BIO-322 Patho Exam 1

Homeostasis

Homeostasis

State of normalcy

Balance

Equilibrium

Disease

Change from normal

Symptoms occur with a pathological state present

Homeostasis is disturbed

Disorder

Abnormality of function

Syndrome

Symptoms caused by specific disease

Ex. Runny nose and cough are symptoms of upper respiratory infection

Pathology

Study of disease

pathologist

One who studies disease

Pathogens

Microorganisms or agents that cause disease

Pathologic

Caused by disease process

Pathogenesis

Description of how a particular disease progresses

Acute

Short term with sudden onset

Chronic

Long-term, or slow healing process

Comes on gradually

Lasts a lot longer

Etiology

Cause of disease

3 categories:

1. Idiopathic

   1. Cause unknown

2. Latrogenic

   1. Problem related to treatment

   2. Ex. N/V from chemotherapy

3. Nosocomial

   1. Disease acquired from hospital

   2. Ex. UTI (most common), bedsores, upper respiratory infection, etc.

Risk factors

Increases the chances / likelihood of a patient developing a disease

2 categories:

1. Nonmodifiable

2. Modifiable

1. Age

2. Sex

3. Environment

4. Lifestyle

5. Hereditary

Risk factors

1. Age

   1. Non-modifiable

   2. Ex. Alzheimers, cardiovascular disease

2. Sex

   1. Non-modifiable

   2. Hypothyroidism is more common in women, PCOS in women

3. Environment

   1. Varied in modifiable or non-modifiable

   2. Pollution, radiation

4. Lifestyle

   1. Modifiable

   2. Tobacco, drugs, unprotected sex, stress, lack of exercise, poor diet.

5. Hereditary

   1. Non-modifiable

   2. Genetic

   3. ADHD, type 1 diabetes, Sickle cell anemia

Steps to making a diagnosis

1. Medical history

2. Physical Exam

3. Diagnostic labs and tests

Medical history in making a diagnosis

1. Chief complaint

   1. “What brought you in today?”

2. HPI

   1. History of present illness

   2. Many questions about the chief complaint (where are symptoms at, character of the pain, etc.)

   3. “OLDCARTS”

Physical exam in making a diagnosis

1. Inspection (looking at the patient)

2. Auscultation (listening to sounds made by the body)

3. Palpation (Physical touch)

4. Percussion (Tapping, often abdomen)

Diagnostic tests and labs in making a diagnosis

Blood sample and imaging

Medical History

SOAP

1. Subjective

   1. Chief complaint

   2. History of present illness (HPI)

   3. Other history (medical, surgical, family, social, medications, allergies)

2. Objective

   1. What you find based on examination/labs

   2. Physical exam, vitals, tests, labs

3. Assessment

   1. Diagnosis

   2. Taking the S and the O and coming up with a diagnosis

4. Plan

   1. Treatment plan

Nucleus

DNA synthesis

DNA transcription → RNA

Ribosomes

-Organelles

-Free floating or attached to the ER

-RNA translation → proteins

-Responsible for the translation of new proteins

Mitochondria

-Powerhouse of the cell

-Makes ATP

-Produces bulk of the cells ATP (cells energy) via Aerobic metabolism (requires oxygen) (36 ATP)

Aerobic Metabolism

-Happens in the mitochondria

-Makes 36 ATP

-Requires oxygen

-Consumes glucose and oxygen

-Oxygen + glucose = 36 ATP

-Uses glycolysis, krebs cycle, and oxidative phosphorylation

Anaerobic Metabolism

-No oxygen

-Lactic acid is produced in the cytoplasm for much less ATP (only 2 net ATP)

-Only consumes glucose

-Also produces lactic acid

-Relies solely on glycolysis

Free Radicals

-Contained in the mitochondria

-Atom (oxygen) who has an unpaired electron

-Carries a charge

-Can do damage when not in mitochondria

2 types of cellular metabolism

1. Anabolic reactions

   1. Consume energy “building” “synthesis”

   2. Ex. taking glucose molecules and building them into glycogen

2. Catabolic reactions

   1. Release energy “break down” “digestion”

   2. Ex. breaking glycogen into individual glucose molecules

What happens to a patients blood pH if they are relying heavily on anaerobic respiration/metabolism?

-Blood pH would become more acidic

What two things denature proteins?

1. Heat

2. Acid

Plasma membrane

-Has a phospholipid bilayer (semi-permeable)

-Permeable to lipid soluble molecules

-Impermeable to water soluble molecules

Lipid soluble molecules

1. Oxygen

2. T3 and T4

3. Estrogen

4. Vitamins A, D, E, and K

5. Steroid derived hormones

6. Gases (O2 and CO2)

Water soluble Molecules

1. Na+

2. K+

3. Glucose

How do water soluble molecules enter the cell?

-Channel mediated Diffusion

-Uses a carrier protein to enter

What membrane proteins help carry large molecules or water soluble molecules into the cell?

1. Receptors

2. Transporters (channels)

3. Enzymes

4. Surface markers

5. Adhesion molecules

6. Catalysts

Diffusion

-Movement of substances down its concentration gradient

-From high to low concentration

-Passive process

-Lipid soluble substances pass right through the phospholipid bilayer through simple diffusion

-Water soluble substances have to use channels to enter cell. (transmembrane protein channels)

1. Electrolytes (Na+)

2. Water

Osmosis

-Diffusion of water

-Water follows solutes

1. Pulled to area of higher solute concentration

Tonicity

The osmotic effect of a solute on a cell

-What is the extracellular fluid concentration like that the cell is submerged in

What is a isotonic solution?

-Equal amount of solutes inside and outside the cell

-No net gain or loss of water

What is a Hypotonic solution?

-Less solutes in the solution than the cell

-Water is going to want to enter the cell and it will swell

1. If it gains to much water the cell membrane can rupture

What is a hypertonic solution?

More solutes in the solution than the cell

-Water will want to exit the cell and it will shrink

-Ex. dehydration

Active Transport

-Substances move against its concentration gradient

-Requires energy (ATP)

What is the most abundant intercelluar ion?

K+

What is the most abundant extracellular ion?

Na+

How do the ion leak channels in the cell membrane work?

-Very small

-Always open

-Allow ions to move down their gradient in small amounts

1. Potassium diffuses out of the cell

2. Sodium diffuses into the cell

3. Calcium diffuses into the cell

Why are ions always moving from high to low concentrations?

They are trying to reach their electrochemical equilibrium

How does the cell reestablish that ion gradient to get back to homeostasis if these leak channels are always allowing ions to move in and out?

-Active transport

-Uses ATP

What is required to move an electrolyte against its concentration gradient?

ATP

What would happen to intracellular concentrations of K+, Na+, and Ca2+ if there was no ATP available?

-Na+ would increase

-K+ would decrease

-Ca2+ would increase

What is a negative consequence if we are not able to run our active pumps because of no ATP available?

Cell will swell due to Na+ entering the cell and being followed by water

What is a cell stressor?

Anything that can cause potential harm to the cell.

What ways does a cell try to respond to a stressor?

1. Cellular adaption

   1. Cell tries to change/adapt to the stress

2. Reversible cell injury

   1. Cell is damaged but can come back from damage

3. Irreversible cell injury

   1. If stressor is too great the cell undergoes irreversible cell injury

   2. It undergoes cell death

      1. Apoptosis (cell suicide)

      2. Necrosis

The type of cell response to cell stress depends on what?

1. The cell type

2. The type of stress

3. How long the stress is present

Persistent stress can cause cancer, malignancies, Neurodegenerative disease (neurons to degenerate), and cardiovascular disease.

What are some cell stressors?

1. Hypoxic Injury (lack of oxygen) (most common)

   1. Unintentional / intentional physical trauma

2. Oxidative stress

   1. Too many free radicals

   2. Things that lead to an increase in free radical formation include:

      1. Prolonged exposure to ionizing radiation, UV rays, and X rays

   3. Lead to the body making too many free radicals and they can lead to cell injury

3. Nutritional imbalances

   1. Not getting enough of the essential nurtrients

   2. Excess in saturated fats (atherosclerosis)

   3. Excess in sugar (type 2 diabetes)

   4. Deficiencies

      1. Anemia = iron, Vit B9, B12

      2. Scurvy = Vit C

      3. Beriberi = Vit B1 [thiamine]

      4. Pellagra = Vit B3 [Niacin]

      5. Kwashiorkor’s = protein deficiency

      6. Marasmus = low all macronutrients

4. Chemical Injury

• Exposure to toxic chemicals (ex. chemotherapy)

5. Infectious agents

• Bacterial infections, fungal infections, viral infections, parasitic infections

6. Immunologic

• Our immune system can cause cell stress/injury

• Autoimmune disease

7. Temperature extremes

• too hot or too cold can damage tissue and leave someone susceptible to cell injury.

8. Trauma

• Injured tissue can disrupt blood flow

9. Electrical injury

• Cell membrane relies on electrochemical gradient

• When someone undergoes electrical energy its disrupts cell membrane causing cell membrane to be more permeable

• Allowing these ions or additional cell contents like organelles to seep out and cause cell death

Oxidative Stress cell stressor

Too many free radicals

1. Things that lead to an increase in free radical formation include:

   1. Prolonged exposure to ionizing radiation, UV rays, and X rays

2. Lead to the body making too many free radicals and they can lead to cell injury

Nutritional imbalances cell stressor

1. Not getting enough of the essential nurtrients

2. Excess in saturated fats (atherosclerosis)

3. Excess in sugar (type 2 diabetes)

4. Deficiencies

   1. Anemia = iron, Vit B9, B12

   2. Scurvy = Vit C

   3. Beriberi = Vit B1 [thiamine]

   4. Pellagra = Vit B3 [Niacin]

   5. Kwashiorkor’s = protein deficiency

   6. Marasmus = low all macronutrients

What can happen if you have an excess of saturated fats

Atherosclerosis (plaque buildup in the arteries)

What can happen if you have a excess of sugar

Type 2 diabetes

What deficiencies cause anemia

iron, Vit B9, B12

What deficiencies cause scurvy

Vitamin C

What deficiencies cause beriberi?

Vitamin B1 [thiamine]

What deficiencies cause pellagra?

Vitamin B3 [Niacin]

What deficiency causes Kwashiorkors?

Protein deficiency

What deficiency causes Marasmus?

Low calories

Low all macronutrients

Free radicals

-Electrically uncharged atom or group of atoms having an unpaired electron (unstable)

-Can cause damage

-In the mitochondria

Categories of free radicals

1. Physiologic

2. Pathologic

Physiologic Free Radicals

-Used in electron transport chain

-Released from neutrophils and endothelial cells during inflammation to help kill the pathogen (can also cause damage to neighboring cells)

Pathologic Free radicals

-Formed by prolonged exposure to ionizing radiation

Can free radicals damage the cell membrane?

Yes, leading to cell stress and injury

What can lead to an increase in free radical formation?

1. Smoking

2. Ionizing radiation

3. Pollution

4. Inflammation

5. UV light

6. Mitochondria

What is oxidative stress?

-When the amount of free radicals is higher than antioxidants that you have

-Antioxidants can neutralize free radicals

What can neutralize free radicals?

-Antioxidants

-Can help stabilize them by giving up an electron

What happens when we have more free radicals than antioxidants?

-Oxidative stress

-Damages the cell membrane

-Damages proteins causing alterations in protein synthesis

-Damages DNA causing alterations in DNA synthesis

Examples of antioxidants

1. Vitamin C

2. Vitamin E

3. Beta-carotene

Hypoxia

-Lack of sufficient oxygen to the cell

-Most common cause of cell injury

Hypoxemic Hypoxia

-Partial pressure of oxygen is below normal because of an:

1. Environmental reason

2. Respiratory disease

Ischemic Hypoxia

-Decrease in perfusion of oxygen to a tissue

-Result of delivery to oxygen

-Ex of things that could cause:

1. Atherosclerosis (plaque buildup in arteries)

   1. Not getting enough blood through

Anemic Hypoxia

-Oxygen carrying capacity of blood

-Seen in patients with anemia

1. Lack of iron available, they are not making hemoglobin

   1. No hemoglobin = not binding, transporting oxygen

Hypoxic Hypoxia

-Due to tissue not being able to use oxygen because it has been poisoned

-Ex. cyanide poisoning

-Disrupts the electron transport chain

1. Can breath O2 in but the cells cannot utilize it

Anoxia

Total lack of oxygen

Mechanisms of cell injury (how does it unfold)

1. ATP depletion (no O2, cant make ATP)

2. Mitochondrial damage (free radicals come out)

3. Ca2+ influx (no ATP to pump it out, activates catabolic enzymes, breaks things down and leads to cell damage)

4. Accumulation of reactive oxygen species (free radicals)

5. Damage of DNA and Protein

6. Increased plasma membrane permeability (including organelles)

   1. Things can get into the cell that normally wouldnt

   2. Things can leave the cell that normally wouldnt including organelles

Effects of hypoxic cell injury

-Cell is not getting adequate amounts of ATP

1. ATP depletion

   1. Cell relies on anaerobic metabolism until glycogen stores are depleted

   2. Without ATP you cant run the active pumps

      1. Increase in Na+ and Ca2+ into the cell

      2. H20 then follows = cell swells

2. Increased intracellular Ca2+ concentrations

   1. Enters cell due to lack of ATP

   2. Increased Ca2+ levels in cell activates catabolic enzymes which break things down

   3. When catabolic enzymes break down ATP it can damage the cell membrane, nucleus, and the mitochondria

      1. Increases its permeability so free radicals can get out and damage the cell more

3. Oxygen-derived free radicals = Reactive oxygen species)

   1. destruction of cell membrane and nucleus

4. Defects in membrane permeability

   1. leakage of intracellular enzymes can be in detected in the blood

What can give us good information on a patients condition?

Amount of intracellular enzymes found in the blood

-Troponin = myocardial infraction (heart attack)

-AST, ALTP = liver failure

Hypoxia

-Decrease oxygen delivery to cells

-Lack of O2, have to rely on anaerobic respiration

1. Not making as much ATP

2. Generates Lactic acid

   1. Lowers pH (more acidic)

   2. Low pH can interrupt our normal enzyme activity (

      1. Since pH is too acidic it can damage or disrupt enzyme activity

      2. Without enzymes working it can disrupt normal cell reactions

3. Lack of ATP we cant run active transport pumps

   1. Cell starts to take in Na+ and Ca2+

   2. Water follows (cell swells)

-If cell membrane becomes damaged and leaky the intracellular enzymes start to get into the blood

1. Can be used to diagnose a patient and estimate if they have a particular cell damage and how bad the damage is

What do the different internal enzymes in the blood mean?

1. Troponin = Myocardial infraction (heart attack)

2. Amylase/lipase = pancreatitis (inflammation of pancreas)

3. ALT/AST = liver damage brought on by hepatitis

What does calcium activate

Catabolic enzymes

-including ATPase

1. Breaks down ATP

-The enzymes damage the cell membrane and the nuclease

Mechanisms of Cellular Injury

1. Reversible

2. Irreversible

What happens if calcium levels start to accumulate inside the cell?

1. Calcium is a cofactor needed to catabolic enzymes

2. Enzymes get activated with calcium

3. Break stuff down including ATPase

4. ATPase breaks down ATP

5. Cell and cell membrane are being broken down

6. As the cell membrane is being broken down we are on the line between reversible and irreversible cell injury

7. If plasma membrane gets broken down too far the cell will start to lose contents = irreversible cell injury

Reversible Cell Injury

-Hypoxia due to ischemia (lack of blood flow)

-No oxygen = decreased ATP production

-Relying on anaerobic respiration (glycolysis)

-Not high energy yielding and lactic acid is produced

-Lactic acid lowers pH (more acidic)

-pH changes affect all enzymatic activity in the cells

-May trigger apoptosis

Irreversible cell injury

-Lack of oxygen is going on for a long period of time

-Sustained anoxia (no O2)

-Increase in cell membrane permeability

-If the cell membrane becomes leaky intercellular contents can now get out (ex. enzymes)

-If you see enzymes that should be in a cell out of the cell, it is a sign that cell is damaged/injured (ex. troponin is from myocardial infarction)

How do our cells respond to stress?

-Cellular adaption

1. Reversible cell injury

2. Irreversible cell injury

-Varies based on cell type and the type of stress they have undergone

Cellular adaption

-Cell adapts/changes as a response to the stress

-Seen in tissues that generate/replicate cells very well (Epithelial tissue)

Where do we see cellular adaption in the body?

-Cells that generate/replicate cells very well

-Epithelial tissue !!

Reversible Cell Injury

-Cell undergoes some type of stress/damage

-Cell membrane always stays intact

-If stress is removed the cell goes back to normal

-If stress isn’t removed the injury may progress to irreversible

Two types of cell death

1. Apoptosis (programmed cell death)

2. Necrosis

Cellular Adaptation

-The cells response to protect itself from injury

1. Atrophy

2. Hypertrophy

3. Hyperplasia

4. Metaplasia

5. Dysplasia

Atrophy

-Cellular adaptation

-Shrinking in size

-Happens in cells that do not replicate

-EX. Neurons, Cardiac and skeletal muscle

Hypertrophy

-Cellular adaptation

-Increase in size

-Cells do not replicate just enlarge

-EX. Neurons, Cardiac and Skeletal muscle

Hyperplasia

-Cellular Adaption

-Cells increase in number

-Applies to epithelial tissue

Metaplasia

-Cellular Adaption

-Happens with epithelial tissue

-If cell injury gets reversed it goes back to normal

-One epithelial tissue that is normally supposed to be there undergoes some type of stress and responds to it by adapting to a new type of epithelial tissue

-The new tissue is less mature

-If new tissue keeps having to replicate we undergo a risk in that new cells DNA

1. More likely for mistakes if there is more turnover

   -If stressor remains it could progress to dysplasia

Dysplasia

-Cellular Adaptation

-Deranged cellular growth

-Abnormal cellular changes in the size, shape, and organization of mature cells

-Cells of abnormal shape and size

• Setting the framework for cancer

• Irreversible

What is hypertrophy caused by?

-Increased work demand

-Response to hormones

-Ex. skeletal muscle hypertrophy = bigger muscles

-Ex. High blood pressure (hypertension) increases the workload for cardiac muscle cells

• cardiac muscle cells increase