Chapter 1 & 2 - The Cell in Health and Illness & Cell Injury, Adaptations, and Maladaptive Changes

Homeostasis

maintains balance (equilibrium) of the internal cellular environment in response to internal and external changes

Plasma membrane

Maintains the integrity of the cell and protects the ICF

acts as a barrier to the cell’s external environment and protects the internal organelles from injury

• phospholipid bilayer which contains proteins and cholesterol

• semipermeable

• core lipid region is impermeable to water but will allow lipids and oxygen through

Cellular edema

excess fluid → ICF

= more H20 in the ECF than ICF

causes swelling (edema)

Cellular dehydration

ICF fluid → out of the cell

= more H2O in the ICF than the ECF

causing shrinkage of the cells

Cytoplasm

colloidal cell internal fluid environment that contains:

• water

• ions (Na, K, Ca, Mg, PO4)

• proteins

• carbohydrates

• lipids

Glycoproteins

also called antigens (surface markings)

• allow the body to attack foreign bodies

• summons WBCs

• allergies, autoimmune diseases, transplant rejection, blood transfusion rxns

• identifying self from non self substances

• EX: RBC containing surface markers to identify an individual’s blood type. When giving the wrong blood type, the antigens provoke an attack on the cell

Na and K ions with the Plasma Membrane

• K+ ions need to be higher concentration in the ICF

  • 2 potassium ions into the cell

• Na ions need to be higher concentration in the ECF

  • 3 Sodium ions out of the cell

plasma membrane soluble to K ions, but Na? NAH

Sodium Potassium pump

3 sodium out of the cell

2 potassium into the cell

Use ATP → active transport

• establishes RMP

• maintains the fluid volume

drugs can alter the pump activity

• cardiac glycosides (inhibit Na and K pump which increases the output force of the heart and decreases contractions)

• keeps more calcium in the heart muscle cells to strengthen the force of contraction

Dysfunction of pump:

• normal osmotic pressure balance is altered

• ICF Na concentration increases and draws in water leading to edema

Mitochondria

converts organic nutrients into cell energy in the form of ATP

• contain own DNA

  • mutations in this DNA play a role in diabetes, cancer, and heart disease

• more cellular activity means more mitochondria (ie more in muscles cells)

• Aerobic metabolism: O2

  • glucose → pyruvate → Krebs

  • 34 net ATP (max)

• Anaerobic metabolism: no O2

  • glucose → pyruvate → lactic acid

  • 2 ATP

  • CLINICAL APPLICATION: symptoms of fatigue and cramping due to lactic acid buildup

Discuss what is happening microscopically to a patient with hypoxia

1. tissues are not getting Oxygen from the blood due to ischemia (lack of circulation)

2. therefore cells within these tissues get no oxygen

3. that leads to anaerobic metabolism starting

4. ribosomal protein synthesis ceases

   1. can lead to cell degeneration or death

5. only creates a net 2 ATP

6. uses a lot of energy

Symptoms: fatigue and cramping, myalgia due to lactic acid, problems with RBCs, pulmonary issues

Treatment: supplemental oxygen via cannula, simp mask, etc

Dysfunction of Ca pump leads to cell degeneration due to dysfunction of Na/K pump

free radicals

reactive oxygen species

• contain unpaired electrons which interact with and disrupt plasma membrane

broken down by perioxisomes

• formed during aerobic metabolism

Causes:

• aging

• diabetes

• cancer

• heart failure

• smoking*

lysosomes

• macrophages of WBC contains large amounts

• contain digestive enzymes such as lysozyme, proteases, and lipases

• release digestive enzymes to destroy dead cell debris in a process called autolysis

• digestive enzymes destroy foreign material ingested by macrophages in heterolysis

Lack of lysosomes:

• can increase the number of cellular debris

• *Tay Sachs disease: a lipid storage disease resulting from a deficiency in a lysosomal enzyme

  • leads to accumulation of ganglioside: lipid found in the CNS, can cause organ wide dysfunction

Proteasomes and peroxisomes

• organelles with enzymes similar to lysosomes

• Proteasomes: degrate polypeptide chains

• peroxisomes: break down long chain fatty acids and free radicals

Malfunction can lead to:

• *Adrenoleukodystrophy: dysfunctional peroxisomes → leading to fatty acid accumulation in the NS → causes slow deterioration of NS

ER

• smooth and rough

• Smooth: location for lipid production → corticosteroids, oils, and phospholipids

• Rough: ribosomes attached that synthesize proteins

ER Stress can increase risk of cancer, obesity, and diabetes

Ribosomes

small spherical organelles composed of ribosomal rRNA

• they synthesize proteins

EX:) ribosomes in pancreatic beta islet cells synthesize the proteins to make insulin

• thyroid cell ribosomes manufacture proteins that build thyroxine

Golgi

processes, packages, and secretes proteins

EX:) adrenocorticoid hormone (ACTH) (during stress), insulin (increases uptake of glucose)

1. initial protein is manufactured in ribosome and called a preprohormone

2. transferred from the ribosome to the ER → now called prohormone

3. prohormone gets converted to actual hormone

4. stored in secretory granule until cell is triggered to release the hormone

Secretory vesicles, microtubulues, and microfilaments

Secretory vesicles:

• formed from the ER Golgi apparatus

• store substances to be secreted

Microtubules

• made of tubulin

• constantly being broken down and reformed

• allow secretory vesicles to the cell’s perimeter

Microfilaments

• help cell change shape

• actin and myosin": key proteins in contractile units of muscle cells

• help with cell movement

etiology

original cause of cell alteration or disease

• infection or disease

• cells exhibit characteristic changes associated with specific etiologic agents or changes in their environment

  • extreme cold temperatures → localized frostbite → tissue necrosis

  • exposure to electrical current —> burn tissue → cause cardiac rhythm distrubances

  • alcohol abuse → liver to becomy fatty

Adaptive versus maladaptive

Compensatory changes in an attempt to maintain homeostasis versus develop maladaptive changes, which are derangements of structure or function

Pathognomonic changes

• unique identifying disease presentations

• Ex: peptic ulcer: crater formation in stomach → ulcer → diagnosed through endoscopy or autopsy

Atrophy

• decreased size

Causes:

• disuse or diminished workload

• lack of nerve stimulation

• loss fo hormonal stimulation

• inadequate nutrition

• decreased blood circulation → ischemia

• aging

  Ex: shrinking of skeletal muscle cells on individual with upper extremity paralysis

Hypertrophy

Physiological: increase in individual cell size due to training but creates an enlargement of functioning tissue mass

• stimulates angiogenesis

• increases number of mitochondria

• increases actin and myosin use

Ex: a triathalon runner notices an enlargement of the left ventricle heart muscle cells

Pathological: increase in cellular size without an increase in supportive structures

• can be maladaptive due to change in environment

Ex: individual comes in with hypertension

• BP within the aorta and systemic arterial circulation is elevated

• High aortic BP creates an increase in the workload for the left ventricle causing pathological hypertrophy

• no angiogenesis

• without new blood vessels to compensate → effects of inadequate blood flow → poor ischemia

Hyperplasia

increase in number of cells in a tissue

• only in cells capable of mitosis (epithelium and glandular tissues)

EX: pregnant patient comes in with excess breast tissue

• estrogen stimulation results in mitotic division of breast gland cells

Maladaptive hyperplasia:

• excessive tissue can have detrimental effects

• Ex: keloid formation → hyperplastic accumulation of epithelial cells and connective tissue dueing wound healing

Metaplasia

replacement of one cell type for another

Ex:) in GERD, squamous cells of the esophagus are replaced with columnar cells of the stomach because acid has travelled back up the esophagus due to acid reflux

Dysplasia

deranged cellular growth

• on histological examination dysplastic cells vary in size, shape, and architectural organization

• Ex: cervical dysplasia detected on a Pap smear → can lead to cervical cancer

Neoplasia

new growth

disorganized, uncoordinated proliferative cell growth that is cancerous

invasive and destructing to surrounding cells

• Benign: cells resemble normal cells

  • well differentiated

  • do not metastasize

  • well define borders

• Malignant:

  • poorly differentiated

  • increased liklihood of metastasis (means moving location from one body part to another)

  • poorly define borders

Causes of Cell Injury

• Hypoxia

• free radicals

• Physical agents (lacerations, falls temperature extremes, burns, electrical shock)

• chemical injury

  • Endogenous: elevated ions → high BG

  • Exogenous: drugs, pollutants, smoking

• infectious agent injury: bacteria fungi, parasites

• injurious immunological rxns: autoimmune diseases, chronic inflammation

• genetic defects: mutated DNA will transcribe in the nucleus to produce mutated RNA → abnormal proteins which can initiate apoptosis

• nutritional imbalances

Intracellular accumulations

excessive deposits can disrupt cell function

Ex: fatty liver

• xanthomas:

• xanthelasma: IC accumulation of cholesterol within the skin cells around the eyelids, usually seen in people with hypercholesterolemia

Endothelial Cell Injury

• line arterial blood vessel

• key role in vascular function

• influenced by: blood flow changes, shear, stress force, inflammatory mediators, and varied circulating substances

Secretes:

• VEGF which stimulates angiogenesis

• Nitric oxide: vasodilating substance

• Endothelin: vasoconstricting substance

can lead to atherosclerosis* →HTN, hyperglycemia, free radicals, persistent secretion of angiotensin II, hyperlipidemia

Hypertension

1. one main cause of endothelial injury

   1. Exerts a stronger than normal shearing force against endothelial membrane

      1. aneurysm: weakened area of arterial wall could rupture (common in aorta and brain)

Hyperglycemia (diabetic)

• cause of endothelial injury (reacts with the endothelium

• stimulates endothelin: vasoconstrictor

Continuous angiotensin secretion

• vasoconstrictor that increases BP force on the endothelium

Atherogenesis

• formation of atherosclerotic plaque

• injury to endothelium leads to inflammation

• WBC and platelets flood the scene

• less dilation capability of vessel

• LDL (bad cholesterol) arrives and accumulated with the WBC to form foam cells which increase plaque

• NO levels reduced leading to further blockage

Apoptosis

programmed cell death w/o any inflammation or adverse effects on surrounding tissues

Physiological:

• adult ovaries during menopause

• WBCs that participated in immune rxns

Dysfunctional:

decreased apoptosis: longer cellular life span → prostate cancer for example

increased apoptosis: increased cell deaths → spinal muscular atrophy

Necrosis

cell death bc of injury

irreversible

inflammatory rxn

Infarction

ischemic necrosis

• results from prolonged ischemia

• myocardial infarction for ex

  • 5 minutes of chest pain = URGENT

Gangrene

prolonged ischemia infarction and necrosis due to Clostridium perfringens which emits gas and destroys tissues

Interventions for Cell Injury

• transplant

• regenerative medicine with stem cells

• therapeutic and reproductive cloning