SEARCH RESULTS FOR: sickle

central-retinal-artery-occlusion-pathogenesis-and-clinical-findings

Central Retinal Artery Occlusion: Pathogenesis and clinical findings Inflammatory Disease: Cardiogenic Embolism: Hypercoagulable state: Hematologic Disease: (i.e. GCA, SLE, GPA) (i.e. Valvular, arrhythmias, congenital defects) (i.e. OCP, Protein C&S deficiency, ATIII deficiency) (i.e. leukemia/lymphoma, sickle cell, polycythemia) Endothelial cell damage Abnormal blood flow 1` coagulation and/or 1 blood viscosity and creates hypercoagulable state causing localized stasis 4, anti-coagulation inflammation Abbreviations: • GCA — Giant Cell Arteritis • SLE — Systemic Lupus Erythematosus • GPA — granulomatosis with polyangitis • OCP — Oral contraceptive pill • ATIII — Anti-thrombin Ill Thrombus formation Blockage of central retinal artery Central Retinal Artery Occlusion (CRAO) Authors: Graeme Prosperi-Porta Reviewers: Stephanie Cote Usama Malik Johnathan Wong* * MD at time of publication Carotid Artery Atherosclerosis Atherosclerotic plaque dislodges from carotid artery The retina becomes pale 4, perfusion of retinal Slow retinal artery blood Acute retinal edema Ganglion cells and axons from NI, perfusion arterioles due to upstream flow allows for caused by ischemia results death due to ischemia CRAO segmentation of the blood column in a blurred appearance of the retina results in disc pallor seen months after CRAO The choroidal vessels supplying the macula via the posterior ciliary artery become more prominent within a background of retinal pallor

Acute Chest Syndrome (Sickle Cell Disease)

Hemolytic Anemia - Pathophysiology

Hemolytic Anemia: Pathophysiology behind the Normocytic Anemia Note • Extreme bone marrow compensation for hemolysis (↑ RBC synthesis/reticulocytosis) may result in slightly macrocytic anemia (because reticulocytes have larger volumes than RBCs) Defects in the RBC’s environment Defects in RBC membranes Ex. Hereditary Spherocytosis: mutation causing deficiency of RBC structural proteins like ankyrin or spectrin RBC membranes become weakened and form blebs that break off ↓ RBC surface area while volume remains constantà RBC becomes spherical Spherocytes in spleen trapped and phagocytosed by splenic macrophages (extravascular hemolysis) Defects in RBC internal contents (thalassemia, hemoglobinopathies, and metabolic defects) Ex. Sickle Cell Disease: point mutation in hemoglobin (Hgb) structure (GluàVal) Inappropriate Hgb polymerization in low oxygen environments due to mutationàRBC becomes rigid, forms a sickle shape Inflexible RBCs become trapped in the spleen’s sinusoid membranes àphagocytosed by splenic macrophages (extravascular hemolysis) Infection triggers immune system activation Autoimmune processes TTP/HUS (abnormal platelet aggregation blocking blood vessels) Production of abnormal antibodies and immune complexes targeted against RBC surface antigens Immunoglobulin-bound RBCs are marked for destruction by the immune system (by either the cell- mediated or complement- mediated pathways) DIC (fibrin deposition blocking blood vessels) Artificial heart valve RBCs are sheared when they flow past an abnormal surface Rate of hemolytic RBC destruction > rate of bone marrow RBC synthesis (reticulocytosis) ↓ total number of RBCs in the body (despite normal RBC production/volume) Normocytic anemia Authors: Yan Yu Katie Lin Man-Chiu Poon* Reviewers: Andrew Brack Julia Heighton JoyAnne Krupa Lynn Savoie* * MD at time of publication Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Re-Published June 15, 2019 on www.thecalgaryguide.com

Priapism

Priapism: Pathogenesis Post-cavernosal venous occlusion ↑ nitric oxide from cavernous nerve plexus and cavernosal sinus endothelia Impaired detumescence (erection-ending) pathways Post-cavernosal venous drainage is mechanically obstructed e.g. sickle cell disease, dialysis etc. Ischemic (Low-flow): Inadequate venous function Blood pools in corpora cavernosa Cavernosal cell metabolism uses O2 and releases CO2 into pooled blood Trabecular smooth muscle relaxes Cavernosal artery smooth muscle relaxes Lack of norepinephrine action on penile SM Post-cavernosal venules are compressed against tunica albuginea Trabecular smooth muscle and cavernosal artery smooth muscle do not contract ↑ pressure in corpora ↑PCO2 ↓pH Acidosis ↓PO2 Tissue hypoxia Tissue damage Irreversible fibrosis leading to erectile dysfunction Priapism Prolonged erection lasting more than 4 hours; in absence of sexual stimulation; not relieved by ejaculation Trauma to penis or adjacent areas Authors: Arsalan Ahmad Reviewers: Alec Mitchell Darren Desantis* Yan Yu* * MD at time of publication Cavernosal artery is damaged Excessive, unregulated arterial blood flow into corpora cavernosa Pain Non-ischemic (High-flow): Uncontrolled arterial flow ↑ volume of blood in corpora ↑ pressure in corpora Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published September 22, 2019 on www.thecalgaryguide.com

急性胸部综合征镰状细胞贫血发病机制和临床表现

急性胸部综合征(镰状细胞贫血):发病机制和临床表现

Sickle Cell Disease Pathogenesis Clinical Findings and Complications

Sickle Cell Disease: Pathogenesis, Clinical Findings, and Complications DNA point mutation in chromosome 11 causes a substitution of glutamate to valine for the sixth amino acid of the β-globin chain Authors: Yang (Steven) Liu Priyanka Grewal Reviewers: Alexander Arnold Luiza Radu JoyAnne Krupa Yan Yu* Lynn Savoie* * MD at time of publication Hemoglobin S (HbS) variant formed instead of normal Hemoglobin A (HbA) Hb electrophoresis shows approximately 45% HbS, 52% HbA (ααββ), 2% HbA Hb electrophoresis shows approximately 90% HbS, 8% HbF, & 2% HbA . No HbA present (ααδδ), & 1% HbF (ααγγ;2 fetal hemoglobin) Heterozygous: point mutation in one of the two chromosomes (Hb AS) Sickle cell trait (asymptomatic unless severely hypoxic) Homozygous: point mutation in both chromosomes (Hb SS) Sickle cell disease An inherited blood disorder characterized by defective hemoglobin that leads to red blood cells sickling 2 Dehydration Hypoxemia Acidosis ↓ Volume of RBC cytoplasm ↓ O2 Saturation of Hb O morereadily 2 released from Hb in low pH environment ↑ Concentration of deoxygenated HbSinred blood cells (RBCs) Hydrophilic glutamate→ hydrophobic valine substitution makes HbS less soluble in the cytoplasm & more prone to polymerization & precipitation in its deoxygenated state ↑ Concentration of deoxygenated Hb in RBC leads to ↑ polymerization rate Polymerized & precipitated HbS forms long needle-like fibers RBC shape becomes sickled Sickle cells on peripheral blood smear Vaso-occlusion (sickled RBCs lodge in small vessels, blocking bloodflow to organs & tissues) Blockage of venous outflow Occlusion of vessels in lungs ↑ pulmonary blood pressure Fluid extravasates into interstitial tissue leading to pulmonary edema Acute chest syndrome (chest pain, hypoxemia (↓blood oxygen), etc.)** to the penis: to the spleen: Priapism (persistent, painful erection) Splenic Sequestration (blood pools in spleenà splenomegaly & hypotension) Extravascular hemolysis (macrophages in the spleen phagocytose sickled RBCs) Normocytic anemia ↑Marrow erythropoiesis (RBC production) to compensate for hemolysis Infarction of bone Pain crises If occurring in hands Dactylitis (inflammation of digits) Blockage of arteries ↓ oxygenation of organs & tissues Vaso-occlusion of the splenic artery Splenic infarction (↓ blood supply leads to tissue death) RBC inclusions (structures found in RBCs) not removed by spleen Howell-Jolly bodies (RBC DNA remnants) on blood smear Vaso-occlusion of other arteries (cranial, renal, etc) Stroke, renal failure ↑ RBC breakdown ↑ Unconjugated bilirubin released from RBC breakdown RBC precursors (reticulocytes) are released into the blood stream Reticulocytosis (increased number of immature red blood cells) on peripheral blood smear Patient’s RBC level becomes dependent on increased marrow activity Bone marrow infarction or viral infections (i.e. Parvovirus B19) suppresses bone marrow activity Aplastic crises (profound anemia) ** See corresponding Calgary Guide slide(s) ↑ Serum level of unconjugated bilirubin Some of the circulating unconjugated bilirubin deposits in the skin Jaundice (yellowing of skin) ↑ Conjugation of bilirubin in liver ↑Amounts of conjugated bilirubin released into bile Gallstone formation Cholelithiasis (presence of gallstones in the gallbladder) Spleen releases invasive encapsulated bacteria (eg. Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis) into circulation, which causes infections Meningitis Sepsis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Sept 16, 2013, updated Apr 29, 2024 on www.thecalgaryguide.com

Unconjugated Hyperbilirubinemia

Pre-hepatic causes of ↑ bilirubin production Pathologic Unconjugated Neonatal Hyperbilirubinemia: Pathogenesis and clinical findings Hemolytic disease of the newborn** Isoimmune- mediated hemolysis Rhesus (Rh) factor incompatibility Maternal sensitization against Rh-positive fetal cells Maternal antibodies against Rh factor attack fetal RBCs ABO incompatibility Native maternal antibodies against non- native blood types attack fetal RBCs Sepsis** Widespread systemic inflammation Cytokines & complement factors damage RBC membranes Disseminated intravascular coagulation** (clotting proteins become overactive) Clots form in systemic circulation Small clots shear & damage RBCs in circulation Red blood cell (RBC) enzyme defects Glucose-6 phosphatase dehydrogenase (G6PD) deficiency** G6PD protects RBCs against oxidative damage ↑ RBC sensitivity to oxidative stress (during acute stressors) Pyruvate kinase deficiency (PKD) Abnormal glycolysis & cellular energy production ↓ RBCs life spans RBC membrane defects Hereditary spherocytosis RBCs are abnormally round (spherocytes) RBC membranes easily damaged in circulation Bilverdin reductase Hereditary elliptocytosis RBCs are abnormally elongated or oval converts bilverdin to Sickle cell Abnormal hemoglobin (HbS) RBCs become abnormally unconjugated bilirubin disease** polymerizes under ↓ O2 sickle shaped Hemoglobinopathies Thalassemia's** Defective hemoglobin chains in RBCs Irregularly shaped RBCs trapped in spleen RBC sequestration ↑ Production of RBCs (Polycythemia**) Accumulation of blood (i.e. Cephalohematoma, hemorrhage) ↑ RBC load & turnover Causes of ↓ hepatocellular bilirubin clearance Genetic defects in uridine diphosphate glucuronosyltransfe rase (UGT) enzyme (conjugates bilirubin in liver) Gilbert syndrome Unconjugated bilirubin ↓ UGT production remains insoluble & cannot Crigler–Najjar be excreted in bile syndrome Type II Crigler–Najjar syndrome Type I No UGT production Breast milk jaundice Breast milk contains β-glucuronidase Causes of ↑ entero-hepatic bilirubin circulation Intestinal obstruction Obstruction blocks bile flow from liver to intestines Breastfeeding jaundice Inadequate milk intake (volume depletion/dehydration) ↑ Reabsorption of bilirubin in the intestines **See corresponding Calgary Guide slide Legend: Macrophages engulf old or damaged RBCs in spleen & liver ↑ Hemolysis (RBC breakdown) RBCs release cellular contents including heme (from hemoglobin) Heme oxygenase converts heme to bilverdin ↑ Unconjugated (indirect) bilirubin accumulation in blood ↑ Total serum bilirubin levels Excess bilirubin deposition into elastin- rich tissues (eg. skin, sclera) due to ↑ affinity for elastin Pathologic neonatal jaundice (yellow discoloration of skin within first 24 hours of life) Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published July 13, 2025 on www.thecalgaryguide.com Authors: Merry Faye Graff Khushi Arora Reviewers: Annie Pham Emily J. Doucette Danielle Nelson* * MD at time of publication Hemolytic anemia** ↓ Bilirubin conjugation β-glucuronidase deconjugates bilirubin Bilirubin builds up in hepatic system Unconjugated bilirubin crosses blood-brain barrier Bilirubin-induced neurologic dysfunction (BIND) Kernicterus (bilirubin- induced neurological damage) Scleral icterus (yellowing of sclera in eyes)