Metabolic Disorders
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Regenerative Anemias Hemolysis – Metabolic Disorders Pyruvate kinase deficiency ↓ ATP production leads to reduced RBC lifespan and hemolysis Dogs: Basenji dogs, many other breeds Markedly regenerative (up to 50% reticulocytes!!) Myelofibrosis and osteosclerosis Survival 3-5 years Cats: Abyssininians, Somalis, DSH Variable anemia with regeneration Normal lifespan Regenerative Anemias Hemolysis – Metabolic Disorders Phosphofructokinase deficiency English Springer spaniels Decreased 2,3 DPG production – less O2 offloading, greater alkaline fragility Acute, intravascular hemolytic anemia triggered by respiratory alkalosis (exercise, excitement) Not anemic between hemolytic crises Hereditary methemoglobinemia Brown blood, decreased O2 capacity Dogs, cats and horses No anemia, anesthesia concern Regenerative Anemias Hemolysis – Micro-organsisms Red cell parasites Primarily via a secondary IMHA Predominantly extravascular, but many have some intravascular component Other microorganisms Clostridium and Leptospira species – intravascular hemolytic anemia E. coli hemolyic uremic syndrome Equine infectious anemia Acute stages of disease Likely immune mediated Occasionally see thrombocytopenia as well Regenerative Anemias Hemolysis – Miscellaneous Severe hypophosphatemia (<1 mg/dl, canine RI 3-5.3 mg/dl) causes intravascular hemolysis Post parturient hemoglobinuria, hypophosphatemia believed to play a role DM (cats) loss through urine, intracellular movement with insulin administration Hyperalimentation Snake venom – IV hemolysis, echinocytes, spherocytes Non-Regenerative Anemias The most common type of anemia Anemia of inflammatory disease Reduced erythropoiesis (hypocellular Anemia of endocrine disease – marrow) mild to occ mod Defective erythropoiesis (hypercellular Hypoadrenocortisism (Addison’s marrow) disease), hypothyroidism, Additional information hypopituitarism Cell lines affected, only RBCs or WBCs Myelophthesis (crowding out of and platelets? bone marrow) – severe! Chemistry panel and endocrine testing Chronic, severe, iron deficiency Bone marrow findings Microcytic, hypochromic, +/- ↑ History and PE platelets and ↓TP Weeks to months to manifest – long Certain infectious diseases RBC lifespan Drugs and toxins Causes Idiopathic Chronic renal failure – severe! ↑ BUN, Creat, Phos, isosthenuric USG Non-Regenerative Anemias Anemia of Inflammatory Disease (AID) Most common cause! Inflammatory, infectious and neoplastic diseases Typically is mild to moderate (PCV 20-30%) Normocytic and normochromic; Rarely microcytic and/or hypochromic Parameter Iron deficiency AID Serum iron Decreased Decreased TIBC (transferrin) Normal to increased Normal to decreased Transferrin saturation Decreased Decreased Ferritin Decreased Normal to increased BM iron (dogs, not cats!) Decreased Normal to increased History, other findings Nutrition, blood loss Underlying inflammation, neoplasia Response to Resolves Does not respond supplementation Non-Regenerative Anemias Infectious Agents AID – any infectious agent Ehrlichia canis Feline Leukemia Virus Classic findings Selective damage to erythroid ↑ globulins, ↓plts, ↑ lymphocytes precursors (pure red cell aplasia) Mild non-regenerative anemia AID Neoplasia or myelodysplastic Immune-mediated syndrome resulting in myelophthesis Chronic disease may result in pancytopenia Aplastic anemia Immune-mediated Anemia of inflammatory disease Aplastic anemia Macrocytic, normochromic, Equine infectious anemia non-regenerative anemia Bone marrow suppression Bone marrow dysplasia Non-Regenerative Anemias Drugs and Toxins Many implicated drugs and Estrogen in dogs and ferrets chemicals Can be idiosyncratic or overdose May result in only anemia or in dogs aplastic anemia Sertoli or granulosa cell tumors of dogs Aplastic – all cell lines affected Mismate shot, pseudopregancy Can be idiopathic or predictable termination in dogs Can be reversible or permanent Hyperestrogenism related to prolonged estrus in ferrets Idiosyncratic – many reported causes Bracken fern toxicity in cattle Classic causes of aplastic anemia Chloramphenicol Chloramphenicol Griseofulvin in cats Anti-neoplastic and Trimethoprim-sulfa, chemotheraputic agents cephalosporin in dogs Non-Regenerative Anemia Drugs and Toxins - Lead Species sensitivity varies Highly sensitive: Dogs Intermediate: Cattle, horses, sheep Resistant: Pigs Classic blood smear findings Most likely seen in dogs Anemia with inadequate regeneration Basophilic stippling Inappropriate nRBCs Polycythemia (aka Erythrocytosis) Some breeds normally have higher Hcts: Racing horses, warm- blooded breeds, Greyhounds, sight hounds, some Dachshunds Polycythemia Relative Absolute a) Dehydration True increase in RBC ↑TP, USG, azotemia, PE production findings, PP:Fib > 15 b) Splenic contraction Primary Secondary Excitable animal (young cats, (Epo independent) (Epo dependent) foals), epinephrine response Polycythemia vera, dx of ↑ Epo exclusion, N or ↓ epo levels Appropriate Inappropriate Hypoxia induced; ↓arterial PAO2, No hypoxia, N arterial PAO2, CHF, R→L shunting, pulmonary Renal tumors or cysts, tumors dz, high altitude secreting epo WBCs – Major Patterns of Response Neuts Left Toxic Lymphs Monos Eos shift change Classic inflammation ↑ + * +/- N, ↓, ↑ ↑ N to ↓ Inflammation, ↓ + + ↓ N to ↑ ↓ overwhelming tissue demand** Stress ↑ - - ↓ ↑ ↓ (corticosteroid resp.) Inflammation with ↑ +/- +/- ↓ ↑ ↓ stress Epinephrine ↑ - - ↑ N N to ↓ *Could be normal with chronic or mild inflammation **More likely in cattle d/t small storage pool Inflammation Degenerative left shift Species with less responsive BM: Immature forms > mature forms OR ruminants, +/- horses significant left shift with normal or low Plasma protein / fibrinogen ratio neuts <10 inflammation, >15 normal or Regenerative left shift dehydration Mature forms > immature forms in Ruminants, inverted N:L ratio (may patients with a normal or high not be true, but everyone says it) neutrophil count Neutropenia, other causes Toxic change – moderate to marked, Chemotheraputic agents, causes of think infection! aplastic anemia/pancytopenia, Döhle bodes, cytoplasmic basophilia, immune mediated, cyclic vacuolization, toxic granulation** hematopoiesis of grey collies and A rare Döhle body in cats is OK FeLV+ cats, familial neutropenia of **Rare in LAs, nearly unheard of in SAs, Belgian Tervuren dogs, idiopathic common in avian, reptile and amphibian species Toxic change ≠ degenerative changes! Neutrophils, Hereditary Disorders Leukocyte adhesion defect – neuts can’t leave blood Holstein cattle, Irish setters Marked to extreme leukocytosis Recurrent infections with failure to form puss Pelger-Hüet anomaly: failure of granulocyte nuclei to segment, no function defect, don’t mistake for LS! Lysosomal storage disorders; group of disorders May see dwarfism, skeletal abnormalities, hepatomegaly, neurologic signs Blood smear; neutrophils with pink-purple granules, lymphocytes with vacuoles or lymphocytes with granules Birman cat neutrophil granulation anomaly Granulated neutrophils, no defect. Also seen in some Orientals Neutrophil Inclusions Granulocytic Ehrlichiosis and Anaplasmosis E. ewingii: Can also find in joint fluid in acute disease with polyarthritis A. phagocytophila (formerly E. equi) Primarily dogs, rarely cats Thrombocytopenia and anemia Morulae Pale blue to lavender, ‘raspberry’ or ‘asterisk’ like Distemper inclusions Extreme Neutrophilia (Leukamoid Response) Think localized, purulent responses, ‘puss pockets’: Pyometra (esp. closed), walled off abscesses, pyelonephritis, pyothorax Hepatozoon infection in dogs: tick transmitted protozoal infection of canids H. americanum , SW and SE United States Pyogranulomatous myocytis and periosteal bone reactions Gamonts rarely found in peripheral blood neutrophils and monocytes Very pale staining elongated structure, ‘Tick-tacs’ Immune mediated hemolytic anemia Atypical response to parasitic infections - HW disease Leukocyte adhesion deficiency Paraneoplastic; production is cause by neoplasia Chronic myelogenous leukemia – RARE! Eosinophils and Basophils Eosinopenia Paraneoplastic: Mast cell tumor (dogs, Corticosteroid response horses), T-cell lymphoma, various carcinomas Promoted by epinephrine, not a consistent feature Hypereosinophilic syndrome Eosinophilia: “Wheezes, sneezes and weird Rottweiler dogs, other dog breeds diseases” Infiltration of multiple tissues with eosinophils Parasitic infections, especially those with tissue Presumed to be dysregulation stages of eosinophils Heartworm disease is often NOT associated with significant eosinophilia Feline hypereosinophilic granuloma complex Hypersensitivity reactions: Asthma, dermatitis, flea bite allergy Hypoadrenocortism: 20% of patients Localized eosinophilic responses Hyperthyroidism in cats May NOT see peripheral eosinophilia Eosinophilic leukemia – rare! Eosinophilic keratitis, eosinophilic granuloma, Basophilia without eosinophilia canine panosteitis Uncommon likely similar Ddx as Infections: Bacteria (staph and strep), fungal eosinophilia; horses, canine HW disease, infections – Cryptococcosis, pythiosis myeloproliferative disorders Lymphocytes Predominant in adult ruminants, many birds, Lymphocytosis pigs, mice and rats Epinephrine response: young cats, foals Ruminants can have large lymphocytes Chronic antigenic stimulation Lymphopenia Chronic canine Ehrlichiosis – not Corticosteroid