Section 1
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• Secondary amyloidosis
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Last updated
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Date created
Mar 1, 2020
Cards (162)
Section 1
(50 cards)
• Secondary amyloidosis
Secondary to chronic inflammatory states(Crohns, lupus, RA, autoimmune diseases); Deposition of AA amyloid derived from SAA;
○ Vitamin A deficiency
§ Night blindness, § Required for maturation of immune system § Metaplasia of the epithelium of the conjunctiva = keratomalacia
• Chediak-Higashi Syndrome
Microtubule defect = inability to traffic a phagosome; Failure to merge a phagosome with a lysosome; high pyoghenic infection rate, neutropenia , giant granules in leukocytes, defective primary stasis, albinism, peripheral neuropathy
Toll - Like Receptors
recognize pathogen associated molecular patterns (PAMPS); found on macrophages and dendritic cells; CD14 recognizes lipopolysaccharide (LPS) - on gram negative bacteria
Carbon monoxide
sources: car exhaust gas heaters smoke of a hour fire Cherry red apparence of skin, headache (early sign), coma
LTB4
neutrophil activation and attraction
○ CCl4
Dry cleaning industry, Converted to CCl3 in the liver causing reversible swelling to hepatocytes, § Swelling inhibits protein synthesis and apolipoproteins cannot be formed
Karyolysis
pieces broken down to building blocks
Fibrinoid necrosis
○ Necrotic damage to blood vessel wall Proteins leak into vessel wall - stains bright pink Seen in malignant hypertension or vasculitis
IL-8, C5a, LTB4
Chemoattractants
Amyloidosis
Misfolded protein that deposits in extracellular space causing damage; Stains congo red with apple-green birefringence; ○ Tends to deposit around blood vessels
PGE2
mediates feeever and pain
Leukocyte Adhesion Deficiency
Delayed separation of umbilical cord, increased circulating neutrophils, recurrent bacterial infections without pus; Defect in CD18 subunit
Methemoglobinemia
oxidized Fe to Fe3+ § Cannot bind O2 Seen with oxidative stress
selectin (P and E)
Factors for margination and rolling of immune cells
Cytochrome C
Leaks from mitochondria when damaged, activates apoptosis
PGI2, PGD2, PGE2
these factors cause vasodilation (arteriole) and increases permeability (venules)
Primary amyloidosis
Derived from immunoglobulin light chain; Plasma cell dyscrasias; Overproduction of the light chain
Mesenchymal tissues
bone, blood vessels, cartilage, fat (connective tissue))
• Caseous necrosis
"cottage cheese like apparence" ○ Liquefactive necrosis with coagulation TB and fungal infections
○ Cardiomyoctyes ○ Skeletal muscles ○ Nervous tissue
• Permanent tissues that cannot make new cells, only undergoes hypertrophy
Mast cells
activated via issue trauma, C3a and C5a, surface IgE; Dumps histamine: vasodilatory (arteriole) and increase vascular permeability (venules); Produces leukotrienes (LTs) from arachidonic acid
Fever
Pyrogens induce IL-1 and TNF release from macrophages; Increases COX activity in perivascular cells of hypothalamus; Increased PGE2 raises temperature set point
Classical pathway
C1 binds to IgG or IgM that is bound to a surface antigen "GM is classic"
Phagocytosis
Enhanced via opsonins (IgG, C3b)
○ Barrett esophagus
§ Metaplasia of the lower esophagus from squamous epi to columnar epi (with goblet cells) (handles acid better)
P selectin
released by Weibel-Palade bodies with von Willebrand factor
transferrin
tightly binds Fe
Shock
generalized decreased perfusion of the organs; Vital organs all under ischemia and hypoxia
Ubiquitin
tags intermediate filaments in order to be degraded by a proteosome
Granzyme
actiaves caspases, released by CD8 T cell
Pyknosis
shrinkage of the nucleus
caspases
Activates proteases and endonucleases, activated by cytochrome C
Karyorrhexis
nucleus breaks down into pieces
• Bud chiari syndrome
○ d/t polycythemia vera (inc'd RBCs) Occlusion in the hepatic vein induces ischemia in the hepatic parenchym
Familial mediterranean fever
Dysfunctional neutrophils; Induces inflammation when there is no threat; Attacks serosal surfaces
Reperfusion injury
when oxygen and inflammatory cells perfuse the necrotic tissue, an inflammatory process generates free radicals, increasing damage
E selectin
induced by TNF and IL-1; binds to sialyl Lewis X on leukocytes
Alternative pathway
microbial products activation
Perforin
creates a hole in the membrane, released by CD8 T cell
familial amyloid cardiomyopathy
mutated serum transthyretin; causes restrictive cardiomyopathy
Wilson's disease
excess copper in the system
Myositis ossificans
□ Trauma to skeletal muscle is converted into bone
senile cardiac amyloidosis
Serum transthyretin deposits in the heart
vitamins A, C, E
Antioxidants
Hageman factor
Produced by liver; Activated when exposed to subendothelial or tissue collagen; Activates Coagulation and fibrinolytic system Complement Kinin system: produces bradykinin - vasodilatory, increased vascular permeability, pain
Mannose-binding lectin pathway
binding of mannose on microorganisms induces actiation
5' - lipooxygenase
Produces leukotrienes
ferritin
stores Fe in macrophages
LTC4, LTD4, LTE4
smooth muscle contraction; vasoconstriction, bronchospasm, increased vascular permeability
Section 2
(50 cards)
Ferroportin
transporter of Fe from enterocytes to blood stream
Complement Deficiencies
C5-C9 deficient = Neisseria Infection (gonorrhea, menigitidis) C1 inhibitory deficiency - hereditary angioedema, periorbital and mucosal surfaces
TGF -beta
inhibits inflammation, fibroblast growth factor
IL-5
-From Th2 cells -Promotes differentiation of B cells. Enhances class switching to IgA. Stimulates growth and differentiation of eosinophils.
Ferritin
binds Iron intracellularly
TIBC
how many transferrin molecules are in the blood
Mixed connective tissue disease
Mixed features of SLE, systemic scleroderma, polymyositis Antibodies against U1 ribonucleoprotein
Keloid
out of proportion of scar tissue Excess type III collagen Seen in blacks Affects earlobes, face, upper extremities
Non-caseating
Granulomas WITHOUT central necrosis - cells HAVE nuceli Reaction to foreign material;
IL-4
-From Th2 cells -Induces differentiation into Th2 cells. -Promotes growth of B cells. -Enhances class switching to IgE and IgG.
Platelet derived growth factor
growth factor for endothelium, smooth muscle and fibroblasts
Secondary intention
Wound healing where edges can't be easily approximated and wound fills with granulation
B cell activation
Antigen binding to surface IgM; Or, B cells consume an antigen, present in on MHC II and present it to CD4 t helpers, Second signal involves CD40 and CD40L, T helper matures B cell via IL4 and IL5
Transferrin
binds to iron in the blood and delivers it to the liver and bone marrow macrophages
Copper deficiency:
cofactor for lysyl oxidase - crosslinks lysine and hydroxylysine to form stable collagne
Zinc deficiency:
needed to replace type III collagen with Type I
Systemic Lupus Erythematosus
Malar "butterfly" rash with sun exposure Arthritis erosal inflamamtion (pleuritis, pericarditis) CNS psychosis Diffuse proliferative glomerulonephritis □ Libman-sacks endocarditis - vegetations on both sides of the mitral valve Anemia, thrombocytopenia, leukopenia
Microcytic Anemia: MCV < 80
One extra division occurs due to inadequate concentration of hemoglobin The RBC is trying to raise the concentration of hemoglobin in the cell by being a smaller cell
X-Linked Agammaglobulinemia
Bruton's disease No B cell maturation - naïve B cells don't mature into plasma cells; Mutated Bruton tyrosine kinsase; Increased infections with bacteria, enteroviruses, and giardia lamblia Avoid live vaccines
Chronic Granulomatous Disease
NADPH oxidase deficient - cannot for O2-; cannot form bleach; Catalase blocks production of hydrogen peroxide DX: nitroblue tetrazolium test - Tests the reaction of O2 to superoxide
Labile tissue
continuously regenerate tissue Small and large bowel (stem cells in mucosal crypts) Skin (stem cells in basal layer) Bone marrow (hematopoietic tissue)
Vitamin C deficiency
cofactor for hydroxlation of proline or lysine in procollagen residues, hydroxylation needed to cross-link collagen
Wiskott-Aldrich Syndrome
Thrombocytopenia, eczema, recurrent infections (defective humoral and cellular immunity) Mutated WASP gene
Thalassemia
decreased production of globin chain
Caseating necrosis
Central necrosis; Tuberculosis and fungal infection
Sjogren Syndrome
type IV HSR Destruction of salivary and lacrimal glands Keratoconjunctivits, xerostomia, recurrent dental carries Anti-ribonucleoprotein antibodies Increased B cell lymphoma risk - Presents as unilateral enlargment of parotid gland late in course
Heme
iron and protoporphyrin
granuloma formation
1) Macrophage present antigen to CD4 t helper via MHC II 2) Macrophages release IL-12 inducing Th1 subtype differentiation 3) Th1 secreted IFN-gamma converting macrophages to epithelioid histiocytes
SCID etiologies
A) Loss of cytokine receptors (needed for activation b) Adenosine demainase deficient: adenosine must be deaminated so it can be excreted, without demainase, adenosine buildup is toxic to lymphocytes c) MHC class II deficiency: without MHC II, CD4 Tcells cannot be activated and cytokines will not be released
Primary intention
primary union of the edges of a wound, progressing to complete scar formation without granulation, minimal scar formation
Anemia of chronic disease
poor avaiablility due to stored iron in macrophages
% Saturation
percentage of transferrin bound to iron
IgA Deficiency
Most common immunoglobulin deficiency; Increased risk for mucosal infections, especially viral;
Serum ferritin
how much Fe is present in the bone marrow macrophages and the liver
Fibroblasts growth factor
Growth factor important in angiogenesis involved in tissue regeneration and repair; also mediates skeletal development
scleroderma - diffsue type
Tissue damage activates fibroblasts and deposition of collagen Affects skin and any visceral organ early Commonly esophagus is presenting as dysphagia Anti-DNA topoisomerase (Scl-70) antibodies
Systemic Lupus Erythematosus diagnosis
Anti dsDNA antibodies
TGF-alpha:
epithelial and fibroblast growth factor
Permanent tissues
once cells are lost, they are gone Cardiomyocytes, skeletal, and neurons
Severe Combined Immunodeficiency
Loss of cell mediated immunity (T cells) and humoral immunity (B cells); Increased infections with fungal, bacterial, viral, protozoan infection; Treatment: stem cell transplantation
Stable Tissue
cells are quiescent, but can reeneter cell cycle if necessary Liver: partial resection induces hyperplasia of liver
scleroderma - localized
Tissue damage activates fibroblasts and deposition of collagen Skin and late visceral involvement C: calcinosis, anti- centromere antibodies R: raynaud's E: esophageal dysmotility S: slcerodactyly T: telangiectasias
(IL-10, TGF-Beta
anti-inflammatory cytokines, shuts down inflammation process; released by macrophages
Granulomatous Inflammation
Key cell: epitheloid histiocyte - macrophage with abundant pink cytoplasm; form of chronic inflammation
Iron Deficiency Anemia
Koilonycia (spoon shaped nails), PICA
Repair
Occurs when stem cells of the tissue is lost and a fibrous scar is put in place
Sideroblastic anemia
low production in protophorphyin
DiGeorge Syndrome
22q11 microdeletion; 3rd and 4th pharyngeal arches fail to form; No thymus = no T cells; No parathyroids = hypocalcemia; Abnormalities of great vessels, face, and heart
Systemic Lupus Erythematosus
○ Antibodies against self-tissues (HSR II = cytotoxic) and deposition of Antigen-antibody complex (HSR III)
Hyper-IgM Syndrome
Class switching for B cells is impaired as B cells lack a CD40 receptor or T cells lack a CD40 ligand; Without CD40 interaction, cytokines cannot be released to initiated class switching Low IgA, IgE, IgG, leading to recurrent pyogenic infections from poor opsonization
Section 3
(50 cards)
sickle cell anemia
Autosomal recessive mutation in beta chain of Hb Glutamic acid --> valine Protection against falciparum malaria
Ferrochelatase
Enzyme that catalyzes joining of iron and protoporphyrin to make heme in the mitochondria
Paroxysmal nocturnal hemoglobinuria
Red urine in the morning, fragile RBCs Disease results due to loss of GP-I Hemoglobinemia, hemoglobinuria, Hemosiderinuria RBCs, WBCs, and Platelets are all lysed With shallow breathing at, we become slightly acidotic, activating complement, causing degradation to RBC
DAF MIRL
prevent damage due to complement bound to cell via GP-I
Macrocytic anemia and Hypersegmented neutrophils Glossitis Subacute combined degeneration of spinal cord increased homocysteine increased methylmalonic acid
lab findings of Vitamin B12 deficiency
Ringed sideroblasts
Build up Fe in the mitochondria due to lack of available protoporphyrin
ALAD
converts ALA to porphobilinogen
haptoglobin
Binds free hemoglobin after RBC lysis to be destroyed by spleen decreases during intravascular hemolysis
Anemia with splenomegaly Jaundice due to unconjugated bilirubin Increased risk for bilirubin gallstones Marrow hyperplasia with corrected reticulocyte count
lab findings - extravascular hemolysis
Sickle cell disease
2 abnormal beta genes, >90% HbS in RBCs HbS polymerizes when deoxygenated into needle-like structures HbF protects against sickling
Vitamin B12
found in animal proteins binds to R-binder (from salivary glands) cleaved by proteases (of pancreas) Binds to intrinsic factor (from parietal cells) absorbed in ileum
Hereditary spherocytosis - extravascular hemolysis
RBC membrane defect in tethering proteins: spectrin/band 3.1/ankyrin, Hemolytic anemia, jauncide, and splenomegaly often after URIs
Loss of central pallor Increased RDW and increased mean corpuscular hemoglobin concentration Splenomegaly, jaundice with unconjugated bilirubin and increased gallstones Increased risk for aplastic crisis with parvovirus B19B of erythroid precursors
Lab features of hereditary spherocytosis
Metabisulfite
used to screen for sickle cell = causes cell to sickle
Hydroxyurea
treatment for sickle cell anemia, increases HbF concentrations
Reticulocyte
baby RBC 1-2% normally bluish cytoplasm - due to RNA
ALAS deficiency
enzyme convers succinyl CoA into amino-lavulinc acid with vitamin B6 as a cofactor deficiency results in sideroblastic anemia (no protoporphyrin)
poor diet (alcohol and old people) increased demand (pregnancy, cancer, hemolytic anemia) Folate antagonists (methotrexate, dihydrofolate reductase inhibitor)
folate deficiency causes
>3%
good marrow response, peripheral destruction
Beta thalassemia major
Microcytic anemia where alpha tetramers aggregate extravascular hemolysis due to splenic macrophages massive erythroid hyperplasia due to increase in RBC need risk of aplastic crisis with Parvovirus B19 infection No HbA, increased HbA2 and HbF
Heinz bodies
Intracellular inclusions seen in thalassemia, G6PD deficiency, and postsplenectomy removed via splenic macrophages producing bite cells
Increased ferritin, decreased TIBC increased serum iron and % saturation
Sideroblastic Anemia lab findings
thalassemia
carriers are protected against plasmodium falciparum malaria with this microcytic anemia
Ferritin increases, TIBC decreases decreased serum Iron, decreases % saturation increased free erythrocyte protoporphyrin
Anemia of chronic disease
IgG-mediated disease (extravascular hemolysis)
Membrane of antibody-coated RBC is consumed by splenic macrophages, producing spherocytes treatment: Steroids, IVIG, splenectomy
Hemoglobin C
Lysine is substituted for Glutamic Acid at the 6th position on the Beta chain. Mild anemia due to extravascular hemolysis
HbA2
Alpha2 Delta2
Plummer-Vinson syndrome
Esophageal webs with iron deficiency anemia and atrophic glossitis
Sickle cell trait
Asymptomatic One mutated and one normal beta chain <50% HbS in RBCs Does sickle in renal medulla due to hypoxia and hypertonicity
Increased RDW Ferritin decreases, TIBC increases Serum iron decreases % Saturation decreases Free erythrocyte protoporphyrin increases
Iron Deficiency Anemia Lab Findings
HbF
Alpha2 Gamma2
Unconjugated bilirubin
macrophage degradation of heme; lipid soluble; never in urine bound to albumin delivered to liver for conjugation and excreted through bile
Irreversible sickling
leads to vasoocclusion and 1.Dactylitis, 2.Autosplenectomy, 3.Acute Chest Syndrome, and 4.Renal Papillary Necrosis
pernicious anemia
lack of mature erythrocytes caused by inability to absorb vitamin B12 into the bloodstream due to autoimmune attack of the parietal cells
Macrocytic anemia
due to folate or vitamin B12(cobalamin) deficiency THF-M --> VitB12-M --> homocyteine --> methionine, (transfer of methyl groups)
Hemosiderinuria
Represents the IRON that has been retained by renal tubular cells as they reabsorb filtered hemoglobin and slough during urination
jejunum
Folate absorbed here
alcoholism - poisons mitocondria Lead poisoning - denatures ALAD and ferrochelatase Vitamin B6 deficiency - needed with ALAS
acquired sideroblastic anemia causes
Subacute combined degeneration of the spinal cord
degeneration of the posterior and lateral columns of the spinal cord due to a buildup of methymalonic acid vitamin B12 is a cofactor for converting methylmalonic acid to succinyl CoA
Alpha Thalassemia
Microcytic anemia due to a gene deletion, 3 gene deletions causes a severe anemia in which beta chains form tettamers (HbH) 4 gene deletions: lethal in utero causing "hydrops fetalis", gamma chains forms tetramers (Hb Barts)
Glucose-6-phosphate dehydrogenase deficiency
RBCs become susceptible to oxidative stress Cannot produce glutathione - cannot be oxidized by H2O2 Protective against falciparum malaria Oxidative stress causes Heinz bodies
Normocytic anemi
peripheral destruction of RBCs or underproduction of RBCs
Macrocytic RBCs and hypersegmented neutrophils Glossitis increased homocysteine decreased serum folate normal methylmalonic acid
folate deficiency lab findings
massive erythroid hyperplasia
Hemaopoiesis in the skull and facial bones Extramedullary hematopoiesis with hepatomegaly Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
Osmotic fragility test
Diagnostic test for hereditary spherocytosis.
Ferrous Sulfate
Treatment of iron deficiency anemia
Howell-Jolly bodies
occurs after splenectomy as the spleen cannot remove nuclear fragments from RBCs
<3%
poor marrow response = underproduction
Hemoglobinuria Hemoglobinema Hemosiderinuria
lab findings - intravascular hemolysis
HbA
Alpha2 Beta2
Section 4
(12 cards)