent cell-mediated cytotoxicity) - 33B cells1. Recognize antigen - somatic hypermutation --> optimize antigen specificity
2. Produce antibody - differentiate into plasma cells --> secrete specific Ig's
3. Maintain immunologic memory - memory B cells persist and accelerate future response to antigen - 34T cell differentiation
- 35Th1 cellsCD4+ T cells (thymic medulla) --> Helper T cells (in lymph nodes) + IL-12/IFN-g --> T(h1) cell
1. Secrete IFN-g (self-induction???)
2. Activates macrophages and cytotoxic T cells via IFN-g
3. Differentiation inhibited by IL-4 and IL-10
***macrophages/APCs secrete IL-12*** - 36Th2 cellsCD4+ T cells (thymic medulla) --> Helper T cells (in lymph nodes) + IL-4 --> T(h2) cell
1. Secretes IL-4, 5, 10, 13
2. Recruits eosinophils for parasite defense
3. Promotes IgE production by B cells
4. Inhibited by IFN-g (Th1 cells)
IL4: promotes class switching to IgE + IgG
IL-5: promotes class switching to IgA
IL-10: attenuates inflammatory response (with TGF-B) - 37T(h17) cellsCD4+ T cell (thymic medulla) --> Helper T cell (lymph node) + IL-6 + TGF-B = T(h17) cell
***NOT Regulatory T cells*** - 38Cytotoxic T cellCD8+ T Cell (thymic medulla) --> Cytotoxic T cell (lymph node)
Binds MHC-I on target cells --> kill via apoptosis induction via cytotoxic granules:
1. Virus-infected cells
2. Neoplastic cells
3. Donor graft cells
4. Delayed hypersensitivity (Type IV)
Cytotoxic granules have perforin and granzyme B - 39Regulatory T cells- Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions
- Expresses CD3, CD4, CD25, and FOXP3
- Activated regulatoryT cells produce anti-inflammatory cytokines (IL-10, TGF-B) - 40APCsB cells, macrophages, dendritic cells
*two signals* are required for T-cell activation, B-cell activation, and class switching - 41Naive T-cell activation1. Dendritic cell (APC) samples and processes antigen
2. Dendritic cell migrates to the draining lymph node
3. T-cell activation (#1):
a. antigen is presented on MHC II, recognized by TCR on CD4 (Th1 or Th2) cell
b. endogenous antigen is presented on MHC I, recognized by TCR on CD8 (Tc) cell
4. Proliferation and survival (#2): CD28 on T cells interact with CD80/CD86 on APCs
(CD80 upregulation via TLR)
5a. Th cell activates + produce cytokines
5b. Tc cell activates --> recognize and kill virus-infected cells
if signal (#2) isn't present --> T cells become anergic
- 42B-cell activation + class switching1. Th (CD4+) cell activation
2. B-cell receptor-mediated endocytosis --> foreign antigen is presented on MHC-II --> recognized by TCR on Th (CD4+) cell
3. CD40 receptor on B cell binds CD40L on Th (CD4+) cell
4. Th (CD4+) cell secretes cytokines that determine Ig class switch of B cell
5. B cell activates --> undergoes class switch + affinity maturation + antibody production
if signal #2 isn't present --> B cells become anergic
- 43Antibody structureFab region:
1. F-ragment, a-ntigen b-inding
2. Unique antigen-binding pocket, only 1 antigenic specificity expressed per B cell
Fc region:
Constant
Carboxy terminal
Complement binding
Carbohydrate side chain
Determines isotope (IgM, IgD, etc)
- 44Generation of antibody diversity1. Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT)
3. Random combination of heavy and light chains - 45Generation of antibody specificity1. Somatic hypermutation + affinity maturation (variable region)
2. Isotype switching (constant region) - 46IgG (about)- Main antibody in delayed response
- Most abundant isotype in serum
- Fixes complement - opsonizes bacteria - neutralizes bacterial toxins and viruses
- Crosses placenta - 47IgA (about)- Prevents attachment of bacteria/viruses to mucous membranes
- DOES NOT fix complement
- Monomer (circulation)....Dimer (w/ J chain)
- Produced in Peyer's Patches
- Secreted in tears, saliva, mucus, milk - 48IgM (about)- Immediate response to an antigen
- Fixes complement
- DOES NOT cross placenta
- Monomer on B cell surface, Pentamer with J chain when secreted - 49IgD (about)Unclear
- 50IgE (about)- Binds mast cells basophils
- Allergen exposure --> cross-link --> Type I hypersensitivity through histamine release
- Activates eosinophils --> mediates immunity to worms
- Lower concentration in serum - 51Acute-phase reactants (that increases)Positive:
1. CRP - opsonin, fixes complement, facilitates phagocytosis (binds phosphocholine)
2. Ferritin - binds + sequester iron to inhibit microbial iron scavenging
3. Fibrinogen - Coagulation factor, correlates with ESR
4. Hepcidin - decrease iron absorption (it degrades ferroportin) + decrease iron release --> anemia if chronically inflammed
5. Serum amyloid A - prolonged elevation leads to amyloidosis - 52Acute phase reactants (that drops)1. Albumin - reduction conserves protein for positive reactants
2. Transferrin - internalized by macrophages to sequester iron - 53Complement (activation, functions, etc)Activation:
1. Classic - IgG or IgM mediated
2. Alternative - microbe surface molecules
3. Lectin - mannose/other sugars on microbe surface
Functions:
C3b - opsonization
C3a, C4a, C5a - anaphylaxis
C5a - neutrophil chemotaxis
C5b-9 - cytolysis by MAC
Inhibitors: DAF (decay-accelerating factors - CD55) and C1 esterase inhibitor --> help prevent complement activation on self cells - 54Complement schematic
- 55Macrophage-secreted Cytokines"Hot T-bone stEAK"
IL-1: fever (Hot) + endothelial adhesion molecules (hot as in sexy)
IL-2: stimulates T cells (all types + NK)
IL-3: stimulates bone marrow (stem cells)
IL-4: stimulates IgE production, Th2 cell differentiation
IL-5: stimulates IgA production
IL-6: stimulates aKute-phase protein (&fever)
"clean up on aisle 8"
IL-8: chemotactic factor for neutrophils
IL-12: Th1 cell differentiation, NK cell activation
TNF-a: vascular leak --> WBC recruitment + septic shock - 56Respiratory Burst (oxidative burst)- NADPH oxidase complex (in neutrophils, monocytes) --> uses O2 as a substrate --> generates ROS to kill microbes --> uses NADPH again to get rid of excess ROS
1) O2 --> NADPH oxidase --> O2 superoxide
2) O2 superoxide --> superoxide dismutase
--> H2O2
3) Myeloperoxidase (blue/green heme pigment) of ROS generation that gives sputum its color
- 57Interferon a and B- Inteferons are glycoproteins that cleave viral nucleic acid and protein
- Virally infected cells synthesize inteferons --> that protect un-infected cells from viruses - 58T cell surface proteinsTCR - binds antigen-MHC complex
CD3 - assoc. w/ TCR for signal transduction
CD28 - binds B7 (CD80/86) on APC
CXCR4/CCR5 - co-receptors for HIV
Helper T cells - CD4, CD40L
Cytotoxic T cells - CD8, CXCR4/CCR5
Regulatory T cells - CD4, CD25 - 59B cell surface proteinsIg - binds antigen
CD19, CD20, CD21 (EBV receptor), CD40
MHC II, B7 (CD80/86) - 60MacrophagesCD14 - receptor for PAMPs (i.e. LPS)
CD40
MHC II, B7 (CD80/86)
Fc and C3b receptors - phagocytosis - 61NK cellsCD16 - binds Fc of IgG
CD56 - unique marker for NK - 62Hematopoietic stem cellsCD34
- 63Type I Hypersensitivity"anaphylactic and atopic"
- IgE on surface of pre-sensitized mast cells and basophils --> free antigen cross-links these IgE --> trigger immediate release of vasoactive amines (histamine)
-Action at postcapillary venules
- FAST action
i.e. Rhinitis, eczema, hives, asthma, bee sting - 64Type II Hypersensitivity"cytotoxic"
IgM, IgG bind to fixed antigen on enemy cell -->
1. Opsonization + phagocytosis
2. Complement and Fc receptor mediated inflammation
3. Antibody-mediated cellular dysfunction
i.e. Coomb's tests:
1. Direct = testing for antibodies already bound to RBC surfaces
2. Indirect = testing for antibodies that CAN adhere to RBC surfaces - 65Type III hypersensitivityImmune complex (antigen-IgG) activate complement --> attract neutrophils --> neutrophils release lysosomal enzymes
Can be assoc. w/ vasculitis + systemic manifestations.
Serum sickness - antibodies to foreign proteins are produced (takes 5 days) --> immune complexes form --> deposited in membranes --> fix complement --> tissue damage
Arthus reaction - local subacute reaction. Intradermal injection of antigen into presensitized (IgG circulating) individual --> immune complex formation in skin --> edema + necrosis + complement activation - 66Type IV HypersensitivityDelayed (T-cell mediated) type
Sensitized T cells encounter antigen --> release cytokines --> macrophage activation
I.E. Transplant rejection, TB skin tests, Touching (contact dermatitis) - 67Blood transfusion reactions (4)Allergic reaction - type I hypersensitivity against proteins in transfused blood
1. Urticaria (red skin patches) 2. Pruritus 3. Wheezing 4. Fever
Treat with anti-histamines
Anaphylactic reaction - severe allergic run
1. Dyspnea 2. Bronchospasm
3. Hypotension 4. Respiratory arrest
5. Shock
Treat with epinephrine
Febrile non hemolytic transfusion reaction - Type II reaction against donor HLA antigens and WBCs
1. Fever 2. Headaches 3. Flushing
Acute hemolytic transfusion reaction - Type II reaction. Intravascular hemolysis (ABO incompatibility) OR extravascular hemolysis
1. Fever 2. Hypotension 3. Tachypnea
4. Tachycardia 5. Hemoglobinuria (if intravascular hemolysis) 6. Jaundice (if extravascular) - 68Hyperacute transplant rejectionOnset within minutes
Pre-existing recipient antibodies react to donor antigen
(type II hypersensitivity reaction) --> activate complement --> widespread thrombosis of graft vessels --> ischemia/necrosis - 69Acute transplant rejectionWeeks to months onset
CD8+ T cells activated against MHCs (type IV hypersensitivity reaction)
Vasculitis of graft vessels w/ dense interstitial lymphocytic infiltrate
Prevent/reverse w/ immunosuppressants - 70Chronic transplant rejectionMonths to years onset
CD4+ T cells respond to recipient APCs presenting donor antigens.
Type II AND IV hypersensitivity reactions
Recipient T cells react --> cytokine secretion --> proliferation of vascular smooth muscle + parenchymal atrophy + interstitial fibrosis --> arteriosclerosis
i.e. lung --> bronchiolitis obliterans
heart --> accelerated atherosclerosis
kidney --> chronic graft nephropathy
liver --> vanishing bile duct syndrome - 71Graft-versus-host diseaseVariable onset
Grafted immunocompetent T cells proliferate in immunocompromised host and reject host antigen --> organ dysfunction. Type IV hypersensitivity
1. Maculopapular rash
2. Jaundice
3. Diarrhea
4. Hepatosplenomegaly
Bone marrow transplant; liver transplants - 72Apoptosis - intrinsic pathway-ATP-dependent programmed cell death
-Activate caspases (cytosolic proteases)
-Chromatin condensation + membrane blebbing + apoptotic body formation
-Eosinophilic cytoplasm + basophilic nuclei
~ intrinsic pathway ~
- mitochondrial
- for tissue remodeling (embryogenesis)
- occurs when:
1. regulating factor withdrawn from a proliferating population (less IL-2 after a completed immunological reaction)
2. Injurious stimuli (radiation, toxins, etc)
Regulated by Bcl-2 family of proteins:
BAX/BAK (proapoptotic)
Bcl-2 (antiapoptotic) - 73Apoptosis - Extrinsic pathway-ATP-dependent programmed cell death
-Activate caspases (cytosolic proteases)
-Chromatin condensation + membrane blebbing + apoptotic body formation
-Eosinophilic cytoplasm + basophilic nuclei
~extrinsic pathway~
1. Ligand receptor interactions (FasL binds to Fas, TNF-a binds to TNF)
2. Immune cell (CD8+ T cell release perforin + granzyme B) - 74Necrosis - coagulativeSeen in: ischemia/infarcts in most tissues (not brain)
Due to: ischemia/infarct --> protein denaturation --> enzymatic degradation
Histology: cell outlines preserved --> eosinophilic
- 75Necrosis - liquefactiveSeen: Bacterial abscesses + brain infarcts (cuz there's a lot of fat content)
Due to: neutrophils release lysosomal enzymes digesting the tissue. Enzymatic degradation THEN protein denaturation
Histoloy:
Early: cellular debris + macrophage
Late: cystic spaces + cavitation (brain)
*neutrophils + cell debris seen w/ bacteria*
- 76Necrosis - caseousSeen: TB, systemic fungi (histoplasmosis), nocardia
Due to: Macrophages wall off the infecting microorganism --> granular debris
Histology: fragmented cells + debris surrounded by lymphocytes, macrophages
- 77Necrosis - FatSeen in:
1. enzymatic - acute pancreatitis (saponification of pancreatic fat)
2. Nonenzymatic - traumatic (breast injury)
Due to: damaged cells release lipase --> break down triglycerides in fat cells
Histology: outlines of dead fat cells w/o peripheral nuclei + saponification of fat (appears dark blue on H&E stain)
- 78Necrosis - fibrinoidSeen: immune reactions in vessels (polyarderitis nodes, giant cell arteritis)
Due to: Immune complexes combine with fibrin --> vessel wall damage
Histology: vessel walls are thick and pink
- 79Necrosis - gangrenousSeen in: distal extremity post-chronic ischemia
Due to: ischemia (if dry) --> coagulative histology
superinfection (if wet) --> liquefactive superimposed on coagulative
- 80Infarcts (red)Hemorrhagic infarcts.
Happen in:
1. Venous occlusion
2. Tissues w/ multiple blood supplies (intestine, liver, lung, testes)
Reperfusion injury due to damage by free radicals
- 81Infarcts (pale)Pale (anemic) infarcts occur in solid organs with a single blood supply (i.e. heart, kidney, spleen)
- 82Inflammation (acute and chronic)Rubor-Dolor-Calor-Tumor-Functio laesa
Vasculature:
increased vascular permeability + vasodilation + endothelial injury
Cellular:
neutrophils leave circulation to injured tissue to participate in inflammation
1. phagocytosis
2. degranulation
3. inflammatory mediator release
Acute: neutrophil + eosinophil + antibody mediated. Rapid onset + short duration.
Outcome:
1. complete resolution
2. abscess formation
3. chronic progression
Chronic: mononuclear cell (monocyte/macrophages, lymphocytes, plasma cells) + fibroblast mediated. Persistent destruction + repair.
Granuloma (nodular collections of epithelioid macrophages + giant cells)
Outcome:
1. scarring
2. amyloidosis - 83Chromatolysis-Reaction of neuronal cell body to axonal injury
-Change reflects increased protein synthesis to repair damaged axon
1. Round cellular swelling
2. Nucleus displacement to periphery
3. Cytoplasmic dispersion of Nissl substance
Concurrent with Wallerian degeneration
- 84Leukocyte extravasationOccur mostly at post capillary venules
1. Margination and rolling
Vasculature: E-selectin, P-selectin
Leukocyte: Sialyl-Lewis(X), L-selection
2. Tight-binding
Vasculature: ICAM-1, VCAM-1
Leukocyte: CD11/18 integrins
3. Diapedesis
Vasculature: PECAM-1
Leukocyte: PECAM-1
4. Migration
Vasculature: Chemotaxis (C5a, IL-8)
- 85Scar formation (hypertrophic)- Increased parallel collagen synthesis
- Scar confined to borders of original wound
- possible spontaneous regression
- 86Scar formation (keloid)- Massively increased collagen synthesis
- Disorganized collagen organization
- Extends past borders of original wound
- May progress over the year
*higher incidence in darker skin ethnic groups* - 87Granulomatous diseasesTh1 cells secrete IFN-g --> macrophages activated --> TNF-a from macrophages induce + maintain granuloma formation
Bacterial:
1. Mycobacteria (TB, leprosy)
2. Bartonella henselae
3. Listeria monocytogenes
4. Treponema pallidum (3* syphilis)
Fungal:
1. Endemic mycoses (histoplasmosis)
Parasitic:
1. Schistosomiasis
Chronic granulomatous disease
Autoinflammatory:
1. Sarcoidosis
2. Crohn disease
3. Primary biliary cirrhosis
4. Subacute (de Quervain) thyroiditis
5. Granulomatosis w/ polyangiitis (Wegener)
6. Eosinophilic granulomatosis w/ polyangiitis (Churg-Strauss)
7. Giant cell (temporal) arteritis
8. Takayasu arteritis
Assoc. w/ hypercalcemia due to calcitriol (1,25-[OH]2- vitamin D3) production
Caseating necrosis more common w/ infectious causes
Diagnosing sarcoidosis needs non-caseating granulomas on biopsy - 88ExudateCellular (cloudy)
[protein], [LDH] > [serum]
Specific gravity > 1.020
Due to:
1. Lymphatic obstruction
2. Inflammation/infection
3. Malignancy - 89TransudateHypocellular (clear)
[protein], [LDH] < serum
Specific gravity < 1.012
Due to:
1. Increased hydrostatic pressure (CHF, Na retention)
2. Decreased oncotic pressure (cirrhosis, nephrotic syndrome) - 90Erythrocyte sedimentation rate (ESR)products of inflammation (fibrinogen) coat RBCs and cause aggregation
Increase:
1. Most anemias
2. Infections
3. Inflammation (temporal arteritis, etc)
4. Cancer
5. Renal diseases (end-stage, nephrotic)
6. Pregnancy
Decrease:
1. Sickle cell disease
2. Polycythemia (more RBC dilutes aggregation factors)
3. Heart Failure
4. Microcytosis
5. Hypofibrinogenemia - 91AmyloidosisAbnormal aggregation of proteins into B-pleated linear sheets --> damage and apoptosis
- Congo red stain + apple tree birefringence on polarized light
AL - deposition of proteins from Ig Light chains (from multiple myeloma, etc)
1. Nephrotic syndrome
2. Restrictive cardiomyopathy
3. Arrhythmia
4. Splenomegaly
5. Neuropathy
AA - seen w/ chronic inflammatory conditions (Rheumatoid arthritis, IBD, familial mediterranean fever, etc)
- composed of serum amyloid A
- multi-system like AL amyloidosis
Age-related (senile) - deposition of normal transthyretin (TTR) predominantly in cardiac ventricles.
1. Slower progression of cardiac dysfunction relative to AL amyloidosis
- 92LipofuscinYellow-brown pigment assoc. w/ normal aging formed by oxidation + polymerization of autophagocytosed organelle membrane
1. Eyes
2. Colon
3. Liver
4. Heart
- 93Preneoplastic and neoplastic cellular changesNeoplasia - Uncontrolle, clonal proliferation of cells...can be benign or malignant
Dysplasia - disordered, non-neoplastic cell growth, used only with epithelial cells.
Mild usually reversible; severe usually progresses to carcinoma in situ
Differentiation - degree to which a malignant tumor resembles its tissue of origin.
Anaplasia - complete lack of differentiation of cells in a MALIGNANT neoplasm