Biochem Clinicals (LOCO) PDF

# Biochem Clinicals (LOCO) ## 1- Scurvy ### Type: Infantile Scurvy (Barlow's Disease) ### Signs & Symptoms: - Collagen synthesis or. - Capillary hemorrhage. - Muscle weakness. - Bone weakness. - Swollen and soft gums. - Wound healing. - Development of bones (cartilage (dentine and - Dealli. ###...

# Biochem Clinicals (LOCO) ## 1- Scurvy ### Type: Infantile Scurvy (Barlow's Disease) ### Signs & Symptoms: - Collagen synthesis or. - Capillary hemorrhage. - Muscle weakness. - Bone weakness. - Swollen and soft gums. - Wound healing. - Development of bones (cartilage (dentine and - Dealli. ### Cause: - Low intake of fresh veges. - (Ascorbic Acid) - **VIT 'C'** related questions. ### Sources: - Citrus fruits (Banana, apple). - Tomato, onion, carrot, potato. - Liver, milk. ### Forms: - Ascorbic Acid - Dehydroscorbic Acid. ## Production - **L-Ascorbic Acid Pathway:** - Glucose - L-Glucono lactone - Vit 'C' - Oxidase. - No production in human body due to lack of L-Glucono lactone oxidase enzyme. ## Functions: - **Collagen Hydroxylation:** - Collagen has protein and lysein. - Better network - Formation of collagen. - **Iron Absorption:** - Fe+2 + Vit C ➡️ Fe+3 (absorbed) - Prevent Fe+ 2 (ferrous form) from conversion into Fe+3 (feric form). See that, how helps in iron absorption. - **Antioxidant:** - Prevent heart, cancer diseases. - Tryptophan and Tyrosine metabolism. - Role in production of Immunoglobulins. - Corticosteroids. - THF formation. - Wound healing. ### Toxicity: - Dehydro ascorbic Acid ➡️ Oxalate ➡️ Kidney stones. - Common cold treatment. (Megadore of Vit (C) ## 2- Osteoporosis ### Cause: Low Ca++ intake. ### Postmenopausal Osteoporosis - Age ➡️ 750 - Estrogen ➡️ Bone growth and maturation. - Estrogen ➡️ osteoclast activity ↑ ### Treatment: - Inc. Calcium absorption by inc 1,25-(OH)2 D (Serum). - Vit D (active form) ➡️ Bone Calcium absorption ↑ ## CALCIUM **Related Questions:** - Source: Milk, cheese, and dairy products. - Daily intake: - Adult men and women: 8oo mg (day). (0.8g/day). - Kids: 1-3 yr: 700 mg (day). (0.7 g/day) 4-8 yr: 1000 mg/day (1g/day) 7-18 yr: 1300 mg/day (1.3g/day) - 99% - Human body ➡️ 1-1.5 by calcium - 99%-bones - 1% - muscle, blood ### Function: - Muscle contraction. - Bone and teeth development. - Blood coagulation. - Cell to cell junction. - Hormone release. - Nerve transmission. - Activation of enzymes. ### Absorption: - Duodenum. Me. ### Factors: - **Absorption ↑** - Vit D - PTH - Low pH - Lactose - Amino Acid (lysine, Arginine) - **Absorption ↓** - Fatty Acids. - Dietary Fibers. - High pH - Phytate, Oxylate - Ca:P 1:2 2:1 - Ca or Phosphate should not be more than 2 times. ### Plasma level: 9-11 mg/dL. (ionized form) ### Regulators - **Vit D ↑** - Enzymes activation by: - Pyrophosphatase. - Collagenase. - Bones (demineralization) ➡️ Ca++ ↑ - Kidney (excretion) ➡️ Ca++ ↑ - Intestine (absorption ↑) - **PTH ↑** - Bones (demineralization) ➡️ Ca++ ↑ - Kidney (excretion) ➡️ Ca++ ↑ - **Calcitonin: antagonist to PTH.** - **Ca:P** - Adults: Ca:P 40 - Children: Ca:P 50 ➡️ normal. - Def. disease: Ca: P <30 ## 3- Hypercalcemia. - Calcium plasma level ➡️ >9-11 mg/dL. - Due to hyperthyroidism (PTH↑) - Stones, muscle weakness, nausea - Constipation ## 4- Hypocalcemia - Calcium plasma level ➡️ < 9-11 mg/dL. - Due to hypothyroidism (PTH↓). - Treatment: - Vit D ## 5- MBD (Marble Bone Disease) / Osteopetrosis: - Bone demineralization can't be done. - High level of Calcium in bones. ## 6- Rickets: (children). - Cause: due to dec. Serum 1,25(OH)2 D (Vit D). - Vit D ➡️ ea mineralization of bones. - Low exposure of sunlight. - Symptoms: - Muscle weakness. - Joint pain. - Bowed legs. - Rachitic rosary (beaded appearance of chest). - Swollen wrist, ankle joint. - Treatment: - Vit D supplementation. - Sunlight exposure. - **Types:** - **1- Resistant / Renal Rickets** - Can’t be treated by inc. vit D intake. - Due to abnormality in kidney so then kidney can’t convert Vit D inactive form into active one. - **2- Nut. Rickets ➡️ low intake of Vit D** ## Vit D **Related Question:** - Active form: 1,25-dihydroxycholecalciferol / calcitriol. - Storage form: 25-hydroxycholecalciferol. ### Metabolism: - **Skin:** - 7-dehydrocholesterol ➡️ UV ➡️ Cholecalciferol - **Liver:** - Cholesterol ➡️ 25-hydroxytase ➡️ 25-hydrocholecalciferol. - **Kidney:** - 25-hydroxy ➡️ 25-OH cholecalciferols ➡️ 1-hydroxylase ➡️ 1,25(OH)2 ### Regulation of 1-hydroxylase: - Plasma Ca++ ➡️ directly regulate. - Plasma P ➡️ directly regulate. - Low plasma level of phosphorus ➡️ stimulates 1-hydroxylase ➡️ activated ➡️ more 1,25-(OH)2D, hence Plasma P ↑ - When Ca++ and PTH ↑ ➡️ enhance 1-hydroxilase ➡️ 1,25-6H/2D, Ca++ ↑ ### Function of Calcitriol: - **Ca++ absorption:** - Intestine: bind to calcitriol receptors. Produce protein "calbindin" binds to Ca++ for absorption. - **Kidney:** - excretion of Ca++ ↓ - **Bone:** - Osteoblast activity ↑➡️ Ca++ absorption. ### Sources: - **Plant:** Ergocalciferol (Vit D₂) - **Animal:** Cholecalciferol (Vit D₃) - Fatty fish - Liver - Egg yolk - The sunlight exposure. ### Toxicity: - Nausea. - Kidney stones. - Loss of appetite. - Thirst. ### Why Hormone? - Body may produce hormone. - Particular sites of action (kidney, bone, intestine). - Regulation (Ca++ and PTH) ### Regulation: - Regulate its own production by prohibiting PTH and 1-hydroxylase (negative feedback). - RDA - 1-70 yrs ➡️ 15mg/day (1ng Vit D = 4010) - >70 yrs ➡️ 20mg/day - Breast milk = poor source. So, supplementation necessary for breast-fed babies. ## 6- Osteogenesis Imperfecta/ Brittle Bone Disease: - The condition in which the bones are inadequately formed into body. ### Cause: - Lack of the protein collagen. That cause brittle bones that break easily. ### Signs & Symptoms: - Curved spine - Hearing loss (starts 20-30's) - Baring loss (age) - Cause spine curvature called as kyphosis lead to a hunchback. ### Treatment: - No cure ## 7- Ehlers-Danlos Syndrome (EDS): - **Types of OI** - **Type 1** - Most common - Mild bone fragility. - Heavily loss. - Blue sclerae (curvature of eye becomes blue). - **Type II** - Most severe form. - Lethal in prenatal period due to pulmonary complications. - Short statue - In utero fractures. - Kyphosis. - Blue sclerae. - **Type III** - Also severe form. - Multiple fractures. ## 7- Ehlers-Danlos Syndrome: (EDS): - Due to Lysyl hydroxylase enzyme. - Or mutations in the sequences of amino acids in collagen type 1, II, V. - **Vascular form of EDS** - Defect in collagen, type 8III - Lethal arterial rupture. - **Classic form of EDS** - Defect in collagen. type - Skin extensibility and fragility and joint hypermobility. ## Collagen: ### Related Questions: - Fibrous protein (rod/ wire like shape). - Structural protein. - Insoluble in H2O. ### Collagen: - Most abundant protein in human body (25%). - 3 polypeptide chains (a-chains) - Rich in glycine-- te imp. in the formation for triple-stranded helix. - Glycine-- 3rd position of polypeptide chain. - Hydroxyproline and hydroxylysine-- present in collagens (not on olwyn protein) - Result from hydroxylation. - Hydroxy proline-- stabilize triple helicle structure. - Hydroxylation required molecular oxygen and vit 'C'. - Hydroxylating enzymes (Lysyl hydroxylase and polyyl hydroxylase) are unable to function without vit 'C'. ## 8- Marfan Syndrome. - A connective tissue disorder. ### Cause: - Mutations in fibrillin-1 protein (FBN-1) ### Signs & Symptoms: - Impaired structmal integrity in the skeleton (tall, especially aorta) - Eye (swollen walls) - Long slender arms, legs, fingers, and toed. - Flexible joints. - May have scoliosis (abnormal lateral curvature of spine). ## Elastin: ### Related Questions: - A fibrous hotein. - Rich in Proline and lysine - Have hydroxyproline. - No Hydroxylysine. ### Precursor Tropoelastin: - ~700 Amino acids - Primarily small, non-polar (Valine, glycine, alanine) - Tropoelastin secreted into ECM by cells. - Interacts with specific glycoproteins such as microfibrils, fibrilin. - Some of lysyl sides are oxidatively deaminated by lysyl oxidase, forming allysine residues. - 3 Allysyl sides + 1 lysyl side-- Forms desmosine-- cross-link - This produces elastin, interconnected, a rubbery network that can stretch and bend, stressed, giving elasticity to connective tissue. - Mutations in tibtrilin-1--- Marfan Syndrome. ## 9- Osteomalacia: Rickets. - Osteomalacia: - Lo only age difference. ### Difference between osteomalacia and osteoporosis: - Osteomalacia: softened and weakened bones, bone pain due to Vit D and Calcium def. Age may be <40 - Osteoporosis: weak bones, fracture. Age is always ➡️ 40. - Osteoporosis: due to vit D def, calcium def, and estrogen low ## 10- Mucopolysaccharidoses (MPS)s: - Rare inborn errors in degradation of GAGS. - (Glycosaminoglycans). - Hereditary disorders. - Deficiency in enzyme: accumulation of GAGS: MPS Symptoms - **Main signs**: - Mental retardation. - Structural defects. - **Types:** - **MPS Type I.** - Def of which enzyme: - Alpha-L-iduronidase - Accumulation: - Hepanan sulfate - Dermatan - Name: - Hurler syndrome - **Type II** - Iduronate sulfatase - Same for type II - Hunter syndrome - **Type III** - 4 enzymes: - Hydrolases. - N-acetyltransferase. - Heparan sulfate - Sanfilippo syndrome ## GAGS: ### Related Questions: - Large complexes of -ve charged heteropolysachride chains. - Can bind with large amount of water. - Produce gel matrix-- basis of body ground substance. - Composition of ECM: fibrous protein and GAGS. ### Functions: - Component (Major) of ECM. - Lubricate joints. - Give flexibility to cartilage. ### Absence: - Trauma/ osteoarthritis. ### Classification: - **GAGS** - **Sulphate free** - Hyaluronic acid - **Sulphate containig** - Chondroitin sulphate. - Keratin sulfiale I - Heparin & Heparin sulpfile - Dermatan sulfate. ## Maple Syrup Urine Disease (MSUD): - The urine of patients smells like maple syrup or burnt sugar. - **Other Name:** - Branched chain Keto Aciduria. - **Deficiency:** - Brauch chain keto aid dehydrogenase. - **Types:** - **1- Classical:** severe deficiency. - **2- Juterrmittent:** Enzyme activity ↓. - **3- Thiame responsive:** Defect stabilized by Vit B1. - Seen in childhood; don’t take food, vomiting. ### Genetic: - Autosomal recessive disorder. ### Accumulation: - Accumulation and execetion of branched amino acids by their keto acids. - Accumulation cause impairment in function, transport of their amino acids. - Protein biosynthesis reduced. - BLAAS inhibit glutamate dehydrogenase. ### Signs & symptoms: - Severe MR. - Convulsions. - Vomiting. - Acidosis (ketoacidosis). - Coma. - Death. ### Diagnosis: - **Enzyme Analysis:** - Plasma and urine : ↑ Leu, Ile, Val of their a-keto acids. - Smell of Urine= Burnt Sugar. - Chromatography of Urine. - Rother’s test +ve. ### Treatment: - Diet low in BCAAs. - High in prey thiamine. - BCAAs: Valine, isoleucine, leucine.