Exam 1: L2 Flashcards
(55 cards)
1
Q
Identify features that differentiates reversible and irreversible cell injury
A
2
Q
Define necrosis. Explain the pathogenesis, identify morphological features, relevant investigations, and clinical importance of various types of necrosis
A
3
Q
What are the types of intracellular accumulations. Give clinical examples of intracellular accumulations and explain clinical correlations
A
4
Q
Explain the pathogenesis of pathologic calcification. Understand the differences between dystrophic and metastatic calcification. Discuss the clinical importance of pathologic calcification
A
5
Q
What is the point of no return in cell death?
A
amorphous densities in mitochondria
6
Q
What happens to cellular components following cell death?
A
lytic lysosomal enzymes act on cell components leading to self-digestion(autolysis)
7
Q
What determines irreversible cell injury? (2)
A
- inability to reverse mito dysfunction
- altered membrane function
8
Q
Coagulative Necrosis
- caused by
-mechanism
-morphology
-clinical lab correlation
A
- caused by: ischemia to tissues
- mechanism: denaturation of proteins and enzymes; blocks complete proteolysis of the dead cells (dead cells are eventually phagocytosed)
-morphology: localized area is infarct; cell outlines have tombstone appearance or are ghost outlines - clinical lab: leakage of enzymes (cardiac troponins, CKMB)
9
Q
Describe Osteonecrosis/ avascular necrosis
A
- represents loss of blood supply to a region of bone
- common affected sites: femur, talus, lunate, and scaphoid
- cause: trauma, corticosteroid, and idiopathic
10
Q
Liquefactive Necrosis
-caused by
-mechanism
- morphology
-clinical importance
A
- caused by: focal bacterial, or fungal (abscess); seen in CNS ischemia
-mechanism: 1) activated leukocytes release proteases… damage the cell 2) leads to digestion of dead cells - morphology: localized area: abscess; in brain ischemia: dissolution of neural tissue w/o inflammation
clinical: lung abscess; in CNS ischemia: infarct area shows dissolution, and later cystic space
11
Q
Gangrenous Necrosis
- caused by
- mechanism
-morphology
A
-caused by: slowly developing occlusion of blood vessel; seen with diabetic foot
-mechanism: form of coagulative necrosis due to atherosclerotic narrowing causing less blood to flow to tissue .. slow ischemia of the tissue……develops over a long period of time
- morphology: 2 forms, wet and dry
12
Q
Dry Gangrene
A
- produces a line of demarcation and blackening tissue
-RBC leaks out and is lysed to release HB. - Hb is converted by bacteria, enzymes or medications to iron sulphide
- accumulation of iron sulphide causes blackening of the tissue (produces line of demarcation)
13
Q
Wet Gangrene
(give examples)
A
- combination of coagulative and liquefactive necrosis
- creating yellow pus
examples:
- diabetic foot
- inguinal hernia
-volvulus
-mesenteric ischemia
-intussusception
14
Q
Caseous Necrosis
-Caused by
- mechanism
-Morphology
-clinical correlation
A
caused by: TB
mechanism: form of coagulative necrosis; macrophages that ingested microbes are destroyed by T lymphocytes; Microbes are within caseous necrotic tissue and cannot divide in anoxic(wiyhout oxygen) conditions
- morphology: “cheese like”; on microscopy: caseating granuloma
- clinical correlation: caseous material will calcify… indicative of TB
- vacuole cannot break down TB engulfed by macrophage, so forms necrosis due to decrease oxygen
15
Q
Tuberculosis
-caused by
-transmission
-mechanism
-symptoms
-treatment
A
- asymptomatic; may cause fever and pleural effusion
-fibrocalcific pulmonary nodule; pathologic lesions (caseating granulomas and cavitation)
-Tuberculin (PPD or Mantoux) skin test - mechanism: initial infection of macrophages, T1 response
16
Q
Fat Necrosis
-caused by
-mechanism
-morphology
-clinical correlation
A
- commonly caused by alcohol; acute pancreatitis
- Mechanism: 1) alcohol injures the pancreatic acinar cells 2) cells release activated enzymes like amylase and lipase 3) fat destruction occurs due to the release of the enzymes into the pancreas and peritoneal cavity 4)activated lipases split TAG..FA combines with calcium to create chalky white areas called fat saponification (calcium soap deposits)
- morphology: shadowy cells, surrounding inflammation, and calcification may be present
- clinical correlation: binging alcohol leads to acute pancreatitis; presents as acute abdomen medical emergency; may be fatal due to shock ( acute hemorrhagic pancreatitis); calcification in plain x ray of abdomen
- cullen and Grey Turner signs
- Labs: elevated serum amylase and lipase
17
Q
Acute Pancreatitis
A
18
Q
Traumatic Fat Necrosis
A
19
Q
Fibroid Necrosis
-caused by
-mechanism
-morphology
-clinical correlation
A
- caused immune vasculitis and hyperplastic arteriolosclerosis
- Morphology: immune vasculitis ( dense inflammation); Hyperplastic arteriolosclerosis ( minimal inflammation)
- Clinical correlation: immune vasculitis (SLE)–> cutaneous vessels in SLE are usually involved
- immunofluorescence helps in detecting Ig and complement factors; hyperplastic arteriolosclerosis is referred to as malignant hypertension
- commonly involves the kidney
20
Q
Immune Vasculitis
A
- can be seen in SLE (autoimmune disease)
- Mechanism 1)AgAb deposits on the vessel wall 2) endothelial wall injury, inflammation, complement 3) injury causes coagulation, so fibrin is produces 4) fibrin left behind, causing damage to vessels 5) leading to necrosis due to vascular leakage, permitting cells and fibrin to leak out
- bright pink color to the involved areas
- Morphology: dense inflammation
21
Q
Hyperplastic Arteriolosclerosis
A
- seen with severe hypertension; smaller blood vessels; smaller ones are injured
- vessels exhibit concentric, laminated (onionskin0 thickening of the walls with luminal narrowing
- could be benign hypertension or malignant hypertension (blood pressure over 200mmHg)
Morphology: shows minimal inflammation
22
Q
What are the enzyme markers for cell death?
A
- aspartate aminotransferase (AST) –> diffuse liver cell necrosis, viral hepatitis
- alanine aminotransferase (ALT)–> diffuse liver cell necrosis, viral hepatitis
- creatine kinase (CK-MB) –> acute myocardial infarction or myocarditis
- Amylase and lipase –> acute pancreatitis
23
Q
What is the pathogenesis of necrosis?
A
- leakage of lysosomal enzymes (acid hydrolases) damages cellular constituents—–> producing denaturation of proteins and enzymes
– membrane damage allows leakage of cellular contents - leakage attracts inflammatory cell response
24
Q
What is the morphology of necrosis?
A
- earliest histologic evidence of myocardial infarction takes 4-12 hours
- microscopy: pyknosis, karyolysis, and karyorrhexis
25
Distinguish between Karyolysis, pyknosis, and karyorrhexis
Karyolysis--> nucleus fades and dissolves
Pyknosis--> nucleus shrinks and becomes dense
Karyorrhexis--> nucleus fragments
26
How the femoral head impacted by osteonecrosis/ avascular necrosis?
- fractures of the femoral neck causes disruption of metaphyseal vessels and epiphyseal branches
27
What happens with diabetic patients with peripheral arterial disease?
dry gangrene is slowly developing, leads to sluggish venous drainage
28
What is diabetic foot?
- small abrasion not felt by the patient allows access for microorganisms
- organisms proliferate due to hyperglycemia (liquefactive necrosis)
29
What is inguinal hernia?
incarceration of small bowel loop within inguinal canal
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Volvulus
twisting of segment of intestine
31
What is the association with diabetic patients and mesenteric ischemia?
bowel ischemia may arise with atherosclerotic narrowing of the mesenteric vessels
32
What is Intussusception?
-most seen in pediatric age group
- telescoping of a segment of bowel due to obstruction
33
What is traumatic fat necrosis?
- trauma to breast can cause fat necrosis
- mimics breast cancer on mammogram
- ex. seatbelt restrainers in automobile accident
34
What is trypsin's role in the acute inflammatory reaction due to the release of pancreatic enzymes?
- unintentional activation of pancreatic protrypsin can cause the activation of other proenzymes such as prophospholipase and proelastase, which then degrade fat cells and damage the elastic fibers of blood vessels
-
35
What is the purpose of measuring troponin levels?
36
What is the purpose of measuring creatine kinase?
37
What re the physiologic causes of apoptosis?
38
What are the pathologic causes of apoptosis?
39
What is the mechanism of apoptosis?
40
What is the morphology of apoptosis?
41
What are the 4 pathways of abnormal intracellular accumulation?
- inadequate removal of a normal substance (fatty change)
- accumulation of endogenous abnormal substance (defect in protein folding)
- failure to degrade a substance (storage disorder)
- deposition/accumulation of abnormal exogenous substances (silica, carbon)
42
Intracellular accumulation: Fatty Change
- abnormal accumulation of triglycerides within parenchymal cells
- most common: fatty change liver
- cause: alcoholism, non-alcholic fatty liver (NAFLD), malnutrition/ starvation
43
Reye's syndrome
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Accumulations of versions of lipids:
- triglycerides-->
- phospholipids-->
- cholesterol/cholesterol esters -->
- fatty change
- atherosclerosis/ xanthoma
- as a component of myelin figures: necrotic cells )
45
what is Acute Fatty Change seen with?
hepatoxins like carbon tetra chloride and DDT poisoning
46
Intracellular accumulations: Hyaline change
- appears glassy pink on H/E
- alteration within cells or in extracellular space
- cause: hypertension and diabetes associated changes in vascular wall
- in benign hypertension- vessel wall undergoes injury die to hemodynamic process
- in diabetes- vessel wall damage by AGE binds to basement membrane
47
What does accumulation of NADH result in ?
- anion gap metabolic acidosis: lactic acidosis and ketoacidosis
- in fasting hypoglycemia: cause inhibition of conversion of cytosolic malate to oxaloacetate, increase in oxaloacetic acid to malate: impaired gluconeogenesis, inhibition of TCA cycle
- in heptosteatosis: in glycolysis, leads to increased conversion of DHAP to glycerol3 phosphate (G3P)
48
Hyaline Change: Diabetes
- formation of advanced glycation end products
- excess AGE formation in hyperglycemia
- AGE binds a receptor: RAGE expressed by endothelial cells, inflammatory cells, vascular smooth muscle cells
49
Intracellular hyaline
- russell bodies
- mallory bodies
- reabsorption droplets
50
AGE-RAGE ( hyaline change) signaling results in...
- release of cytokines and growth factors
- generation of free radicals
- increases procoagulant activity
- increased proliferation of vascular smooth muscle cells and ECM
51
Intracellular accumulations: Pigments
- endogenous vs exogenous
- exogenous: carbon ( appears black in lungs)
- endogenous: lipofuscin ( brown appearing.. due to old age); melanin; hemosiderin
52
Describe pathologic calcification
- abnormal deposition of calcium slats together with smaller amount of iron, magnesium, and other mineral salts
- dystrophic calcification
- metastatic calcification
53
Metastatic calcification
- deposition of calcium salts in normal tissue
- results from hypercalcemia secondary to some disturbance in calcium metabolism
-ex. hyperparathyroidism , sarcoidosis
54
Dystrophic calcification
- occurs locally in dying tissue
- coagulative, caseous, or liquefactive type, and foci of enzymatic necrosis of fat
- present in the atheromas of advanced atherosclerosis
- commonly develops in aging or damaged heart valves
- normal serum levels of calcium
55
Psammoma bodies
- round, concentric laminated, onion-like, calcium deposits
- in meningioma, papillary carcinoma thyroid, serous carcinoma ovary
