Other Pathology Flashcards
Heme synthesis, porphyrias, and lead poisoning
The porphyrias are hereditary or acquired conditions of defective heme synthesis that lead to the accumulation of heme precursors. Lead inhibits specific enzymes needed in heme synthesis, leading to a similar condition.
Lead poisoning
Affected enzyme: Ferrochelatase and ALA dehydrates
Accumulated substrate: Protoporphyrin, δ-ALA (blood)
Sxs: Microcytic anemia, GI and kidney disease.
Children—exposure to lead paint –> mental deterioration.
Adults—environmental exposure (battery/ ammunition/radiator factory) –>headache, memory loss, demyelination.
Acute intermittent porphyria
Affected enzyme: Porphobilinogen deaminase
Accumulated substrate: Porphobilinogen, δ-ALA, coporphobilinogen (urine)
Sxs: (5 P’s):
-Painful abdomen
-Port wine–colored urine
-Polyneuropathy
-Psychological disturbances
-Precipitated by drugs, alcohol, and starvation
-Treatment: glucose and heme, which inhibit ALA synthase.
Porphyria cutanea tarda
Affected enzyme: Uroporphyrinogen decarboxylase
Accumulated substrate: Uroporphyrin (teacolored urine)
Sxs: Blistering cutaneous photosensitivity.
Most common porphyria.
Coagulation disorders
PT—tests function of common and extrinsic pathway (factors I, II, V, VII, and X). Defect–> incr PT.
PTT—tests function of common and intrinsic pathway (all factors except VII and XIII). Defect –> incr PTT.
Hemophilia A or B
Incr PTT. Intrinsic pathway coagulation defect.
- A: deficiency of factor VIII –> incr PTT.
- B: deficiency of factor IX –> incr PTT.
- Macrohemorrhage in hemophilia—hemarthroses (bleeding into joints), easy bruising, incr PTT.
- Treatment: recombinant factor VIII (in hemophilia A).
Vitamin K deficiency
incr PT and PTT.
General coagulation defect. Bleeding time normal. Decr synthesis of factors II, VII, IX, X, protein C, protein S.
Vitamin K deficiency
incr PT and PTT.
General coagulation defect. Bleeding time normal. Decr synthesis of factors II, VII, IX, X, protein C, protein S.
Platelet disorders
Defects in platelet plug formation–> incr bleeding time (BT).
Platelet abnormalities–> microhemorrhage: mucous membrane bleeding, epistaxis, petechiae, purpura, incr bleeding time, possible decr platelet count (PC).
Bernard- Soulier syndrome
Defect in platelet plug formation.
Decr GpIb –> defect in platelet-to-vWF adhesion
-Decr platelet count
-Incr bleeding time
Glanzmann thrombasthenia
- Defect in platelet plug formation.
- Decr GpIIb/IIIa –> defect in platelet-to-platelet aggregation.
- Labs: blood smear shows no platelet clumping.
- Incr bleeding time
Immune thrombocytopenia
- Defect: anti-GpIIb/IIIa antibodies –>splenic macrophage consumption of platelet/antibody complex.
- May be triggered by viral illness.
- Decr platelet survival.
- Labs: Incr megakaryocytes on bone marrow biopsy.
- Decr Platelet count
- Incr bleeding time
Thrombotic thrombocytopenic purpura
- Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) –> decr degradation of vWF multimers.
- Pathogenesis: incr large vWF multimers –> incr platelet adhesion –> incr platelet aggregation and thrombosis.
- Decr platelet survival.
- Labs: schistocytes, incr LDH.
- Symptoms: pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia.
- Treatment: exchange transfusion and steroids.
- Decr platelet count
- Incr bleeding time
von Willebrand disease
-Intrinsic pathway coagulation defect: decr vWF–> normal or incr PTT (depends on severity; vWF acts to carry/protect factor VIII).
-Defect in platelet plug formation: decr vWF –>defect in platelet-to-vWF adhesion.
-Mild but most common inherited bleeding disorder.
-Autosomal dominant.
-Diagnosed in most cases by ristocetin cofactor assay
(decr agglutination is diagnostic).
-Treatment: DDAVP, which releases vWF stored in endothelium.
-Incr bleeding time
-Incr PTT
DIC
- Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state.
- Causes: Sepsis (gram-negative), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion (STOP Making New Thrombi).
- Labs: schistocytes, incr fibrin split products (D-dimers), decr fibrinogen, decr factors V and VIII.
- Decr platelet count
- Incr bleeding time
- Incr PT
- Incr PTT
Factor V Leiden
Hereditary thrombosis syndromes leading to hypercoagulability
Production of mutant factor V that is resistant to degradation by activated protein C. Most common cause of inherited hypercoagulability in whites.
Prothrombin gene mutation
Hereditary thrombosis syndromes leading to hypercoagulability
Mutation in 3′ untranslated region –> incr production of prothrombin –> incr plasma levels and venous clots.
Antithrombin deficiency
- Hereditary thrombosis syndromes leading to hypercoagulability
- Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration.
- Can also be acquired: renal failure/nephrotic syndrome –> antithrombin loss in urine –> incr factors II and X.
Protein C or S deficiency
Hereditary thrombosis syndromes leading to hypercoagulability
Protein C or S deficiency
-Hereditary thrombosis syndromes leading to hypercoagulability
-Decr ability to inactivate factors V and VIII. Incr risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.
-Skin and subcutaneous tissue necrosis after warfarin administration –> think protein C deficiency.
“Protein C Cancels Coagulation.”
Protein C or S deficiency
-Hereditary thrombosis syndromes leading to hypercoagulability
-Decr ability to inactivate factors V and VIII. Incr risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.
-Skin and subcutaneous tissue necrosis after warfarin administration –> think protein C deficiency.
“Protein C Cancels Coagulation.”
Blood transfusion therapy
-Blood transfusion risks include infection transmission (low), transfusion reactions, iron overload, hypocalcemia (citrate is a calcium chelator), and hyperkalemia (RBCs may lyse in old blood units).
-Packed RBCs: Incr Hb and O2 carrying capacity
For acute blood loss, severe anemia
-Platelets: Incr platelet count (incr ∼5000/mm3/unit)
To stop significant bleeding (thrombocytopenia, qualitative platelet defects)
-Fresh frozen plasma: Incr coagulation factor levels
For DIC, cirrhosis, warfarin overdose, exchange transfusion in TTP/HUS
-Cryoprecipitate: Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
To treat coagulation factor deficiencies involving fibrinogen and factor VIII
Leukemia
Lymphoid or myeloid neoplasms with widespread involvement of bone marrow. Tumor cells are usually found in peripheral blood.
Lymphoma
Discrete tumor masses arising from lymph nodes.
Presentations often blur definitions.
