Biochem - Final - Disease and Conditions - Part 1

davidwurbel7's version from 2015-04-20 01:10

Diseases and Conditions

Question Answer
Loss of function mutation of ALAS2 gene result inX-linked Sideroblastic Anemia
Increase in δ-ALA levels in the blood, and hence decrease in hemoglobin synthesisLead Toxicity
Ferrochelatase enzyme is blocked leading to increased levels lead protoporphyrin levels in bloodLead Toxicity
Protoporphyrin IX will bind with zinc released from delta-ALA dehydratase to form zinc-protoporphyrinLead Toxicity
Deficiency of cytosolic enzyme uroporphyrinogen decarboxylase. Accumulation of uroporphyrinogens results in their conversion to uroporphyrins by sunlight. Uroporphyrins react with molecular oxygen to form oxygen radicals. This disease primarily affect the skin, causing photosensitivity (photodermatitis), blisters, necrosis of the skin and gums, itching, and swelling, and increased growth of facial hair. Often there is no abdominal painPorphyria Cutanea Tarda (PCT)
Deficiency of the enzyme porphobilinogen deaminase (HMB synthase, Uroporphyrinogen I synthase). More common in females. Porphobilinogen and δ-ALA accumulates in the plasma, and found at increased concentration in the urine. Intermittent acute abdominal pain without any anatomical cause. Acute neuropathy, muscle weakness, and seizures. Neuropsychiatric symptoms, including hallucinations, depression, anxiety, and paranoia. Cardiac arrhythmias and tachycardia may develop as the autonomic nervous system is affected. Photosensitivity is not generally observedAcute Intermittent Porphyria
Porphyria with photosensitivity and lack of abdominal painPorphyria Cutanea Tarda (PCT)
Porphyria with acute abdominal pain and lack of photosensitivityAcute Intermittent Porphyria
Deficiency of uroporphyrinogen decarboxylasePorphyria Cutanea Tarda (PCT)
Deficiency of porphobilinogen deaminase (HMB synthase, Uroporphyrinogen I synthase)Acute Intermittent Porphyria
Overproduction of bilirubin. Impaired uptake or conjugation. Impaired excretion of bilirubin. Regurgitation of unconjugated or conjugated bilirubin from damaged hepatocytes or bile ducts.Hyperbilirubinemia
Overproduction of bilirubin. Impaired uptake or conjugationIncreased Unconjugated Bilirubin
Impaired excretion of bilirubin. Regurgitation of unconjugated or conjugated bilirubin from damaged hepatocytes or bile ductsIncreased Conjugated Bilirubin
Caused by Hemolytic disorders including Hereditary spherocytosis, G6PDH deficiency, Sickle cell anemia, Paroxysmal nocturnal hemoglobinuria (PNH), ABO incompatibility, physiological jaundice, hemolytic disease of newborn (Rh incompatibility) or ineffective erythropoiesis which includes deficiency of cobalamin, folate and ironIsolated Elevation of Unconjugated Bilirubin
Increase of AST levels in serum, darkening of the stool and urine, other liver function tests like alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) levels are normalIsolated Elevation of Unconjugated Bilirubin
Hemolytic disorder with coexisting hepatocellular disease or acute hemolytic crisis; serum total bilirubin>5 mg/dL
Complete absence of UDPGT1A1 activity, mutation in 3’ exon of UDPGT gene. Severe unconjugated hyperbilirubinemia (>2o - 25 mg/dL), at high risk of developing kernicterus. Only treatment is orthotopic liver transplantationCrigler-Najjar Syndrome Type 1
Reduced but not complete absence of UDPGT1A1 activity. Mutation in UDPGT gene. Serum unconjugated hyperbilirubinemia (6-25 mg/dL). UDPGT activity can be induced by administering phenobarbital. At risk of kernicterus at times of stress of illness or surgeryCrigler-Najjar Syndrome Type 2
Reduced UDPGT activity. Of several causes, mutation in TATA box of UDPGT gene promoter is best known. Mild unconjugated hyperbilirubinemia (<6 mg/dL). Jaundice is identified only during periods of fasting.Gilbert’s Syndrome
Caused by insufficient UDPGT activity to handle conjugation process. More severe in premature infants. Unconjugated bilirubin can reach >25 mg/dL in premature neonates, risk of kernicterus. Treatment: phototherapy-UV light (blue light), conversion to water soluble photoisomers, exchange transfusion. Jaundice within the first 24 hours of life or which takes longer then 10 days to resolve is usually pathologicalPhysiological Jaundice of the Newborn
Asymptomatic jaundice in the second generation of life. Autosomal recessive mutation in gene for MRP-2 or MOAT. Altered secretion of conjugated bilirubin into biliary canaliculi. Liver: darkly pigmented on gross inspection and may be enlarged. Histopathology: centrilobular dark brown pigment granules (polymers of epinephrine metabolites), otherwise normalDubin-Johnson Syndrome
Defect in hepatic storage of bilirubin. Bilirubin values range from 2 to 5 mg/dL, and other LFTs are normal. The liver is normal (no pigmentation)Rotor's Syndrome
Crigler-Najjar syndrome type 1 and 2 and Gilbert’s syndrome have elevated levels ofUnconjugated Bilirubin
Dubin-Johnson syndrome and Rotor's syndrome have elevated levels ofConjugated Bilirubin
Combined hyperbilirubinemia. Conjugated bilirubin between 20 – 50% of total bilirubin. AST and ALT elevated out of proportion to ALP with ALT higher than AST. Serum UCB is increased. Serum and urine CB are increased. Urine UBG is increased. Urine is dark. Stool color is normalCombined Hyperbilirubinemia with Viral Hepatitis
Combined hyperbilirubinemia. Conjugated bilirubin between 20 – 50% of total bilirubin. AST and ALT elevated out of proportion to ALP with AST higher than ALT. GGT level increased also. Serum UCB is increased. Serum and urine CB are increased. Urine UBG is increased. Urine is dark. Stool color is normalCombined Hyperbilirubinemia with Alcoholic Hepatitis
Combined hyperbilirubinemia. Conjugated bilirubin between 20 – 50% of total bilirubin. ALP and GGT elevated out of proportion to AST. Serum UCB is increased. Serum and urine CB are increased. Urine UBG is increased. Urine is dark.Combined Hyperbilirubinemia with Biliary Pattern
An increase in serum and urine CB. CB% >50% with marked increase in serum ALP and GGT (+++) and only a slight increase in serum AST and ALT. Malabsorption lipids and lipid soluble vitamins. Xanthomas, xanthelasma. Urine is dark (Tea color). Stool is light in color (Clay colored)Hyperbilirubinemia with Cholestasis (Obstruction)
In muscle and adipose tissue - Decreased or absolute deficiency of insulin which decreases the GLUT4 over the cell membrane. Decreased transport of glucose across the cell membrane of skeletal and cardiac muscle, and adipocytes. Low glycogen stores in skeletal muscle. Glucagon mediated lipolysis in adipocytes and low insulin mediated proteolysis in skeletal muscle. Amino acids from skeletal muscle and, fatty acids and glycerol from adipocytes floods the circulation. Peripheral tissues like skeletal muscle and cardiac tissue will start to use fatty acids as fuel. In the liver, Decreased glycolysis: low glucokinase, inactive PFK-1, pyruvate kinase, pyruvate dehydrogenase. Decreased glycogen synthesis; low glycogen synthase activity. Decreased fatty acid synthesis; low acetyl CoA carboxylase activity, decreased expression of fatty acid synthase complex.Increased gluconeogenesis: increased expression of gluconeogenic enzymes, increased availability of gluconeogenic substrates from muscle and adipose tissue. Increased beta-oxidation, ketogenesis and fatty acid esterification: Fatty acids from lipolysis flood into liver which undergo beta-oxidation, ketogenesis, and also undergo esterification to make TAGs.Diabetes Mellitus Type 1
Protein deficiency. Severe loss of visceral protein. Stunted growth, edema, skin lesions (flaky paint dermatosis), depigmented hair (Flag sign), anorexia, enlarged fatty liver, and decreased plasma albumin. Commonly seen after weaning, when their diet consists predominantly of carbohydrates.Kwashiorkor
Calorie deficiency. Usually seen in children younger than 1 year of age. Arrested growth, extreme muscle wasting (emaciation), weakness and anemia. Do not generally show edema.Marasmus
Absolute or relative insulin deficiency – hyperglycemia and elevated ketone bodies leading to volume depletion and acid-base imbalance. Presents with nausea and vomiting are often prominent, and their presence in an individual with diabetes warrants laboratory evaluation for DKA. Abdominal pain may be severe and can resemble acute pancreatitis or ruptured viscus. Kussmaul respirations and a fruity odor on the patient's breath. Primarily seen in Diabetes mellitus Type 1.Diabetic Ketoacidosis
Risk factors for include-Family history of diabetes, obesity (BMI > 25 kg/m2), habitual physical inactivity, previously identified IFG or IGT, history of GDM or delivery of baby >4 kg (>9 lb)Diabetes Mellitus Type 2
Insulin resistance, the decreased ability of insulin to act effectively on target tissues (especially muscle, liver, and adipose tissue). Hhyperglycemia. Increases FPG levels. Decreased peripheral utilization. In skeletal muscle – greater impairment of glycogen synthesis (insulin dependant) than glycolysis. Glucose metabolism in insulin-independent tissues is not altered. Insulin resistance in liver – decreases glycogen synthesis and increase in gluconeogenesis. Insulin resistance in adipose tissues – free fatty acids flux from adipose tissues to liver. Abnormality in lipid secretion out of liver may lead to nonalcoholic fatty liver (NASH). Increase in chylomicrons and VLDL (hypertriacylglycerolemia). Ketosis is usually minimal or absent Diabetes Mellitus Type 2
Profound dehydration and hyperosmolality and reveals hypotension, tachycardia, and altered mental status. (notably absent symptoms of nausea, vomiting, and abdominal pain and the Kussmaul respirations). Often precipitated by a serious, concurrent illness such as myocardial infarction or stroke.Hyperglycemic Hyperosmolar State (HHS)
Defect in branched chain α-keto acid dehydrogenase complex. Burnt sugar smell of urine. Buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their byproducts in the blood and urine. If untreated, suffer severe brain damage (mental retardation), and eventually deathMaple Syrup Urine Disease
Due to defective PAH gene (phenylalanine hydroxylase gene). Accumulation of phenylalanine in the blood that is well above the normal concentration. Appears normal at birth. Gradually develops varying degrees of irreversible mental retardation if not diagnosed or treated within the first month of life. Baby develops tremors, seizures, eczema, and hyperactivity "musty or mousy odor“ of baby's sweat and urineClassical Phenylketonuria (PKU)
Autosomal recessive deficiency of homogentisic acid 1,2-dioxygenase (homogentisic acid oxidase or homogentisate oxidase). Homogentisic acid accumulates in the body fluids. Quinone derivative accumulates over the cartilage. Oxidized pigments are deposited in bones, connective tissue, sclera, skin, and elsewhere (Ochronosis). Low back pain, Ochronotic arthritis, Presence of dark urine prior to development of other signs. Foci of gray-brown scleral pigment and generalized darkening of ear develop after 30 years of ageAlkaptonuria (Alcaptonuria)
Deficiency of the enzyme fumarylacetoacetate hydrolase, is the most severe form of tyrosinemia. The acute form is associated with liver failure, a cabbage like body odor, renal tubular dysfunction, rickets, polyneuropathy, accumulation of fumarylacetoacetate and maleylacetoacetate, both of which are alkylating agents and can lead to DNA alkylation and tumorigenesis, death generally occurs within first year of lifeHereditary Tyrosinemia type 1 (Hepatorenal Tyrosinemia or Tyrosinosis)
Deficiency of skin pigment melanin. Hypopigmentation of the skin and the eyes.Albinism
Single nucleotide change in one of the β globin gene at 6th position (β6 Glu→Val)Sickle Cell Trait (Hb AS)
Single nucleotide change in both β globin genes at 6th position (β6 Glu→Val)Sickle Cell Anemia (Hb SS)
Produced when lysine is substituted for glutamic acid in 6th position in β chain, β6 Glu→Lys . No splenomegaly or vaso-occlusive crisis.Hemoglobin C Trait (Hb AC)
Compound heterozygosity, one β-globin have sickle cell mutation, while the other is mutant for HbC. Hb S and Hb C is found in equal amounts, splenomegaly and vaso-occlusive crisis is seen.Hemoglobin SC Disease (Hb SC)
One sickle beta-globin and other beta-globin is absent, >90% Hb S, splenomegaly and vaso-occlusive crisis seen.Sickle Beta (0) Thalassemia (Sβ0 Thalassemia)
One sickle beta-globin and other beta-globin is in decreased amounts, >60% Hb S, splenomegaly and vaso-occlusive crisis seen.Sickle Beta (+) Thalassemia (Sβ+ Thalassemia)
Deletion of one of the four α-globin loci is deleted. No clinical manifestations.α-Thalassemia-2 Trait
Deletion of two of the four α-globin lociα-Thalassemia-1 Trait
Deletion of three of the four α-globin loci; Incusions seen in erythroblasts and precipitates seen in circulating RBCsHbH Disease
Deletion of all four α-globin lociHydrops Fetalis with Hb Barts (γ4)
Unpaired α-globins accumulate and form toxic inclusion bodies. Toxic inclusion bodies kill proerythroblasts and reduces RBC life span producing severe hemolytic anemia. Increased erythropoietin leads to extramedullary erythropoiesis. Massive bone marrow expansion leads to “chipmunk” facies and pathological fractures. Microcytic and hypochromic red blood cells are seen that resemble the red blood cells of severe iron deficiency anemia. Many elliptical and teardrop-shaped red blood cells are noted.β-Thalassemia Major
Characterized by dusky discoloration to skin and chocolate-colored blood, anemia (presence of Heinz bodies). Symptoms are related to tissue hypoxia – anxiety, headache, dyspnea, in rare cases coma and death. Treatment is use of methylene blueMethemoglobinemia
Mutation in gene coding for type IV collagen leads to what diseaseAlport Syndrome
Auto immune dysfunction where the immune system attacks the basement membranes of the glomeruli and the alveoli.Goodpasture’s Syndrome
Deficient cross-linking secondary to functional copper deficiencyMenkes Disease
Depigmented (steely) hair, arterial tortuosity, rupture, cerebral degenration, osteoporosis, anemiaMenkes Disease
A disorder of copper transport caused by mutations in the copper-transporting ATPase gene (ATP7A).Menkes Disease
X-linked recessive trait, Lysyl oxidase enzyme is affected which leads to a defect in cross-linkingMenkes Disease
What degrades elastin of alveolar walls and other tissue proteins.Neutrophil Elastase

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