Pathophysiology: Unit 3

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Disorders of Electrolyte imbalances, Disorders of Endrocrine Function, Disorders of Nephritic Functions, and disorders of hepatic function

4 Forces that control Capillary Fluid Exchange

1. capillary Filtration Pressure
2. capillary colloidal osmotic pressure
3. colloidal osmotic pressure
4. interstitial hydrostatic pressure

Capillary Filtration Pressure

1. pushes H₂O out of capillaries into interstitial space
2. movement is through pores
3. aka Capillary Hydrostatic Pressure

Capillary Colloidal Osmotic Pressure

1. pulls H₂O into capillaries
2. osmotic pressure is generated by plasma proteins

Colloidal Osmotic Pressure

pulls H₂O out of capillaries into interstitial space

Interstitial Hydrostatic Pressure

1. opposes movement of H₂O out of capillary
2. outward movement of H₂O into interstitial spaces

What is the effect of Hypercalcemia in the RMP

1. Hyperkalemia raises RMP
2. from -10 to - 5

What effect does a K⁺ of 7.5 mEq/L have on RMP?

RMP becomes less negative, and it takes less of a stimulus in order for cells to fire.

Potassium

1. ICF ion
2. normal level is 3.5-5.0 mEq/L
3. maintains IC osmolarity
4. controls cell resting potential
5. needed for Na⁺/K⁺ pump
6. exchanged for H⁺ to buffer changes in blood pH

Primary Endocrine Disorders

endocrine dysfunction originating in target gland for production of hormone

Secondary Endocrine Disorders

target gland is normal but its function is altered by defective levels of stimulating hormones and releasing factors from pituitary gland.

Tertiary Endocrine Disorders

results from Hypothalamus dysfunction; thus pituitary and target organ are underestimated.

Syndrome of Inappropriate ADH (SIADH)

1. results from failure of negative feedback system that regulates release and inhibition of ADH
2. causes marked H₂O retention and dilutional Hyponatremia
3. can occur because of stress, pain, temperature changes, or cancer, particularly the lungs.
4. fluid restriction, furosemide (diruesis and free H₂O clearance), and lithium

Magnesium

1. normal level is 1.8-2.7 mg/dL
2. cofactor in enzymatic reactions that required for ATP reactions, DNA replication, and mRNA production
3. binds to Ca²⁺ receptors
4. can block Ca²⁺ channels

Hypoparathyroidism

1. deficient PTH secretion that can cause Hypocalcemia
2. causes are congenital absence of Parathyroid glands, after neck surgery, autoimmune, tumors, infection, and Mg Deficiency
3. Acute Manifestations: tetany, muscle cramps, spasm, convulsions, parathesis
4. Chronic Manifestations: lethargy, anxiousness, personality changes, and cataracts

Hyperparathyroidism

1. hypersecretion of PTH
2. presented as 1⁰: hyperplasia, adenoma, or carcinoma of parathyroid gland or 2⁰: hyperplasia of parathyroid gland commonly seen in renal failure
3. 1⁰ form causes: hypercalcemia, ↑ Ca²⁺ urine filtrate, and potential for development of Renal canaliculi
4. cause chronic bone resorption leading to diffuse demineralization, bone fractures, and cystic bone lesions

Parathyroid Hormone

1. regulates plasma Ca²⁺ and PO₄²⁻
2. ↑ Ca²⁺→ ↓ PTH
3. ↓ Ca²⁺ → ↑ PTH

Three major buffering systems of ECF and ICF

1. Body Proteins: can act as acid or bases, ionizable, and plasma globulin (albumin)
2. Bicarbonate Buffering system: H₂CO₃ ↔ HCO₃⁻ + H⁺, strong acid is substituted for weak acid, and will supply or excrete CO₂ as needed
3. Transcellular H⁺ - K⁺ exchange system: indirectly proportional as H⁺ moves in K⁺ moves out and vice versa

3 types of pH regulation in the body

1. ICF and ECF buffer systems
2. Respiratory control
3. renal control mechanisms

Respiratory Control

1. eliminates CO₂ into air
2. requires the use of buffer systems to produce CO₂
3. makes acute or short term adjustments but does not fully regulate pH

Renal Control Mechanisms

1. reabsorbs HCO₃²⁻
2. excretes H⁺ from fixed acids due to lipid and protein metabolism
3. uses Bicarbonate buffer system and phosphate and ammonia buffering system
3. long term pH⁺control

Bicarbonate Reabsorption

1. in ECF: H₂O + CO₂ ↔ H₂CO₃ (with carbonic anhydrase)
2. in ICF (of kidneys): H₂CO₃ ↔ HCO₃⁻ (reabsorbed into ECF) + H⁺ (excreted in urine)
3. requires Na⁺ reabsorption

PO₄²⁻ and NH₃ Buffering System

1. both used in urinary tract to eliminate H⁺
2. PO₄³⁻ system: HPO₄²⁻ + H⁺ ↔ H₂PO₄²⁻
4. NH₃ system: glutamine (amino acid) makes NH₃
NH₃ + H⁺ ↔ NH₄ ⁺, NH₄⁺ + Cl ↔ NH₄Cl (excreted into urine)

Metabolic Acidosis

1. ↓ pH caused by ↓HCO₃⁻
2. compensates by ↑ respiratory rate and ↓ CO₂
3. causes: ↑ metabolic acids - ketoacids and lactic acids that release H⁺, ↓ renal function, ↑ bicarbonate losses due to buffering of excess H⁺, and hyperchloremic acidosis

Metabolic Alkalosis

1. ↑ pH caused by ↑ HCO₃⁻
2. causes excess alkali intake, HCO₃⁻ assoc. with H⁺, Cl⁻, K⁺ loss, excessive adrenocorticosteroid hormones, and ↑ aldosterone levels.

Glomerulonephritis

1. inflammatory response is caused by immune reaction that occurs when circulating immune complexes get trapped in glomerular membrane.
2. capillary swelling becomes permeable to blood and plasma.
3. causes: acute form - strep infection, chronic - anything but strep

Nephrotic Syndrome

1. causes ↑ glomerular permeability to plasma proteins
2. characterized by massive proteinuria and lipiduria, hypoalbuminemia, general edema, and hyperlipidemia
3. lead to thrombotic complications, pulmonary edema, pleural effusions, and ascites.
4. ↓ osmotic pressure, systemic edema → glomerular damage, and overall ↓ GFR

Nephritic Syndrome

1. caused by proliferative inflammatory response of endothelial, mesangial, or epithelial cells
2. damages capillary walls
3. characterized by hematuria, ↓ glomerular filtration, azotemia (N-wastes in blood), oliguria, and hypertension

Main treatment for all types of Renal Caliculi

↑ fluid intake

Types of Renal Caliculi

1. Calcium (Oxalate and Phosphate)
2. Magnesium ammonium phosphate (struvite)
3. Uric Acid (urate)
4. Cystine

Calcium (oxalate and phosphate)

1. contributing factors: hypercalcemia and hypercalcinuria, and immobilization, hyperparathyroidism, Vitamin D intoxication, diffuse bone disease, milk-alkali syndrome, renal tubular acidosis, hyperoxaluria, and intestinal bypass surgery
2. treatment: underlying conditions, ↑ fluid, and thiazide diuretics

Magnesium ammonium phosphate (struvite)

1. contributing factors: urea splitting UTI
2. treatment: of UTI, acidification of urine, ↑ fluid

Uric Acid

1. contributing factors: formed in acid urine with pH of approximately 5.5, gout, and high purine diet
2. Treatment: allopurinol for hyperuricosuria, alkalinization of urine, ↑ fluid

Cystine

1. contributing factors: cystinuria (genetic)
2. ↑ fluid, alkalinization of urine

Urethrovesical Reflux

1. allows bacteria to ascend into ureters and kidneys
2. occurs during coughing or squatting
3. ↑ intraabdominal pressure, urine squeezes into urethra and backflows into bladder

Vesicoureteral Reflux

1. occurs in the bladder and backflows into liver
2. occurs when someone has an abnormal (rt. angled) attachment of ureter to bladder
3. urine is forced into ureter during micturition

Manifestations of Upper UTI

1. affect parachyma and pelvis of kidney - pyelonephritis

Manifestations of Acute Cystitis

1. aka bladder infection
2. frequent and urgent urination, burning pain during urination, cloudy and foul smelling

What makes bile more susceptible to digestive enzymes?

fat

Bile

1. H₂O, bilirubin, cholesterol, fatty acids, lecithin, and electrolytes
2. depends on Na⁺, Cl⁻, HCO₃⁻, and K⁺
3. emulsify dietary fats, necessary for formation of micelles transport fatty acids and fat soluble vitamins to intestinal mucosa

Kupffer Cells

1. reticuloendothelial cells that remove and phaocytize defective RBC, bacteria, and other foreign material from portal vein

Alcoholic Hepatitis

1. inflammation of liver caused by alcohol intake.
2. symptoms: loss of appetite, ascites, jaundice, weight loss, abdominal pain and tenderness
3. leads to brain damage, kidney and liver failure
4. complications: ↑ BP in portal vein, enlarged veins, hepatic encephalopathy, cirrhosis, and fluid retention

Hepatitis A

1. caused by Hep A unenveloped RNA virus
2. usually acute condition is usually self limiting rarely causing death
3. transmitted via feces
4. vaccination available

Hepatitis B

1. caused by double stranded DNA virus
2. produce acute and chronic forms that lead to cirrhosis, hepatic necrosis, and develop into Hepatitis D
3. transmitted through blood and body secretions via oral or sexual contact

Hepatitis C

1. most common cause of chronic hepatitis that leads to cirrhosis and hepatocellular cancer
2. caused by single stranded RNA virus, related to viruses that cause yellow fever and dengue fever
3. asymptomatic usually
4. drug abusers are at most risk for HCV

Hepatitis D

1. caused by RNA virus
2. manifest to acute or chronic form
3. occurs simultaneously with Hep B
4. transmission by blood or Hep B

Hepatitis E

1. caused by unenveloped single stranded RNA virus
2. Transmission by fecal oral route
3. high mortality rate among pregnant women
4. similar to Hep A

Choleostasis

1. ↓ bile flow and reduction in H₂O, bilirubin, and bile acid secretion
2. accumulates in the blood and forms plugs in ducts
3. ducts rupture and damage liver cells
4. causes ↑ bile acids in blood and skin, liver is unable to process bilirubin - itching
5. caused by cirrhosis and portal hypertension

Autodigestion of exocrine pancreas

1. activated enzymes begin to digest pancreas cells causing severe pain and inflammation
2. inflammation produces large amounts of serous exudate → hypovolemia
3. amylase and lipase appear in blood
4. areas of dead cells undergo fat necrosis - hypocalcemia
5. leads to hypovolemic shock

Congenital Hypothyroidism

1. caused by congenital loss of thyroid gland, abnormal biosynthesis of TH, and deficient TSH secretion.
2. commonly causes mental retardation in children - cretinism
3. treatment is hormone replacement

Acquired Hypothyroidism

1. slow down on metabolic processes and myxedema
2. can lead to life threatening myxedematous coma.
3. result from destruction or dysfunction of thyroid gland, pituitary dysfunction, or hypothalamus dysfunction.

Hashimoto Thyroiditis

1. autoimmune disorder where the thyroid may be destroyed in autoimmune processes
2. most common cause of hypothyroidism

Manifestations of Hypothyroidism

1. gradual onset of fatigue, weakness, weight gain with loss of appetite, and cold intolerance.
2. skin is rough, pale, dry, and yellow and hair is brittle and coarse
3. NS involvement - dullness, lethargy, and impaired memory
4. ↓ GI motility - constipation, flatulence, and abdominal distention
5. lead to life threatening myxedematous coma - endstage expression of hypothyroidism

Functions of TH

1. ↑ metabolism and protein synthesis
2. necessary for growth and development in children
3. releases T3 and T4 in the presence of I⁻
4. ↑ metabolic rate by ↑ use of glucose
5. ↑ O₂ consumption
6. ↑ blood volume, CO, and ventilation for metabolic needs
7. ↑ GI motility and appetite
8. more activation of skeletal muscle

T3 and T4

1. made in the Thyroid in with Iodine
2. carried by binding proteins
3. T3 stimulates metabolism and warms the body - active form
4. T4 in inactivated until converted into T3 by T3.
5. Exert negative feedback on Hypothalamus

Thyroid insufficiency due to lack of I⁻

1. T3 and T4 are not made
2. no negative feedback loop to hypothalamus
3. TRH and TSH continue to be made and released
4. a Goiter will result from hypertrophy and hyperplasia of thyroid cells.

Graves Disease

1. hyperthyroidism with goiter, opthalmopathy (bulging eyes), dermopathy (thicking of pretibial area)
2. autoimmune disorder characterized by abnormal stimulation of thyroid gland by thyroid stimulating Ab.
3. assoc. with myasthenia gravis and pernicious anemia.
4. lead to severe occular changes that are not reversible.

Manifestations of Cushings Syndrome

deposition of fat
1. poor wound healing
2. muscle wasting/weakness
3. bruise easily
4. osteoporotic
5. protruding abdomen
6. emotional disturbances
7. buffalo hump
8. moon face
9. ulcerations in the skin/stretchmarks
10. thin limbs

Acromegaly

1. excess GH after puberty and fusion of long bones
2. stimulation of hepatic release of IGF-1
3. most common cause of somatropic adenoma

Manifestations of Acromegaly

1. enlargement of small bones in hands and feet, membranous bones of face and skull, broad and bulbous nose, protruding lower jaw, slanting forehead, and splayed teeth.
2. enlarged larynx and respiratory tract
3. kyphosis, arthralgas, and degenerative arthritis in spine, hips, and knees
4. hypertrophy of sebaceous and sweat glands
5. enlarged heart with accelerates atherosclerosis
6. alterations in fat and carb. metabolism

Type 1 Diabetes Mellitus

1. two types autoimmune (most common) and idiopathic
2. destruction of beta cells
3. catabolic disorder - where there is lack of insulin, ↑ blood glucose, breakdown of body fats, and proteins
4. prone to ketoacidosis

Metabolic adnormalities assoc. with Type 2 Diabetes Mellitus

1. insulin resistance
2. deranged secretion of insulin
3. ↑ Glucose prod. by liver

Insulin

1. promotes uptake of glucose by cells for use and storage (glycogen)
2. prevents fat and glycogen breakdown by inhibiting gluconeogenesis
3. ↑ protein synthesis
4. ↑ fatty acid production and transport into adipose tissue
5. ↑ transport of amino acids into cell

Glucagon

1. ↑ blood glucose levels
2. initiates glucogenolysis - liver breakdown of glycogen
3. maintains blood glucose over time
4. ↑ gluconeogensis - amino acid and fatty acid breakdown in liver
5. liberates fatty acid and glycerol from adipose
6. ↑ conversion of amino acids into glucose precursors

Dawn's Phenomenon

1. ↑ fasting blood glucose or insulin requirement
2. occurs with both types of diabetes
3. associated with fluctuations of circadian rhythm

Diabetic Retinopathy

1. leading cause of retinal blindness
2. leads to cataracts

Factors of Metabolic Syndrome

1.abdominal obesity
2. ↑ blood triglyceride levels
3. ↓ HDL levels
4. Hypertension
5. ↑ fasting plasma glucose

Antidiuretic Hormone (ADH)

1. regulates H₂O output
2. aka vasopressin
3. made in hypothalamus
4. controlled by ECF osmolality and volume via osmoreceptors - senses changes in BP and volume

Respiratory Acidosis

1. ↑PCO₂ levels and H₂CO₃ with ↓ pH
2. assoc. with acute respiratory failure
3. caused by impairment of alveolar ventilation and ↑ in metabolic PCO₂
4. manifestations: hypoxemia, headache, blurred vision, tachycardia and ↑ BP, irritability, muscle twitching, lethargy, coma, and paralysis of extremities

Respiratory Alkalosis

1. ↓PCO₂ and 1⁰ deficient of H₂CO₃ with ↑pH
2. caused by hyperventilation and ↑ respiratory rate to maintain normal PCO₂
3. commonly found in mechanical ventilation
4. Manifestations: Hyperexcitability of NS, ↓ cerebral blood flow, ↑ protein binding Ca²⁺, light headedness, dizziness, tingling, and tetany

Urinary Tract Infections (UTI)

1. bacteria usually enter through the urethra
2. 2nd most common bacterial infection, most common in women
3. Risk Factors: Host agent interactions, obstruction or reflux, catheter induced Infection
4. can affect lower and upper urinary tracts
5. manifestations: frequent urination, burning pain during urination, and cloudy and foul smelling urine.

Host Defenses in the Urinary tract

1. washout phenomenon
2. mucin layer - lines bladder and protects against infection
3. local immune responses
4. normal bacterial flora

Gallbladder

1. pear shaped muscular sac located on ventral surface of liver
2. functions to store and concentrate bile

Where is insulin made?

made in Beta cells of the islets of langerhans in Pancreas

Choleolithiasis

1. gallstones
2. caused by precipitation of substances contained in bile, mainly cholesterol and bilirubin
3. contributing factors: abnormal bile composition, bile stasis, inflammation of gallbladder
4. obstructs bile flow
5. manifestations: indigestion, biliary colic, jaundice, abrupt and sudden pain in the upper rt. quad.

Exocrine Pancreas

1. made of lobules that consist of acinar cells
2.acini produce inactivated digestive enzymes, trypsin inactivator, bicarbonate (antacid)
3. sent to duodenum

Endocrine Pancreas

1. hormonal control of blood glucose levels
2. islets of langerhans secrete glucose regulating hormones
3. beta cells secrete insulin and amylin
4. alpha cells secrete glucagon
5. delta cells secrete somatostatin
6. PP cell secretes pancreatic polypeptide

Simple Goiter

1. ↑ size of thyroid gland due to lack of iodine that does not allow formation of T3 and T4 cells.
2. TSH is constantly releases due to ↓ levels of T3 and T4, making Thyroid cells to hypertrophy and hyperplasia.

Hyperthyroidism

1. causes thyrotoxicosis that leads to thyroid crisis or storm
2. due to hyperactivity of thyroid gland
3. most common cause of Graves Disease
4. Manifestations: excessive sympathetic NS activity, enhanced sensitivity to catecholamines, nervousness, irritability, and fatigue, and Cardiovascular: tachycardia, palpitations, dyspnea, excessive sweating, muscle cramps, and heat intolerance

Hypopituitarism

1. ↓ secretion of pituitary hormones
2. typical loss pattern: GH→LH and FSH → TSH → ACTH
3. symptoms: chronically unfit, weakness, fatigue, loss of appetite, impaired sexual function, and cold intolerance

Cushings Syndrome

1. results form hypercortisolism
2. 3 causes: pituitary tumor → ACTH, benign and malignant adrenal tumors, ectopic cushing syndrome → ↑ release of ACTH without tumor
3. Other manifestations: deranged glucose metabolism that leads to diabetes mellitus, hypokalemia, and hypertension; inhibited inflamm. and immune responses; gastric bleeding and ulceration; hirsutism, mild acne, and menstrual irregularity due to ↑ androgens; and extreme emotional liability due to ↑ glucocortcoids

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