Exam 1 Clinical Correlates Flashcards
Respiratory acidosis
Causes increase in CO2, decrease in pH, and increase in [H+]
Long-term: increase in bicarbonate (HCO3-)
Presentation: hypoventilation, COPD or other respiratory obstruction
Respiratory alkalosis
Causes decrease in CO2, increase in pH, and decrease in [H+]
Long-term: decrease in bicarbonate [HCO3-]
Presentation: hyperventilation
Metabolic acidosis
Caused by an increase in acid in the blood (lactate/ketone bodies, diarrhea), decrease in pH, increase in [H+]
Long-term: increase in PCO2
Presentation: chronic diarrhea
Metabolic alkalosis
Caused by a decrease in acid in the blood (vomiting, antacid), increase in pH, decrease in [H+]
Long-term: decrease in PCO2
Presentation: vomiting, antacid
Adenocarcinoma
Forms a gland-like pattern from epithelial cells of the colon, can grow from colon polyp through the wall of surrounding tissues
Presentation: rectal bleeding, blood in stool, abdominal pain, feeling like you need to go number 2 all the time, weakness or fatigue, unexplained weight loss
Alcoholism
Causes a thiamine deficiency, which inhibits pyruvate dehydrogenase, which in turn inhibits the formation of acetyl-CoA.
Thiamine deficiency also causes alpha-ketoglutarate dehydrogenase (succinyl Co-A)
Excessive lactate is produced (metabolic acidosis)
Amyloidosis
Immunoglobulin chains form an insoluble protein aggregate (amyloid) in organs & tissues.
Disease: Alzheimer’s Disease
Causes: renal damage, cardiac damage, rheumatoid arthritis, neurological damage
Prion disease
Misfolding & aggregation of a neurodegenerative protein. Has the same amino acid composition (PrPc) but folds into a different, more degenerative conformation (PrPsc).
PrPsc has significantly more beta-sheets, lowers the activation energy barrier -> causes proteolytic degradation
Diseases: CJD (mad cow), Scrapies in sheep
Presentation: rapid timespan, descent into madness, via ingested or sporadic occurrence
Angelman Syndrome
A: microdeletion of maternal chromosome 15
Using base methylation to regulate gene expression, and methylation of critical bases within the promoter causes the nonexpression of the gene (epigenetic)
Presentation: Developmental disabilities and neurological problems,such as difficulty
speaking, balancing and walking, and, in some
cases, seizures
Prader-Willi Syndrome
PW: microdeletion of paternal chromosome 15
Using base methylation to regulate gene expression, and methylation of critical bases within the promoter causes the nonexpression of the gene (epigenetic)
Presentation: Poor muscle tone,
intellectual impairment, learning disabilities,
narrow forehead, almond-shaped eyes,
triangular mouth, short stature, small hands and
feet, underdeveloped genitals, delayed or
incomplete puberty, infertile
Androgen insensitivity
Lack of androgen receptors leading to default female sexual characteristics
Anorexia nervosa
Body is in a constant starvation state. Ketone bodies
are extremely elevated in blood due to fatty acids
being converted in the liver to produce energy,
kidneys are excreting ketone bodies, blood glucose is
slightly below the normal range.
Decreased body fat restrict the release of gonadotropic hormones.
Poor diet leads to hypochromic anemia -> reduction of serum & tissue ferritin, but increase in transferrin protein & transferrin receptor
Cholera
Caused by Vibrio cholerae
Mechanism: Cholera toxin A subunit indirectly activated the cystic fibrosis transmembrane conductance regulator (CGTR) channel, resulting in secretion of chloride and sodium ion into the intestinal lumen. Ion secretion was followed by loss of water
Presentation: watery diarrhea & vomiting
Treatment: oral rehydration with high glucose & sodium content, intravenous rehydration
Chronic myelogenous leukemia
Single line of myeloid cells in the bone marrow proliferates abnormally, causing large increase in the number of nonlymphoid white blood due to translocation between chromosomes 9 & 22
Known as the Philadelphia chromosome
Presentation: Pain and tenderness in
various areas of the body, possibly stemming
from the expanding mass of the myeloid cells within bone marrow. Hemorrhagic signs such as bruises
(ecchymoses), bleeding gums, and the appearance of small red spots on the skin (petechiae caused by release of red cells)
Cockayne syndrome
Mutations in protein are specifically responsible for
the transcription-coupled repair, which clinically present
as premature aging. Cells with these mutations
cannot transcribe damage-damaged genes. If the
DNA cannot be repaired because of the defect in
transcription-coupled repair, premature cell death
can result from the reduction of gene expression
Presentation: Small head size, failure
to gain weight and grow, short stature, delayed
development. Increased sensitivity to sunlight,
and hearing loss, vision loss, severe tooth decay,
bone abnormalities
Cystic fibrosis
Function of chloride channels in pancreatic secretory ducts are defective; thickening of mucus occurs
Cystinuria
Large amount of cystine in the urine due to inherited
amino acid substitution in the transport protein that
reabsorbs cystine, arginine and lysine. Cystine is less
soluble and may precipitates in the urine to form
renal stones
Presentation: blood in urine, severe flank pain, nausea and vomiting
Diabetes (type 1)
Insufficient insulin due to immune system attacking beta cells
Diabetes (type 2)
Resistant to insulin in cells
Gout
May be caused by mutations in specific proteins or by dietary habits. Leads to a buildup of uric acid in the blood and precipitates of urate crystals in the joints.
Depression
Diagnosed by behavioral changes, can be treated with a variety of pharmacologic agents and counseling therapy
Obesity
Long-term effects of obesity affect the cardiovascular system and may lead to metabolic syndrome
Insulin resistance
Kwashiorkor
Protein and mineral deficiency even though normal amount of calories in the diet. Leads to marked hypoalbuminemia, anemia, edema (appearance of potbelly), loss of hair, and other indications of tissue injury
Levels decreased: serum albumin
Marasmus
Prolonged calorie and protein malnutrition
Osteoporosis/osteomalacia
Calcium-deficient diet leading to insufficient mineralization of the bones, which produces fragile and easily broken bones. Osteoporosis also runs in families
Iron-deficiency anemia
A low blood vitamin B12 level can be caused by decreased intake, absorption, or transport, but usually takes several years to develop because of large total body stores. Serum albumin was 3.2 g/dL (reference range = 3.5 to 5.0 g/dL), which is an indicator of protein malnutrition, liver disease, or both
Peripheral neuropathy
Vitamin E deficiency
Malnutrition
Reduced nutrient uptake may be caused by genetic mutation in specific proteins or dietary habits leading to reduced nutrient intake. May lead to increased ketone body production and reduced liver protein synthesis
Hypercholesterolemia
Elevated cholesterol as a result of mutation within a specific protein or excessive cholesterol production/intake
Hyperglycemia
High blood glucose levels owing to either mutations in specific proteins or tissue resistance to insulin
Hyperlipidemia
High levels of blood lipids, which may be caused by mutations in specific proteins or ingestion of too many calories
Starvation
When we fast for 3 or more days, we are in a starved state. Muscle continues to burn fatty acids but decreases its use of ketone bodies. As a result, the concentration of ketone bodies rises in the blood to a level at which the brain begins to oxidize them for energy. The brain then needs less glucose, so the liver decreases its rate of gluconeogenesis. Consequently, less protein in muscle and other tissues is degraded to supply amino acids for gluconeogenesis. Protein sparing preserves vital functions for as long as possible. Because of these changes in the fuel utilization patterns of various tissues, humans can survive for extended periods without ingesting food
Salicytate overdose
Caused by aspirin
Complex effects on respiratory center and basic metabolism, causing alterations in acid/base management, among other effects. Leads to impaired renal function
Hyperventilation
Complex effects on respiratory center and acid/base management. Leads to respiratory alkalosis
Diabetic ketoacidosis
Free fatty acids leave her adipocytes (fat cells) and are converted by the liver to the ketone bodies acetoacetic acid and β-hydroxybutyric acid. These compounds are weak acids that dissociate to produce anions (acetoacetate and β-hydroxybutyrate, respectively) and hydrogen ions, thereby lowering her blood and cellular pH below the normal range. As these acids accumulate in the blood, a metabolic acidosis known as diabetic ketoacidosis (DKA) develops
What occurs during diabetic ketoacidosis as a compensatory mechanism?
Kussmaul breathing
What isozyme can be used to detect an MI?
Creatine kinase -> MB
Sickle cell anemia
Single amino acid replacement at the sixth position of the β-chain of hemoglobin, leading to an E6V alteration (instead of glutamic acid at position 6, a valine is in its place)
Myocardial infarction
Primarily environmental factors, which can be exacerbated by genetic conditions. The release of heart-specific isozymes into the circulation is diagnostic for a heart attack.
Malathion is a…
Covalent inhibitor
Penicillin is a…
Transition state analog
Allopurinol is a…
Induced transition state analog
Mechanism of Action: Malathion
Metabolized in liver to malaoxon, which binds to active site serine in enzymes, prevents breakdown of Ach which over stimulates autonomic nervous system
Form a covalent intermediate in active site, preventing enzyme from degrading into product
Penicillin MOA
Binds tightly to glycopeptide transferase which synthesizes cell wall in bacteria
Strong resemblance between peptide bond in B-lactam ring and transition state complex of natural transpeptidation reaction
Also referred to as suicide inhibitors
Allopurinol MOA
Inhibits xanthine oxidase by causing it to oxidize allopurinol to oxypurinol which then binds very tightly to Mo-S complex in active site
What do we use allopurinol for?
Gout
What is altered in prion disease
Tertiary structure, sometimes primary structure
Malathion poisoning
Inhibition of acetylcholinesterase at neuromuscular junctions. This leads to acetylcholine accumulation at the junction, and overstimulation of the autonomic nervous system
Thiamin deficiency (beriberi heart disease)
Leads to lack of energy production because of reduced activity of key enzymes and can lead to disease in the nervous system (Wernicke’s encephalopathy/Wernicke-Korsakoff syndrome) and cardiovascular system (beriberi heart disease). It is most often brought about by alcohol use disorder, as manifest by a poor diet, and by ethanol inhibition of thiamin transport through the intestinal mucosa
Maturity onset diabetes of the young (MODY)
Mutations in various proteins can lead to this form of diabetes, which is manifest by hyperglycemia, but without other complications associated with either type 1 or 2 diabetes. Specifically, mutations in pancreatic glucokinase were discussed
Decreased GK activity results in lower insulin secretion for a given blood glucose level
What stays the longest in the blood stream during an MI?
Troponin
Streptokinase
Streptokinase used therapeutically is actually not a pure enzyme, but a mixture from streptococcus
Activates the fibrinolytic enzyme system
Used to break down blood clots
May be used by vascular specialists (e.g., to reopen vascular access grafts)
Can only be used once, as it elicits an immune response after the first use
Tissue plasminogen activator (t-PA)
Recombinant human t-PA is produced from bioengineered E. coli
t-PA is used to dissolve blood clots after myocardial infarction
Used by some cardiologists
Has the same activity as streptokinase, but because it is essentially the same as endogenous t-PA, it elicits no immune response
Asparaginase
Breaks down asparagine (which is a preferred metabolic substrate for certain tumors)
Used in treatment of certain types of adult leukemia
What do sulphonamides inhibit?
Dihydropteroate synthease
What does sulphonamide inhibitor prevent?
Bacterial infections
What does methotrexate inhibit?
Dihydrofolate reductase
What does methotrexate prevent?
Neoplasms, particularly leukemia
What does allopurinol inhibit?
Xanthine oxidase
What does allopurinol prevent?
Gout
What do ACE inhibitors do?
Inhibit angiotensin-converting enzyme for high BP
What does warfarin inhibit?
Glutamate carboxylase
What does warfarin prevent?
Thrombosis
Statins inhibit…
HMG-CoA reductase
What does statins lower?
Elevated plasma cholesterol
Omeprazole & esomeprazole inhibit… to prevent…
H+K+-ATPase, gastric reflux
Aspirin inhibits
Cyclo-oxygenase
What does aspirin help with?
Pain, inflammation, prophylaxis in CAD
5-FU inhibits
Thymidylate synthase
What does 5-FU prevent?
Cancer
Myasthenia gravis
Autoantibodies to the acetylcholine receptor (and others at the neuromuscular junction), leading to neuromuscular dysfunction
Gas gangrene
Bacterial infection that secretes a toxin which is a phospholipase, leading to cell membrane destruction. This leads to capillary destruction, and impaired blood flow to the affected area
Alcohol use disorder
Ethanol poisoning due to increased production of acetaldehyde, due to the combined actions of alcohol dehydrogenase and the induction of the microsomal ethanol oxidizing system (MEOS). MEOS is induced because of the high levels of ethanol in the patient’s diet
Acquired immunodeficiency syndrome (AIDS)
AIDS is owing to infection by the human immunodeficiency virus (HIV), a retrovirus containing an RNA genome. Through its growth in immune cells, active infection by the virus leads to an immunocompromised state. Nucleoside analogs are one class of drugs used to treat those with HIV infections
Pneumonia
A bacteria-induced illness in the lungs, leading to fever and cough. Treated with antibiotics. Certain antibiotics target bacterial protein synthesis but may also inhibit mitochondrial protein synthesis
Xeroderma pigemtosum
Mutations which are involved in nucleotide excision repair, leading to a greatly elevated risk for the development of skin cancer
Cockayne syndrome
Mutations in enzymes which are required for transcription-coupled DNA repair. Leads to premature cell death, and a failure to thrive and developmental delay
Hereditary non polyposis colon cancer (HNPCC)
Mutations in enzymes which are required for DNA mismatch repair, which can lead to mutations in genes regulating cell proliferation
Hereditary breast cancer
Mutations in the genes BRCA1 and BRCA2, which lead to defects in the repair of single-strand and double-strand breaks in DNA
β-Thalassemia
An anemia because of an imbalance in β- and α-globin chain synthesis. For a β-thalassemia, more α-chain is synthesized than functional β-chain
Tuberculosis
The drug rifampin, among others, is used to treat tuberculosis, via inhibition of bacterial RNA polymerase
Mushroom poisoning (α-amanitin poisoning)
Inhibition of RNA polymerase II by α-amanitin. There is no effective antidote for this poison
What does streptomycin inhibit?
Binds to the 30S ribosomal subunit of prokaryotes, thereby preventing the formation of the initiation complex. It also causes misreading of mRNA
What does tetracycline inhibit?
Binds to the 30S ribosomal subunit and inhibits binding of aminoacyl-tRNA to the A site
What does chloramphenicol inhibit?
Binds to the 50S ribosomal subunit and inhibits peptidyl transferase
What does erythromycin inhibit?
Binds to the 50S ribosomal subunit and prevents translocation
Tay-Sachs disease
Mutation in a gene encoding a lysosomal enzyme, leading to loss of lysosomal function and death at an early age for the patient
Enzyme inhibited: hexoamindinase
I-Cell disease
Mutation in posttranslational processing leads to mistargeting of enzymes destined for the lysosomes. Disease leads to lysosomal dysfunction and early death
Hutchinson–Gilford Progeria syndrome
An example of a silent mutation in terms of amino acid substitution, but the single nucleotide change creates an alternative splice site that leads to a loss of 50 amino acids from the precursor lamin A protein. This leads to altered posttranslational processing and the symptoms of a premature aging disease
Non-Hodgkin lymphoma, follicular type
Treatment with multiple drugs, all targeted to inhibiting cell proliferation, but through different mechanisms. DNA synthesis is targeted, as is tubulin action (to block cell division). DNA damage is induced, and thymidine synthesis is also blocked to inhibit further DNA replication
CML
More than 90% of CML arises owing to the generation of the Philadelphia chromosome, which is created by an exchange of genetic material between chromosomes 9 and 22. This translocation creates a unique fusion protein (BCR-abl), which facilitates uncontrolled proliferation of cells which express this fusion protein
Fragile X disease
A significant number of triplet repeat expansions within a gene may lead to dysfunction of the protein product, leading to disease. In fragile X, impairment of cognitive function is the primary symptom, caused by expansions in the FMR-1 gene on the X chromosome
Phenylketonuria
The congenital condition where an individual cannot convert phenylalanine to tyrosine
