D236 Notes on Homeostasis & Cellular Responses

D236 Notes on Homeostasis & Cellular Responses

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Western Governors University

D236 Pathophysiology

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SECTION 2: Musculoskeletal Disorders and Related Conditions

Degenerative Disc Disease (DDD)

Degenerative Disc Disease (DDD) is a common musculoskeletal condition characterized by the gradual deterioration of the intervertebral discs that provide cushioning and flexibility between vertebrae. Over time, the discs lose hydration and elasticity, reducing their shock-absorbing ability and leading to vertebral malalignment. This malalignment may increase the likelihood of spinal nerve compression, resulting in radiculopathy (nerve root pain).

When DDD affects the lumbar or sacral regions, the impingement of the sciatic nerve can produce sciatica, characterized by pain radiating down one or both legs (Huether & McCance, 2020).

Paget’s Disease of Bone

Paget’s Disease of Bone is a chronic metabolic bone disorder involving accelerated bone remodeling, where newly formed bone is abnormally structured, weak, and brittle. Many individuals remain asymptomatic until diagnosed incidentally through imaging studies.

In active stages, excessive osteoclastic activity leads to the release of large quantities of calcium into the bloodstream, potentially causing hypercalcemia. Symptoms may include bone pain, skeletal deformities, and neurological complications due to bone enlargement compressing nerves (Porter et al., 2021).

Stress Fractures

Stress fractures develop when bone resorption exceeds bone formation, typically due to repetitive mechanical stress or inadequate recovery. This is common in athletes and military personnel. Patients usually report localized pain that worsens with activity and improves with rest.

Causes	Risk Factors	Common Sites
Repetitive impact activities	Vitamin D deficiency, overtraining, poor diet	Tibia, metatarsals, femur

Rickets and Osteomalacia

Rickets (in children)

Rickets is a childhood bone disorder marked by defective mineralization of the growing skeleton, leading to soft, weak bones and skeletal deformities. The primary cause is vitamin D deficiency, though it may also result from malabsorption, liver or kidney disease, or insufficient sunlight exposure.

Typical clinical manifestations include:

• Bone pain and delayed growth

• Craniotabes (soft skull bones)

• Bow legs and protruding abdomen

Osteomalacia (in adults)

Osteomalacia occurs in adults when bone mineralization fails, producing soft, weak bones that fracture easily. Symptoms include diffuse bone and joint pain, muscle weakness, and an increased risk of pathologic fractures with minimal trauma (McCance & Huether, 2020).

Musculoskeletal Trauma

Compartment Syndrome

Compartment Syndrome occurs when elevated pressure within a closed muscle compartment compromises blood flow and nerve function. Without timely intervention, tissue ischemia, necrosis, and permanent functional loss may occur.

Clinical Signs (6 P’s):

1. Pain out of proportion to injury

2. Paresthesia

3. Pallor

4. Pulselessness

5. Poikilothermia (cool extremity)

6. Paralysis (late sign)

Causes	Complications	Diagnosis
Crush injuries, fractures, burns, tight casts or dressings	Tissue necrosis, gangrene, rhabdomyolysis, nerve damage	Compartment pressure >30 mmHg, CT, MRI, CBC

Treatment involves emergency fasciotomy, cast removal, or amputation in severe cases.

Rhabdomyolysis

Rhabdomyolysis refers to the breakdown of skeletal muscle fibers, releasing intracellular components such as myoglobin and creatine kinase into the bloodstream. Excess myoglobin can damage renal tubules, leading to acute kidney injury (AKI).

Classic Triad of Symptoms:

• Muscle pain (myalgia)

• Weakness

• Tea-colored urine (myoglobinuria)

Prompt hydration and correction of electrolyte imbalances are critical for preventing renal complications.

Sequestrum

A sequestrum is a fragment of necrotic bone that separates from healthy tissue, usually following infection or trauma. Management involves surgical debridement of necrotic tissue to facilitate healing and prevent osteomyelitis (Smeltzer et al., 2020).

Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Orthopedic surgeries and immobilization increase the risk of DVT and PE due to venous stasis and vessel injury.

Condition	Key Features	Diagnostic Tests
DVT	Edema, tenderness, warmth, palpable cord	D-dimer, Doppler ultrasound, coagulation profile
PE	Dyspnea, chest pain, cyanosis, tachypnea, hemoptysis	CT pulmonary angiogram, V/Q scan

Prevention includes early mobilization, compression stockings, and anticoagulation therapy.

Fat Embolism Syndrome (FES)

Fat Embolism Syndrome occurs when fat droplets from bone marrow enter the circulation following fractures, especially of long bones. These emboli can obstruct pulmonary or cerebral vessels, leading to respiratory distress or neurological symptoms.

Diagnostic Criteria for FES	Major Criteria	Minor Criteria
Must meet 1 major + ≥4 minor criteria + fat macroglobulinemia	Respiratory insufficiency, cerebral symptoms, petechial rash	Tachycardia, fever, retinal petechiae, renal dysfunction, jaundice, anemia, thrombocytopenia, elevated ESR

Immediate hemodynamic stabilization using fluids such as normal saline or lactated Ringer’s is essential to support perfusion and clear emboli.

Avascular Necrosis (AVN)

AVN results from the loss of blood supply to bone tissue, causing bone collapse and joint dysfunction. It commonly affects the femoral head, scaphoid, and talus. Patients experience pain, weakness, and restricted motion.

Diagnosis involves MRI or bone scintigraphy, while treatment may require core decompression or surgical removal of necrotic tissue.

Delayed Healing of Fractures

Term	Definition	Clinical Implication
Delayed Union	Bone healing takes longer than expected	Persistent pain and dysfunction
Malunion	Bone heals in an abnormal position	Deformity, impaired function
Nonunion	Failure of bone ends to unite	Requires surgical intervention

Consequences of Immobility

Prolonged immobility can have widespread physiological consequences affecting multiple systems.

System Affected	Potential Complications
Skin	Pressure ulcers, infections
Gastrointestinal	Constipation due to decreased peristalsis
Muscular	Atrophy, weakness
Skeletal	Osteoporosis, decreased bone density
Cardiovascular	Venous stasis, thromboembolism
Urinary	Stasis, kidney stones
Respiratory	Pneumonia, atelectasis
Psychological	Depression, social isolation

SECTION 3: The Nervous System (Overview)

Types of Stroke

Strokes are classified based on their underlying cause and mechanism of cerebral ischemia.

Type	Pathophysiology	Clinical Note
Ischemic Stroke	Obstruction of cerebral artery by thrombus or embolus	Most common (≈85% of all strokes)
Thrombotic Stroke	Localized arterial clot due to atherosclerosis	Develops gradually
Embolic Stroke	Traveling clot from the heart or another artery lodges in the brain	Often sudden onset
Hemorrhagic Stroke	Arterial rupture leading to intracerebral bleeding	Associated with high mortality (≈15%)

The ischemic penumbra represents salvageable brain tissue surrounding the infarct core. Timely reperfusion is critical to prevent irreversible neuronal loss (Grossman & Porth, 2021).

Neuropathies and Related Disorders

Peripheral Neuropathy

Peripheral neuropathy involves damage to peripheral nerves, resulting in sensory loss, weakness, and pain.

Type	Mechanism	Example or Cause
Demyelinating Neuropathy	Destruction of myelin sheath	Guillain-Barré Syndrome
Axonal Degeneration	Loss of axonal integrity	Diabetes mellitus, toxins

Common etiologies include diabetes mellitus, chronic alcoholism, and certain chemotherapeutic drugs.

Myasthenia Gravis

An autoimmune disorder causing skeletal muscle weakness due to antibodies targeting acetylcholine receptors at the neuromuscular junction. Characteristic symptoms include ptosis, diplopia, and fluctuating weakness that worsens with activity.

Meniere’s Disease

Meniere’s disease is an inner ear disorder leading to vertigo, tinnitus, and progressive hearing loss, caused by endolymphatic fluid imbalance within the cochlea.

Cerebrovascular and Neurological Differentiations

Condition	Definition	Key Differentiator
Aneurysm	Dilation of a cerebral artery	May rupture, leading to hemorrhage
Hemorrhage	Active bleeding within the brain tissue	Often secondary to hypertension
Hematoma	Localized blood accumulation	May cause compression symptoms
Epidural Hematoma	Bleeding between dura mater and skull	Often linked to temporal bone fracture and middle meningeal artery rupture

Study Review Summary

• Differentiate ischemic vs. hemorrhagic strokes

• Recognize musculoskeletal disorders such as MS, ALS, Myasthenia Gravis, Parkinson’s disease, and Lupus

• Understand eye and ear disorders (cataracts, glaucoma, retinal detachment, Meniere’s disease)

• Identify cardiovascular, respiratory, and endocrine system disorders by cause, mechanism, and presentation

 

SECTION 4: Cardiovascular and Hematologic Disorders

Cardiovascular System Overview

The cardiovascular system functions as a closed circulatory network, transporting oxygen, nutrients, hormones, and waste products throughout the body. It relies on synchronized cardiac electrical activity, vascular integrity, and adequate blood volume to maintain tissue perfusion. Any dysfunction within these components can lead to conditions such as hypertension, atherosclerosis, or heart failure (Huether & McCance, 2020).

Hypertension

Hypertension (HTN) is a chronic disorder characterized by a sustained elevation in arterial blood pressure, typically defined as ≥130/80 mmHg according to the American Heart Association (AHA). It is often termed the “silent killer” because it remains asymptomatic until complications arise.

Classification	Systolic (mmHg)	Diastolic (mmHg)
Normal	<120	<80
Elevated	120–129	<80
Stage 1 HTN	130–139	80–89
Stage 2 HTN	≥140	≥90
Hypertensive Crisis	≥180	≥120

Pathophysiology

Chronic hypertension causes endothelial injury, leading to arterial stiffness, increased peripheral resistance, and left ventricular hypertrophy (LVH). These structural and functional changes elevate the risk of stroke, myocardial infarction (MI), and chronic kidney disease.

Risk Factors

• Genetic predisposition

• Obesity and sedentary lifestyle

• Excessive sodium or alcohol intake

• Chronic stress

• Diabetes mellitus and hyperlipidemia

Clinical Manifestations

Most patients remain asymptomatic. When symptoms occur, they may include headache, dizziness, palpitations, or blurred vision.

Complications

• Heart: Left ventricular hypertrophy → heart failure

• Brain: Stroke, transient ischemic attack (TIA)

• Kidneys: Nephrosclerosis → renal failure

• Eyes: Hypertensive retinopathy

Management

• Lifestyle modification: low-sodium diet, exercise, stress reduction

• Pharmacologic therapy: diuretics, ACE inhibitors, ARBs, calcium channel blockers, beta-blockers

Atherosclerosis

Atherosclerosis is a progressive disease characterized by the formation of lipid-rich plaques within arterial walls. These plaques narrow the vessel lumen, impair blood flow, and may rupture, leading to thrombosis or embolization.

Pathogenesis

1. Endothelial injury (from hypertension, smoking, diabetes)

2. LDL cholesterol infiltration into the intima

3. Inflammation and foam cell formation

4. Fibrous cap development and plaque calcification

5. Plaque rupture → thrombus formation

Risk Factors

• Dyslipidemia (high LDL, low HDL)

• Hypertension

• Diabetes mellitus

• Cigarette smoking

• Obesity and sedentary behavior

Stable Plaque	Unstable Plaque
Thick fibrous cap, gradual narrowing	Thin cap, prone to rupture and thrombosis
Predictable angina	Myocardial infarction or stroke

Coronary Artery Disease (CAD)

CAD results from atherosclerotic narrowing of the coronary arteries, reducing myocardial oxygen supply. The clinical spectrum ranges from stable angina to acute coronary syndromes (ACS) such as unstable angina and myocardial infarction (MI).

Angina Pectoris

Type	Description	Trigger	Relief
Stable Angina	Predictable chest pain due to exertion	Physical or emotional stress	Rest or nitroglycerin
Unstable Angina	Pain at rest or with minimal exertion	Plaque rupture, thrombosis	Emergency intervention
Prinzmetal (Variant) Angina	Vasospasm of coronary arteries	Cold, stress, or drugs	Calcium channel blockers

Myocardial Infarction (MI)

MI occurs when blood flow to the myocardium is completely obstructed, causing cellular necrosis.

Clinical Manifestations:

• Severe chest pain (often radiating to jaw, shoulder, or arm)

• Diaphoresis, dyspnea, nausea, anxiety

• ECG changes (ST elevation or depression, abnormal Q waves)

• Elevated cardiac biomarkers (troponin I/T, CK-MB)

Complications:

• Heart failure

• Arrhythmias (ventricular tachycardia/fibrillation)

• Cardiogenic shock

• Pericarditis

Management:

• MONA (Morphine, Oxygen, Nitrates, Aspirin)

• Reperfusion therapy (thrombolytics, percutaneous coronary intervention)

• Long-term: beta-blockers, ACE inhibitors, statins, lifestyle changes

Heart Failure

Heart failure (HF) is a clinical syndrome resulting from the heart’s inability to pump sufficient blood to meet metabolic demands. It may arise from myocardial infarction, hypertension, or valvular disease.

Types of Heart Failure

Type	Pathophysiology	Key Symptoms
Left-Sided HF	LV cannot effectively eject blood → pulmonary congestion	Dyspnea, orthopnea, crackles, cough
Right-Sided HF	RV fails due to pulmonary hypertension or LV failure	Peripheral edema, ascites, hepatomegaly
Systolic HF	Decreased ejection fraction (<40%)	Fatigue, decreased contractility
Diastolic HF	Impaired ventricular relaxation	Preserved EF, pulmonary congestion

Compensatory Mechanisms

• Renin–Angiotensin–Aldosterone System (RAAS) activation

• Sympathetic nervous system stimulation

• Ventricular remodeling (initially adaptive, later maladaptive)

Treatment

• ACE inhibitors/ARBs

• Beta-blockers

• Diuretics for fluid overload

• Lifestyle modification (salt restriction, exercise, weight control)

Peripheral Arterial Disease (PAD)

PAD is the narrowing or obstruction of peripheral arteries, usually due to atherosclerosis, resulting in impaired blood flow to the extremities.

Clinical Manifestations

• Intermittent claudication (leg pain on exertion relieved by rest)

• Pallor, cold extremities, delayed capillary refill

• Absent or weak distal pulses

• Ulceration or gangrene in severe cases

Diagnostic Tests	Purpose
Ankle-Brachial Index (ABI)	<0.9 suggests PAD
Doppler Ultrasound	Detects blood flow obstruction
Angiography	Visualizes arterial blockages

Management

• Smoking cessation, exercise therapy

• Antiplatelet agents (aspirin, clopidogrel)

• Statins for lipid control

• Surgical interventions (angioplasty, bypass grafting)

Deep Vein Thrombosis (DVT)

DVT involves the formation of thrombi within deep veins, commonly in the lower extremities.

Virchow’s Triad

1. Venous stasis (immobility, long flights, bed rest)

2. Endothelial injury (trauma, surgery)

3. Hypercoagulability (cancer, pregnancy, genetic factors)

Clinical Signs

• Swelling, pain, and redness of the affected limb

• Warmth and tenderness along the vein

• Positive Homan’s sign (pain on dorsiflexion of the foot)

Complications

• Pulmonary Embolism (PE): thrombus dislodges and obstructs pulmonary circulation

• Chronic venous insufficiency

Management:

• Anticoagulants (heparin, warfarin, DOACs)

• Early ambulation

• Compression stockings

• Inferior vena cava (IVC) filter (for recurrent emboli)

Hematologic Disorders Overview

Hematologic disorders involve abnormalities of blood composition, production, or coagulation. Key conditions include anemia, polycythemia, and coagulation disorders.

Anemia

Anemia is defined as a decrease in red blood cell (RBC) count, hemoglobin concentration, or hematocrit, leading to reduced oxygen-carrying capacity.

Type	Cause	Key Features
Iron-Deficiency Anemia	Blood loss, poor diet	Microcytic, hypochromic RBCs, pallor, fatigue
Megaloblastic Anemia	Vitamin B12 or folate deficiency	Large, immature RBCs; glossitis; neurologic deficits (B12)
Hemolytic Anemia	Premature RBC destruction	Jaundice, elevated bilirubin, splenomegaly
Aplastic Anemia	Bone marrow suppression	Pancytopenia, infections, bleeding tendency

Treatment depends on the underlying cause (iron supplementation, B12 injections, transfusions).

Polycythemia

Polycythemia refers to an excessive increase in RBC mass, causing blood hyperviscosity and increased clotting risk.

Type	Mechanism	Examples
Primary (Polycythemia Vera)	Myeloproliferative disorder	JAK2 mutation
Secondary	Increased erythropoietin production	Chronic hypoxia (COPD, high altitude)

Symptoms include ruddy complexion, headache, dizziness, and thrombosis.
Treatment may involve phlebotomy or myelosuppressive therapy.

Disseminated Intravascular Coagulation (DIC)

DIC is a life-threatening condition marked by simultaneous activation of coagulation and fibrinolysis, resulting in both widespread thrombosis and bleeding.

Causes:
Sepsis, trauma, obstetric complications, malignancy, transfusion reactions.

Laboratory Findings:

• ↓ Platelet count

• ↓ Fibrinogen

• ↑ PT, aPTT, D-dimer

• Presence of schistocytes on blood smear

Management:
Treat the underlying cause, provide supportive care (fluids, oxygen), and blood product replacement (platelets, FFP) as needed.

Key Review Summary

• Differentiate hypertension, atherosclerosis, and CAD by mechanism and clinical presentation

• Recognize heart failure types and compensatory mechanisms

• Understand PAD and DVT pathophysiology and prevention

• Identify major anemias and coagulopathies by laboratory and clinical features

References

Huether, S. E., & McCance, K. L. (2020). Understanding Pathophysiology (7th ed.). Elsevier.

Porter, R. S., Kaplan, J. L., & Homeier, B. P. (2021). The Merck Manual of Diagnosis and Therapy (20th ed.). Merck Research Laboratories.

D236 Notes on Homeostasis & Cellular Responses

Smeltzer, S. C., Bare, B. G., Hinkle, J. L., & Cheever, K. H. (2020). Brunner & Suddarth’s Textbook of Medical-Surgical Nursing (15th ed.). Wolters Kluwer.

Grossman, S., & Porth, C. M. (2021). Porth’s Pathophysiology: Concepts of Altered Health States (10th ed.). Wolters Kluwer.