Clinical Pathophysiology Exam 3

What is DI (Diabetes Insipidus)?

Disorder caused by antidiuretic hormone insufficiency, results in excess fluid retention.

Patho of DI

Decreased ADH secretion/insensitive ADH receptor in kidney → Nephron does not reabsorb water → Body loses high amounts of water in the urine → Dehydration and hypernatremia.

Etiologies of DI

Neurogenic: Head surgery, brain tumors

Nephrogenic: Renal tubular defect, genetics, drugs

Clinical Manifestations of DI

Polyuria

Polydipsia (thirsty)

Poor skin turgor

Dry mucous membranes

Hypotension

FVD (fluid volume deficit)

Hypernatremia

Hyperosmolality

Complications of DI

Cerebral Hemorrhage

Coma

Seizures

What is SIADH?

Excessive secretion of antidiuretic hormone from the pituitary gland; results in excessive water retention.

Patho of SIADH

Excessive ADH secretion → Fluid retention by kidneys = edema → Dilutional hyponatremia

Etiologies of SIADH

Head Trauma

Tumors

Infection

Stroke

Emphysema (ectopic source of ADH)

Meningitis

Clinical Manifestations of SIADH

Weight Gain

JVD

Crackles

Decreased urine output

Edema

Hyponatremia

Hypoosmolality

Hypertension

Complications of SIADH

Heart Failure

Cerebral Edema

Coma

Seizures

What is Hyperthyroidism?

Increase in secretions of thyroid hormone. High levels of T3 and T4, low levels of TSH.

Patho of Hyperthyroidism

Body produces TSI or gland enlarges → Elevated T3 and T4 → Negative feedback inhibition of pituitary TSH → Low TSH, more hormone secreted → High basal metabolic rate.

Etiologies of Hyperthyroidism

Graves Disease: Autoimmune disorder/ Type 2 hypersensitivity

Toxic Adenoma (gland gets irritated, hyper-secretes hormones)

Toxic multinodular goiter

Clinical Manifestations of Hyperthyroidism

Nervousness

Weight Loss

Hyperactive reflexes

Diaphoresis

Muscle Cramps

Irritability

Tetany

Positive Trousseau sign

Positive Chvostek’s sign

Complications of Hyperthyroidism

Heart Failure

Heart Murmurs

What is Hypothyroidism?

Decrease in secretion of thyroid hormone. High levels of TSH and low levels of T3 and T4.

Patho of Hypothyroidism

Loss of function → Decreased production on thyroid hormone (TH) → Increased production of TSH → Slows basal metabolic rate.

Etiologies of Hypothyroidism

Congenital Thyroid Defects

Autoimmune: Hashimoto Disease

Surgical removal of the thyroid gland (most common cause)

Thyroiditis

Clinical Manifestations of Hypothyroidism

Fatigue

Weight Gain

Constipation

Delayed reflexes

Feeling cold

Sluggishness

What is Hypoparathyroidism?

Decrease in secretion of parathyroid hormone (PTH).

Patho of Hypoparathyroidism

Destruction of gland → Insufficient PTH secretion → Decrease in Ca2 levels → Low Ca2 levels.

Etiologies of Hypoparathyroidism

Damage or removal of parathyroid gland, typically when removing the thyroid gland.

Clinical Manifestations of Hypoparathyroidism

Muscle Cramps

Irritability

Tetany

Positive Trousseau Sign

Positive Chvostek’s Sign

What is Hyperparathyroidism?

Increase in secretion of parathyroid hormone (PTH).

Patho of Hyperparathyroidism

Excess secretion of PTH → Increased bone reabsorption and GI absorption of Ca2 → Feedback system fails so calcium continues to increase → High Ca2 levels

Etiologies of Hyperparathyroidism

Primary: Adenoma, gland hyperplasia (glands are irritated, hyper-secretion)

Secondary: Chronic hypocalcemia

Clinical Manifestations of Hyperparathyroidism

Deep bone pain

Pathological fractures (complication as well)

Renal Damage

Hypercalcemia

Hypophosphatemia

Kidney stones

Cardiac Dysrhythmias

What is Type 1 Diabetes Mellitus (DM 1)?

Results from destruction of pancreatic beta cells which leads to **NO** production of insulin.

Patho of Type 1 Diabetes Mellitus

Genetic/Environmental Pathway: Activation of Macrophages, T cytotoxic cells, and autoantibodies toward beta cells → Destruction of beta cells with decreased insulin secretion.

Etiologies of Type 1 Diabetes Mellitus

Genetic

Environmental

Immunological

Clinical Manifestations of Type 1 Diabetes Mellitus

Polydipsia

Polyuria

Polyphagia (excessive eating)

Weight Loss

Fatigue

Hyperglycemia

What is Type 2 Diabetes Mellitus?

Results from a decrease in beta cell number or insulin resistance.

What is Insulin Resistance?

Suboptimal response of insulin sensitive tissue (liver, muscle, adipose tissue) to insulin.

What is one of the biggest causes of Insulin Resistance?

Obesity

Patho of Type 2 Diabetes Mellitus

Genetic: Decreased activity of amylin → Decreased beta cell mass and function → Hypoinsulinemia → Increased glucagon → High Blood Sugar

Obesity: Decreased activity of ghrelin → Insulin Resistance → Increased demand for insulin synthesis leads to hyperinsulinemia → High Blood Sugar

Etiologies of Type 2 Diabetes Mellitus

Exact Unknown

Risk Factors: Obesity and Genetics

Clinical Manifestations of Type 2 Diabetes Mellitus

Polyuria

Polydipsia

Polyphagia (excessive eating)

Fatigue

Pruritus (skin irritation, itching)

Recurrent infections (in skin and mouth, yeast infections)

Acute Complications of Diabetes

Hypoglycemia

Diabetic Ketoacidosis (DKA)

Hyperosmolar Hyperglycemia Nonketotic Syndrome (HHNKS)

Hypoglycemia

Abnormally low blood glucose

**More common in Type 1 DM**

Too much or incorrectly timed insulin or exercise or not enough food

Diabetic Ketoacidosis (DKA)

High blood glucose with serum ketones (metabolic acidosis)

**More common in Type 1 DM**

Acute complication that develops quickly

Precipitated by illness, stress, noncompliance with insulin administration

Hyperosmolar Hyperglycemia Nonketotic Syndrome (HHNKS)

High blood glucose without serum ketones

**More common in Type 2 DM**

Develops slower (because the person has insulin)

Precipitated by infection, MI, stroke, acute illness which stresses the already weak functioning beta cells

Chronic Complications of Diabetes

Microvascular Disease: Diseased Capillaries

Macrovascular Disease: Diseased Arteries

Infection

Microvascular Disease: Diseased Capillaries (angiopathy)

Diabetic Retinopathy: Blindness

Diabetic Nephropathy: Kidney Failure

Diabetic Neuropathies: Nerve damage/loss of sensation in the lower extremities and feet mostly

Macrovascular Disease: Diseased Arteries

Cardiovascular Disease: CAD, angina, MI

Ischemic Stroke

Peripheral Vascular Disease: Ulcerations, gangrene, amputation

Infection (DM)

Impaired immunity, hypoxia, decrease perfusion, decreased sensation, delayed wound healing

What is Cushing’s Disease?

Hypersecretion of glucocorticoids (cortisol).

Patho of Cushing’s Disease

Loss of feedback control of ACTH secretion → Constant secretion of ACTH → Increase secretion of cortisol

Etiologies of Cushing’s Disease

ACTH Dependent: Pituitary adenoma; Ectopic secreting non-pituitary tumor (small cell in the lung)

Administration of exogenous steroids (syndrome)

Clinical Manifestations of Cushing’s Disease

Obese trunk

Moon face (edema around the face)

Buffalo hump (fat deposit near shoulder)

Hirsutism (facial hair in women)

Ecchymotic areas (bruising)

Purple straie

Hyperglycemia

What is Addison’s Disease?

Adrenocortical Hypofunction

Patho of Addison’s Disease

Autoimmune destruction of adrenal cortical cells → Adrenal atrophy → Decrease cortisol causes increased ACTH or inadequate corticosteroid and mineralocorticoid synthesis

Etiologies of Addison’s Disease

Autoimmune destruction of adrenal cortical cells.

Clinical Manifestations of Addison’s Disease

Bronze pigmentation

GI distrubances

Weakness

Postural

Hypotension

Complications of Addison’s Disease

Hyponatremia

Hyperkalemia

What is Pheochromocytoma?

Tumor of adrenal medulla resulting in excessive secretion of catecholamines.

Patho of Pheochromocytoma

Excess stimulation of alpha and beta adrenergic receptors → Increased secretion of epinephrine and norepinephrine → Increased peripheral vascular resistance.

Etiologies of Pheochromocytoma

Catecholamine secreting tumor of the adrenal medulla

Clinical Manifestations of Pheochromocytoma

Hypertension

Headache

Tachycardia

Palpitations

Diaphoresis

What is Osteoporosis?

A metabolic bone disease resulting in a reduction in density or mass of bone. Losing more bone than you’re making.

Patho of Osteoporosis

Decreased estrogen → Increase in RANKL (makes osteoclasts which eats bones) → Bone resorption greater than bone deposition → Alterations in bone microarchitecture → Loss of bone mineralization → Diminished bone mass and porous bone.

Etiologies of Osteoporosis

Primary: Postmenopausal

Secondary: Other Conditions

Clinical Manifestations of Osteoporsis

Decreased height

Compression spinal fracture

Kyphosis (spinal curvature)

Decreased bone mass measurements

Pathologic Fractures

Complications of Osetoporosis

Pathological Fractures

What is Osteomyelitis?

Infection of the bone.

Patho of Osteomyelitis

Entry of pathogen (most common Stapphylococcus aureus) and inflammatory response → Pus accumulation in bone → Bone cells become ischemic → Sequestra forms (dead bone tissue) → Involucrum (new bone formation) → Allows sinus tracts to develop and spread disease.

Etiologies of Osteomyelitis

Post-trauma

Vascular insufficiency

MVA (motor vehicle accidents)

Orthopedic hardware

Puncture wound of foot

Clinical Manifestions of Osteomyelitis

Bone pain

Malaise

Headache

Fever

Edema

Erythema over bone

Brodie Abscess (painless abscesses surrounding the wound)

Complications of Osteomyelitis

Sepsis

What is Rheumatoid Arthritis?

A chronic, progressive, systemic, autoimmune disease with inflammation of joints and deformity.

Patho of Rheumatoid Arthritis

T Lymph Activation: RANKL increases → Form pannus (what causes the destruction) → Destruction of cartilage and bone.

B Lymph Activation: Rheumatoid factor is formed and binds with IgG → Inflammatory response → Enzymes destroy collagen → Forms pannus → Destruction of cartilage and bone.

Etiologies of Rheumatoid Arthritis

Unclear

Higher in women

Autoimmune

Clinical Manifestations of Rheumatoid Arthritis

**Symmetrical** pain in small joints

Swelling

Warmth

Erythema

Anorexia/fatigue

Ulnar drift

Swan neck deformity

Boutonniere deformity

What is Osteoarthritis?

A progressive destruction of cartilage in both synovial and vertebrae joints.

Patho of Osteoarthritis

Loss of articular cartilage → Inflammatory response → New bone formation of joint margins (bone spurs) → Subchondral bone changes → Synovitis and thickening joint capsule.

Etiologies of Osteoarthritis

Risk Factors Secondary: Age, obesity, injury, repetitive trauma

Primary: Idiopathic

Clinical Manifestations of Osteoarthritis

Asymmetric join pain increases with activity

Relieved by rest

Herberden’s nodes (DIP)

Bouchard’s nodes (PIP)

What is Gout?

A metabolic disease marked by increased serum uric acid levels and joint inflammation. Acute

Patho of Gout

Body unable to metabolize purine → Leads to increased uric acid in blood → Uric acid crystals form → Deposit into joints → Inflammatory response.

Etiologies of Gout

Familial

DietC

Clinical Manifestations of Gout

Sudden onset of asymmetric joint pain, usually the big toe

Edema

Warmth

Erythema

Elevated uric acid

Fever

Complications of Gout

Kidney Stones

What is Renal Calculi (Nephrolithiasis, Kidney Stones)?

Stones along the urinary tract.

Patho of Renal Calculi

Supersaturation of one or more salts → Precipitation of the salts form a liquid to solid state → Temperature and pH changes → Growth of stone through crystallization or aggregation.

Etiologies of Renal Calculi

Gender (males are more common)

Age

Geographic Location (hotter areas)

Dehydration

Diet (high calcium, purine, uric acid)

Occupation

Clinical Manifestations of Renal Calculi

Pain in flank and abdomen

Nausea

Vomiting

Cool, clammy skin

Hematuria (frank blood, bright red)

Most common stones

Calcium

Struvite

Uric Acid

What is Acute Cystitis?

Inflammation of the bladder.

Patho of Acute Cystitis

Exposure to pathogen → Pathogen travels upwards → Causing Inflammation

Etiologies of Acute Cystitis

Escherichia Coli (most common cause of a UTI)

VUR (Vesicoureteral reflux, urine back-flow from bladder into ureters and possibly the kidneys)

Indwelling catheters

Obstruction

Clinical Manifestations of Acute Cystitis

Frequency

Dysuria (very painful)

Urgency

Lower abdominal and or suprapubic pain

Low back pain

Elderly may experience confusion and lower abdominal pain

What is Pyleonephritis?

Infection of the ureter, renal pelvis, and interstitial tissue.

Patho of Pyleonephritis

Exposure to pathogen → Pathogen ascends from lower urinary tract or bloodstream → Inflammatory process develops → WBC infiltration → Inflammation renal parenchyma.

Etiologies of Pyelonephritis

Bladder Infection

Indwelling Catheter

Renal Stones

VUR (vesicoureteral reflux)

Clinical Manifestations of Pyleonphritis

Fever

Flank pain

Chills

Dysuria

WBC’s in urine

CVA tenderness (patients typically jump)

Urgency

Frequency

What is Glomerulonphritis?

An autoimmune inflammatory process in the glomerulus.

Patho of Glomerulonephritis

Glomerulus injured from antigen-antibody complexes → Precipitates inflammatory process → inflammatory mediators damage basement membrane of glomerulus → Degenerative changes affect all renal tissue.

Etiologies of Glomerulonephritis

Immunologic (untreated strep throat, most common)

Drugs/toxins

Vascular disorders

Systemic disease

Viral causes

Clinical Manifestations of Glomerulonephritis

Headaches

Maliase

Weight gain

Hypertension

Facial edema

Proteinuria (protein in the urine)

Hematuria

Oliguria

Dysuria

Complications of Glomerulonephritis

Chronic Kidney Disease

What is Nephrotic Syndrome?

Excretion of 3.5g or more protein in the urine per day.