Medical Pathophysiology

What is Pathology?

• The study of changes in cells and tissues as a result of injury/disease

• Focus on physical changes present in diseased organs and tissues

What is Pathophysiology?

• Study of the functional changes that occur in the body as a result of injury/disease

• focusses on abnormal functioning of diseased organ with application5 Aspects of Dise to medical procedures

6 Aspects of Disease Process

• Pathogenesis

• Etiology

• Morphologic changes

• Clinical manifestations

• Diagnosis

• Clinical Course

What is Pathogenesis?

• Origination and development of illness or disease

3 Types of Etiology

Study of disease causation (why?)

1. Genetic → genes are responsible

2. Congenital → result of environmental influences that alter gene function

3. Acquired → encountered later in life produce the disease

What is a Nosocomial disease?

Acquired in healthcare

• result of exposure to infection in health care environment

What is iatrogenic disease?

Acquired in healthcare

• result of medical treatment (e.g. catheterization)

Epidemiology is what and needs to include what?

The study of disease in populations

• Incidence, Prevalence, Morbidity, Mortality

What is Endemic?

• Incidence and prevalence of a disease are predictable and stable

What is an Epidemic?

• Dramatic increase in disease incidence in a population

What is a Pandemic?

• Epidemic spreads across continents

What is Cell Atrophy?

• Decrease in the size of the cell

  • Due to: decrease in functional demand, decrease oxygen supply, removal of signals, nutritional deprivation, ageing

What is Cell Hypertrophy?

• Increase in cell size

  • Due to: increase in trophic (growth) signals, increase in demand (strength-building exercise)

What is Cell Hyperplasia?

• increase in the number of cells

  • Due to: increase in growth cells, increase in demand

What is Cell Metaplasia?

• Changing of one cell type to another

• Cells adapt to chronic or persistent stressor

• If the stimulus is removed, cells revert back to their original type

What is Cell Dysplasia?

• change is cell size, shape, uniformity, arrangement and structure

  • Response to chronic and persistent stressors

Cellular Death - Apoptosis

• involves a reduction is cell numbers by a process of self-destruction

• programmed cellular death prompted by genetic signal

• Reasons: cell age, attempt to decrease cell numbers, damaged genetic material

Cellular Death - Necrosis

• Associated with inflammation

• poor ATP production, excessive sodium, toxic chemicals accumulate

Types of Necrosis

Coagulative - protein denaturation, caused by hypoxia

Liquefactive necrosis - lysosomal digestive enzymes are released, leading to autolysis

Caseous - combination of above ^

Fat - adipose tissue, action of lipases

Gangrenous - death of tissue from severe hypoxia, bacterial invasion

Cerebral Atrophy

Pathophysiology

• Reduction is the size of cells in the cerebrum of the brain - reduction in neuron size

• Loss of neural function = neurologic disease

Clinical Manifestations

• As atrophy progresses, the associated function becomes altered

Diagnosis

• Etiology, MHx, signs and symptoms, imaging, neuro exam

Treatment

• Prevention, interruption of injury process, slowing course of disease

Cardiac Hypertrophy (Hypertrophic Cardiomyopathy)

Pathophysiology

• Monocytes don’t continue to divide and replace themselves = increased cardiac muscle mass, increasing cardiac workload

Clinical Manifestations

• variable clinical expression, left ventricle is main pump, impaired cardiac function, SOB, fainting, irregular heart rate

Diagnosis

• family MHx, screening techniques, physical exam, stress testing

Treatment

• Pharmacologic, surgery, alcohol ablation, activity restriction

Acromegaly

Increase in cell numbers (cellular hyperplasia) (abnormal growth)

Pathophysiology

• results from excessive hormonal stimulation leading to excessive growth. If negative feedback loop fails, growth-hormone secretion continues by pituitary gland

Clinical Manifestations

• Organ enlargement, excessive sweating/body odor, deep voice, snoring, skin changes, pituitary adenoma

Diagnosis

• slow and insidious, delayed diagnosis, laboratory analysis, imaging studies

Treatment

• pharmacologic, surgical, radiation therapy

Cervical Metaplasia and Dysplasia

Cells of the cervix respond to hormonal changes throughout reproductive life

Pathophysiology

• Metaplasia: changing of cells types

• Dysplasia: abnormal growth and differentiation

• High estrogen level, precancerous condition,

Clinical Manifestations

• asymptomatic, routine screening, early sexual activity

Diagnosis

• Hx, physical exam, pap spear, diagnostic test, HPV testing

Treatment

• cold therapy/surgery, hysterectomy, cone biopsy

Environmental Toxins and Cardiovascular Disease

Pathophysiology

• exposure to environmental chemicals, air pollution, cigarettes, poisonous gases

Clinical Manifestations

• aortic aneurysm, cataract, pneumonia, stroke, CHD, cancer

Diagnosis

• physical exam (reduced exercise tolerance, difficulty brething, increased heart rate), lab studies

Treatment

• stop smoking, pharmacologic treatment

What are the 3 lines of inflammatory Defense

1st: Skin and mucous membranes (physical barrier)

2nd: Inflammatory response (fever, proteins)

3rd: Immune response (antibodies, lymphocytes)

What are the 3 goals of inflammation?

1. Increase blood flow to site (vascular response)

2. Increase cells for healing at site (cellular response)

3. Remove injured tissue and prepare for tissue repair

Fluid Movement: Exudate

• high protein content and white and red blood cells

• fluid and protein leakage

• vasodilation and stasis

• increased interendothelial spaces

Fluid Movement: Transudate

• low protein content, few cells

• increased hydrostatic pressure

• decreased colloid osmotic pressure

• decreases protein synthesis

Inflammatory mediators can be derived from 2 places?

Cell derived: generated in cell plasma membrane/proteins

Plasma derived: continuously circulating

Cellular response 3 essential steps:

1. chemotaxis → moving cells to site of injury

2. cellular adherence → binding to migration site

3. cellular migration → between endothelial cells

What is Phagocytosis?

• Inflammatory cells release more inflammatory mediators  to attract more  neutrophils

• Neutrophils also release inflammatory mediators

• Aggressive process to destroy/phagocytize causative agents

• Healthy tissue is also damaged

What are the 5 cardinal signs of inflammation?

1. Redness

2. Heat

3. Swelling

4. Pain

5. Loss of function

What is the treatment of inflammation?

1. Reduce blood flow

2. decrease swelling

3. block chemical mediators

4. decrease pain

Acute Gastritis

Pathophysiology

• Inflammation of the gastric mucosa and/or poor gastric perfusion

Cause

• ingestion of irritating substances, too much stomach acid

Clinical Manifestations

• abdominal pain, heartburn, loss of appetite, nausea, vomiting, hematemesis, anemia

Diagnosis

• History, physical exam, endoscopic exam, stool analysis, blood count

Treatment

• discontinue irritation substance, decrease gastric acid production

Pancreatitis

Pathophysiology

• pancreas inflammation, injury of protective digestive feedback mechanism

Cause

• excessive alcohol consumption, gallstones, idiopathic/unknown

Clinical Manifestations

• upper abdominal pain, inflammatory response, digestive signs, nausea, vomiting, anorexia, diarrhea

Diagnosis

• physical exam, labs, imaging, blood count

Treatment

• IV hydration, can result in ICU care, nothing-by-mouth

Burn injuries

Cause

• direct contact with heat, radiation, chemicals, electricity

Classification

1. First-degree (superficial → skin damage only)

2. Second-degree (deep-partial → epidermal and upper dermal damage)

3. Third-degree (full thickness → entire thickness of skin)

Clinical Manifestations

• 1st: warmth, pain, swelling, LOF

• 2nd: blistering, edema, serous exudate

• 3rd: exudate, destroyed nerve ending

Diagnosis

• Wound depths are classified according to the affected tissue layers, critical is more than 25%

Treatment

• changing dressings, fluids/nutrition, antibiotics, cleansing, skin grafts, remove source of injury

Arthritis

Pathophysiology

• inflammation of synovial membranes, onset 36-50 years, lack of trigger, causes deformity and erosion

Clinical Manifestations

• insidious, severity, fever, 5 signs of inflammation, malalignment

Diagnosis

• no definitive test, history, physical exam, bloods

Treatment

• Pharmacologic (anti-inflammatory) and non-pharmacologic (rest, physical therapy, hot/cold therapy)

Chronic Gastritis

Pathophysiology

• Spread by H. Pylori, t-cells infiltrate gastric mucosa, intense inflammation triggered

Clinical Manifestations

• nausea, heartburn, vomiting, loss of appetite, dyspepsia (epigastric discomfort)

Diagnosis

• endoscopic exam, breath test, biopsy, low B12 in blood

Treatment

• antibiotics, raising pH, immunosuppressive drugs, intramuscular injections of B12

Chronic Pancreatitis

Pathophysiology

• ongoing inflammation to pancreas, impacts endocrine functions

Cause

• alcohol abuse, autoimmune, hereditary, idiopathic

Clinical Manifestations

• long-term abdominal pain, diarrhea, fatty stools, weight loss

Diagnostic Criteria

• Endoscopic retrograde cholangiopancreatography (gold std), amylase/lipase levels

Treatment

• pain management, lifestyle changes, surgery

Inflammatory Bowel Disease

Pathophysiology

• chronic inflammatory bowel disorders of unknown origin, Crohn’s/Ulcerative Colitis, affect digestive tract, ulcerations,

Clinical Manifestations

• quick stool transition time, fibrosis, loss of absorbative function, fever, weight loss, fatigue, abdominal pain, blood in stool

Diagnostic Criteria

• History, Physical exam, endoscopy, radiography, stool cultures to rule out infection

Treatment

• pharmacologic, dietary changes, surgery

Ulcerative Colitis

Pathophysiology

• inflammation of the colon, only in large intestine, rectum-descending colon, ulceration occurs

Clinical Manifestations

• diarrhea, rectal bleeding, abdonimcal pain, fever, weight loss, fatigue, anemia

Diagnosis

• history, physical exam, endoscopy, radiograph, blood count

Treatment

• pharmacologic, dietary changes, surgery

3 Phases of Inflammation

1. Inflammatory Phase (0-3 days)

2. Proliferative/Repair Phase (4-21 days)

3. Remodeling Phase (3wks - 6mths)

What is Hemostasis?

• vasocontraction and clot formation

• protective scab formation (thrombus)

• neutrophils move to injured site → followed by macrophages

How is wound structural integrity restored?

• ECM is formed to decrease blood/fluid loss

• attract fibroblasts, endothelial/epithelial cells

• provisional matric is converted by macrophages

• provisional matrix and granulation tissue is reabsorbed once wound is healed

Cutaneous wound healing by intention: Primary

• small wounds with approximated edges heal by primary intention (e.g. paper cut)

• heal quicker and easier

• all areas heal at same time

• scarring is minimal

Cutaneous wound healing by intention: Secondary

• large pen wounds heal by secondary intention

• heal from bottom-up

• risk for infection and scarring

Complications of Healing: Infection

• invasion by microorganisms

• impairs all dimensions of wound healing

• prolongs inflammatory response

Complications of Healing: Ulceration

• Lack of adequate perfusion

• crater-like lesion of skin or mucous membrane

Complications of Healing: Dehiscence

• problem with scar formation

• wound splits open (opens area to infection)

• early after surgery → later in recovery period

Complications of Healing: Keloids

• Hypertrophic scars: excessive collagen formation

• cosmetic problem

• removal = result in another keloid

Complications of Healing: Adhesion

• impaired collagen deposition

• main risk is due to abdominal surgery

• pain, loss of organ function, restrict free movement

What is Granuloma Formation?

Granuloma: nodular inflammatory lesion that encases harmful substance

they form when the injury causing agents are difficult to control/poorly digested, foreign bodies are present