Disease Flashcards
Pathology:
Breakdown of hemoglobin in vessels.
Lab test:
↑free Hgb
↑LDH
↑SGOT
↑RetC-to compensate for hemolysis
↑RDW-fast output old and new cells
Hemoglobinuria/plasma – b/c cannot process all.
↑ Indir bili-overloaded system cannot keep up with demand so bili does not get conjugated to glucuronic acid
↑Metheme/methemoglobin-b/c broken free heme byproduct
↓Haptoglobin-taken out of serum when binds heme to the liver
Disease: Intravascular Hemolysis
Splenomagaly
Pathology:
Ingestion and clearance by macrophages in the Reticulo-endothelial system. Fe stored in ferritin and hemeàbili
Enterohepatic recirculation of urobilirubin after cleavage of glucuronic acid in gutà elevated levels of direct bili.
Lab tests: ↑LDH ↑SGOT ↑RetC ↑RDW ↑Direct bili (enterohepatic recirculation)
Extravascular Hemolysis
Pathology:
Protects against oxidative stressà ↓ G6PDà↓reduced glutathioneàlacks ability to help with oxidative stressà Hgb sticks to spectrin on RBC wallà abnml shapeàlysis by spleen
-sex-linked rec
Lab Test: Protein in urine (?) Perif Smear (sometimes see)à Microspherocytes Blister cellsà cytoskeleton defect Bite cellsà same Usually NO morphology Δ
Treatment: -Folate
- Avoid oxidative foods (fava beans)
- supportive care
Glucose-6-Phosphate Dehydrogenase
Clinical SS:
- Intermittent acute hemolytic anemia
- hyperbilirubinemia
Clinical SS:
- Anemia mild-mod
- Jaundice
- Splenomegaly
- Hyperbili in 1/3rd of neonates
- Aplastic crisis
- Bilirubin -> high stone -> cholecystectomy
Pathology:
Spectrin/ankyrin/
band 3 mutations -> weak cytoskeleton, spherical shape _>splenic entrapment and easy to lyse
Lab Test:Hct-variable Hgb-variable ↑RetCàaccount for hemolysis ↑indir biliàtoo much heme to process ↓MCVàmaking too fast so microcytic Osmotic fragility testàabnml/low Spherocytes on smear
Treatment:
splenectomy
Hereditary Spherocytosis
Clinical SS:
Variable chronic anemia Extravascular hemolysis Splenomegaly Gallstones Aplastic crisis
Pathology:
Problemàpyruvate problemà ↓ATP productionà ↑2,3-BPG and mis-shapen RBCsàsplenic destruction
Lab Test:
↑RetCàaccount for hemolysis
NO morphology Δ
Treatment:
- Folate
- Spenectomy-s.times
- transfusions in severe cases
PK-Pyruvate Kinase Deficiency
Clinical SS: Dark Urine Acute/Chronic anemia Pallor/Jaundice Splenectomy s.times
SAME FOR EXTRA
Pathology:
IgG and IgMàactivates C5-9 complementàRBC damage by complement
Lab Test:
↑RetC ↑Bili Hemoglobinuria Spherocytes Bite cells Direct Coombs (test for IgG, C3D, C4D-bound to RBC)à + Complement (C3D, C4D) Indirect Coombs (test for IgG and Complement-free in plasma)à \+ complement Treatment:
Autoimmune Hemolytic Disorders
COLD/INTRAvascular
Clinical SS: Dark Urine Acute/Chronic anemia Pallor/Jaundice Splenectomy s.times
Pathology:
IgG only
Opsonizing
Macrophages and spleen affected so that the lysis is in the spleen and outside the blood system
Lab Test: ↑RetC ↑Bili Hemoglobinuria Spherocytes Bite cells Direct Coombs (test for IgG, C3D, C4D-bound to RBC)à + IgG (sometimes weak complement) Indirect Coombs (test for IgG and Complement-free in plasma)à \+ IgG
Treatment:
Autoimmune Hemolytic Disorders
WARM/EXTRAvasc.
Clinical SS: Fatigue Pallor Pain with exercise SOB Tachycardia Muscle problems Neurological problems
Pathology: Dietary Absorption problems Inflammation/Infectionà Cytokine production
Lab Test: Microcytic and Hypochromic ↓Hgb-no iron to bind heme ↓Hct-less and smaller RBC’s bc no iron ↓ferritin-iron stores used up ↓RetC-because no iron to make RBC’s ↓serum iron ↑TIBC-bc capacity is increased due to no binding ↑RDW Perif Smear Spherocytes, fragmented cells, target cells
Treatment:
Oral iron salts (150-200 mg tid)
IV/IM iron. 1st see serum Fe respond àRetC nmlizes, Hgb nml after 7- 10 days. Continue treatment until ferritin stores returned and MCV and RDW are nml (which will take 100 days or so until abnml RBC’s have been removed)
Iron Deficiency
Clinical SS:
- Cyanosis without accompanying ↓ in arterial PP
- Brown-blood due to Fe+3 without change when exposed to O2
- In severe casesàbrady, respire depression, convulsions, acidosis.
Pathology:
Acquired
-free radicals (NO, H2O2)
-Drugs (benzocaine)
Hereditary
-homozygous def of cytochrome-b-5-reductase (prevents reduction of Fe+3àFe+2)
-Hemoglobin M (mutation of chains that inhibits reduction of Fe+3)
Lab Test:
Treatment:
Acquired
Remove drug or chemical causing disease
Hereditary
Methylene Blue
Methemoglobinemia
Clinical SS:
- Variable anemia
- Underlying inflammatory disease
- Renal insufficiency
- Thyroid disorder
- Adrenal insufficiency
- fever
- arthritis
- swelling (infections)
Pathology:
Inability to use iron stores and decrease EPO production result from inflammatory cytokines:
-TNF/IL-1à↓iron mobilization/ EPO production
-INFγ/βàinhibits erythropoisis
-Hepcidin (induced by cytokines) à↑ Fe storage, ↓duod abs, block Fe release from macrophages
Lab Test:
-Hgb 8-12
-Usually Normocytic/ normochromic à microcytic /mild hypochroma
↓RetC –reticulocytopenia b/c cannot get iron since sequestered due to presence of hepcidin.
↑Ferritin-due to increased/sequestration of iron(DIFF from Iron defic anemia)
↓TIBC (DIFF from IDA)
↓Serum Iron (like IDA)
↓Transferrin saturation (as with IDA)
↓EPO for degree of anemia (espec with renal disease. But usually not seen until <40% renal function)
Treatment:
-Treat underlying condition to à ↓cytokines and
inflammation
-Give iron
-Give EPO (especially with renal disease)
-Hormone replacement of endocrine disease
Anemia of Chronic Disease/Inflammation
Clinical SS:
- Personality changes
- irritability
- weakness
- wt loss
- abdominal pain and vomiting
Pathology:-Pb inhibits synthesis of protoporphyrin ringà↓heme
Lab Test:
↓MCV =
Microcytic/hypochromic because Pb is preventing production of porphyrin ring
↓RetC-because no heme to make iron so cannot make RBC’s
↑Lead levels
Basophilic stippling-aggregates of RNA(also seen with macrocytic anemia of B12 and Folate)
Treatment:
- . REMOVE source of lead
- Chelation
Lead Based Anemia
Clinical SS:
Variable anemia
Pathology:
Impaired production of protoporphyrin ring or incorporation of Fe into hemeà accumulation of iron in mitochondriaà Ring sideroblasts
Lab Test:
↓MCV =
Microcytic/hypochromic
Pappenheimer bodies (ppt iron in mitochondriaàring around nucleus)
Treatment:
B6-s.times works
Transfusions
Tx of other underlying cause (Cu deficiency, EtOHism, drugs)
Sideroblastic Anemia
Clinical SS:
Slow (months) onset
CNS changes-cognitive dysfunction and emotional changes
Numbness, tingling, loss of fine sensations
Proprioception
Ataxia
CNS changes may be permanent.
Pathology:
Required for synthesis of methionine from homocysteineàprecursors for DNA synthesisàeffect erythropoisis in BM.
So essentially it is a disease of ↓DNA synthesis
Causes
-Vegan Diet-rare cause
-IF deficient = Pernicious Anemiaà (mal-abs of B12)
-autoimmune destruction of parietal cells that secrete IF
-Loss of ilial receptors-surgery, IBD
TcII deficiency
Lab Test:↑MVC = Macrocytic/Normochromic (because increase in size as waiting for DNA to be made-arrest in S phase ↓RBC ↓RetC-because no B12 to make cells Hypersegmented neutrophils-classical sign of B12 or folate deficiency. ↑RDWàanisocytosis -Nuclear-Cytoplasmic Asynchrony M:E ratioàE predominance ↑Homocysteine levels ↑methylmalonic acid ↑ to nml serum folate* ↓B-12 levels (s.times predictive) Shillings Test: If abnml then add IF and see if corrects. If normal then not B-12 abs problem
Treatment: B-12 injections Oral replacement ↑dosesàabs via mass action Watch for other immune diseases -Rapid response to treatment and slowly resolving CNS indicates accurate dx.
B-12 Deficiency
Clinical SS: Quick Onset (weeks)
Pathology:
Required for synthesis of methionine from homocysteineàprecursors for DNA synthesisàeffect erythropoisis in BM.
So essentially it is a disease of ↓DNA synthesis
Causes
Insufficient dietary intake*1⁰
Mal-absàparasitic infection (disrupts enterohepatic recirc)
EtOH consumption excess
Lab Test: ↑MVC = Macrocytic/Normochromic (because ↓RBC ↓RetC-because no B12 to make cells Hypersegmented neutrophils ↑RDWàanisocytosis -Nuclear-Cytoplasmic Asynchrony M:E ratioàE predominance ↑Homocysteine levels ↓serum folate ↓methylmalonic acid
Treatment:
Folate 1mg/d PO/IV/IM
Rapid recovery of CBC.
Folate Deficiency
Clinical SS:
Chronic Hemolytic Anemia
Aplastic crisis - ↓RetC
Pain crisis – Acute chest pain, multi-organ failure, priapism, bone infaction.
Pathology:
Sickling cells are actually “sticky” which leads to vessel damage, endothelial remodeling and vessel narrowing. This microvessel damage affects all organs (lungs, retina, kidneys, spleen, CNS)
Lab Test:
↑RetC-to compensate for hemolysis (except during aplastic crisis)
↑WBC/platelets due to BM response
↑RDW-increase production and constantly changing shape of the sickled cell
↓MCV – Microcytosis (Sβ⁰/Sβ+)
Heme C crystals = red rods in RBC’s (SC disease)
↑Hb Fetal (2-30%)
↑LDH, AST (released from lysed RBC)
↑indirect bilirubin-due to hemolysis
↑Total bilirubin
Perif Smear
Schistocytes
Polychromasia-blue colored cells
Anisocytosis (RDW effect)
Howell Jolly bodies-occur in pt w/out functional spleen due to injury/occlusion from sickled cellsàsplenic sequestration
Treatment:
- BM transplant w/ HLA matched sibling is 90%
- Hydroxyureaà ↑Hb F
- Transfusions – decrease pain crises extend life.
Sickle Cell Anemia
