Cell Injury Flashcards
What are the stages and dynamic evolution of cell injury response?
Normal cell can undergo stress or injury:
- if stress - adaption. If unable to adapt then cell injury.
- Cell injury - if mild then the cell is able to reverse injury. If severe then cell is not able to cope, and it is an irreversible injury (which leads to cell death via necrosis or apoptosis).
What are some causes of cell injury?
- hypoxia/ischemia
- physical agents - trauma, extreme heat/cold, electrical energy
- chemicals, toxins, drugs
- infectious agents
- immunologic reactions/dysfunctions
- genetic derangement
- nutritional deficiencies and imbalances
- workload imbalance
- aging
What are the adaptive cellular responses to stress/injury?
- increased cellular activity = Hypertrophy or Hyperplasia
- decreased cellular activity = Atrophy
- altered cell type or position = Metaplasia or Dysplasia
What is hypertrophy and what cellular events are taking place to cause this?
Increase in cell size = increase in the size of an organ.
Due to increased synthesis of structural components.
May coexist with hyperplasia.
What are the two categories of hypertrophy?
- Physiologic - increased workload, or stimulation by hormones and growth factors. i.e. workload: muscle hypertrophy. hormonal: uterine enlargement/mammary gland enlargement in pregnancy
- Pathologic - hypertrophic cardiomyopathy due to chronic hypertension or valvular defects (intrinsic pathologic hypertrophy).
What are some molecular pathways of cardiomyocyte hypertrophy?
- Mechanical stretch - increased workload.
- Agonists - alpha adrenergic hormones, angiotensin.
- Growth factors - IGF-1.
These lead to signal transduction pathways and the production of transcription factors. These transcription factors then lead to increased synthesis of contractile proteins, transcription of genes involved in mechanical performance of the heart, transduction of genes involved in production of vasodilatory hormones (ANF), and/or production of growth factors.
The overall result is increased mechanical performance and decreased workload.
Feline hypertrophic cardiomyopathy - what are the predisposed animals? What are some common accompanying abnormalities? How does the heart look grossly? How is this different than dilated cardiomyopathy?
- Middle-aged male cats (persian, maine coon, american shorthairs - possible inherited component)
- Congestive heart failure. Saddle thrombosis (thromboembolism of caudal aorta from atrial thrombosis) - leads to posterior paresis.
- Enlarged left ventricular wall and interventricular septum. The ventricular cavity is small and the left atrium is enlarged.
- Dilated cardiomyopathy shows enlarged ventricular and atrial cavities with thinning of the walls. Biventricular dilation makes the heart appear as if it has two apices. Many animals have low tissue concentrations of taurine. It also has an inherited component.
What is hyperplasia? What is it in response to? What are the categries? What is compensatory hyperplasia? What tissue shows comp hyperplasia?
- An increase in cell numbers.
- It is inresponse to hormones and growth factors.
- Physiologic - hormonal or compensatory.
- Pathological - caused by excessive hormonal stimulation or chronic irritation.
- Comp hyperplasia - regeneration subsequent to tissue injury and loss.
- Liver.
What are the molecular mechanisms of response to hepatocyte loss and subsequent compensatory hyperplasia?
Transcription factorrs, anti-apoptotic factors, DNA replication, cellular proliferation.
What category of hyperplasia is responsible for cystic endometrial hyperplasia? What could this develop into? What are some other types of hyperplasia in this category?
Physiologic hyperplasia - hormone induced.
Pyometra
other examples: prostate hyperplasia, thyroid gland hyperplasia (“goiter”).
What is the pathway leading to thyroid gland hyperplasia (“goiter”)?
- Iodine deficiency during pregnancy
- inadequate Thyroxine synthesis
- decreased T4 and T3 serum levels
- feedback on hypothalamus
- synthesis and release of TRH form hyp onto pituitary
- synthesis and release of TSH from pituitary
- TSH stimulation on thyroid inducing thyroid follicular cell proliferation.
What is atrophy? What are the categories of atrophy?
It is a type of cellular adaptation. It is the reduction in size of an organ/tissue resulting from a decrease in cell size and number.
It can be physiologic or pathologic.
Atrophy can be a normal process. What category is the normal process and name some tissues that may undergo atrophy.
- Physiologic atrophy - common during normal development, ageing, upon decreased functional demand
- Embryonic structures (notochord), Thymus, Uterus, Mammary Gland.
What does pathologic atrophy depend on? What are the two types of path atrophy?
- Depends on an underlying cause.
- Local
- Generalised
What are some common causes of atrophy?
- Decreased nutrient supply, starvation = utilization of fat and muscle stores = muscle atrophy
- Deficient blood supply = results in tissue hypoxia
- Decreased workload = disuse atrophy
- Denervation atrophy
- Pressure atrophy = hydrocephalus and buildup of fluid in ventricles compresses brain parenchyma
- Loss of endocrine stimulation = adrenocortical atrophy from prolonged corticosteroid therapy or pituitary tumor
