Physiology

Q1

Case A: 45-year-old Female with a Broken Right Ulna

a.

The most logical size difference when you look at the left and right arms is muscle atrophy in the right arm, due to being immobilized in a cast for five weeks. The muscles of the right arm would appear smaller compared to those in the left arm. This is a common enough phenomenon, as muscles that are not regularly used tend to lose mass (Rogers, 2022).

b.

The tissue that changed in size is the skeletal muscle tissue. Muscle atrophy affects the muscle fibers. In turn there is a reduction in muscle mass, muscle strength, and muscle size. There can also be some alteration in the connective tissues surrounding the muscles, but the skeletal muscle tissue is the main tissue involved (Rogers, 2022).

c.

The type of cellular adaptation that occurred is atrophy, which is a decrease in cell size, which leads to a reduction in the overall size of the affected organ or tissue. In this case, the immobilization of the arm resulted in atrophy from disuse of the skeletal muscles (Rogers, 2022).

d.

In terms of molecules, one would see a reduction in the synthesis of structural proteins like actin and myosin, which allow muscle contraction. There would be an increase in protein degradation pathways, such as the ubiquitin-proteasome pathway, which breaks down muscle proteins.

On the level of organelles, atrophy results in a decrease in the number and size of mitochondria in the muscle cells, as there is less energy demand due to reduced activity. As mitochondrial content decreases, the cell's capacity for ATP production is reduced (Rogers, 2022).

At the cellular level, the muscle fibers (myocytes) shrink as their protein content lessens. There is also a reduction in overall cellular metabolism, with fewer energy-producing organelles. Cells can undergo autophagy, wherein they digest their own organelles to adapt to the decreased need for cellular machinery (Rogers, 2022).

In terms of tissue, skeletal muscle fibers become thinner, and the overall muscle mass of the right arm decreases. This tissue-level change is seen as muscle wasting away and accounts for the observable difference in arm size.

Case B: 68-year-old Male with Atherosclerotic Occlusion in an Artery to His Left Leg Calf Muscle

e.

The most logical form of cellular injury in this case is ischemic injury, which is a type of hypoxia caused by atherosclerotic occlusion of the artery. The reduction of blood flow prevents oxygen and nutrients from getting to the calf muscle tissue. If it goes on long enough, ischemia can lead to cell death (Rogers, 2022).

f.

In terms of ions, ischemic injury results in a failure of the sodium-potassium (Na+/K+) pumps due to the lack of ATP. There is an influx of sodium and water...

Calcium ions also accumulate inside the cell due to dysfunction in calcium pumps, which further damages the cell and its organelles (Rogers, 2022).

At the molecular level, there is a decrease in ATP production as oxidative phosphorylation in the mitochondria is impaired by the lack of oxygen. The cell shifts to anaerobic glycolysis. Lactic acid builds up as intracellular pH balance is lost.

Regarding organelles, the mitochondria are one of the first to be affected by the lack of oxygen. Mitochondrial damage leads to a further decrease in ATP production and the release of pro-apoptotic factors which initiate programmed cell death if the injury persists. The endoplasmic reticulum also becomes stressed, impairing protein synthesis (Rogers, 2022).

At the cellular level, the injury manifests as cell swelling, loss of membrane integrity, and potential cell death if the ischemia is severe and prolonged. If the blood supply is not restored, irreversible injury occurs.

In terms of tissue,...

…can divide without the usual regulatory checks. A well-known tumor suppressor is TP53, which codes for the p53 protein, responsible for detecting DNA damage and inducing apoptosis (programmed cell death). Mutations in TP53 allow damaged cells to survive and proliferate, contributing to cancer development (Rogers, 2022).

Mutations in DNA repair genes can lead to an accumulation of genetic damage because cells lose the ability to fix DNA errors. For instance, mutations in the BRCA1 and BRCA2 genes impair the cells ability to repair DNA double-strand breaks, increasing the risk of breast and ovarian cancers (Rogers, 2022).

Epigenetic Alterations

Epigenetic alterations involve changes in gene expression that do not alter the DNA sequence but modify how genes are turned on or off. These changes are critical in cancer development and often occur alongside genetic mutations. Two main types of epigenetic modifications that contribute to cancer are DNA methylation and histones (Rogers, 2022).

DNA methylation involves the addition of a methyl group to DNA, usually at cytosine bases. In cancer, abnormal methylation patterns can silence tumor suppressor genes, even though their DNA sequence remains intact. Hypermethylation of the promoter region of a tumor suppressor gene like CDKN2A (which encodes the p16 protein) can turn off its expression, allowing unchecked cell proliferation (Rogers, 2022).

Histones are proteins around which DNA is wrapped. Chemical modifications to histones, such as acetylation or methylation, can change the accessibility of DNA for transcription. In cancer, histone modifications can either silence tumor suppressor genes or activate oncogenes, disrupting normal cellular control mechanisms (Rogers, 2022).

Interaction Between Genetic and Epigenetic Changes

Genetic and epigenetic changes often work together in cancer progression. For example, a mutation in a proto-oncogene might activate oncogenic signaling, while epigenetic changes in a tumor suppressor gene could remove the brakes on cell division. This combination of alterations creates a permissive environment for tumor…