Pbd - Week 1

Front 1

Describe the light microscopic morphological changes found in necrosis

Back 1

Cells swell and fat accumulates,
- get degraded by own (autolysis) or neutrophil enzymes (heterolysis)
- develop cytoplasmic eosinophilia (esosin binds to denatured proteins)
- nuclear changes (karyolysis, pyknosis and karyohexis)

Front 2

List 4 distinctive types of necrosis and give a clinical example of each

Back 2

Coagulative – ischemia in all tissue but brain. “Ghost” outlines of cells b/c acidosis denatures autolytic proteins
Liquefactive – bacterial, complete digestion of dead cells (pus) d/t ++ recruitment of inflammatory cells. Bacterial invasion of coagulative cells = gangrene
Caseous – “cheesy”, Xtic of TB, between liquefactive and coagulative (ghosts & pus)
Fat – not distinct patho-physiologically, but distinct morphology and clinical circumstances. Occurs d/t lipases on fatty tissue (e.g. acute pancreatitis)

Front 3

Explain the phenomenon of the tolerance of barbiturate drugs on a subcellular pathologic level

Back 3

Barbiturate tolerance: barbiturates are made more soluble by P450’s in the liver. P450’s are found in the SER’s and over time the drug induces an increase in the SER’s.

Front 4

Explain, on the basis of subcellular pathology, Kartagener’s syndrome

Back 4

Kartagener’s syndrome: abnormalities in the microtubules, resulting in cilliary abnormalities.

Front 5

Explain, on the basis of subcellular pathology, Colchicine in gout

Back 5

Colchicine: Gout = abnormally high uric acid levels. When uric crystals accumulate, neutrophil’s rush in phago them = ++ painful gout attack. Colchicine binds to tubulin and prevents the formation of microtubules (PMN’s can’t move?)

Front 6

Explain, on the basis of subcellular pathology, Vinca drugs in cancer

Back 6

Vinca: Vinca alkaloids prevent the formation of microtubules that are used in the mitotic spindle. By preventing mitosis they prevent tumor divisions.

Front 7

Name 5 classes of intermediate filaments

Back 7

Intermediate filaments:
- Keratin: in epithelium
- Neurofilament
- Desmin in muscle
- Vimentin in connective tissues
- Glial filaments in the glial cells of the brain

Front 8

How can the detection of intermediate filaments can be used diagnostically in 2 different situations?

Back 8

Mallory bodies: accumulations of keratin filaments seen in alcoholic liver disease. Neurofilaments: accumulate in Alzheimer’s disease leading to the xtic neurofibrillary tangles

Front 9

Outline the 4 phases of apoptosis

Back 9

10. Initiation – via transmembrane or intracellular signaling
Control & integration – of pro & anti-apoptotic factors
Executioner phase – mediated by capases that cleave cytoskeletal & nuclear proteins. Also attack the proteins responsible for DNA replication & repair
Removal – apoptotic cells express substances that enhance M-phage recognition (M-phages express substances that help opsonice apoptotic cells)
“ICER”

Front 10

List 4 physiologic examples of apoptosis

Back 10

Embryogenesis (structures regress), normal cell turnover (skin), involution of physiologic processes (post-lactation), cells that have served their purpose (neutrophils) and even aging!

Front 11

Describe extrinsic pathways of apoptosis

Back 11

Extrinsic pathway of apoptosis:
FasL binds Fas on the cell. Fas is then able to bind FADD. When it does FADD triggers a cascade of caspase activity finally resulting in the executioner phase and cell death

Front 12

Describe intrinsic pathways of apoptosis

Back 12

Intrinsic pathway of apoptosis:
Pro-apoptotic class of Bcl proteins dominate and this cause the mitochondria to be leaky. Things like cytochrome C seep out of the mitochondria and activate caspases --> executioner phase and death.

Front 13

List one role of apoptosis in the pathology of the immune system (3)

Back 13

Apoptosis & immune system: failure to apoptose (via Fas-FasL) autoreactive clones = autoimmune disease. Viral depletion of lymphocytes works by forcing apoptosis (AIDS). Cytotoxic T cells kill by injecting granzyme B into cells which activates caspases and causes apoptosis!

Front 14

Describe the actions of p53 in carcinogenesis

Back 14

p53 accumulates when DNA is damaged and will arrest the cell cycle giving the cell time to repair. If cells unable to repair DNA, p53 will force apoptosis.
(cell damaged (UV rays), p53 accumulates & gets P-lated allowing it to unfold & bind DNA. Binding allows the transcription of genes that arrest the cell cycle until repair. If no repair, p53 stimulates apoptotic genes like BAX which antagonizes bcl2, an anti-apoptotic bcl).

Front 15

Describe the mechanism by which apoptosis is important in neurodegenerative diseases.

Back 15

Withdrawal of growth factors favours the pro-apoptotic members of the bcl2 family. This is why a loss of nerve growth factor leads to apoptosis of neurons and subsequent degenerative neurological diseases.

Front 16

What are the 4 macroscopic pathological features of AD?

Back 16

Cerebral atrophy (widening of sulci and narrowing of gyri); compensatory ventricular enlargement, ↓ brain weight and relative sparing of the occipital lobe.

Front 17

What are the 4 microscopic pathological features of AD?

Back 17

Diffuse senile plaques, neurofibrillary tangles, neuronal loss and amyloid angiopathy (AD has both intra & extracellular protein accumulation)

Front 18

What are the 4 types of Creutzfeld-Jakob Disease?

Back 18

Sporadic (85%),
familial,
iatrogenic,
variant

Front 19

What is the possible function of prions? In what tissues are they found?

Back 19

Function not clear but has copper binding ability. Highly expressed in brain and lymphoid tissues.

Front 20

What conformational change produces an insoluble, protease-resistant, amyloid form of prion?

Back 20

Conversion from a high component of a-helices to B-pleated sheets (this is a post-translational event – aa sequence is unchanged). ** Ability to self-replicate makes prions unique and distinguished from other types of amyloid.

Front 21

What is the pathogenesis of prion disease? (how are they first formed? Perpetuated?)

Back 21

Initial conversion to PrPSc is sporadic and r/t gene mutations. The abnormal prion facilitates the conversion of other prions into the abnormal form. Masses of these will form amyloid plaques, however neurotoxicity still not fully understood.

Front 22

What are the 5 microscopic findings associated with prion disease? (3 things that form, 1 lost and 1 missing)

Back 22

Spongiform transformation of the cortex, caudate and putamen.
- vacuoles within neuropil and neurons
- severe neuronal loss and gliosis
- occasional amyloid plaques
- no inflammatory infiltrate

Front 23

Which tissues have a lot of prions? Can you catch prion disease from bodily fluids?

Back 23

Brain, eye, CSF, dura and pituitary with little transmission from blood, urine, feces, etc.

Front 24

The median age for variant CJD is 28yrs. What are the 4 symptoms? What is seen on EEG? MRI?

Back 24

Symptoms: ataxia, sensory disturbances, dementia, depression. Classic CJD signs NOT seen on EEG, and MRI shows increased signal in posterior thalamus. ** Variant CJD’s prion structure resembles that of BSE and not that of sporadic CJD**

Front 25

How is variant CJD transmitted?

Back 25

vCJD jumped species from goats to cow & can be transmitted to humans thru eating.

Front 26

What are the symptoms of Kuru (a neurologic disorder confined to the Fore tribe of Papua New Guinea)?

Back 26

Kuru – progressive cerebellar degeneration, ataxia, tremor and dementia

Front 27

What is the “culprit codon” for CJD?

Back 27

Culprit codon 129 – polymorphic site normally has Valine or Methionine – MM homozygote will influence disease susceptibility and phenotype in both sporadic and inherited disease (MM present in 100% of pt’s with vCJD)

Front 28

What is the etiology for each of the following types of CJD:
Sporadic, familial, iatrogenic, variant

Back 28

Sporadic – random stochastic event
Familial – mutation in PRNP gene
Iatrogenic – inoculation or exposure
Variant – mad cows ( all cases are MM at codon 129)

Front 29

Do bacteria have nuclei?

Back 29

No!! Nor do they have membrane-bound organelles or DNA that’s organized into Xsomes. But they do have both a capsule and a cell wall!

Front 30

How do bacteria divide?

Back 30

By binary fission!

Front 31

What are the 4 steps to do a gram stain?

Back 31

Add crystal violet to make them all purple.
Add iodide (to fix the dye?)
Decolorize them all with EtOH – the gram + will stay purple and the gram – will be clear
Add pink safferin dye --> now the gram – will be red/pink.

Front 32

What color are gram + bacteria? Why?

Back 32

Gram + are purple b/c they have a thick cell wall that makes it difficult to get rid of the crystal violet dye.

Front 33

What is the site of the krebs cycle and oxidative phos in bacteria?

Back 33

Krebs cycle in the cytoplasm. Oxidative phos in the bacterial cell membrane.

Front 34

Define each of the following types of aerobes: strict, facultative, microaerobes, aerotolerant.

Back 34

strict = solely depend on O2 respiration
facultative = can use both respiration and fermentation
microaerobes = killed when O2 is too high
aerotolerant = uses fermentation but can survive in O2
strict anaerobes = killed by O2 b/c they can’t break down the O2 free radicals

Front 35

How do bacteria evade: complement (2), phagocytosis (2) and survive intracullularly?

Back 35

Complement – capsules & biofilms to mask antigens. Surface proteins that bind complement.
Phago – capsules/biofilms & exotoxins.
Intracell – inhibit lysosome – phagosome fusion, escape phagosome, resists lysozymes, inhibit oxidative pway to prevent oxidative killing.

Front 36

What are 6 ways of evading specific defences (ie Ab and cell-mediated immunity?)

Back 36

Immunosuppresion (HIV),
divert lymphocytes (superantigens),
antigenic variation, proteolysis of Ab’s,
prevent opsonization (protein A in S.aureus),
latency (herpes).

Front 37

What are 2 strategies that bacteria use for transmission?

Back 37

Exagerate host defences (coughing, sneezing, diarrhea), survive in env (spores/cysts)

Front 38

What are the 3 ways microbes can cause cell lysis?

Back 38

Cell lysis: toxins that disrupt cell membrane integrity,
multiplying intracell
infected cells being killed by cell-mediated immunity.

Front 39

How does the tetanus toxin work? (ingestion, travel effect)

Back 39

Tetanus: binds to cell membranes and is internalized, sues retrograde transport thru axons to access spinal cord. Toxin then blocks GABA = rigid muscle contraction

Front 40

How does the Botulism toxin work?

Back 40

Botulism: contaminated foods, crosses gut lining and is carried in blood to NMJ where it blocks ACh, interrupting nerve stimulation = descending paralysis

Front 41

List 3 morphologic features of chronic inflammation.

Back 41

- inflammatory cells (lymphocytes, M-phages & plasma cells)
- tissue destruction
- tissue fibrosis and angiogenesis

Front 42

List 3 important roles of Mphages in chronic inflammation (3/5)

Back 42

- produce O2 & N2 intermediates that are toxic to cells
- produce proteases that digest local tissues
- produce g-factors (e.g for F-blasts) = fibrosis & angiogenesis
- display angtigens to T-lymphocytes
- produce cytokines which stimulate T-cell responses

Front 43

List the 6 steps in tissue repair.

Back 43

Tissue repair:
-proliferation & migration of parenchymal & CT cells
-angiogenesis
- migration & proliferation of f-blasts
- deposition of ECMatrix
- tissue remodeling
- acquisition of wound strength

Front 44

Define granulation tissue.

Back 44

Granulation tissue is a mix of vascular tissues and inflammatory cells in a loose stromal framework.

Front 45

Define each of the following types of inflammation (and give an example of each)
- Serous, fibrinous and suppurative/purulent.

Back 45

Patterns of inflammation
Serous – fluid accumulation, often in body cavities or blisters
Fibrinous – fluid as in serous but also w/larger molecules like fibrin (e.g. infectious pleuritis & peritonitis). Can resolve by fibrinolysis and the action of Mphages or can lead to scarring.
Suppurative/purulent – pus (necrotic cells, neutrophils & edema). Bugs like Staph tend to produce this = pyogenic organisms. E.g. abscess

Front 46

What is an ulcer?

Back 46

Ulcer = a local defect in the surface of an organ (e.g. skin or mucosa) that is produced by the sloughing of inflammatory cells and dead tissue.

Front 47

What is a granuloma, and why is this type of inflammation important to recognize?

Back 47

Granuloma is a formed collection of morphologically recognizable activated Mphages called epitheliod Mphages, surrounded by a cuff of Lcytes and plasma cells. Important to recognize b/c it establishes a very narrow differential diagnoses.

Front 48

What are the steps involved in healing by first intention? (@ 24hrs, 3days, 2wks & 1 month)

Back 48

Healing by 1st intention – wound fills with blood & fibrin (“scab”).
24hrs: Neutrophils appear & the lower levels of epidermis proliferate & form a continuous layer below the wound surface.
3days: Neutrophils get replaced by Mphages & granulation tissue invades.
2nd week: Fblasts accumulate & produce collagen
1st month: wound is now cellular CT covered by epidermis

Front 49

How is healing by 2nd intention different than healing by 1st?

Back 49

Healing by 2nd intention – occurs when the wound is so big the edges can’t be opposed. There’s much more inflammation & granulation tissue. In large surface wounds myoFblasts appear and serve to contract the edges of the wound

Front 50

List 8 local or systemic factors that modify wound healing.

Back 50

Factors modifying wound healing:
Systemic: Nutrition (VitC), metabolism (diabetes), circulation (PVD), hormones (steroids), age & anemia
Local: infection, hematomas, mechanical factors (immobilization), foreign bodies, size of wounds, vascularity of site and denervation.

Front 51

List 4 types of dysfunctional wound healing.

Back 51

Dysfunction wound healing:
- Dehiscence & ulceration – d/t inadequate granulation tissue or the assembly of scar tissue
- Excessive scaring
- Exuberant granulation
- Contractures – exaggeration of the normal process of shrinkage of large wounds (common around joints & can impair movement)

Front 52

What is an appropriate renal response to HoTN? (ie what should happen to the urine?)

Back 52

If a person is hypotensive, then you would expect the kidneys to concentrate urine to reabsorb fluid. The sodium should be low and the osmolality high (if ADH is being released and doing it’s job). If the osmolality is 300mosmol/kg then it’s the same as serum and there’s either no ADH or no ADH response.

Front 53

What are 5 pathological changes associated with ATN? (3/5 are in the tubules)

Back 53

ATN: interstitial edema, normal glomeruli, Tubulues: loss of epithelium, dilation & casts

Front 54

In ATN, why does the GFR stay low even after a person is hemodynamically stable?

Back 54

Low GFR persists b/c of obstruction from the casts. The glomeruli are filtering (renal arteries intact), but they can’t drain, causing a back-up of pressure --> proximal dilatation -->backleak of filtrate through injured tubules.

Front 55

In ATN, which regions of the kidney show necrosis and which show apoptosis? Why?

Back 55

The outer medulla has basal low levels of O2 making it ++ vulnerable to hypoxia, and most likely to experience necrosis (low O2 supply with ongoing need for ATP to reabsorb Na+). Apoptosis won’t occur in areas of catastrophic hypoxia b/c it is a energy dependant process.

Front 56

What is the specific effect of sub-lethal cell injury that is associated with ATN? (4 effects of this injury)

Back 56

In ATN, sublethal cell injury causes a loss of integrity of actin cytoskeleton:
Loss of polarity – Na/K/ATPase on luminal membrane moves to other end
Brush border sloughs into lumen – add to debris, casts & obstruction
Cells detach from B-membrane – attach to each other in the lumer = casts & obstruction
Loose integrity of tight junctions = back leak

Front 57

What 4 things are typically found in the urinalysis of a pt with ATN?

Back 57

Blood – leaked through damaged tubules
Protein – from damaged tubules & cell Bdown
Cells – intact tubule cells that lost their adhesion molecules
Casts – Hgb, brush border, cell organelles & intact cells

Front 58

In a person with ATN, would their urine Na+ and osmolality be high or low? Why?

Back 58

Na+ – high, b/c of abnormal location of Na/K/ATPase = impaired reabsorption
Osmolality – should be high but is low b/c ischemic damage to loop of henle in outer medulla means kidney unable to respond to ADH (giving ADH can be a useful diagnostic test)

Front 59

What are 4 clinical consequences of ATN

Back 59

↑ urea & CR = uremia.
Hyper-K+
ECF volume expansion = (pulmonary) edema
Most need dialysis – if in ICU & need dialysis mortality rate is 60% (may be b/c of systemic inflammatory process)

Front 60

What are 5 other causes of Acute Renal Failure?

Back 60

Toxic – E.g. gentamicin which accumulates in the proximal tubules causing necrosis
Acute glomerulonephritis – e.g. post-stretococcal infection
UT obstruction – prostate or pelvic CA
Allergice interstitial nephritis
Hemolytic-uremic syndrome – reaction to bacterial toxin causing glomeruli, epithelial & systemic hemolysis.

Front 61

What are the 4 main functions of immunoglobins?

Back 61

Immunoglobulins:
- neutralize bacterial toxins
- lyse bacteria
- activate complement
- opsinize bacteria to enhance phago

Front 62

What is the function of IgG, IgM, IgE and IgA?

Back 62

Ig M – first one to appear after exposure
Ig G – memory, rapid appearance on re-exposure
Ig E – allergies
Ig A – in secretions

Front 63

What are the 4 main functions of Helper T-cells?

Back 63

Enhance activation of CD8 T-cells
Enhance activation of B-cells to produce Ab’s
Stimulate further proliferation of B & T cells
Enhance innate immunity

Front 64

During acute inflammation, what do cytokines do in addition to directly mediating vascular permeability? (4 things)

Back 64

Cytokines will:
- enhance histamine release
- ↑ activation of WBC
- stimulate bone marrow to make more WBC (neutrophils then monocytes)
- induce fever, sleep & loss of appetite