Lecture 2 (Quiz 2) Flashcards
Plasma Membrane
Phopholipid bilayer with proteins, lipids, and carbohydrates integrated into it at varying levels. (Fluid Mosaic) Acts as a protective membrane that regulates what enters and leaves a cell (selectively permeable),
Mitochondria
POWER HOUSE OF THE CELL. Takes oxygen and broken down components of the diet to make ATP. Houses ETC = largest ATP producer. Also utilizes proton gradient that the ETC produces to create ATP by pumping in protons.
Transport Types
Simple Diffusion
Facilitated Diffusion
Active Transport
Group Translocation
Rough Endoplasmic Reticulum
Covered in ribosomes, located directly by the nucleus, site of protein synthesis
Smooth Endoplasmic Reticulum
No ribosomes, connected to RER but further from the nucleus, site of lipid & carbohydrate synthesis as well as some detoxifying functions.
Golgi Apparatus
Final check and packaging point to send things out of cell or accept things in from out of the cell.
Categories of Cellular Stress/Injury Response (3)
- Reversible
- Adaptive
- Death
Reversible Response
Withstands assault with quick, adaptive change, then returns to normal. Short-term stress/injury
Adaptive
Changes structure/function to adapt and is USUALLY reversible when assault is gone. Longer term stress/injury
Death
Apoptosis or necrosis of cell with stress/injury is too severe
Types of Reversible Responses (2)
- Hydropic swelling
2. Accumulation of Macromolecules
Hydropic Swelling
Accumulation of water in cells that cause swelling of the organ (ex: hepatomegaly)
How does Hydropic Swelling Happen?
Sodium-Potassium pumps fail which disrupts their corresponding gradients, causing water to follow sodium into the cell.
Why do the pumps fail?
Decreased availability of oxygen (hypoxia) and increased concentrations of chemicals that inhibit the ETC cause the ETC to stop, the hydrogen gradient to not be maintained, and, therefore, ATP not to be produced. In most cells, 30% of their ATP supply goes to keeping the pumps going, even higher in organs like the brain (90%).
Issues Associated with Accumulation (3)
- Toxicity
- Inflammation
- Crowding that disrupts cellular function
Categories of Accumulation (3)
- Accumulation of Normal Substances
- Accumulation of Abnormal Proteins
- Accumulation of Indigestional Particles
Normal Substances to Accumulate (3)
- Lipids
- Carbohydrates
- Proteins
Examples of Accumulating Lipids
- Chronic Alcohol Ingestion - preferentially metabolizes alcohols over lipids leading to excess fatty vacuoles in the liver (fatty liver)
- Tay-Sachs Disease
- Gaucher Syndrome
Example of Accumulating Carbohydrates
Diabetes Mellitus - impaired uptake of glucose causes it to enter filtrate and leads to excess glycogen stores in renal tubule cells
Example of Accumulating Proteins
Renal tubules accumulating proteins due to leaky glomerular capillaries, endocytosis of escaped proteins, or excess accumulation
How Abnormal Proteins Accumulate
Stress causes protein denaturation. The denatured proteins can then be fixed and refolded by things like chaperone proteins or be “murdered” via ubiquitination. If either of these pathways are not working properly, abnormal proteins can build up and accumulate in the cell.
Types of Indigestional Particles (2)
- Exogenous - tattoos, Black Lung, etc.
2. Endogenous - Bilirubin
Bilirubin Accumulation
Example of Endogenous Indigestional Particle Accumulation. Pigmented byproduct of metabolized RBCs and heme. Lots of reasons can lead to its accumulation like bad livers, excessive breakdown of RBCs, overproduction of hemoglobin, etc. If it does accumulate it causes a yellowing of the white of the eyes (sclera) and even the skin, in high levels.
What causes brain damage in neonates?
Unconjugated Bilirubin
Reasons Bilirubin Accumulates in Neonates (3)
- Rh-factor mediated hemolysis
- Lack of intestinal bacteria (metabolize conjugated bilirubin into unconjugated bilirubin which is reabsorbed)
- B-glucuronidase found in breast milk
What is done to treat neonates with bilirubin accumulation?
Phototherapy (450 nm). Breaks down Bilirubin into water soluble photoisomers that can be excreted.
Five Classes of Adaption to Stress
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
Atrophy
Decrease in size and function. Minimizes nutrient consumption, energy consumption and production, and a decrease of organelles and structures (NOT cytosol).
Causes/Example of Atrophy
Causes: Bedridden, disuse, ischemia, age, chronic injury/disease, lack of trophic signals (growth factors)
Example: Alzheimer’s, brain atrophy
Hypertrophy
Increase in size and function due to increased physiologic or mechanical demands
Hypertrophy Examples
- Increase in skeletal muscle cells size. Increased demand, increases myosin and actin, adds thickness to the cell (enlargening present cells, not adding more)
- Increase in heart muscle size to try and counteract weak muscle contractions
Hyperplasia
Increase in cell number (mitosis).
Hyperplasia Examples
- Increase in endometrial cells in response to estrogen to prepare for pregnancy
- Chronic irritation leading to calluses and corns
- RBC production when changing from low to high altitude
- Neutrophils (WBCs) increase during bacterial infections
Metaplasia
Conversion of one cell type to another. Adaptive response to chronic injury.
Metaplasia Examples
- Chronic smokers have a change from columnar with villi to stratified squamous
- Chronic acid reflux leads to cells of esophagus changing to cells of intestinal tract that produce things like goblet cells
Dysplasia
Abnormal variations in size, shape, and arrangement with no pattern. Significant change to become cancerous.
Irreversible Cell Death Reason + Paths
Injury too severe or prolonged to be repaired.
Paths:
- Apoptosis - precise & controlled, clean, via phagocytosis
- Necrosis - decomposes & “explodes,” leads to inflammation
Apoptosis
“Programmed Cell Death.” Regulated tissue recycling (remodeling) can use this to balance between cell death and mitosis of new cells. Occurs in myocardial infarcation, cancer cell death, and Alzheimer’s as well
Extrinsic Signals for Apoptosis
- Lack of survival signals activating cell (growth, cell to cell interactions, or oxygen)
- Activation of death receptors by Fas ligand.
Intrinsic Signals for Apoptosis
- DNA damage too great
- Mitochondrial failure
- Oxidative stress
- P53 protein - key signal (cancer cells don’t have)
Examples of Apoptosis
- Cellular aging leading to DNA damage and activating apoptosis signals
- Predetermined cell death by telomeres becoming too short after multiple mitotic cycles (can be offset b germ/stem cells lengthening the telomeres)
Hypoxia v.s. Ischemia
- Hypoxia - oxygen deficiency that impairs ATP production
- Ischemia - most common cause of hypoxia, faster than other methods (lung disease, RBS disorders), involves lack of waste removal and nutrient delivery
Brian + Hypoxia/Ischemia
Ischemia - most acute brain injury. Primary - stroke, secondary - vasospasm, conpression, etc.
Hypoxia - Less severe, still damaging
Neurons + Oxygen
HYPERSENSITIVE to oxygen levels. High demand of ATP (80-90% used for NA+/K+ pumps), lack of oxygen storage molecules, can’t function anaerobically
Hypoxia Events in Neurons (7)
- Lose ATP Production
- Na+/K+ Pumps Fail
- Hydropic Swelling
- Mitochondrial Failure
- Lactic Acidosis
- Excessive Glutamate
- Reperfusion
Mitochondrial Failure Events (5)
- Control of intracellular calcium lost
- Destructive proteases activated
- Oxidative stress builds leading to free radical formation
- Membrane integrity lost
- Strong signals for apoptosis
Lactic Acidosis
Lack of oxygen causing anaerobic fermentation to occur and lactic acid to build up. Damages membrane proteins and instigates apoptosis signals
Excessive Glutamate
Excitatory amino acid that is released excessively during ischemia events and induces cell injury and impacts ion channels
Ion Channels Affected by Glutamate
- AMPA - sodium floods into cell and depolarizes membrane
- NMDA - depolarized membrane causes magnesium to release. More sodium enters cell along with calcium which causes more reactive species to form and oxidative stress
Reperfusion
Presents danger in prolonged ischemic events. Increased calcium overloads cells –> oxygen radicals form –> increased damage to proteins and membranes –> triggers apoptosis
