Pathoma 1

What are the two processes via which an organ can increase in size?

What are the two processes via which an organ can increase in size?

Hyperplasia (increase in number of cells) and hypertrophy (increase in size of cells)

Hyperplasia

Increased number of cells

Hypertrophy

Increase in cell size

What are three processes/events that occur in hypertrophy?

Gene activation, protein synthesis, production of organelles

Where do the new cells in hyperplasia come from?

Stem cells

What tissues cannot undergo hyperplasia, only hypertrophy?

Permanent tissue, i.e. skeletal muscle, cardiac muscle, nerve tissue

What is the only type of muscle that can undergo hyperplasia?

Smooth muscle (i.e. uterus)

How do cardiac myocytes respond to hypertension?

Hypertrophy, not hyperplasia

Hyperplasia that occurs due to underlying pathologic process

Pathologic hyperplasia

Pathologic hyperplasia pathway

Hyperplasia --> dysplasia --> cancer

exception is BPH

What is one exception to the rule that pathologic hyperplasia can lead to cancer?

Benign prostatic hyperplasia does not increase the risk for cancer

What leads to atrophy?

Decrease in stress

What are the two processes that cause atrophy?

A decrease in the size of cells (via ubiquitin-proteosome degradation of the cytoskeleton and autophagy) and a decrease in the number of cells (via apoptosis)

Where are the three places stem cells are found?

Bone marrow, skin, base of intestinal crypts

Ubiquitin

Protein put on intermediate filaments of the cytoskeleton to mark them for degradation in ubiquitin-proteosome degradiation (decrease cell size)

Proteosome

Destroys ubiquitin-tagged proteins, often intermediate filaments

What destroys ubiquitin tagged proteins?

Proteosomes

Autophagy

Cell consumes its own components in vacuoles, which fuse with lysozomes, whose hydrolytic enzymes break the cellular components in the vacuoles down

What are the two processes in atrophy that can decrease cell size

Ubiquitin-proteosome degradation (to decrease cytoskeleton) and autophagy (to decrease organelles)

What promotes metaplasia?

A change in stress on a cell

Epithelium

Cells that line body surfaces

What type of cells are most commonly involved in metaplasia?

Change of one type of surface epithelium to another (i.e. squamous, columnar, urethelial/transitional)

Barrett's Esophagus

Non-keratinized squamous epithelium of the esophagus becomes non-ciliated, mucin producing columnar cells (normal cell in stomach)

Is metaplasia reversible?

Yes

How does metaplasia occur?

Via reprogramming of stem cells

What type of metaplasia does not produce an increase in cancer risk?

Apocrine metaplasia of the breast, which is seen in fibrocystic change of the breast

Metaplasia to cancer pathway

Metaplasia --> dysplasia --> cancer

What vitamin deficiency can result in metaplasia?

Vitamin A deficiency

Vitamin that differentiates specialized epithelial surfaces (i.e. conjunctiva of the eye)

Vitamin A

What happens to the conjunctiva of the eye during Vitamin A deficiency?

Undergoes metaplasia from goblet cell/columnar epithelium to keratinizing squamous epithelium

Xerophthalmia

Dry eyes (caused by vitamin A deficiency and metaplasia); can lead to keratomalacia

Keratomalacia

Corneal destruction due to vitamin A deficiency; can eventually result in blindness; example of metaplasia, columnar epithelium becomes squamous, and can lead to xerophthalmia (dry eye)

Myositis ossificans

Connective tissue within muscle changes to bone during healing after a trauma; example of mesenchymal metaplasia

Example of mesenchymal (connective) tissue metaplasia

Myositis ossificans

Sign of vitamin A deficiency

Loss of night vision

Types of mesenchymal/connective tissue

Bone, blood vessels, fat, cartilage

Dysplasia

Disordered cell growth, most often referring to proliferation of precancerous cells

CIN

Cervical intraepithelial neoplasia is an example of dysplasia and is a precursor to cervical cancer

What two processes commonly lead to dysplasia?

Pathologic hyperplasia and metaplasia

Is dysplasia reversible?

Yes, if the inciting stress is relieved

Is carcinoma reversible?

No

Aplasia (and give an example)

Failure of cell production during embryogenesis; unilateral renal agenesis

Hypoplasia

Decrease in cell production during embryogenesis, resulting in a small organ

Example of hypoplasia

Streak ovary in Turner's (45 X)

When does cellular injury occur?

When stress exceeds a cells ability to adapt

What does cellular adaptation versus cellular injury depend on?

1. Type of stress 2.Severity of stress 3. Type of cell

Neurons versus skeletal muscle in ischemic injury

Neurons are highly susceptible (3-5 minutes) whereas skeletal muscle more resistant

Slowly developing ischemia versus acute ischemia

Slowly developing ischemia will lead to adaptation (i.e. renal artery atherosclerosis will result in renal atrophy) whereas acute ischemia (i.e. renal artery embolus) will result in injury

Hypoxia

Low oxygen delivery to tissues

Why does hypoxia cause problems?

Oxygen is the final electron acceptor in oxidative phosphorylation electron transport chain. Without oxygen to complete oxidative phosphorylation, low ATP results in cell injury

Name three general causes of hypoxia

Ischemia, hypoxemia, decreased oxygen carrying capacity of the blood

Ischemia

Decreased blood flow through an organ

What are three causes of ischemia?

Decreased arterial blood flow, backed up venous blood (Budd-Chiari Syndrome), shock (hypotension/low cardiac output resulting in decreased perfusion to tissues)

What is the most common cause of Budd Chiari Syndrome, and what is a second cause?

Polycythemia Vera (too many red blood cells, causing blood to be viscous and unable to flow well through hepatic vein). Second cause is lupus, due to lupus anticoagulant

Budd Chiari Syndrome

Thrombosis of hepatic vein, preventing fresh blood flowing through the liver

Hypoxemia

Low partial pressure of oxygen in the blood (PaO2 < 60 mmHg, resulting in SaO2 < 90%)

Path of oxygen from atmosphere to hemoglobin

FiO2 --> PAO2 --> PaO2 --> SaO2

Shock definition and the different types

Decreased perfusion of vital organs (cardiogenic, hypovolemic, anaphylactic, septic)

Disease where air is trapped in the lung

COPD

Example of diffusion defect

Interstitial Pulmonary Fibrosis

PaO2 and SaO2 in anemia

Normal

Anemia

Decreased RBC mass

PaO2 and SaO2 in CO poisoning

PaO2 normal; SaO2 decreased

Treatment for CO poisoning

100% O2

Cherry Red Appearance of Skin

CO poisoning

First sign of CO poisoning

Headache

PaO2 and SaO2 in Methemoglobinemia

PaO2 normal; SaO2 decreased

Drug causes of methemoglobinemia

Sulfa and nitrate drugs

Methemoglobinemia

Fe2+ oxidized to Fe3+

Two signs of methemoglobinemia

Cyanosis and chocolate colored blood

Treatment for methemoglobinemia

Methylene blue (ascorbic acid as ancillary treatment)

Population susceptible to methemoglobinemia

Newborns

Three functions low ATP (as a result of hypoxia) disrupts

Na-K pump

Ca pump

Aerobic glycolysis (pyruvate and produces 34 ATP)

Hallmark of reversible cell injury

Cellular swelling (including loss of microvilli, membrane blebbing, and decreased protein synthesis due to ribosomes popping off ER)

Goal for Ca in cytosol, and why?

Goal is to keep Ca low in the cytosol, because Ca can activate enzymes. When the Ca pump is dysfunctioning due to a lack of ATP, Ca concentration increases in the cytosol of the cell

Hallmark of irreversible cellular injury

Membrane damage (phospholipid, mitochondrial, and lysosome membrane)

Two results of phospholipid membrane damage due to low ATP

1. Enzymes leak into the blood (i.e. what you are measuring when you get troponins and LFTs) Increased Ca in the cytosol

Where is the electron transport chain?

Inner mitochondrial membrane

Two results of mitochondrial membrane damage due to low ATP

1. No electron transport chain, 2. Cytochrome c leaks into the cytosol, activating apoptosis

One result of lysosome membrane damage due to low ATP

Hydrolytic enzymes leak into the cell, are activated by Ca

Morphologic hallmark of cell death

Loss of the nucleus

Steps in losing the nucleus in cell death

Pyknosis (condensation), karyorrhexis (fragmentation), karyolysis (dissolution)

Two mechanisms of cell death

Apoptosis and necrosis

Necrosis definition

Death of a large group of cells followed by acute inflammation

What follows necrosis?

Acute inflammation and neutrophils

Necrotic tissue that remains firm, with cell shape and organ structure preserved by coagulation of proteins, but the nucleus disappears

Coagulative necrosis

What type of necrosis follows ischemic infarction in all organs except the brain?

Coagulative necrosis (liquefactive in the brain)

What is the shape and color of infarcted tissue due to ischemia/coagulative necrosis?

Wedge shaped with pale color

Two causes of acute inflammation

Infection

When can a red infarction (as opposed to pale) arise?

Blood reenters a loosely organized tissue (lungs, testicle, bowel)

What is the pathogenesis of ischemia in a testicular infarction?

The testicle twists on the spermatic cord, causing the vein to be compressed but the artery is not compressed, so blood gets backed up and fresh blood can't flow into the tissue

Necrotic tissue becomes liquefied due to enzymatic lysis of cells and proteins, causing liquefaction

Liquefactive necrosis

Three processes that present with liquefactive necrosis

Brain infarction

What causes liquefactive necrosis in the brain?

Microglial cells (equivalents of monocytes) release proteolytic enzymes, which liquefy the brain

Abscess

Walled off area of dead tissue (neutrophils inside walled off area)

Why does an abscess present with liquefactive necrosis?

Proteolytic enzymes of neutrophils liquefy the tissue

Why does pancreatitis present with liquefactive necrosis?

Proteolytic enzymes from the pancreas liquefy the parenchyma

Gangrenous necrosis

Coagulative necrosis that resembles mummified tissue

What artery is commonly occluded in diabetics, leading to gangrenous necrosis of the foot?

Popliteal artery

Wet gangrene

Superimposed infection on top of dry gangrene, resulting in liquefactive necrosis