Pathophysiology Exam #4

renal system organs

kidneys, ureters, bladder, urethra

kidney parts

8-18 lobes

1.3 million nephrons

filters ~1100 mL of blood/min

kidney job

regulates osmolarity

regulates long-term acid/base balance

secretes EPO for stimulation of RBC production

produce a protein-free urine

why is it good the kidneys are outside the peritoneal space?

1. more protected

2. protects peritoneal cavity from injury through urine and waste products

renal blood supply

25% of cardiac output

renal artery arises from aorta and divides into segmental, interlobular, arcuate, and cortical arteries which then divide into afferent arterioles

afferent arteriole

supples blood to the 1.3 million nephrons

enter glomerulus and has a larger diameter than the efferent arteriole

control the flow and pressure of blood in the glomerulus

efferent arteriole

exits the glomerulus

smaller so there is resistance to blood flow as it exits

increased glomerular pressure → forms filtrate

fluid exiting contains blood, solutes, and water that was not filered and return them to the circulation

why is it important that the efferent glomerular capillary is an arteriole rather than a venule?

1. venules do not normally constrict

2. they are both arterioles so there is the ability to constrict or dilate allowing for continuous glomerular capillary pressure regardless of fluctuations of blood flow

hydrostatic pressure in the glomerular capillaries

3x hight than other capillary beds

difference in diameters between afferent and efferent arterioles

filtration fraction

amount of blood plasma in the afferent arterioles that ends up as glomerular filtrate

normal: 16-20%

nephrons

functional unit of the kidney

clense the blood by taking filtrate and forming it into urine through the process of filtration, reabsorption, secretion (renin, erythropoietin, & calcidiol), excretion

nephron function over a life span

adults lose 10% of nephrons for each decade after 40 years

cortical nephrons

85%

short, thick loops of Henle

excretory and regulatory function

juxtamedullary nephrons

15%

larger and have longer, thinner loops of Henle

primary site of urine concentration or dilution

glomerulus

receives blood from the afferent arteriole

1. glomeruluar capillary membrane is composed of three layers and has the highest filtration rate of any capillary bed in the body

   1. fenestrated capillary endothelial layer

      1. pores in the endothelial cells so that small molecules can pass through quickly and easily but large particles are prevented from being filtered

   2. basement membrane

   3. epithelial foot processes (podocytes)

2. allows substances to diffuse based on size

   1. allow many substances to diffuse or filter from the blood based on size

   2. if urine contains RBCs or proteins like albumin?

      1. there is a problem with the kidney

3. Filtrate and glomerular filtration rate: filtered fluid is forced into bowman’s capsule and is then known as filtrate

4. between 90-125 mL/min of filtrate is formed each minute and is known as GFR

GFR

total amount of filtrate formed by two million renal corpuscles

finely controlled

men filter ~180 L/day

women filter ~150 L/day

Bowman’s capsule

surrounds the glomerulus and is a double-walled space

composed of inner visceral and outer parietal layers

bowman’s space

space inside bowman’s capsule

PCT

reabsorption beings as soon as the filtrate enter the PCT

reabsorption returns 99% of all filtrate back to the bloodstream

most foreign substances are excreted

loop of henle

transports flitrate from the PCT to the DCT and concentrates or dilutes urine

descending limb

highly permeable to water but completely impermeable to ions

large amount of water is reabsorbed back into circulation here

ascending limb

impermeable to water but is highly permeable to ions

most solutes are returned to the circulation

cells full of mitochondria are used to generate energy (powerhouse of the LOH)

use energy to pump sodium-chloride out of the filtrate (water cannot follow→filtrate less osmostic)

DCT

most water reabsorption in this segments occurs in the initial portion of the DCT under the influence of ADH

sodium reabsorption is under the regulation of aldosterone

maintaines blood pH and electrolyte balances

collecting duct

reabsorbs solutes and water (ADH) from filtrate PRN by body

autosomal dominant polycystic kidney disease

adult polycystic disease

manifested by destructive large bilateral fluid-filled cysts in the kidneys where kidney function slowly declines

diagnosed based on family history, total kidney volume, and ultrasound evaluation

ADPKD pathophysiology

cysts rise from the endothelial cells

when they grow a few millimeters in size, they separate, detach, and continue to fill wth fluid secretion

ADPKD physical assessment findings

high BP

CV complications

compression of intrarenal blood vessels activating the RAAS

flank or abdominal pain is the most common

HTN

hematuria

cerebral aneurysms

ADPKD management

no cure

drink 2-3 L/day water

low sodium diet

control HTN

screen for aneurysms

autosomal recessive polycystic kidney disease (ARPKD)

diagnosed early in life→many die within hours of birth

manifests as enlarged kidney→life threatening breathing problems

growth failure

low amniotic fluid

no curative treatment→support RR, salt restriction, diuretics for edema, dialysis

renal caliculi

stones can form in any part of the urinary tract and in the kidneys and are the most common cause of upper UTI

made when particles in urine crystallize to form stones (inadequate hydration/low urine volume)

calcium oxalate

75-80%

associated with higher serum calcium levels and lower levels of citrate in the blood and urine

citrate is a natural stone inhibitor and when present, it decreases calcium crystallization

conditions that can cause higher serum calcium levels include excessive bone reabsorption through immobility, bone disease, hyperparathyroidism, tubular renal acidosis

form when pH is <7.2

struvite stones (infection stones)

5-15%

results of UTI by urease-forming organisms

bacteria breaks down urea resulting in very alkaline urine which prmotes stone development

only stone that forms in alkaline environment >7.2

uric acid stones

7%

low urine pH <5

high intake of purine foods

increased BMI

Crystine stones

1-3%

cystine is an amino acid important in making the protein found in nails, collagen, hair

cystinuria is a rare genetic disorder that causes cystine to build

develop acids pH

tx: urine alkalinization

kidney stone manifestations

pain is predominate

1. renal colic: severe pain caused by a stone in the urinary system. pain acute, intermittent, excruciating pain in the flank and upper outer quadrant of the abdomen

2. non-colicky renal pain: produced by stones and distension of the renal calyces or renal pelvis. pain is deep, dull ache in the flank or back ranging from mild to severe. worse when drinking large amount of water

kidney stone treatment

mostly supportive

stones less than 5mm in diameter can pass spontaneously

percutaneous nephrolithotomy for treatment of renal or proximal ureteral calicular or lithotripsy

UTI

bacterial infection

lower: cystitis

upper: pyelonephritis

UTI pathogenesis

e. coli through urethra is most common

bloodstream or from intestinal fistula also

increased risk: impaired bladder emptying, sexually active women, post menopausal women, men is prostate disease, older adults, spermicides

UTI clinical manifestations

malaise, nocturia, fever, frequency, lower abdominal back discomfort, burning and pain on urination, cloudy, bloody, foul smelling urine

alterned mental status

UTI diagnosis

10,000/mL of bacteria is diagnostic for UTI

elevated leukocyte esterase level should get urine culture and sensitivity test

urine culture obtained for nitrite levels

• bacteria reduce nitrates in the urine to nitrites

• nitrite level supports presence of bacteria

acute pyelonephritis

gram-negative bacterial infection causing inflammation of the kidneys and ascending urinary tract

AP manifestation

chills, fever, nausea/vomiting, burning with urination, increased frequency, urgency, flank pain

AP treatment

IV antibiotics and IV hydration

wilms tumor (nephrobastoma)

most common pediatric renal and abdominal cancer

manifests as abdominal mass with pain

UTI, HTN, fever, anemia

treatment requires nephroectomy followed by systemic chemotherapy

increased risk for invastive breast cancer

renal cell cancer (RCC)

most common malignant kidney tumor

strongest risk factor is smoking and then obesity

arises from epithelial cells of the nephron

flank pain, hematuria, flank fullness, possible swelling of the testicle with engorged varicose vein

diagnosed by ultrasound, CT, MRI

surgical resection

acute kidney injury (AKI)

sudden and often reversible reduction in the kidney function reflected by increased creatinine levels and below normal urine output

NRR: 0.3-1.5 mg/dL

acute kidney injury (AKI) definition

1. increased serum creatinine by 0.3 mg/dL or more within the last 48 hrs

2. increase in serum creatinine to 1.5 times more of baseline within the prior seven days

3. urine volume less than 0.5 mL/kg/hr for at least 6 hours

prerenal AKI

any factor that reduces blood flow to the kidneys

hypoperfusion of any cause

drop in BP or volume (hemorrhage, hypovolemia, severe burns…)

AVOID: diuretics and NSAIDS

intrarenal AKI

factors that affect the glomerulus or the tubule

can be direct injury from NSAIDS or prolonged pre-renal injury which converts to intrarenal if renal ischemia extended

• HTN emergency

• glomerulonephritis

• ATN from sepsis

• rhabdomyolysis

AVOID: aminoglycosides, vanc, amphotericin B, high-molecular weight contrast

post-renal AKI

anything that obstructs urine leaving the body

AKI pathophysiology

commonly seen in hospitalized pt

requires frequent monitoring of drugs levels

AKI phases

1. onset phase: lasts hours to days → tubular injury occurs

2. oliguric (anuric) phase: lasts 8-14+ days

   1. marked decrease in GFR

   2. urine output at lowest

   3. edema, water intox, HTN, pulmonary congestion

3. diuretic phase: kidneys try to heal and UO beings to increase

   1. urine output higher than clearance of waste products

   2. UO increases to 400 mL/day

4. recovery phase: renal function beings to improve with normalization of fluid and electrolyte balances

AKI dx and tx

watching UO and serum blood levels of BUN and creatinine is important

may been hemodialysis or continuous renal replacement therapy to keep electrolytes and water balance in control

how to differentiate if kidney dysfunction is pre-renal

give fluid, if urine output increases, we know it is pre-renal

CKD

presence of kidney damage or estimated GFR of <60 mL/min/m² persisting for 3+ months

classifications of CKD (values)

1. GFR >90 mL/min → mild kidney damage

2. GFR 60-89 mL/min → mild renal insufficiency

3. GFR 30-59 mL/min → moderate renal insufficiency

4. GFR 15-29 mL/min → severe renal insufficiency

5. GFR <15 mL/min → near total kidney failure

CKD manifestation

high BUN, imbalances in electrolytes, acid-base balance, anemia, coagulation disorders, HTN, skin integrity issues, neurological complications, immune disorders

CKD treatment

slow rate of nephron destruction

• treat urinary infections quickly

• control BP

• control BS

• stop smoking

when are dialysis and transplantation indicated?

GFR lower than 15 mL/min

exocrine glands

secrete substances into ducts that carry their secretory produce to the surface

sweat, sebaceous, mammary glands, digestive enzymes

NOT part of the endocrine system

endocrine glands

ductless, secreting directly in the blood stream

hypothalamus

master switchboard

secretes both releasing and inhibiting hormones to the anterior pituitary

hypo releases TRH which stimulates the ant. pituitary to secrete TSH. TSH stimulates the thyroid gland to release thyroid hormone (t3 and t4)

pituitary

controls functions of the greatest number of target glands and cells

anterior pituitary

FSH, LH, ACTH, TSH, prolactin, GH

posterior pituitary

stores hormones only

ADH (regulates serum osmolarity) and oxytocin increases contractions during childbirth & lactation

thyroid gland

two lobes

functions to synthesize and store TH

TSH stimulates T3 and T4 secretion

TH is crucial throughout the entire life of client

helps develop the brain in childhood and drives the metabolic function of nearly all body organs (major effect on bones, heart, and metabolism

when the thyroid increases in size d/t dysfunction it can be felt under the skin at the neck

parathyroid gland

vital for maintaining blood calcium homeostasis and phosphate levels

functions to produce and secrete PTH

PTH inhibits osteoblast activity and stimulates osteoclast activity leading to bone breakdown and calcium release into the blood

PTH and blood serum Ca+ are inversely proportional

PTH controls Ca+ level

at low blood serum Ca+ levels

PTH and vitamin D work to mobilize calcium stores and increase calcium absorption

increases serum blood calcium levels by breaking down bones which release calcium

high blood serum Ca+ levels

PTH receptors are bound which inhibits production and release of more PTH

stops the release of calcium from bones

thymus

responsible for the production and maturation of immune WBCs

starts making T-cells before birth and is most active during childhood

adrenal glands

regulate the body’s stress response, control BP, and maintain the body’s water, sodium, and potassium levels

release aldosterone, cortisol, epinephrine, & norepinephrine

aldosterone

mineralocorticoid hormone for sodium reabsorption and potassium excretion

cortisol

glucocorticoid hormone acts to increase glucose levels in the body

can increase appetite

raises BP, decreases bone formation, decreases inflammatory and immune responses

epinephrine

released in times of great stress

increases CO and increase or decrease SVR (afterload)

norepinephrine

potent vasoconstriction and mild increase in CO

how much insulin do lean, healthy adults release every day?

normal amount of insulin is 18-40 units/day. this is a basal secretion of 0.5-1.0 units/hr

every unit of regular insulin should drop BS by about 30 units

steady-state

release where blood levels of hormones fluctuate very little

intermittent

release where hormones are released in relatively large amounts but only as needed

diurnal

release based on time of day

ACTH acts on adrenal cortex to produce cortisol

cortisol is higher in the morning and lower at night

normal body growth hormones

GH, TH, insulin, androgens

GH linear bone growth in children

thyroid disorders

TSH from the pituitary gland is the stimulus for the thyroid gland to release t3 and t4 into the blood stream

only free t3 or t4 can enter target cells

hyperthyroidism

excess thyroid hormone production

risk: woman, smoking, iodine deficiency, iodine excess, genetic factors, drugs

30-50 years

graves disease

most common, causes increased production and release of THs

manifests: hyperthyroidism, goiter, ophthalmopathy 1/3 of clients

hypermetabolic state: weight loss, palpitations, tremors, heat intolerance, dyspnea, increase anxiety, irritability, fatigue, muscle weakness, increase frequency of bowel movements, hair loss, loss of libido, menstrual changes

treatment: thyroid gland can be destroyed by radioactive iodine. beta blockers can be given for palpitations, anxiety, and tremor

thyroid storm

rare, potentially life-threatening complication of hyperthyroidism

preceded by stress (infection), physical or emotional trauma, manipulation of hyperactive thyroid gland

manifests: extremely high fever, tachycardia, CHF, angina, agitation, psychosis, restlessness, delirium

treatment: must be stabilized hemodynamically and treated aggressively

management:

1. propylthiouracil: blocks new hormone synthesis

2. propanolol: blocks conversion of t4 to t3

3. prednisone: blocks conversion of t4 to t3

4. potassium iodide: blocks new hormone synthesis and hormone release

aspirin should be avoided in treatment as it increases TH levels of free TH

hypothyroidism

low level of TH d/t congenital or acquired causes

shortage of dietary iodine most common cause

hashimoto thyroiditis

autoimmune disorder where the immune system destroys the thyroid gland

iodine level is normal

at onset, goiter may be present

manifests as:

1. feeling cold, constipation, muscle weakness, weight pain, joint or muscle pain, feeling sad or depressed

2. skin is scaly, dry, and pale. hair has slow growth and is dry, coarse, dull, and brittle. slow HR, less sweating

3. more than usual menstrual bleeding (anemic)

postpartum thyroiditis

often undiagnosed, affect about 10% of women

1. phase one starts 1-4 months after giving birth and typically lasts 1-2 months. possible to see hyperthyroidism as TH leaks. women usually feel tired and moody

2. second phase starts 4-8 months after delivery and lasts 6-12 months. show symptoms of hypothyroidism. returns to normal within 12-18 months after symptoms begin

manifestations of hypothyroidism

1. babies born without TH will show significant symptoms such as jaundice, hypotonia, large tongue, coarse facial features, mental retardation, short stature, umbilical hernia, difficulty breathing, excessively sleepy

2. can lead to developing cretinism (dwarfism and mental retardation)

3. myxedema occurs on rare occasions. presence of non-pitting mucus-type edema in connective tissue in the body (shin, feet, tongue)

4. goiter—overall enlargement of the thyroid gland

myxedema coma

life-threatening, long-standing, hypothyroidism that negatively affects every cell in the body

occurs when the body can no longer tolerate the changes caused by severe hypothyroidism

CV collapse, decreased RR, hyponatremia, lactic acidosis

treat with IV TH

addison’s disease or adrenal insufficiency

adrenal glands make too little cortisol and, often, too little aldosterone

manifests: hyponatremia, hypoglycemia, loss of ECF, decreased CO, and hyperkalemia

1. dehydration, fatigue, weakness, orthostatic hypotension

2. client has poor tolerance to stress

3. hyper-pigmentation results from elevated levels of ACTH

treatment: life-long hormone replacement therapy

Cushing syndrome

excessive amount of glucocorticoids due to any cause

clinical manifestations

1. obesity with protruding abdomen and buffalo hump

2. moon face, wasting of the muscles in the limbs

3. delayed healing d/t decrease protein synthesis

4. osteopenia/back pain/compression fractures/osteoporosis

5. high BS, BP

6. infections d/t suppressed immune and inflammatory response

7. decreased stress reponse

8. skin is fragile with increased hair growth and purple stretch marks, easily bruised with petechia

Dx and Tx: salivary cortisol level and then a 24-hour urinary free cortisol level

• stop excessive steroid use, remove tumor surgically or use radiation

DM

characterized by hyperglycemia resulting from imbalances between insulin secretion and cellular responsiveness to insulin

A client with DM is unable to transport glucose into cells which leads to breakdown of fats and protein

There are many subclassifications: prediabetes, type 1 (T1DM) & latent autoimmune diabetes in adults (LADA), type 2 (T2DM) and maturity-onset diabetes of the young (MODY), gestational diabetes, and neonatal diabetes.

DM epidemiology

About 1 in 10 adults world-wide have DM (37 million) with most being T2DM

Onset of T1DM increases from birth and peaks between 4-6 years and then again between 10-14 years.

Onset of T2DM is later in life although adolescent obesity has led to increasing rates in teens. T2DM is 2 to 6 times more prevalent in Blacks, Native Americans, Pima Indians, and Hispanic Americans compared to Whites in the U.S.

fasting plasma glucose (FPG) with values

Test checks for fasting blood glucose levels.

Test is completed in the morning. After 8 hours of fasting, plasma glucose is measured.

FPG: 80-100 mg/dL is considered normal.

FPG: 100-125 mg/dL is borderline (impaired).

FPG: >126 is diagnostic for DM.

random plasma glucose test

blood is sampled for glucose without regard to eating

>200 mg/dL is diagnostic

oral glucose tolerance test (OGTT)

body’s ability to remove glucose from the blood

OGTT <140 mg/dL = normal

OGTT 140-199 mg/dL = prediabetes

OGTT level >200 mg/dL is diagnostic for DM

capillary whole blood glucose monitoring

most common type of capillary blood glucose monitoring

tiny drop of capillary blood

hemoglobin A1C (glycated HGB testing) values

measures a subtype of HGB where glucose molecules have been bound to the HGB molecule

it is used to estimate glucose control during the proceeding 1-3 months

predicts the progression of diabetic microvascular complications

A normal A1C is <5.7% (equal to a blood sugar of <117 mg/dL)

Prediabetes is 5.7 - 6.4% (equal to a blood sugar of 117 - 137 mg/dL)

Diabetes is 6.5% or above (> 140 mg/dL)

In clients with DM, the goal for A1C is <7

urine test

glucose detected in the urine means the renal tubular maximum has been exceeded (>180 mg/dL)

prediabetes

when blood glucose is elevated but does not meet the threshold for a diagnosis of DM

counseled to change diet, increase exercise, and lose weight.

Risk for T2DM decreases by 58% if the client:

• Loses 7% of their body weight or 15 lbs if they weigh >200 lbs

• Exercises moderately 30 minutes a day, five days a week.