Translational Physiology Block 1 Flashcards
What is Paroxysmal Nocturnal Hematuria?
Hemoglobin appearing in the urine at night
What is the complement cascade?
Complement is a complex collection of proteins that circulate in the blood plasma. The complement system recognizes antibodies that are bound to the surface of a bacterium or polysaccharides in the bacterial membrane. This recognition initiates a cascade of enzymatic cleavages that results in the assembly of a subset of complement proteins to form the membrane attack complex, which inserts itself into the membrane of the target organism and forms a large pore that allows water to rush in (osmotic lysis)
Is the complement cascade very selective? (Give an example and what condition it causes; why does this happen)
No; hemolysis of erythrocytes or paroxysmal nocturnal hematuria; a spontaneous mutation occurs in the PIG-A gene (f(x)s in anchoring of GPI-linked proteins) which prevents two proteins (DAF and CD59) from being expressed on the membrane to prevent lysis by the complement cascade
What is an inclusion cell or I cell? What is the pathophysiology are result of?
Characterized by lysosomes lacking hydrolases (overstuffed lysosomes); phosphosugar transferase, which creates mannose-6-phosphate signal, is mutated (hydrolases are exocytosed from cell)
What is the pathophysiology of Tay-Sachs disease?
Hex A mutation preventing degradation of certain sugar linkages in lysosomes
How does cholera toxin cause diarrhea?
The cholera toxin has multiple subunits; following proteolytic cleavage, one of the subunits transfers the ADP ribosylation moiety of NAD+ to Gs (prevented it from being inactivated by ADP) causing increasing in cAMP and loss of chloride from the cell (water follows it)
How does whooping cough increase cAMP production?
Pertussin bacteria adds ADP ribosylation moiety to Gi (inactivating the GTPase) preventing the suppression of adenylyl cyclase and production of cAMP
What is the difference between COX1 and COX2? (What drugs acts on them and what is their side effects?)
COX1: thrombosis and prostacyclins in GI (aspirin blocks clotting at the expense of GI bleeding); COX2: inflammation (aspirin at high doses is weak inhibitor; NSAIDs block inflammation but are not suggested for cardiac patients)
What are the important molecules associated with anaphylaxis in the lungs? (what other diseases are they present in)
Leukotrienes (bronchoconstriction); psoriasis, Crohn’s, RA, and bowel syndromes
What is an important characteristic of oncogenes?
Aberrant (constitutive) signaling of key signaling pathways (i.e. Ras and RTKs)
What are β-Thalassemias?
Anemic disorders caused by deficiency in production of B-chain of hemoglobin (deletion of the LCR)
What is aberrant in patients with acute premyelocytic leukemia?
Fusion of PML and RARalpha repressing differentiation by constitutively binding to N-Cor repressor for differentiated genes
What is a result of extremely high extracellular osmolality from dehydration? Why is this difficult to solve clinically?
Shrinkage of brain cells and possible intracerebral hemorrhage; returning the fluid levels back to normal too quickly may result in brain edema and possible tentorial herniation
What is the pathophysiology of Charcot-Marie Tooth disease?
neuropathy (peripheral nerves); mutations in connexins important for communication between different Schwann cells (demylelination syndrome)
What is hyperkalemic periodic paralysis?
mutations in membrane-spanning segment S5 of domain II and S6 of domain IV in sodium channels (abnormal kinetics) results in increased extracellular potassium
What is paramyotonia congenita?
mutation in the linker region of sodium channels (important for sodium inactivation); disease phenotype presents by exposure to cold temperature
What is long QT syndrome?
cardiac arrhythmia caused by mutation in linker region of sodium channel; or by mutation in potassium channels (defective repolarization can lead to premature heartbeats or asynchronous ventricular contraction)
What is Lambert-Eaton syndrome? How is different from myasthenia gravis?
Patients afflicted with this condition produce antibodies against presynaptic Ca 2+ channels; attacks limb muscles; repetitive stimulation of a particular muscle leads to enhanced amplitude of the postsynaptic action potential, whereas in patients with myasthenia, repetitive stimulation leads to progressive lessening of the action potential. Thus, repeated muscle stimulation leads to increasing contractile strength in patients with Lambert-Eaton syndrome and to decreasing strength in patients with myasthenia.
What type of channel is altered by hypokalemic periodic paralysis?
Skeletal DHP receptors
What is the definition of myasthenia?
weakness in the absence of primary muscle disease, neuropathy, or CNS disorder
What is a characteristic of young people who are affected by myasthenia gravis? older people? why is is this gland so important?
woman who have hyperplasia in the thymus; cancer of the thymus gland; The cells of the thymus possess nicotinic AChRs, and the disease arises as a result of antibodies directed against these receptors.
What are the symptoms of myasthenia gravis?
general fatigue and weakness of skeletal muscles (one subtype only affects the extraocular muscles); symptoms fluctuate (greatest weakness at the end of the day or following exertion)
Why does prolonged activation of acetylcholine receptors result in acute paralysis?
overstimulation of the postsynaptic receptors, prolonged depolarization of the postsynaptic membrane, inactivation of neighboring Na + channels, and thus synaptic blockade.
What are treatment options for myasthenia gravis?
Immunosuppression: corticosteroids (prednisone) and IV IgGs or plasmapheresis; removal of thymoma; AchE inhibitors (pyridostigmine)
What kind of mutation was clearly described in the textbook to demonstrate congenital myasthenic syndrome?
The burst duration of AChR openings was greatly prolonged in comparison with that of normal human AChR channels; The molecular defect is a point mutation of Thr to Pro at position 264 in the adult ɛ subunit of the AChR. This amino acid residue corresponds to an evolutionarily conserved position in the M2 membrane-spanning segment, which is involved in formation of the channel pore. Thus, a human mutation in the pore region of the AChR protein results in failure of the channel to close normally
What is effect of botulism toxins?
Patients begin to complain of symptoms attributable to inhibition of synaptic vesicle release in the autonomic nervous system, such as dry mouth, double vision, and difficulty in swallowing and speaking, and later begin to experience gastrointestinal complications, including vomiting, pain, and diarrhea. Symptoms attributable to inhibition of synaptic vesicle release at the neuromuscular junction, such as weakness and paralysis of the limbs, may soon follow; ultimately, paralysis of the respiratory muscles can be fatal.
What is the effect of tetanus toxin?
The organism gains entry to its host through a cut or puncture wound. The toxin then travels along the peripheral nerves to the spinal cord, the major site of its attack. There, the toxin inhibits synaptic vesicle release by interneurons that normally inhibit firing of the motor neurons that, in turn, activate skeletal muscle. Thus, because the toxin suppresses inhibition of the normal reflex arc, muscle contraction leads to profound spasms, most characteristically of the jaw muscles but potentially affecting any muscle in the body.
