Topics A6-11 - Cell Injury, Accumulations, Pigment, Calcification, Stones Flashcards Preview

Y Pathology I (Dustin) > Topics A6-11 - Cell Injury, Accumulations, Pigment, Calcification, Stones > Flashcards

Flashcards in Topics A6-11 - Cell Injury, Accumulations, Pigment, Calcification, Stones Deck (62)
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3 morphological kinds of cell injury (the reversible state between healthy cells and necrosis)

1. Hydropic/Vacuolar Degeneration, aka Cellular Swelling. Low energy -> poor sodium/water pumping

2. Parenchymal Degeneration. Mostly in liver, heart, kidney. Looks like boiled meat

3. Fatty Degeneration. Also mostly parenchymal organs, but injured cells accumulate lipid droplets


5 causes of fatty degeneration / "steatosis"

1. Starvation: increases fat mobilization from periphery

2. Hypoxia: fat catabolism blocked

3. Toxins, alcohol: Decrease in NAD, increase in NADH. NAD needed for beta oxidation

4. Protein malnutrition: cannot produce ApoB-100 and thus cannot export TAG

5. Obesity: fat overload


How does fat accumulation in cells look with H-E stain?

Looks like there are empty holes in the cell due to unstained fat deposits


What is the difference in morphology between fatty degeneration caused by toxins vs hypoxia?

Toxins -> diffuse fatty degeneration

Hypoxia -> mottled / spotty fat degeneration


What is steatoris diffuse hepatis?
What are 2 causes?

Diffuse liver fat accumulation, liver appears enlarged and yellow
Caused by obesity or alcoholism, with cirrhosis


What is nutmeg liver?

What part of the liver is most affected?

Aka Degeneratio adiposa insularis hepatis, occurs due to build up of pressure in the IVC (typically first due to increased pressure in lung, then right ventricle, then IVC, then liver). Increased pressure leads to decreased oxygenation.

The pericentral area around the central vein receives the least oxygen (it's at the end of the arterial-venous gradient), and so it is affected the most by hypoxia. Makes a mottled appearance.


What is degeneratio adiposa diffusa myocardii?

Entire heart appears yellowish due to fat deposits, pumping failure occurs. More related to sepsis


What is degeneratio adiposa insularis myocardii?

Aka "Tiger Heart" - has stripes on it from hypoxia. There is subendocardial degeneration due to anemia, acute respiratory problems, decreased oxygen, or increased muscle effort. Subendocardium cells accumulate fat in a striped fashion.


What are 3 autosomal recessive diseases that cause glycogen accumulation?

1. von Gierke's disease (Hepatic glycogenosis), lacks glucose 6 phosphatase

2. McArdle's Disease (myopathic glycogenosis) - muscle phosphorylase missing

3. Pompe Disease: lysosomal acid maltase deficiency, causes glycogen to accumulate in lysosomes


2 parts of the intimal plaque in atherosclerosis, and what do they contain?

What is the most dangerous part for rupture?

1. Lipid/Necrotic Core: cholesterol crystals, EC matrix, cell debris, and foam cells. This is surrounded by inflammatory cells (lymphocytes, macrophages) and plasma proteins

2. Fibrous Cap: new vascularization (proliferating blood vessels), endothelial cells, smooth muscle. The most dangerous part for rupture is the cap's "shoulder" where it meets the vessel wall


Framingham Study: What are the 3 major constitutional risk factors for atherosclerosis?

(note: for the risks described in the Framingham study, each one when combined is not summative but multiplicative.. so having 2 risks increases your risk by 4x, and so on)

1. Age. Risk increases after ~40 years old. Atherosclerosis takes a long time to become clinically significant.

2. Sex: higher risk in males. Female hormones have a protective role. This benefit decreases after menopause though

3. Genetics: no single gene, but some that influence obesity, hyperlipidemia, diabetes, etc.


Framingham Study: What are 4 major modifiable risk factors for atherosclerosis?

1. Hyperlipidemia (more specifically hypercholesterolemia): High LDL / low HDL. Obesity and smoking increase LDL and decrease HDL. Small amount of alcohol increases HDL, but large amount is damaging.

2. Hypertension: puts stress on endothelial cells

3. Cigarete smoking

4. Diabetes mellitus


Framingham Study: 5 additional risk factors to atherosclerosis, besides the major constitutional and modifiable ones

1. Chronic Inflammation. Even something like poor dental hygiene can increase MI risk because oral bacteria stimulate inflammation
2. Obesity
3. Low physical activity
4. Stressful life (related to hypertension)
5. Type "A" Personality - competitive, also more common in men


How do endothelial non-denuding cell injuries relate to atherosclerosis?

What causes endothelial non-denuding injury? (2 main causes to know)

Endothelial cell injury doesn't cause cell death but rather dysfunction with increased ROS and decreased NO produced by endothelial cells.

Injury occurs from hypertension (pressure and turbulent flow, especially on arterial branches) and hyperlipidemia (macrophages eat up oxLDL and die -> subendothelium has cholesterol with necrotic debris). Also cigarette smoke, infectious agents, etc.


What are the 3 morphological types of atherosclerosis?

1. Fatty Streak: early atherosclerosis, reversible, begins in childhood. Does not impede flow

2. Primary atherosclerotic plaque: classic description, has intimal thickening and blood flow impeded

3. Complicated plaque: on top of primary plaque there are additional changes.. separate card for that


What are 6 changes to an atherosclerotic plaque that make it "complicated" versus primary?

1. Aneurysm: plaque causes pressure atrophy on vessel wall
2. Thrombus formation: via Ulceration, Erosion, or Rupture
3. Bleeding: bleeding into plaque can cause hematoma and rupture. Bleeding can also occur from vaso vasorum
4. Calcification
5. Stenosis: (related to calcification)
6. Cholesterol Embolism


What should be done for primary prevention of atherosclerosis (pt has no symptoms yet)?

1. Quit or don't start smoking. A pack a day increases risk by 200x
2. Treat hypertension, diabetes, reduce LDL cholesterol, etc. Control all problems related to coronary artery disease.

Prevention should start in childhood, good health education, start good habits early


What should be done as secondary prevention of atherosclerosis? Pt already has atherosclerosis, maybe already had an MI

Again treat hypertension, diabetes, etc. Also give statins to lower LDL cholesterol (maybe the new PCSK9 inhibitors too). May need surgical intervention, such as stent placement.


What causes amyloidosis when it's associated with hemodialysis?

Beta2 microglobulin (component of MHC class I) is retained in circulation because its not efficiently filtered out in hemodialysis machines.


What special type of histology staining is used for amyloidosis? What is the annoying buzzword that is used to describe it?

Congo staining
Congo red turns amyloid red, and polarizing microscope shows an "apple green birefringence"


What causes amyloidosis?

Protein misfolding and aggregation. Maybe 30 different compounds known to create amyloidosis. These look like a starch (amylose in particular) when stained, hence the name.

Have beta pleated sheet structure; linear non-branching filaments


What type of amyloidosis is related to Alzheimer's disease?

Amyloid Beta (AB) - spherical plaques. The precursor is Amyloid Precursor Protein (APP)


What type of amyloidosis is seen in myelomas?

Amyloid light chain (AL) - made from immunoglobulin light chains, lambda or kappa.

(Note: not the same thing as Russell bodies)


What type of injury is created by amyloidosis?

Pressure injury, because amyloid deposits compress cells and block their functions. They're insoluble, have a very bad prognosis. Do not evoke an inflammatory response.

Most important organ damaged is the kidney


What type of amyloidosis is associated with acute phase inflammation?

AA: Amyloid-Associated, precursor is SAA: Serum Amyloid A. If patient has chronic inflammation, the liver produces a lot of SAA, and misfolding creates amyloidosis


What type of amyloid is related to thyroid hormone? What important area can it deposit in?

Transthyretin: protein misfolding takes place in liver that transports thyroxine and retinol-binding protein. When it's misfolded, it's resistant to proteolysis, and deposits as amyloid. Mutation of gene encoding this causes familial amyloid polyneuropathies.

Can deposit in heart -> called Senile Systemic Amyloidosis


4 diseases of Hyaline accumulation

1. Hyalinic arteriosclerosis: related to diabetes and hypertension. Kidney most affected: "nephrosclerosis"

2. Hyaline membrane disease: relates to alveoli

3. Hyalinic glomeruli: end-stage kidney disease

4. Mallory Hyaline - hepatocytes get Mallory bodies with alcohol toxicosis


How does a kidney affected by nephrosclerosis look?

Surface is granular and shrunken, like grain leather


What is the pathogenesis of hyaline membrane disease? What 2 conditions does it occur in?

Hyaline membrane in alveoli results from leaky capillaries secreting protein-rich exudate

-IRDS: infant respiratory distress syndrome, caused by hypoxia
-ARDS: adult version. Caused by sepsis, toxins


What are 2 types of spleen conditions resulting from splenic amyloidosis?

Nodular deposition -> "sago spleen"

Red pulp deposition -> "sausage spleen"

Both cause splenomegaly and are "clinically unimportant" but probably still have to know it

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