patho midterm

  1. Caseous necrosis
    • gross appearance alteration (white and cheesy) in necrotic area
    • tissue structure obliterated
    • granulmatous inflamation seen microscopically
  2. What is necrosis? What are the 2 essential concurrent processes that are involved?
    • Premature death of cells caused by infection/interruption of blood supply
    • requires enzymatic digestion of cells, and denaturation of proteins
  3. What is liquefactive necrosis?
    • Often associated with bacterial or fungal infections
    • Accumulation of inflamatory cells as well as digestion of dead cells and the presence of pus (white goop)
  4. Compare hypoxia and ischemia
    • hypoxia: oxygen deficiency
    • ischemia: lack of oxygen delivery due to lack of blood flow
  5. 2 branches of consitutional disease? 3 branches of environmental disease?
    • Hereditary vs non-hereditary
    • Dietary, living external agents, non living external agents
  6. What is metaplasia?
    Reversible change in which one differentiated cell type is replaced by another
  7. What is coagulative necrosis?
    • Dead tissue is preserved for a span of time (ex. myocardial infarction)
    • Characterized by intracellular acidosis (resulting in denaturation of proteins and enzymes but not proteolysis

    • essentially cells are dead but remain undigested
    • localized area of coagulative necrosis is called an infarct
  8. what are the 4 types of necrosis?
    • coagulative
    • liquefactive
    • caseous
    • fat
  9. How does excess cytosolic calcium impact the cell?
    • increases activity of ATPase (decreased ATP)
    • phospholipase (decreases phopholipids)
    • proteases [these first 3 lead to membrane damage]
    • incudces endonuclease release by ER (chromatin damage)
  10. Why are depleted levels of ATP problematic for cells?
    • Decrease in membrane transport-> Swelling of cell
    • Decrease in protein synthesis (ribosomal detachment)
    • Increase in anaerobic glycolysis (decreased pH, decreased glycogen)-> the decrease in pH will clause clumping of nuclear chromatin
  11. Explain some components of the progression of apoptosis, from earliest to latest
    • cell shrinkage
    • chromosome condensation
    • formation of cytoplasmic blebs and apoptotic bodies  (cell fragments)
    • phagocytosis of apoptotic cells or cell bodies
  12. What are some biochemical changes in apoptotic cells?
    • protein cleavage (activated caspases)
    • DNA breakdown (by activated endonucleases)
    • protein cross-linking (activated transglutaminase which cross-links cytoplasmic proteins-> leads to cell shrinkage)
    • phagocytic recognition (phospatidylserine expressed on outer membrane of apoptotic cells is recognized by macrophage)
  13. What are some ways genes are altered in their pattern of expression?
    DNA methylation, histone acetylation, RNA interference
  14. What are the three forms of colour blindness?
    • Monochromacy: no cones
    • Dichromacy: one one is missing
    • Anomalous Trichromacy: one cone has altered spectral sensitivity
  15. Which gene is linked to colour blindness?
    16 genes on 19 chromosomes, though most commonly is x-linked
  16. What is the life-expectancy of patients with Down's Syndrome?
    • 75% of patients will die in utero
    • 15% will die within one year of birth
    • 35% of those who were born will die before age 50
  17. What are 3 types of tests that can be done to detect for Down's syndrome?
    • Amniocentesis/chonrionic sampling (invasive)
    • HCG/hormonal sampling (week 15-20)
    • Ultra sound (week 12)

    usually you combine 2+3 to get a high detection rate while staying non-invasive
  18. What is thallasemia, and how is it transmitted?
    • Missing or defective genes of HB resulting in anemia
    • usually single gene defect (both copies affected=homozygotes will have severe thalassemia)
  19. What is sickle-cell disease, and how is it transmitted? what are the four crises in sickle cell disease?
    • people are homozygous for HbS subunit gene. 
    • vaso-occlusive crisis: caused by cells blocking blood flow, leading to necrosis, pain, and ischemia
    • splenic sequestration crises: filtration function of the spleen is compromised; splenectomy or death
    • sickle-cell crisis: parvovirus B19 shuts down erythrocyte production for 2-3 days, potentially fatal in sickle-cell patients (treatment: blood transfusions)
    • Hemolytic crisis: rapid loss of erythrocytes, particularly in G6PD patients (treatment: blood transfusions)
  20. What is PKU, and how is it transmitted? Why might it have been selected for?
    • absence of penylalanine hydroxylase (Phenylalanine -> Tyrosine)
    • additional symptoms at birth: albinism, seizures, mousy odor
    • single gene, thus both parents must be carriers
    • Confers protection in damp areas by protecting against fungal toxins (elevated phenylalanine levels confer protection)
  21. What are the two forms of PKU, which is most prevalent? What is the treatment?
    • PAH enzyme deficiency (98%): patient must restrict phenylalanine intake
    • Biopterin-deficient PKU (2%): missing co-factor; supplement with biopterin-> no dietary restrictions
  22. What is cystic fibrosis?
    • Mutation in cystic fibrosis transmembrane conductance receptor (CFTR)
    • people with CF produce overly sticky and thick mucous resulting in continuous lung infection
    • heterozygotes may be protected from cholera
    • medications can only control symptoms
    • patients usually die from infection, thus treat patient until they become resistant to antibiotics
  23. How should you alter the diet of a patient with cystic fibrosis?
    • High fat, protein, calories and fat soluble vitamins 
    • -due to thick digestive mucous that can prevent pancreatic secretion -> decreased fat absorption
  24. What is muscular dystrophy?
    group of genetic mutations that cause progressive weakness in voluntary muscles

    multiple recessive genes (however Duschene muscular dystrophy is x-linked)
  25. Duschenne Muscular dystrophy
    • leads to muscle degeneration (ultimately resulting in loss in ability to breathe-> death)
    • caused by dysfunctional dystrophin gene (which maintains muscle fiber)
    • death by late teens~mid 20s
  26. What are two common problems associated with neural tube defects?
    • Spina bifida-> neonatal death of life-long paralysis
    • Anencephaly-> miscarriage, still born, or brief live birth

    tough to conclusively diagnose beforehand (measure a-fetoprotein, which varies during development)
  27. Calcium's atomic number? molecular weight? valence #? Abundance in nature?
    • 20
    • 40
    • +2
    • 5th most
  28. What are the three most important functions of calcium?
    • stability of biological membranes
    • subcellular signalling
    • bone (least important)
  29. How does calcium confer membrane stability?
    Ca2+ interacts with negative phosphoric part of phospholipid, which anchors lipids, making membranes more permeable. 

    • As a general rule, higher [Ca] will make it more difficult for membranes to depolarize
    • This is why low calcium causes random neural firing (spasticity of muscles)
  30. 2 bed-side tests to check for low [Ca]
    • Chvostek sign: touch angle of jaw to see if face twitches
    • Trousseau sign: cut off bp in arm, wait for hand to spazz
  31. How is extracellular calcium regulated?
    • Calcitonin (increases bone formation)
    • PTH [fast response](increases bone resorption->osteoclasts + increases renal Ca reabsorption)
    • 1,25(OH)2D (increases intestinal calcium absorption)
  32. Explain how PTH and Calcium levels can indicate various disease states
    • Hi PTH+ Hi [CA]= primary hyperthyroid
    • Low PTH+ low [CA]= post-treatmen hyperparathyroid
    • Hi PTH+ low [CA]=renal disease
    • Low PTH+ Hi [CA]=cancers (certain cancers increase calcium levels)
  33. What are the two types of bones in the human skeleton?
    • Trabecular bone: prevents vertical collapse (crushing)
    • Cortical bone: prevents bending/snapping
  34. Summarize the process of bone formation
    How does this relate to rickets?
    • Ossification begins in an area of preformed cartilage 
    • 2 epiphyseal plates (and each plate deposiproximal and distal ends)
    • after puberty, the epiphyseal growth plates will also calcify

    During puberty, if you don't get appropriate amounts of calcium, you will get soft collagenous bones-> rickets.
  35. What does a -2.5t score represent? What does a -2.5 Z score represent?

    What is the cut off age for comparison?
    • t score= you are in the bottom 1 percentile of BMD compared to young women, and you are an older woman
    • z-score= you are in the bottom 1 percentile of BMD compared to young women, and you are a young woman

    • Older than 35? Use t-score
    • Younger than 35? Use z-score
  36. when is BMD a better predictor of mortality than BP or cholesterol?
    After the age of 70.
  37. What are the stages of bone turnover?
    • Initiation
    • Resorption (osteoclasts)[2weeks]
    • Reversal phase [collagen laid down]
    • Formation[osteoblasts deposit Ca]
    • Completed [from reversal to completion takes 10 weeks, thus 12 week process]
  38. 1.What are some markers for bone resorption? 2. What are some markers for bone formation?
    • 1.
    • a) incompletely digested peptides (collagen crosslinks from N or C terminus of mature bone collagen)
    • b) urine calcium (not specific for resorption)
    • 2.
    • alkaline phosphatase: reflects osteoblast activity
    • serum osteocalcin: non-collagen bone peptide, reflects rate of bone protein synthesis by osteoblast
    • amino and carboxy terminal propeptides of collagen: (PINP and PICP)
  39. How are bone markers important in diagnosis
    • baseline markers are higher in osteoporosis patients compared to healthy controls
    • BMD expected to be inversely proportional to bone marker levels
    • However, substantial overlap between osteoporosis and normal subjects
  40. How can you predict future bone loss?
    • Culmination of bone markers + BMD
    • BMD predicts 50% of fracture risk (but not the rate of bone loss)
    • Bone markers shown to be predictive of bone loss
  41. What are some limitations of bone marker usage?
    • Rates of bone turnover vary widely over a range
    • large overlap between disease and normal state
    • few studies connecting bone histology with markers of bone turnover
  42. What are some things that affect bone marker levels?
    • Bone markers do not change with age in men
    • Bone markers are elevated during menopause, and remain elevated (in women)

    as a general rule of thumb: if some bad shit happens to the bone-> increase in markers; if good shit is happening[i.e. exercise]-> decrease in markers
  43. Why is it good to get 1000mg of calcium?
    • Calcium protects intestinal mucosa by binding compounds (excess calcium excreted in stool)
    • You get a net =0 if you get 1000mg, compared to 200mg eating=-5 net loss
  44. How can you measure BMD?
    • dual energy x-ray absorptiometry
    • ultrasonography -> predictive of fracture risk, but threshold yet to be determined
  45. What is osteomalacia?
    • Equivalent to childhood rickets
    • Caused by little vitamin D or little calcium 
    • Can treat with calcium  supplementation + VitD
    • Lots of collagen, but no calcium deposition. thus soft bones
  46. What can you do to facilitate absorption of calcium?
    • Take with food (to increase their ionization)
    • only ionized calcium is absorbed
  47. What's the metabolic pathway of calcitriol?
    • 7-dehydrocholesterol->
    • Vitamin D3(also dietary)-> this step occurs in liver
    • 25-(OH)D-> this steps occurs in kidney
    • 1,25(OH)2D
  48. Half-lives of compounds in the calitriol pathway
    Vitamin D3=~a day (stored in muscle and fat due to a carrying protein OR converted to 25 (OH)D

    25(OH)D-long half-life (~2months)-> this is usually what's measured for indicating Vit D deficiency

    1,25(OH)D-stimulated by PTH and lowering of Calcium levels; thus serum levels are not directly affected by vit D
  49. What does 1,25(OH)2 D do? how is its production stimulated? where is it made?
    • Increase gut absorption of calcium
    • Increased PTH or decreased [Ca]
    • it's made in multiple tissues, however the place where it is released as a hormone is in the kidney
  50. What is asthma? What is the most important risk factor?
    • Chronic inflammation leading to airway hyperresponsiveness, leading to widespread but variable airflow obstruction that is reversible
    • Genetics is the most important risk factor.
  51. What is the trend of asthma incidence and mortality in Canada over the last 20 years

    What is the worldwide prevalence?
    Incidence increased by 15-20%, however mortality has decreased by 50%

    300 million cases worldwide
  52. What is asthma decompensation? What are some triggers for asthma decompensation?
    • Not adequately controlled asthma
    • ----------------------
    • Non-compliance
    • Respiratory tract infections
    • Allergens
    • Irritants
    • Drugs (NSAIDs/B-Blockers)
    • Preservatives (sulfites, MSG)
    • GERD, anxiety, cold air/exercise
  53. What are some characteristics of high risk asthmatics?
    • Lack of consciousness during attack, intubation, frequent ICU/ER visits
    • frequent use of B-agonists without anti-inflammation treatment
    • night-time symptoms (2-4am you get further constriction of airways-> exacerbated in asthmatics)
    • limited respiratory reserve (symptoms when FEV<60%)
  54. How has asthma control changed over the last decade? What percentage of people have successfully controlled their asthma? What percentage of people believe their asthma is under control? % of people who are concerned about ICS? % of patients who did not plan to fill their ICS prescription? Of those that did fill it, what percentage did not take the medication?
    • No real change over the last decade
    • About 55%
    • 97%
    • 75%
    • 33%
    • 20%
  55. What is atopy?
    predisposition towards developing certain allergic hypersensitivity
  56. Why is ciclesonide advantage over traditional ICS?
    • lower systemic side-effects
    • high protein binding+high first pass+rapid bile elimination +requires activation in lung
  57. Routine Liver Tests
    marks functioning of hepatocytes and billiary tract distal to the site of metabolism

    metabolic product of heme metabolism
  58. Routine Liver Tests
    Alkaline phosphatase
    • Not specific to liver injury
    • Marker of open billiary tract-> cholestasis
  59. Routine Liver Tests
    • Found elevated when liver is injured, and the enzymes leak into blood
    • AST-less specific (found in many other tissues)
    • ALT-more specific for liver injury(but also found in other tissues)
  60. Routine Liver Tests
    Gamma-glutamyl transferase
    Tends to be elevated in all liver disorders (particularly useful for alcoholic abuse)
  61. Routine Liver Tests
    • synthesized in the liver, long turnover rate (3 weeks)
    • indicative of liver synthesizing ability chronically
  62. Routine Liver Tests
    • Clotting factors synthesized in liver
    • Shorter half-life, thus more acute marker of liver synthesizing ability
  63. Specific liver tests
    • Breakdown product of amino acids
    • Metabolized to urea in liver, which is excreted in urine
    • Indicative of liver metabolic insufficiency
  64. Specific liver tests
    • fetal albumin
    • increase in a-fetoprotein is indicative of primary hepatoma (not metastatic cancers)
  65. Specific liver tests
    LDH (Lactate dehydrogenase)
    increased if there's general metastasis into liver or congested blood flow of liver.
  66. Specific liver tests
    Increased in cholestasis
  67. Specific liver tests
    • shuts off proteases
    • if diminished in capacity or amount-> cirrhosis
  68. Specific liver tests
    • important in copper metabolism (Wilson's disease)
    • thus decrease can detect copper overdose ???
  69. Specific liver tests
    TIBC (total iron binding capacity), Ferritin, [Fe]
    • TIBC: assesses transferrin levels (increased when iron is low)
    • Ferritin: assesses iron stores (increased when iron is high)
  70. Specific liver tests
    Viral Antigens and antibodies
    helpful in detecting hepatitis
  71. Specific liver tests
    • IGG, IGA, IGM may be elevated in chronic liver disorders
    • not very specific
  72. Specific liver tests
    • usually antibodies to smooth muscle or mitochondria
    • not specific to liver but useful in autoimmune disorders
  73. What type of bilirubins and their derivatives get into urine?
    • Conjugated bilirubin
    • bilinogens (which are then called urobillinogens)
  74. Low cellular energy of liver selectively affects:
    • secretion 
    • then it affects metabolism

    thus lower cellular energy will more readily
  75. What are the four different types of billiary obstructions?
    • Drug induced: diffuse throughout liver
    • Autoimmune: slow, chronic, process of destruction of billiary tracts
    • Focal obstruction: billiary tract is obstructed in the vicinity of a metastatic module
    • extrahepatic obstruction (cholidocholithiasis, cancer in pancreatic head, scar tissue from operations, gall bladder inflammation)
  76. What markers will be elevated in diffuse billiary tract obstruction?
    • ALP, 5'NTD, GGT (10-20X)
    • conjugated bilirubin

    • Acute: negative immune markers
    • Longer duration: Increase in AST and ALT
    • Chronic (AKA primary billiary cirrhosis): immune markers will be positive (especially to mt); destruction of billiary tree leading to metabolic insufficiency
  77. How can you identify focal billiary tract obstruction?
    • Increase in cholestatic marker enzymes (ALP, 5'NTD, GGT)
    • Not as much of an increase in bilirubin (as it can still be metabolized in other parts of the liver)
    • Note that AST may be normal or slightly elevated, and a-fetoprotein may be normal or slightly elevated
  78. How can you identify hepatocellular jaundice?
    • (AKA sick hepatocytes or end-stage liver failure)
    • greater increase in bilirubin (especially in unconjugated bilirubin, compared to conjugated) compared to cholestatic markers (5'NTD, ALP, GGT)
  79. Identifying acute viral hepatitis
    • Biggest three things are :
    • a) AST and ALT are highly increased
    • b) ALT>AST
    • c) positive immune markers

    • note that prothrombin (even though acute), may not necessarily decrease
    • also note that peak height is not related to disease severity
  80. What can immunoglobulins tell you about an infection?
    IgM mounts the initial immune response (will rise as ALT is starting to fall). IgG mounts a life-long immunity(thus you had Hep A sometime in the past)
  81. Identifying Toxic hepatitis
    • AST>ALT (note how it's not ALT>AST, thus not acute viral hepatitis)
    • Increase in Bu and Bc
    • you would also see liver insuffiiciency (prothrombin, ammonia, Bu>Bc)
    • No viral serology
    • thus toxic insult by exlcusion (ex. halothane)
  82. Chronic viral hepatitis
    • a)waxing and waning of AST and ALT
    • b) AST>ALT (one of 3 instances where this occurs)
    • c) immune markers (IgG, mitoantibodies, muscle antibodies)
    • d)late-stage-> a-fetoprotein
  83. Identifying Gilbert's syndrome
    • loss of function in conjugating enzyme (Glucoronide transferase)
    • would see a decrease in bilirubin in urine (as conjugated bilirubin is filtered)
    • urobilinogen will seem normal (even though it's actually reduced, due to urinary dipstick shortcomings)
    • liver cell is otherwise healthy
  84. Identifying alocoholic hepatitis
    How to determine if alcoholic hepatitis is severe?
    How to determine chronicity?
    • AST>ALT (~10fold elevation, but AST:ALT = 2:1)
    • Increase in GGT, lesser increase in ALP

    • can determine severity if:
    • Bilirubin increases 5X
    • PT increases

    • Can determine chronicicty if: 
    • albumin is low
  85. What are 3 conditions in which AST>ALT, but they are both elevated?
    • Alcoholic hepatitis (2:1 ratio)
    • Acute Toxic hepatitis
    • cirrhosis (ability to make/release ALT is impaired more than AST)

    Chronic viral (although he didnt say it)
  86. Why are women more susceptible than men to alcoholic liver disease?
    • More alcohol consumed/kg
    • Less ADH
  87. Alcoholic liver disease is the _____ leading cause of death. Rate? 
    Alcoholic liver disease is the _____ leading cause of liver disease in NA. How many of these patients are infected with Hep C
    ALD requires daily drinking of ____g of alcohol
    • 10-12th
    • 4.4/100,000
    • 2nd
    • 25%
    • 80g
  88. Why is acetaldehyde toxic?
    Produces protein adducts (which produce antibodies) leading to impairment of mitochondrial function and glutathione function
  89. 3 factors that are altered after continuous alcohol intake
    • Increased gut permeability-> chronic inflammation
    • Decreased antioxidants
    • Increased acetaldehyde
  90. What are two important genes that may prove useful in preventing Alcoholic liver disease
    • PNPLA3 (lipid storage protein)-> if defective, increases ALD
    • TNF-a-> if defective, increases ALD
  91. What is the earliest sign of alcoholic fatty liver progression
    • redox imbalance due to metabolism of ethanol -> acetate leading to increased lipogenesis
    • can be seen in biopsys very early
  92. Describe alcoholic hepatitis
    • infiltration of liver with neutrophils and lymphocytes
    • AST + ALT increase (AST>ALT)
    • 35-40% mortality if severe presentation, or continued drinking
    • Prednisone improves outcome, especially if presentation includes encephalopathy
    • Pentoxifylline (anti-TNFa) may be helpful
  93. What is liver cirrhosis?
    Diffuse process characterized by fibrosis and nodules

    Requires biopsy to diagnose (unless portal hypertension+accompanying symptoms present)

    fibrosis is reversible, but the nodules are not

    • 90% 5 year survival=compensated patients
    • 70% 5 year survival=continued drinking patients+clinical compensation
    • 30%=no compensation+continued drinking

    • best treatment is abstinence+transplant
    • will eventually lead to hepatoma
  94. 3 types of liver cirrhosis
    • active cirrhosis: increased ALT/AST, increased PT, increased Bili, decreased Alb
    • inactive cirrhosis: no, or minore liver function test abnormalities
    • end-stage cirrhosis: normal ALT/AST, but everything else is fucked
  95. True or false: most heavy, long-term drinkers will develop cirrhosis

    True or false: coffee confers a dose-response adverse effect on alcoholic cirrhosis
    • false; most will not develop cirrhosis
    • false; dose-response protective effect
  96. What do the major complications of liver cirrhosis stem from?What are the major complications of liver cirrhosis?
    • Portal hypertension
    • Ascites, esophageal varices, encephalopathy
  97. Explain ascites:
    • Fluid buildup in peritoneum, leading to fluid infection, breathing difficulty, hepatorenal syndrome
    • Caused by splanchnic vasodilation due to accumulation of NO

    • very poor survival rate without transplant (30-40% without, 75% with)
    • Treatment: Na restriction, paracentesis, diuretics, and antibiotics
  98. Esophageal Varices
    • a)engorgement of veins in esophageal and stomach mucosa because of blood shunting away from liver
    • b)thrombocytopenia due to spleen enlargement

    • management:
    • sclerosing and or banding
    • somatostatin/octreotide
    • b-blockers
  99. Hepatic encephalopathy due to alcoholic liver cirrhosis
    accumulation of CNS toxins (ammonia) and increased sensitivity to GABA

    can only do a bed-side diagnosis (people will flap their hands when their arms are up arhythmically)

    management: enema, laxatives, protein restriction (to decrease ammonia)
  100. What are the 4 rules of body fluid compartments
    • 1. Water goes to where particles are
    • 2. ECF volume is determined by Na+ content
    • 3.Water crosses cell membranes rapidly to equalize osmolarity of ECF+ICF
    • 4.Volume of cells depends inverse on ECF somolarity
  101. What are the three effects of ANG II?
    • Increase reabsorption directly (PT) and indirectly (aldosterone)
    • Increase vasoconstriction
    • Increase thirst and ADH
  102. What are three ways in which the body responds to a loss in ECF volume? What is the body trying to prevent?
    • RAAS
    • SNS
    • ADH

    Shock due to low perfusion of vital organs
  103. What are four causes of excessive ECF volume?
    • Renal failure
    • Nephrotic syndrome (filtration of proteins)
    • CHF (low CO causes increase in SNS, RAAS, ADH)
    • liver cirrhosis: causes very vasodilated circulation, leading to increased SNS RAAS ADH
  104. What are the three diuretics that were learned in kidney section?
    • Furosemide: acts in ascending limb of loop of henle where it binds NKCC and inhibits its action (no reabsorption of NKCC)
    • Hydrochlorothiazide: acts in distal convoluted tubule, where it binds NaCl transporter (mimics chlorine)
    • Spironolactone: binds to aldosterone receptor in collecting duct (decreases reabsorption of sodium) (potassium sparing)
  105. What are some major causes of water excess? Treatment?
    • Severely reduced GFR
    • ADH not being inhibited
    • -cancers (lung cancers)
    • -patient with severe diarrhea only replaces with water (baroreceptor mediated increase in ADH)
    • -patient with congestive heart failure (baroreceptor mediated)
    • -ecstasy
  106. What are some major causes of water deficit? Treatment?
    • Increases loss of water without accompanying NaCl
    • Diabetes insipidus

    Give water orally, or as Dextrose (D5W)
  107. What is diabetes insipidus? What can it cause?
    • Lack of ADH effect due to either 
    • a) ADH not being made (treat by giving DDAVP)
    • b) ADH not detected by kidney (usually due to lithium)
  108. What can affect potassium balance?
    • Na/K atpase
    • insulin (facillitates potassium entry into cell)
    • B2 agonist (facillitates potassium entry into cell)
    • Bicarbonate
    • Aldosterone (increased sodium reabsorption receptor expression, which facillitates potassium loss) (note also that ACE-i and ARB will affect this too!!!!)
  109. What are some causes of hypokalemia
    • Increased insulin
    • Increased beta agonism
    • NaHCO3 administration
    • Anabolism
  110. What are the symptoms of hyperkalemia? Hypokalemia?
    • Hyperkalemia-> mostly cardiac symptoms
    • Hypokalemia-> Cardiac arrhythmias, and skelatal muscle weakness and rhabdomyolysis
  111. How can you produce new bicarbonate?
    • Kidneys: glutamine->ammonia+HCO3-
    • Liver: Lactate-> HCO3-
  112. What is respiratory acidosis
    increase in [H+] due to increase in [CO2] (hypoventilation)

    • won't breathe: sedative drugs
    • can't breathe: lung disease(guillan-barre syndrome)
  113. What is respiratory alkalosis?
    • Reduced [H+] due to decreased [CO2]
    • usually due to hyperventilation
  114. What is the compensatory mechanism for respiratory alkalosis/acidosis?
    • respiratory alkalosis: Decreased bicarbonate
    • respiratory acidosis: increased bicarbonate
  115. What is metabolic acidosis?
    Accumulation of H+ due to low HCO3-

    due to loss from body, or used up during buffering excess acid

    compensation: increased ventilation to decrease CO2
  116. What is lactic acidosis?
    NADH accumulation in absense of O2, inhibits pyruvic acid-> acetyl coA, leading to more pyruvic acid conversion to lactic acid

    Essentially two causes: hypoxia (Type A), and failure to metabolize (type B)-> liver disease, metformin etc.
  117. What is ketoacidosis?
    triglycerides in fat cells are subject to either low insulin or high adrenaline, which converts them to acetyl-coA

    acetyl co-A will make acetoacetic acid or b-hydroxy butyric acid (favoured by low insulin or high adrenaline)

    • Causes: type 1 diabetes mellitus (b-cell destruction-> low insulin)
    • starvation-> insulin deficiency due to hypoglycemia
  118. How does salicyclic acid cause acid base disturbance? How can you treat it?
    causes both acidosis (overdose, inibition of etc, activates lipolysis) and alkalosis (stimulates ventilation), leading to acid base disturbance

    alkalize plasma and urine (encourages conversion to salicylate-)
  119. What is renal tubular acidosis?
    occurs due to a failure of kidney reabsorption/synthesis of HCO3-

    very similar to what happens with acetazolamide

    treatment: administer NaHCO3 chronically
  120. Metabolic alkalosis, and causes of it
    • Low[H+] due to increased HCO3-
    • Cause: vomiting, diuretics, hypokalemia
    • Consequence: high pH causes neuromuscular twitchyness and risk of arrhythmias
  121. Summarize Respiratory/Metabolic Acidosis/Alkalosis
    • pH low, CO2 high= respiratory acidosis
    • pH high, CO2 low=respiratory alkalosis
    • pH low, HCO3- low= metabolic acidosis
    • pH high, HCO3- high=metabolic alkalosis
  122. Define neoplasia, neoplasm, oncology, dysplasia:
    • neoplasia: process of new growth
    • newplasm: a new growth/tumour (with unco-ordinated growth which persists after stimuli that evoked the change)
    • oncology: study of neoplasms
    • dysplasia: disordered growth (precursor to cancer, thus can detect dysplasia to prevent cancer)
  123. What does -oma signify? Carcinoma? Sarcoma?
    • oma: benign tumours
    • sarcoma: malignant stromal tumours
    • carcinoma: malignant epithelial tumours
  124. What are the four phases of tumours?
    • Transformation
    • Growth
    • Local invasion
    • Distant Metastases

    the last 2 are only characteristic of malgnant tumours
  125. How might a cancer undergo distant metastases?
    • 1) direct seeding of body cavities and surfaces
    • 2) lymphatic vessels
    • 3) blood vessels
  126. What are the three categories of hereditary predisposition to cancer (and give examples)
    • Autosomal dominant inherited cancer syndromes (inheritance of single mtant gene that increases cancer risk; mutant rb gene-> retinoblastoma+ osteosarcoma)
    • Defective DNA repair syndromes-defective dna repair genes (MSH/MLH/MSH-> HNPCC syndrome [colon cancer-most common predisposition syndrom]
    • Familial cancers
  127. What is the normal cell division cycle signalling process, and what are the proteins that regulate it?
    • Binding of growth factor on cell surface
    • Signal transduction
    • Transmission to nucleus
    • activataion of dna transcription

    • cyclins
    • cyclin-dependent kinases
    • inhibitors of cyclins and CDK (ex. RB and CDK-Inhibitors)
  128. What is the function of RB? What is the function of p53?
    • Tumour suppressor genes that :
    • enforces the S-> G1 checkpoint (RB)
    • G1 and G2 arrest and induces DNA repair and then apoptosis (if repair fails) (P53)
  129. How do cancer cells maintain a limitless replicating potential?
    Reactivation of enzyme telomerase-> relengthens telomeres
  130. How might cancer cells invade and metastasize?
    Produce VEGF (gives cells access to vasculature)

    • Cancer cells lose their intercellular junction (E-cadherin)
    • Cancer cells bind surrounding tissue (laminin + fibronectin)
  131. Define cancer cachexia. Define Paraneoplastic syndromes
    Cancer cachexia: loss of body fat and muscle with weakness and anorexia and anemia due to cytokine production by tumour and host cells (also produces abdominal striae) 

    Paraneoplastic syndromes: symptoms that present due to tumour presence, but not because of the actual tumour
  132. What is Cushing's syndrome? What condition might it be seen in?
    Cushing's syndrome may be seen secondary to lung cancer-> increased ACTH-> Increased cortisol
  133. Compare and contrast staging and grading
    staging: based on TNM (size of primary TUMOUR, spread to regional lymph NODE, METASTASIS to distant site); a measure of spread

    Grading: based on degree of differentiation, number of mitoses, acrhitectural features; a measure of the appearance of cancer
  134. What are some ways in which you can diagnose cancers?
    • Histology: tumour samples looked under light microscope to determine subtype/grade/prognosis
    • Immnohistochemistry: antibodies to categorize poorly differentiated/anaplastic malignant tumours, determine site of origin, and molecules of prognostic significance
    • Molecular techniques: (PCR/FISH-> maligant neoplasm; hereditary predispositions)
    • Tumour associated enzymes
Card Set
patho midterm
patho midterm