Path Weeks 1-4

Describe cellular atrophy. What causes it? What are some examples?

Cellular atrophy is decreased cell size due to loss of cellular components. The number of cells stay the same but their size shrinks. Cellular atrophy is a response to decreased workload on the cells over time. Examples include; muscular atrophy, atrophy of glands due to not getting hormones sent to them, nerve atrophy.

Describe cellular hypertrophy. What causes it? What are some examples?

Hypertrophy is an increase in cell size (not number of cells) in response to an increased work load over time. Examples include; cardiac hypertrophy (can be beneficial or pathological due to high BP pushing agains the left ventricle)

Describe hyperplasia. What causes it? What are some examples?

Hyperplasia is an increased number of cells in a specific region or area of the body, it is a response to increased cellular stress or demand. Examples; callus on the skin, increase in hormonal stimulation to one area of the body, BPH.

Describe metaplasia. What causes it? What are some examples?

metaplasia is the replacement of one normal cell type with another normal cell type that does not belong in that region. Metaplasia is a response to a harsh environment and is not cancerous but can increase risk of cancer. Ex; chronic GERD can cause stomach cells to grow in the esophagus, airway that is frequently exposed to cig smoke can shift from ciliated epithelium into nonciliated epithelium

Describe dysplasia. What causes it? What are some examples?

Dysplasia is disordered growth of cells with no clear organization or consistent size. Ex; cervical dysplasia

Explain the process of reversible cell swelling

Cell swelling is a response to acute ischemia. When there is a sudden lack of o2, the cell goes into anaerobic metabolism and there is an influx of h2o due to osmosis. This cell swelling can be reversed if o2 supply is restored

Explain the process of necrosis

Necrosis, or cell death, occurs when there is a sudden lack of blood supply that is not quickly restored. Cell swelling occurs and the pH in the cell decreases to the point that the enzymes in the cell can not function appropriately, calcium levels in the cell rise, and the lysosomes in the cell rupture. The rupture of lysosomes causes digestive enzymes to be released and the cell begins to digest itself. Finally the cell ruptures and releases the contents of the cell into the interstitial space, this cell contents can cause cause inflammation.

What are some things that can cause cell injury or death?

• Ischemia

• Free radicals

• Physical or Chemical Agents

• Radiation

• Nutritional Imbalance

What are the types of gangrene and where do they occur?

• Coagulative necrosis occurs in the heart, kidney, and most other tissues

• Liquefactive necrosis occurs in the brain and areas where pus forms

• Fat necrosis occurs where there is adipose tissue

• Caseous necrosis is causes by Tb

• Dry Gangrene

• Wet Gangrene

• Gas Gangrene

Describe the process of apoptosis

Unlike necrosis, apoptosis is a normal and self-regulatory process.Can be triggered by death receptors on the surface of cells or by the formation of a procapase in the cell which is inactive enzymes in a normal cell. A procapase becomes a capase, which begins to dismantle the cytoskeleton of the cell. The cell then condenses and shrinks and becomes an “atopic body” which attract other cells to come phagocytosis it.

What are the clinical manifestations of inflammation and what are the mechanisms that cause them?

Heat: Caused by vasodilation at the site of the injury and the increased amount of blood flow that is entering the region

Redness: Caused by vasodilation at the site of the injury and the increased amount of blood flow that is entering the region

Pain: Prostaglandins that are released in response to injury bind to the pain receptors in the region and make the receptors more sensitive. They don’t actually cause an action potential to occur but they increase the sensitivity so that the neuron fires more easily

Swelling: Swelling is caused by the increase in hydrostatic pressure in the vessels forcing fluid and proteins out of the plasma and into the interstitial space (exudate)

What are the vascular events that occur during an inflammation response?

• Immediate vasoconstriction to achieve hemostasis

• Longer period of vasodilation in response to mast cell activation.

• Increase capillary permeability and the ability fluid and proteins to leave the vessel

What are the cellular events that occur during an inflammation response?

• All of this is happening about 6-24 hours after the injury

• Cells in the epithelium are activated. They sort of “round” and add adhesion factors to their surfaces which are helpful in binding to immune cells

• White blood cells from the blood vessels enter the tissue. Neutrophils undergo margination and diapedesis (movement of neutrophils into the interstitial space by rearranging their cytoskeletons to fit through the vessel walls)

• Chemotaxis and phagocytosis occurs (neutrophils are drawn to the site where inflammatory markers are most concentrated and then they begin to clean up the area

• Monocytes also arrive to the area and become macrophages once they enter the tissue.

What is the difference between regeneration vs. connective tissue repair

• Regeneration is when a region replaces damaged cells with active and functioning cells of the same type. Regeneration primarily occurs in the liver, bones, and skin

• Connective tissue repair is when cells are replaced but not by functioning cells, creating a scar

What is the difference between primary and secondary intention

• Primary intention: Edges of the wound are approximated, faster process

• Secondary intention: Open or gaping wound where the edges are not together. Wounds that are healing by secondary intention have to heal from the bottom up so they take much longer

What occurs at the proliferation/reconstruction phase of healing?

• This phase of healing usually occurs within several days and can last up to several weeks

• Epithelial cells migrate across the wound

• Fibroblasts are drawn to the wound by the presence of macrophages. These fibroblasts create collegen and lay it down to create a framework for the tissue to repair itself

• Angiogenesis occurs which is when new capillaries form. The capillaries sort of create “buds” that form what is called granulation tissue

What occurs during the remodeling or maturation stage? How long does it take?

• This stage usually happens about 3 weeks after the injury

• The collagen that has been deposited by fibroblasts is not in any organized structure. During remodeling, the body reorganizes the collagen fibers into a more linear structure and strengthens the area.

What are some factors that might lead to prolonged inflamation time?

• Infection

• Biofilms

• Ongoing injury or chronic inflammation

What are some factors that might lead to limited tissue healing?

• Foreign body or a large hematoma at at wound site

• Immunosuppression

• Wound dehiscence

• Poor blood supply to the area

• Localized edema or swelling

What are some systemic factors or conditions that might suppress inflammation and/or wound healing?

• High levels of glucocorticoid steroids

• Chronic stress

• Immunosupresent drugs

• AIDS

• Diabeetes

• Poor nutrition

• ETOH Use

• Elderly

• Poor profusion

• Chronic hypoxia

• Chronic ischemia

What is edema?

Excessive accumulation of fluid in the interstitial space

What are the names of the forces that move fluid in and out of capillaries? What are the key considerations in how these forces function?

Hydrostatic pressure: Pushes fluid OUT of the capillary and into the interstitial space. Tends to be stronger at the arterial end of the vessel

Blood colloid osmotic pressure: Pushes fluid and proteins out of the interstitial space and into the vessel. Stronger at the venous end

Lymph Vessels: Protein rich fluid from the interstitial space flows into these vessels and then back towards the lymph nodes.

What are the overarching causes/mechanisms that cause edema? What are some of the causes/conditions that could cause each mechanism to occur?

1. Increase the hydrostatic pressure within the vessel (more fluid pushing OUT) :

• Increasing blood flow into the arterial end of the vein

• Blocking up the venous end of the artery and creating a back up

  • Right sided heart failure

  • Venous thrombosis

  • Pressure from other source (tumor, pregnancy)

  • Paralysis (muscle contraction is inadequate to pump blood back up to heart)

2. Decrease the blood osmotic pressure (less fluid pushing IN) :

• Albumin is the primary protein that facilitates protein going back into the blood

  • Decrease, or limit the production of albumin d/t liver disease or starvation (not enough protein in the diet)

3. Increase permeability of the capillaries (fluid can get out of vessel easier)

• Inflammation

4. Poor lymphatic drainage (inability for fluid to get moved to lymph sx)

• Tumors

• Goiters

• Removal of lymph nodes

Explain the function and mechanism of ADH

• Produced in the posterior pituitary

• Managed by how concentrated fluids are

• Causes renal tubules to increase reabsorption or water

• Ultimately causes urine to be concentrated and blood to become more dilute

Explain the function and mechanism of aldosterone

• Produced in the adrenal cortex

• Released by angiotensin II when BP drops low or potassium is high

• causes reabsorption of sodium and water. Ultimately increases blood volume

What are some examples of ways fluid can leave the body?

• Urine

• Feces

• Insensible fluid loss

• Respiration

• Wound drainage or Burns

• Vommiting

• Hemorrhage

• Removal of GI fluids

If you give someone a isotonic sodium-containing fluid, were will that fluid be distributed in the body? What about a hypotonic fluid without sodium? What are examples of these types of fluids that you might give IV?

Isotonic Sodium Containing Fluid:

• One third will be in the vascular space

• Two thirds will be in the interstitial space

• None will go into the cells because you are not creating a concentration gradient for osmosis to occur

• Ex; 0.9% normal saline, Ringers lactate

Hypotonic Fluid w/o sodium:

• 1/3 of the total volume goes into the extracellular space. Of that 1/3, 2/3 is in the interstitial space and 1/3 is vascular

• 2/3 of the total volume is intracellular

• Ex; D5W

What defines clinical dehydration?

ECV deficit and Hypernatremia

What are some factors or conditions that could decrease sodium and Na+ output (causing ECV excess) ?

Renal Issues:

• Oliguria

• Acute kidney injury

• Kidney Disease

• Nephrotic Syndrome

Issues that cause excessive aldosterone (will cause retention of sodium and water):

• Heart Failure

• Cirrhosis

• Hyperaldosteronism

• Excessive black licorice injestion

Cushings Syndrome

Meds that cause renal retention of Na+

Ascites

What are some factors that could increase Na+ and water OUTPUT (causing ECV deficit)?

• Vomiting

• Diarrhea

• NG suction

• Fistula Drainage

• Use of diuretics

• Bedrest

• Adrenal insufficiency (decreases aldosterone)

• Burns

• Blood loss

• Bowel obstruction

What are some signs and symptoms of ECV Excess?

• Sudden weight gain (1 kg or more in a 24 hour period)

• Edema in the lower region of the body

• Bounding Pulse

• Distended neck veins when upright

• In infants, bulging fontanel

• Crackles or rales

• Dyspena and/or orthropena

What are signs and symptoms of ECV deficit?

• Sudden weight loss (1kg or more in 24hrs)

• Poor skin tugor

• Dry mucous membranes

• Lack of sweating or tears

• Orthostatic hypotension and tachycardia

• Slow cap refill time

• Slow small vein filling time

• Collapsing neck veins when laying down

• Thready pulse

• Suncen fontanel

• Syncope

• Oliguria

What is the normal range for serum sodium concentration and what does that value represent?

Serum Na+ represents osmolality of the blood, NOT the whole body. Normal ranges is 135-145 mEq/L

What are some factors or conditions that could cause hypernatremia? What is the overarching principle that each factor falls into?

Loss of More Water Relative to Salt:

• Diabetes insipidus (not enough ADH, peeing out too much water which makes concentration of solutes increase)

• Diarrhea

• Excessive sweating

• Tube feeding that is high in water but low in solutes

Gain of More Salt Relative to Water:

• Lack of thirst sensation or inability to respond to thirst (older adults and neonates)

• Lack of clean water

• Tube feeding that is high in solutes but low in water

• Too much hypertonic saline

What are some factors or conditions that could cause hyponatremia? What is the overarching principle that each factor falls into?

Gain of More Water Relative to Salt

• Excessive IV D5W

• Excessive tap water enemas

• Drinking large volumes of water rapidly

• Irrigation of wounds with water and not saile

• Nonselective NSAIDS

• Conditions that cause too much ADH

  • Stress or pain

  • anesthesia

  • SIADH (Syndrome of inappropriate ADH)

  • Some tumors can produce ADH

Loss of More Salt Relative to Water

• Diuretic use

• Replacing only water but not salt following sweating, vomiting, or diarrhea

What are the clinical signs and symptoms of hypernatermia and hyponatremia?

Hypernatremia:

• Thirst (sometimes)

• Oliguria

• Confusion

• In severe cases, seizures

• Coma

Hyponatremia:

• Malaise

• Nausea and vommiting

• Confusion

• Seizures (if severe

• Coma

The signs and symptoms of both are very similar, a serum sodium concentration is the most reliable indicator of what kind of imbalance you are dealing with and how to treat it.

How does potassium get into the cells? What causes potassium to leave the cells?

Drawn out of the cells:

• Acidosis

Pushed into the cells:

• Alkalosis

• Insulin

• Epinephrine

Explain what potassium secretion is and where it occurs

• Potassium secretions moves K+ out of the blood and into the renal tubules

• Aided by aldosterone

• Primarily occurs in the distal renal tubule and the start of the urine collecting duct

What is the process for potassium excretion

• Occurs in the kidneys and is flow dependent

  • Higher flow= Higher amounts of k+ in the urine= Lower amounts of K+ in the blood

• Aldosterone and glucocorticoid hormones increase the amount of K+ that gets excreted

  • Low aldosterone= excess K+ in the blood

  • Aldosterone surplus= low K+ in the blood (being excreted)

What is the normal range for K+ serum concentration?

3.5-5.0 mEq/L

What are factors or conditions that would put someone at risk for hypokalemia?

Decreased K+ intake:

• Anorexia

• No K+ by mouth (diet, NP)

Increased K+ Output:

• Diuretics (furosemide, thiazides)

• Conditions that increase aldosterone (hyperaldosteronism, heart failure, cirrhosis)

• Conditions that increase glucocorticoid steroids (Chushings, steroid medications)

• Hypomagnesemia

• Black Licorice

• Osmotic diuresis

• Diarrhea

• Laxative overuse

What are factors or conditions that could cause hyperkalemia?

Increased K+ intake:

• Rapid IV infusion

• Blood transfusion

• Deceased urine output

• Large amounts of IV penicillin

Decreased K+ Output:

• Medications

• Oliguria

• hypovolemia

• decreased aldosterone (Addisons disease, lead poisoning)

What is the clinical assessment for potassium imbalances?

Hypokalemia= Floppy

• Abdominal distention

• Decreased bowel sounds

• Constipation

• Paralytic ileus

• Polyuria

• Orthostatic hypotension

• Flaccid skeletal muscles

• Cardiac dysththmias

Hyperkalemia= Floppy

• Some intestinal cramping

• Flaccid weakness and paralysis

• Cardia. dysrhythmias and possible cardiac arrest

What are potassium rich foods?

• Apricots

• Bananas

• Cantaloupe

• Dates

• Figs

• Grapefruit

• Kiwi

• Oranges

• Peaches

• Prunes

• Rasins

• Strawberries

• Asparagus

• Beets

• Bok Choy

• Broccoli

• Carrots

• Cauliflower

• Celery

• Potatoes

• Pumpkin

• Squash

• Tomatos

• Almonds

• Brazil Nuts

• Cashews

• Molasses

• Sunflower Seeds

Where is calcium stored in the body, how does it shift between these pools?

• Ionized (active)

• Protein bound to albumin (inactive)

• Bound to organic anions like citrate (inactive)

Parathyroid hormone shifts calcium from the BONES to the BLOOD

Calcitonin shifts calcium from the BLOOD to the BONES

Calcium is absorbed in the duodenum and requires vitamin D, calcium also binds to fat which makes it unable to be absorbed by the body

What is the normal range for total Ca+ serum concentration??

9-11 mg% or 4.5-5.5 mEq/L

What are some factors or conditions that could lead to hypocalcemia?

Decreased intake or absorption:

• Malnutrition

• Vitamin D deficiency

• Antacid overuse

• Chronic diarrhea

• Steatorrhea

Increased Ca+ excretion or loss by abnormal routes:

• Steatorrhea

• Acute pancreatitis

Shift of Ca+ from plasma into bones:

• Transfusion of citrated blood

• Alkalosis

• Hypoparathyroridsm

• Hypomagnesemia

• Increased phosphate

What are some factors or conditions that could lead to hypercalcemia?

Shifting Ca+ from bones into plasma:

• Long term immobilization

• Types of cancers

• Bone Tumors

• Hyperparathyroidism

Decreased output:

• Thiazide diuretics

Increased absorption:

• Excessive vitamin D intake

What are the clinical signs and symptoms of calcium imbalances?

Hypocalcemia= Twitchy

• Positive Chvostek sign (face)

• Positive Trousseau sign (hand)

• Grmacing

• Parasthesias

• Carpal and pedal spasm

• Tetany

• Laryngospasm

• Seizures

• Dysrhythmias

Hypercalcemia= Floppy

• Anorexia

• Constipation

• Nausea and vomiting

• Weakness and fatigue

• Confusion

• Mood changes

• Polyuria

What is the normal range for a Mg+ serum lab?

1.5-2.5 mEq/L

What are the risk factors and conditions that can lead to hypomagnesimia?

Decreased Mg+ Absorption:

• Malabsorption syndromes

• Chronic diarrhea

• Steatorrhea

• Chronic malnutiton

• ETOH use

• IIeal resection (primary site of mg+ absorption)

Increased Mg+ output:

• Diauretic use

• AKI

• Diabetic ketoacidosis

• Hyperaldosteronisim

• Chronic ETOH use

• Steatorrhea

Shift into being protein bound:

• Citrated blood transfusion

What are the risk factors and conditions that can lead to hypermagnesimia?

• Excessive intake of Mg+

• Aspiration of sea water

• Oliguric kidney disease

• Adrenal insufficiency

What are the clinical signs and symptoms of magnesium imbalances?

Hypomagnesemia= Twitchy

• Positive Chvostek

• Positive Trousseau

• Hyperreflexia

• Insomnia

• Muscle excitability

• Tetany

• Dysphagia

• Nystagmus

• Seizures

• Confusion

Hypermagnesemia= Floppy

• Hypotension

• Feeling warmth

• Bradycardic

• Drowsiness

• Weakness in tendon reflexes

• Flaccid paralysis

• Decreased respiratory function

• Cardiac dysrhythmias and arrest

Of all the electrolyte imbalances, which are considered “floppy” and which are “twitchy”?

Floppy:

• Hyper and Hypo Potassium

• Hypercalcemia

• Hypermagnesemia

Twitchy:

• Hypocalcemia

• Hypomagnesemia