Cell Injury

CELL INJURY

Well... lets see how we can make this the easiest. CELL INJURY is simply some sort of injury to cell that might have a bad effect on your body and tissues. lets sat u got your finger cut by a sleek paper. that means some of your cells in the finger got injured and might have some Bad consequence as a result.

in this post we will know what Cellular Injury is, the types of cell injury, Cellular response to different kinds of injury and the ultimate consequence of injury.

So LETS  GET STARTED!!!

First of all we must know a little about CELLULAR ADAPTATION.

Cells can react by modifying themselves slightly and thus adapt to the injury (such as hypertrophy, hyperplasia, atrophy, and metaplasia). Such adaptations may be reversible and called Cellular adaptation.

Cells can also react by becoming permanently altered and then living a new "lifestyle" (such as radiation changes in cells). They may also react to injury by being overwhelmed, and unable to continue life, and so they die. 

When cells die, they can do so in a pre- and proscribed manner of planned cell death, called apoptosis. Degeneration of cells after the death of the organism is termed autolysis (cells basically rot). Cells which die before the death of the organism undergo necrosis, a process which will be explored with examples, and contrasted with apoptosis and autolysis. 

 Necrosis

Definition:

If the limits of adaptive responses are exceeded or if cells are exposed to injurious agents or stress, deprived of essential nutrients, or become compromised by mutations that affect essential cellular constituents, a sequence of events follows that is termed cell injury.

Cause:

• Hypoxia
• Physical Agents: (mechanical trauma, burns, frostbite, sudden changes in pressure (barotrauma), radiation, electric shock).
• Chemical Agents: glucose, salt, water, poisons (toxins), drugs, pollutants, insecticides, herbicides, carbon monoxide, asbestos, alcohol, narcotics, tobacco.
• Infectious Agents: prions, viruses, rickettsiae, bacteria, fungi, parasites.
• Immunologic Reactions: anaphylaxis, autoimmune disease.
• Genetic Derangements: Congenital malformations, normal proteins (hemoglobinopathies), enzymes (storage diseases). 
•  Nutritional Imbalances: protein-calorie deficiencies, vitamin deficiencies; excess food intake (obesity, atherosclerosis).
  

Cell death:

The end result of progressive cell injury is called Cell Death.

 Fig: Stages of the cellular response to stress and injurious stimuli.

Courtesy of Pathologic Basis of Disease, Robbins and Cotran 

 Types of cell Injury: 

1. Reversible Injury
2. Irreversible Injury

 Reversible cell injury are again seen as two types: Cellular Swelling and Fatty Change,

 and

Irreversible cell injury can be of tow types: Necrosis and Apoptosis.

We will be discussing these topics in detail in the next post of mine. Meanwhile, watch this video an please leave a comment if u like my page.

 

Check out this video, its a bit long but a lot helpful.

1. Reversible Cell Injury 

As stated at the beginning of the chapter, cell injury results when cells are stressed so severely that they are no longer able to adapt or when cells are exposed to inherently damaging agents or suffer from intrinsic abnormalities. Injury may progress through a reversible stage and culminate in cell death.

to summarize we may say, 

Reversible cell injury. 

• Is an early stages or mild forms of injury. 
• The functional and morphologic changes are reversible if the damaging stimulus is removed. 
• The hallmarks of reversible injury are reduced oxidative phosphorylation with resultant depletion of energy stores in the form of adenosine triphosphate (ATP),
• Cellular swelling caused by changes in ion concentrations and water influx. 
• In addition, various intracellular organelles, such as mitochondria and the cytoskeleton, may also show alterations. 

  Now lets discus these points in a little bit more detail. First we are going to look at reversible cell injury from a Macroscopic view and then from a Microscopic view.

Macroscopic Changes:

Primarily all cell injury involves cellular swelling. Therefore under naked eye we may observe these following features:

• it causes some pallor, 
• increased turgor, 
• and increase in weight of the organ.

Microscopic Changes:  

under a light microscope, cells appear 

• "moth eaten" by which it means small clear vacuoles may be seen. These vacuoles represent distended and pinched-off segments of the ER. This pattern of nonlethal injury is sometimes called hydropic change or vacuolar degeneration.
• In addition increased eosinophilic staining may be seen. These become more prominent if the tissue progresses towards necrosis.

Fig: Hydropic change in kidney tubules

also there are some ultra-structural changes, these are visible under an Electron Microscope.

• Plasma membrane alterations, such as blebbing, blunting, and loss of microvilli.
• Mitochondrial changes, including swelling and the appearance of small amorphous densities.
• Dilation of the ER, with detachment of polysomes; intracytoplasmic myelin figures may be present (see later)
•  Nuclear alterations, with disaggregation of granular and fibrillar elements.

Fig: Cellular swelling on the left, and normal structure on the right. 

Mechanisms of Cellular Injury: 

In the following section we will discuss the biochemical mechanisms that may be activated by different injurious stimuli and contribute to cell injury.

Cell injury results from different biochemical mechanisms acting on several essential cellular components. These mechanisms are described individually below:

These will include the following:

1. Depletion of ATP
2. Mitochondrial Damage
3. Increased Influx of Calcium ion into cells
4. Increased accumulation of Reactive Oxygen species
5. Cell Membrane damage
6. Defect in protein formation and Nucleic acid formation. 

 1. Depletion of ATP:  

it is best to explain this mechanism by a flow chart,

Haemopoisis

Haemopoiesis
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 10¹¹–10¹² new blood cells are produced daily in order to maintain steady state levels in the peripheral circulatio


Site of haemopoiesis
Fetus:  0–2 months (yolk sac)
           2–7 months (liver, spleen)
           5–9 months (bone marrow)
Infants: Bone marrow (practically all bones)
Adults: Vertebrae, ribs, sternum, skull, sacrum
           and pelvis, proximal ends of femur

Haematopoietic stem cells (HSCs)

Before we know about what haematopoetic stem cells are we must first know what a stem cell is..

So, here is a great interactive video for you to learn what a stem cell is..

Simply a stem cell is a cell that gives rise to many other cells. when it is in the embryo its called Embryonic Stem Cell, and when they are in the bone marrow ready to form Blood Cells they are simply called Haematopoietic Sem Cells or HSCs. This haemopoietic stem cell is rare, perhaps 1 in every 20 million nucleated cells in bone marrow

HSCs are normally found in the bone marrow.

Now lets see why a HSC is so important for.
1. they have self renewal capacity.
2. they can proliferate and differentiate into progenitor cells which in turn are commited to one specific cell line.

sounds too tough?? well it simply means they can easily divide and when they do some of them REMAINS as  HSCs for further use.
the divided one then can again multiply many times and form into specific blood cells.

here is a simple diagram of the stem cell making different cells:

now, this picture shows all types of haemopoiesis in detail. meaning to say all the cell forming line ups. As the diagram shows, most of the work happens in the bone marrow itself nd some in the blood and very few in the tissues.
[to get a full resolution picture and more image visit this link]

The Bone Marrow

The bone marrow forms a suitable environment for stem cell survival, growth and development. It is composed of:
1.stromal cells and
2.a microvascular network - it provides:
       i) nutrition
       ii) acts as a transport system to bring new cells into system.



The stromal cells include adipocytes, fibroblasts, endothelial cells and macrophages and they secrete extracellular molecules such as collagen, glycoproteins (fibronectin and thrombospondin)
and glycosaminoglycans (hyaluronic acid and chondroitin derivatives) to form an extracellular
matrix. In addition, stromal cells secrete several growth factors necessary for stem cell survival.
Mesenchymal stem cells are thought to be critical in stromal cell formation.

Haemopoietic growth factors:

Haemopoietic growth factors are hormones that regulate the proliferation & differentiation of haemopoeitic & progenitor cells and function of a mature blood cell. these effects are mediated thorough specific receptor on target cells.
haemopoietic growth factors mainly come from:
1. T-Lymphocyte
2. Monocyte
3. Stromal cells.

Here is a table showing Haemopoietic growth factors and the cells they act on:


Act on stromal cells
IL-1
TNF
Act on pluripotential stem cells
SCF
Flt-L
Act on multipotential progenitor cells
IL-3
GM-CSF
IL-6
G-CSF
Thrombopoietin
Act on committed progenitor cells
G-CSF*
M-CSF
IL-5 (eosinophil-CSF)
Erythropoietin
Thrombopoietin*







This video will help you learn how the real cells look like under microscope. watch with patience....

Haematology

Welcome Fellow Medical Students, this is an interactive website to help build up ideas and sharing them about medical knowledge.

Today my blog will be starting with Hematology, What is Hematology and a normal peripheral blood film.

HEMATOLOGY

















 fig: Electron micrograph showing a RBC, a WBC and a Platelet.


Hematology, is the branch of internal medicine, physiology, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases. Hematology includes the study of etiology, diagnosis, treatment, prognosis, and prevention of blood diseases.
Normal Peripheral Blood Film



i personally think if u watch this video closely, tou will not have any problem identifying a normal peripheral blood film.

a - erythrocytes

b - neutrophil

c - eosinophil

d - lymphocyte