Patho Week 1 Cell death.txt

• Necrosis is pathological and apoptosis can be
• both

Hypoglylcemia is low blood glucose (sugar), it is important because cells need glucose for blycolysis (production of ATP). The brain is most affected.

Blycolysis is anaerobic. Most of the glycolysis is made/stored through aerobic means. Goycolysis requieres two molecules of ATP and only produces 4.

Diabetes. Note, the role of insulin is to lower blood glucose levels, so if a diabetic takes too much insuline, or does not eat after taking insulin it may result in hypoglycemia.

Hypoxia

Hypoxia is low oxygen levels in the Tissue, Hypoxemia is low oxygen levels in the Blood.

Mitochondria

• 1. Respiratory obstruction or disease
• 2. Ischemia
• 3. Anemia
• 4. Alteration of Hemoglobin (hemoglobinopathies)

The earliest clinical signs are distubances of the normal level of consciousness. This happens becaue failure of energy production will first affect cells with the highest demand for oxygen beause of their high basal metabolic rate which makes brain cells maximally affected.

When ATP is not available, the Na+ pumps cannot function. This means the sodium is left inside the cell with the calcium, and since water follows sodium, the cells swells and ruptures. This also leaves elevated potassium in the ECF.

When the cell swells, the endoplasmic reticulum sweels as well, this causes detachment of ribosomes that hang on to the rough ER. Since protein synthesis happens in the ribosomes, when they pop off protein sysnthesis stops. When protein synthesis stops it causes lipid buildup in the cell an dthe cell stops functioning.

Aerobic metabolism requires oxygen, thereofre when there is not enough oxygen our cells switch to anaerobic metabolism (glycolysis). Since the cells need glycogen for glycolysis our glycogen levels quickly decrease and the bi-product of glycolysis is lactic acid. when lactic acid builds up, the intracellular pH goes down, making the cell more acidic.

When the pH lowers, it causes Pyknosis (nuclear chromatic clumping) which leads to Karyorrhexis (nuclear clumping fragments/ruptures). Karyolysis then occurs (auto-digestion of cell contents). A low pH also causes lysomomes to be lyse, which releases lysosomal enzymes (hydrolases) which promote cellular auto-digestion.

Lysosomes are cellular organelles that contain acid hydrolase enzymes used to break down waste and cellular debris.

ROS: Reactive Oxygen Species

Odd number of electrons

They disrupt to the structure of the cell membrane by interacting with the lipids in the membrane

Calcium

The effects of cell/plasma membrane damage are loss os structural integrity and loss of function.

Clostridium perfringens, the causative agent of Gas Gangrene, uses lipase-like enzyems to damage cell membranes, it does this to get deeper into the tissue.

Cytopathic viruses damage cell membanes by direct insertion into the cell membrane. As the virus leaves it forms a bud that tears off and causes cell membrane damage. Both HIV and Hep B do this.

HPV is an acquired genetic alteration, it alters the DNA which promotes cancer growth in the cervix.

- abnormalities in: structural proteins, enzymes, mitosis, or regulator proteins

Exogenous toxic agents

• 1. Increased mobilization of fatty acids: If breakdown occurs too fast, such as starvation or diabetes mellitus, there is an accumluation of fat in the liver.
• 2. Increased conversion of faty acids to lipids: This happnes with chronic alcohol abuse because alcohol is a hepatic enzyme inducer which converts fatty acids to lipids
• 3. Decreased oxygenation: hypoxia/krebs gets backed up du to decreased ATP production, therefore things like cholesterol, triglycerides, and pholpholipids get accumulated.
• 4. Decreased synthesis of lipoproteins: a sick liver can't make proteins, so there isnothing for lipids to bind with. Therefore, you get a backup of lipids because of the lack of protein.

• 1. Acute: sudden and severe. Ex: poisoning with carbon tetrachloride
• 2. Chronic: slowly progresses, such as in alcoholism

The breakdown product of RBCs

• 1. Hemolytic jaundice
• 2. Hepatocellular jaundice
• 3. Obstructive jaundice

Increased RBC desctruction; the increased RBC destruction ovewhlems the liver so it cannot conjugate it all, since teh bilirubin is bound to albumin in the blood, it stays in the blood stream instead of bein excreted from the body. Pathologic would be sickle cell - Physiologic would be a new born baby who was born with an excessive amount of RBCs

When the liver is sick there is a decreased uptake, conjugation or excretion of bilirubin, the bilirubin will build up in the liver.

Biliary tract obstruction of the flow of bilirubin, perhaps due to a stone.

Encephalopaty

Normally, bilirubin binds with albumin. This can be an issue for babies because they have immature livers that are not able to produce enough albumin.

Kernicterus. Basil ganglia

• 1st stage is Pyknosis where the chromatic (nucleic acid and proteins) clump
• 2nd stage is Karyorrhexis where the clumps fragment/ruptue
• 3rd stage is Karyolysis where the fragments are digested

The cell retains some fo its shape, but the insdie of the cell looks like a scrambled egg. An example of this is gangrene.

Dry gangrene usually occurs on an extremity, the necrotic area appears black, dry and mummified.

Wet Gangrene resuts from evere bacterial infection superimposed on necrosis. Wet gangrene can be internal or external, it is very smelly and appears red.

Gas Gangrene is Wet gangrene that has gas bubbles (with crepitus), usually caused by Clostridium perfringens.

Debridement

Crepitus is a crackling sound or feeling. We can encounter this under the skin with gas gangrene, in the lungs when gas and liquid mix, or in the joints due to joint wear.

Caseous necrosis

Liquefactive necrosis, we see it in the brain with stroke patients becuase of ischemia

We develop as a fetus with webbed feet, at a particular point the webbing is removed by apoptosis.

In HIV, infected CD4 cells can signal other non-infected CD4 cells to undergo apoptosis.

Labile cells are found in the skin, GI system and the lining of our lungs. Yes, the regenerate often.

Permanent cells are found in the brain and they cannot regenerate.

Stable cells are found in the liver and yes, they can regenrate but at a slow pace.

Cell shrinkage and weakening. The cell becomes smaller.

• 1. Disuse
• 2. Loss of nutients to the cell
• 3. Loss of trophic hormones
• 4. Denervation

• Physiologic: lifting weights - muscles get bigger but will return to their smaller size when you stop.
• Pathologic: cells will not return to normal size, Ex: when we develop heart failure, the heart tries to overcompensate and the cells will get bigger and stay that way, plus they develop scar tissue instead of getting stronger.

Hyperplasia is an increase in the number of cells, hypertrophy is an incresae in the size of a cell.

Permanent cells cannot experience hyperplasia because they cannot reproduce.

• Metaplasia is when normal cells of one type are replaced by norlal cells of another type.
• Dysplasia is when normal cells of one type are replaced by precancerous cells of another type.

• The Rough ER has the ribosomes on it which are responsible for protein synthesis.
• The smooth ER is involved with the synthesis of steroids, lipids, morphine as well asregulates calcium levels and drug metabolism.

Cyanide poisoning

• Total: 0.2 - 1.5 mg/dl
• Direct: 0.0 - 0.3 mg/dl
• Indirect 0.2 - 0.8 mg/dl

We find Direct (conjugated) bilirubin in bile because it has already been to the liver. If there was an excess in Direct bilirubin we might suspect a biliary obstruction.

Bilirubin adheres to proteins which make it a large molecule, if the vilirubin does not bind with protein it is very small and can cross the blood/brain barrier of a newborn causing Kernicterus.

• 1. Hypoglycemia
• 2. Hypoxia
• 3. Enzyme Tampering

• 1. Intreacellular accumulation of water
• 2. Changes in organelles
• 3. Switch to anaerobic metabolism

• 1. Production of ROS
• 2. Activation of Compliment
• 3. Lysis by enzymes
• 4. Lysis by Virus
• 5. Lysis by physical or chemical agents

• 1. Hemolytic
• 2. Hepatocellular
• 3. Obstructive

Pancreas

Heart

Liver

Liver or bile ducts