High yield intro Flashcards
What amino acid is a precursor to heme?
Glycine
What is not contained in serum?
Clotting factors
What kind of infection may be suspected (other than viral) when lymphocytes are raised?
- Fungal
- Bordetella pertusis infection
What does iron incorporate into to make heme?
Protoporphyrin ring
Where does heme synthesis occur?
Cytoplasm and mitochondria
Glycine and succinyl coA make what molecule in the heme synthesis pathway?
Delta ALA
- enzyme: Delta ALA synthase
What enzyme is inhibited in Sideroblastic anemia? (X-linked)
Delta ALA synthase
Reaction:
- glycine + succinyl coA -> Delta ALA
What are the signs of sideroblastic anemia?
- Anemia
- Basophilic remnants of rRNA
- Male - X-linked
Porphobilinogen is converted to what in the heme synthesis pathway?
Hydroxymethylbilane
- Enzyme: PGD De-Aminase (PROD)
- Affected in acute intermittent porphyria
What enzyme is affected by Acute Intermittent Porphyria?
PBG De-Aminase (PROD)
Reaction:
- Porphorobilinogen -> Hydroxymethylbilane
What are the symptoms of acute intermittent porphyria?
4 Ps
- Intermittent abdo pain
- Port wine urine
- Polyneuropathy
- Psychosis
What are the symptoms of Porphyria Cutanea Tarda?
- Painful blisters post sun exposure
- Red urine
URO-Decarboxylase
What reaction does Porphoryia Cutanea Tarda affect?
Uroporphyrinogen -> Corporophyrinogen
- Enzyme: URO-Decarboxylase
What kind of drugs may induce acute intermittent porphyria?
- CYP Inducing drugs
- Anti-convulsants
- Alcohol
What are the CYP inducing drugs?
- May induce acute intermittent porphyria
- Griseofulvin
- Carbamazepine
- Phenytoin
- Barbiturates
- Rifampin
- St Johns Wort
What is the function of Griseofulvin? (MOA and used to treat)
- Tinea Capidis, unguium (head, toe fungal infections)
- Inhibits MTs and thus fungal mitosis
What is the function of Carbamazepine? (MOA and used to treat)
- Anti-seizure, trigeminal neuralgia
- Inactivates Na+ channels
What is a possible side-effect of Carbamezepine?
SIADH
What is the function of Barbiturates?
Increase the duration of GABA Cl- channel opening
What is the function of Rifampin?
- Blocks DNA dependent RNA polymerase -> decreases bacterial protein synthesis
- Used for TB
- Meningococcal or Hib prophylaxis
WHat is St Johns Wort used for?
Depression (increases serotonin)
What does lead inhibit?
- Ferrochelatase (iron into protoporphyrin ring)
- ALAD (d-aminolevulinic acid dehydratase)
Where is Ferrochelatase located and what is its function?
- Mitochondria
- Catalyses reaction of iron and protoporphyrin IX into heme (heme synthesis)
What will a blood smear show in a patient with lead poisoning?
Basophilic stippling
- Represents remnants of rRNA in RBCs
What non-specific symptoms may a patient with lead poisoning present with?
- Headaches
- Constipation
- Developmental delay
Other family members will have symptoms
What are the causes of Target cells?
GET A PICTURE
HALT
- Hemoglobin C disease (patient with hemolytic anemia, splenomegaly, and Glu-> Lysine)
- Asplenia
- Liver disease (alcoholism, obstructive)
- Thalassemia (chipmunk facies, hairon-end appearance, chronic transfusions)
What are the 2 mechanisms behind the making of target cells?
- Low RBC mass (thalassemia)
- Redundant membrane (liver disease, splenectomy)
(Increased surface area to volume ratio)
What is basophilic stippling due to?
GET A PIC
Denatured ribosomes
- Alcoholic or patient on isoniazid (thru B6 deficiency) for TB
- Sideroblastic anemias, thalssemias
- Lead poisoning
What are Howell-Jolly bodies?
GET A PIC
DNA remnants
- Functional (sickle) or anatomic asplenia
What are Heinz bodies caused by?
- Drug trigger + normal MCV anemia + jaundice
- Patient with drug trigger and hemolytic anemia
- G6P deficiency (bite cells)
What do heinz body cells become in the spleen?
Bite cells
What do heinz bodies require to be visualised?
Crystal violet
What are general symptoms indicative of anemia?
- Fatigue
- SOB
- Pallor
- Angina
- Tachycardia
What are reticulocytes and why are the pathologically important?
- Immature RBCs
- Indicate whether bone marrow is responding (in hemolytic anemia)
What is the opposite of ferritin?
- Ferritin is the storage form of iron
TIBC (Total iron binding capacity)
What is the opposite of ferritin?
- Ferritin is the storage form of iron
TIBC (Total iron binding capacity)
What will the level of ferritin be like in iron deficiency anemia?
Decreased
What kind of patients are characteristically have iron deficiency anemia?
- Teenage female
- Colon cancer (old, weight loss)
- Pregnancy causing a dilutional anemia
- 3rd world child
What type of anemia is anemia of chronic disease typically?
- Microcytic (normocytic sometimes in early stages)
What causes anemia in conditions like RA and SLE? (anemia of chronic disease), may also be due to chronic infection
- Hepcidin increases - decreasing iron absorption
- Increases trapping of iron in bone (ferritin) from IL-1
What are the ferritin and TIBC levels like in anemia of chronic disease?
- Ferritin high
- TIBC low
What are the positive acute pahse reactants?
- CRP
- Ferritin
- Fibrinogen
- Hepcidin
- Serum amyloid A
What are the negative acute phase reactants?
- Albumin
- Transferrin
What does amyloid look like and on what stain?
Stained by Congo red
- Apple-green biferingence in polarised light
What kind of meglaoblastic anemia gives neurological deficits?
B12 (due to increased MMA)
- Folate does not
What do megaloblastic anemias show on blood smear?
Hypersegmented neutrophils (more than 5)
How do B12 and folate create hypersegmented neutrophils?
- Unable to undergo cytokinesis (high segmentation)
What is a type 2 hypersensitivity reaction due to?
Auto-antibody to antigen
What kind of anemia are vegans most likely to suffer from?
Macrocytic
- Not enough dietry B12
WHat fish tapeworm may cause malabsorption and therefore B12 deficient macrocytic anemia?
Diphyllobothrium latum
What enzyme does not function when there is no B12?
Methyl malonyl coA mutase
increased MMA
How can normocytic anemias be divided?
- Intravascular vs Extravascular
- Intrinsic vs Extrinsic
What are the signs of an intravascular normocytic anemia?
- Low haptoglobin (haptoglobin binds to heme from destroyed RBCs)
- Hemoglobinuria
- Increased LDH
- High indirect BR
What are the signs of an extravascular normocytic anemia?
- Splenomegaly
- Normal haptoglobin
What do reticulocyte levels represent?
Bone-marrows response to anemia
WHat are the causes of extra-vascular hemolytic anemia?
- Autoimmune Hemolytic Anemia
- Heredetary spherocytosis
- G6P deficiency
- Thalassemia
WHat are the causes of intra-vascular hemolytic anemia?
- Microangiopasthic hemolytic anemia
- Prosthetic heart valves
- Paroxysmal noctural hemoglobinuria
What gene is defective in PNH?
- PIGA gene
Low decay accelerating factor making it more susceptible to complement
What are the intrinsic hemolytic anemias
- Hereditary spherocytosis: (membrane defects)
- G6PD, pyruvate kinase (enzyme defects)
Hemoglobin defects:
- Sickle cell anemia
- Paroxysmal nocturnal hemoglobinuria
HUS (Hemolytic uremic syndrome) and TTP (Thrombotic thrombocytopenic purpura) common symptoms/signs
- Infectious diarrhoea
- acute renal failure
- Shishtocytes
- Endothelial injury (microthrombi, reduced platelets)
- Low platelets
What is the triad for HUS?
- Anemia
- Thrombocytopenia
- Acute renal failure
What is the pentad for diagnosis of TTP?
- Anemia
- Thrombocytopenia
- Acute renal failure
- Fever (>38)
- Altered mental status
What are the different causes of polycythemia?
JAK-2 positive - polycythemias Vera (itchy female)
JAK-2 Negative *Reactive)
- Cyanotic heart disease
- Sleep apnea / COPD
- EPO tumor RCC
What does high hematocrit mean
Polycythemia
What does DDAVP do for clotting?
- Increases vWF
- Increases factor 8
What does the vignette for vWF Disease usually include?
Mucocutaneous bleeding after trigger (i.e. dental) or aspirin use
What is vWF treated with?
DDAVP
What kind of hemostasis is affected in DIC?
- Primary and Secondary hemostasis (low platelets and PT, PTT etc.)
- Big trigger!
What does heparin increase the activity of?
AT3
What are the different types of heparin?
- UFH (Unfractionated Heparin) - PTT
- LMWH (-parin) - Xa specific
- Fondaparinux - Xa specific
What can reverse the effects of heparin?
Protamine
- Also can use prothrombin complex precipitate
What does vit K epoxide reductase do?
Gamma-carboxylation of 2, 7, 9, 10, C, S
- Warfarin prevents this
What ca be used to reverse warfarin?
- Acutely: fresh frozen plasma
- Vit K supplements long term
What are some signs of multiple myeloma?
- Back pain
- Hypercalcemia
- Reccurrent infection
- Abnormal blood smear
