Pulmonary CN Flashcards
Megaloblastic Macrocytic Anemia
Cause: deficient in folate and Vit. B12
- large erythrocytes (MCV= 100-140 fL normal is 80-100)
- have normal Hb content despite size
- Volume increases
Bone Marrow- large erythroblasts (megaloblasts), and hyper-segmented neutrophils (more than 5 lobes)
Pernicious Anemia
-B12 deficiency due to lack of intrinsic factor protein
- certain fatality in 1900s
- type of megaloblastic macrocytic anemia
- common cause is gastric mucosa destruction from autoimmune mechanism
- usually in elderly Northern Europeans, with possible autoimmune disease
- serum folate: <3 ng/mL
- serum B12: <350 pg/mL
If B12 deficient need to know if diet or absorption
- Gold Standard: Schilling Test- give small amount radioactive B12 and lots unlabeled to saturate receptors, if it is absorbed through GI you find it in urine, collect urine and if it is there the pt. Has dietary issue, if not there then absorption issue, then do same giving labeled B12 and intrinsic factor and if it shows up in urine the pt doesn’t have intrinsic factor themselves
Lead Poisoning
- Pb inactivated ALA dehydratase and Ferrochelatase
- ALA and Protoporphyrin IX accumulate
- ALA neurotoxic (resembles GABA) hence neurological symptoms
- heme production lowered causing anemia (macrocytic and hypochromic)
- impacts ATP synth and energy metabolism through the ETC b/c cytochromes are not synthesized
Acute intermittent porphyria
- Defective Enzyme: PBG deaminase in liver
- autosomal dominant
- deficiency leads to excessive production of ALA and PBG
- Periodic attacks of abdominal pain and neurologic dysfunction
- Hepatic Porphyria
Congenital Erythropoietic Porphyria
- Defective Enzyme: Uroporphyrinogen III Synthase (in erythrocytes)
- Autosomal recessive
- deficiency leads to accumulation of Uroporphyrinogen I and its red-colored, air oxidation product uroporphyrin I
- photosensitivity, red color urine and teeth; hemolytic anemia
- Erythropoietic Porphyria
Porphyria Cutanea Tarda (PCT)
- Defective Enzyme: uroporphyrinogen decarboxylase
- autosomal dominant
- deficiency leads to accumulation of uroporphyrinogen III, which converts to uroporphyrinogen I and its oxidation products
- most common porphyria in US
- photosensitivity resulting in vesicles and bullae on skin of exposed area; wine red colored area
- Hepatoerythropoietic Porphyria
Variegate Porphyria
- Defective Enzyme: Protoporphyrinogen IX oxidase
- Autosomal Dominant
- Photosensitivity and neurologic symptoms and developmental delay sin children
- Hepatic Porphyria
- “celebrity” version
Jaundice
- hyperbilirubinemia
- elevated levels of BR in blood stream
- Unconjugated/indirect (0.2-0.9 mg/dL)
- Conjugated/direct (0.1-0.3 mg/dL)
- imbalance between production and excretion of BR
Pre-hepatic Jaundice
- excessive hemolysis (hemolytic anemias)
- eg: glucose-6-PO4 dehydrogenase deficiency
- internal hemorrhage
- problems with incompatibility of maternal-fetal blood groups (in neonates)
- capacity of liver to uptake exceeded
- increase of unconjugated BR in blood
- normal conjugated BR
- normal serum ALT and AST
- Urobilinogen present in urine b/c liver cant conjugate and excrete BR
Intra-hepatic Jaundice
- impaired hepatic uptake, conjugation, or secretion of conjugated BR
- occurs in: liver cirrhosis, viral hepatitis, Criggler-Najjar Syndrome, and Gilbert syndrome
- variable increases in unconjugated and conjugated BR depending on cause (pre- or post-conjugation)
- increase in serum ALT and AST
- Urine Urobilinogen normal
Post-Hepatic Jaundice
- AKA Cholestasis (decreased bile flow)
- problem in excretion
- causes: obstruction to biliary drainage (in liver or bile duct), Cholangiocarcinoma, gall stones, infiltrate liver disease, lesions (tumor, abscess or granulomaous disease), drugs (anabolic hormones, chlorpromazine, phenytoin)
- red urine ( conjugated BR, no Urobilinogen) and pale stool ( no stercobilin)
- normal AST and ALT
- small increases in unconjugated BR form
- elevated blood levels of conjugated BR
- ## elevated alkaline phosphates (ALP) a canalicular enzyme (part of system that helps release bile to gallbladder)
Neonatal Jaundice
- elevation of un-conjugated BR
- physiological jaundice
- immature hepatic metabolic pathways —> unable to conjugate and excrete BR
- deficiency of UDP-GT enzyme
- breakdown of fetal hemoglobin as its replaced with adult hemoglobin
- premature birth aggregates this situation
- BR may diffuse into basal ganglia and cause
Phototherapy
- used to treat jaundiced newborns
- exposure to Blue fluorescent light breaks photo-converts BR to more soluble isomers
Intramuscular Injection of Tin-mesoprphyrin
Strong inhibitor of heme oxygenase
- prevents heme breakdown to form BR
Criggler-Najjar Syndrome Type 1
UDP-GT deficiency
Severe Hyperbilirubinemia
BR accumulation in brains of babies
Causes kernicturus (encephalopathy) and brain damage
Therapy:
- Blood Transfusions
- Phototherapy
- Heme Oxygenase inhibitors
- oral calcium phosphate and carbonate (form complexes with BR in gut)
- liver transplantation ( before brain damage occurs and before phototherapy becomes ineffective)
