• Head
• Spinal cord

• Traumatic insult to the brain
• produces physical, intellectual, and vocation changes
• high risk groups include: young people (15-24 years), infants (6mo-2yrs), young school children, and the elderly
• people in high crime areas are at great risk
• BLUNT(closed) and OPEN(penetrating) trauma

• more common than open head trauma
• head strikes hard surface or moving object hits head
• dura stays intact and brain not exposed
• causes focal and diffuse axonal injuries

• less common than blunt head trauma
• break in the dura with exposure of cranial contents
• causes focal injury
• Ex: gun shot wound

• mild concussion and cerebral contusion are common
• 75-90% head injuries are not severe
• most common causes are transporation-related events and falls
• sports-related injuries and those involving crime are common
• mild concussion-temporary axonal disturbance without loss of consciousness

• coup (impact)- head moves forward (impact against an object), shearing of subdural veins, trauma to skull base
• contrecoup (rebound)-  head moves backward (impact within the skull), shearing forces through brain
• one continuous motion

• associated with contusions
• caused by forceful impacts (car accidents and falls)
• compound fractures are causes by objects hitting head with great force or head hitting object with great force

• Damage to the body after sustaining head injury occurs by primary, secondary, and tertiary mechanisms
• Primary is caused by impact
• involves neuronal and glial injury and the vascular response

• includes cerebral edema, brain swelling, hemmorhage, infection, and high ICP
• occurs from reduced circulation and brainshift

• caused by apnea, low BP, and other lung and cardiac problems

• Types:
• focal 
• diffuse

• specific with grossly observable brain lesions (coritcal contusion, epidural hemmorhage, subdural hematoma)
• usually result of violent impact
• damage results from compression of the skull at the point of impact and rebound effect
• contusions and bleeding from small tears in blood vessels
• severity of contusions associated with amount of energy transmitted by skull to underlying brian tissue
• may be coup or contecoup
• brain edema forms around and in damaged tissue - contributes to increased intracranial pressure
• in contused areas are infarction and necrosis, multiple hemmorhages and edema
• tissue is pulpy
• maximum effects of injury related to contusion, bleeding and edema peak from 18 to 36 hours after injury
• accounts for 2/3 of head injury death

• epidural hematoma or epidural hemmorhage
• subdural hematoma (10-20% of focal injuries - usually skull fractures)
• intracerebral hematoma (can have delayed symptoms)

• results from shaking effects - inertial effects of mechanism input to head associated with acceleration and deceleration
• twisting produces strains and distortions in the brain
• shear stresses result with striking the freely moving head attached to the neck
• shearing, tearing, and stretching of nerve fibers occurs with axonal damage (need EM to see)
• gradient of injury established with torn axons and small hemmorhages
• later, torn axons regress

• more frequently occurring 
• any abnormaility in the brain caused by a pathological processes in the blood vessels
• account for 50% of neurologically-related hospital admissions
• cerebrovascular accident (CVA - Stroke) is the most common clinical manifestation
• CVA is a sudden, nonconvulsive focal neurological deficit
• CVAs are the 3rd leading cause of death in the US
• CVA outcome ranges. minimal damage and deficits almost unnoticed. severe with hemiplegia, coma and/or death

• can be: 
• thrombogenic (arterial occlussions caused by thrombi - blood clots),
• embolic (fragments breaking from thrombus outside the brain), or 
• hemmorhagic (intracranial bleeding)

• cerebral thrombosis most frequently due to atherosclerosis and arterial wall inflammatory conditions
• can be due to increased perfusion
• inadequate cerebral perfusion (dehydration, low BP, andprolonged vasoconstriction) increase risk
• Subdivisions:
• transient ischemic attacks (TIAs)
• stroke-in-evolution
• completed stroke

• Type of Thrombotic CVA
• may be due to intermittent blockage by thrombotic particles or spasm
• all neurological deficits clear in 24 hrs leaving no residual deficit
• 35% completed strokes preceded by TIAs
• Vital that intervention is done

• Type of Thrombotic CVA
• step-by-step process over minutes to hours
• intermittent progression over hours to days characteristic of thrombotic stroke or slow hemmorhage
• Something like heparin usually given

• Type of Thrombotic CVA
• CVAs that reach maximum destructiveness in producing neurological deficits

• clot fragments from heart, aorta, common carotid artery, or thoracic vessels
• often obstructs bifurcation of small artery
• associated with atrial fibrillation, rheumatic heart disease, artificial valves, atrial septral defects, and arterial disorders
• less common cuases are air, fait, and tumors
• embolus often in middle cerebral artery

• causes include hypertension, ruptered anuerysms, and AV malformation
• mass of blood forms and may displace/compress adjacent brain tissue
• blood seepage into the ventricular system may occur

• "time is brain"
• best to treat within 6 hours
• antithrombotic and metabolic protection therapies
• future may include stem cell transplants

• result from vascular wall defects, which allow thinning and ballooning of vessel wall
• potential for bleeding and repture occurs

• tangled masses of dilated vessels that may be congenital

• results when area of brain loses blood supple due to vascular occlusion
• may be ischemic or hemmorhagic

• primary cause is hypertension
• walls of small arteries and arterioles thicken
• microaneurysms may form and bleed
• bleeding may displace/compress adjacent brain and cuase ischemia and edema

• blood from injured/defective vasculature enters subarachnoid space
• blood clogs arachnoid granulations (so CSF non reabsorbed) and foramina in ventricular system (CFS circulation impaired)
• ICO rises for ~ 10 min
• cerebral blood flow and perfusion reduced
• expanding hematoma compress/displaces brain
• associated with 50% mortality
• early manifestation - headache, altered mental status, motor weakness, and numbness, and tingling
• vasospasm is a complication causing brain ischemia and infarction

• primary or metastatic
• can cause seizures, visual problems, unstable gait, and cranial nerve dusfunction

• one of the most common causes of severe cognitive dysfunction in the elderly
• forms:
• familial early-onset dementia
• late-onset familial dementia
• nonhereditary or sporatic late-onset
• cause unknown; theories proposed:
  
• loss of neurotransmitter choline transferase
• genetic defects involving amyloid precursor protein
• alteration of apolipoprotein E, which binds beta amyloid
• pathologic activation of N-methyl-D-asperate (NMDA) receptors with excess calcium influx
• prions and autoimmune reactions

• amyloid precursor protein in chromosome 21
• presenilin on chromosome 14 (PSEN1)
• presenilin on chromosome 1 (PSEN2)

• defect in apolipoprotein E on chromosome 19
• APOE2, APOE3, and APOE4 occur most frequently
• APOE4 allele is marker of increased susceptibility...but NOT determinant

• Alzheimer's disease
• Parkinson's Disease
• MS
• ALS

• common disease of basal ganglia
• primary forms involve degeneration of dopamine-secreting nigrostriatal pathway, which causes dopamine depletion and excess cholinergic activity
• tremor and rigidity caused by excessive cholinergic activity
• also there are secondary (drug-induced) forms
• mainstay of treatment involved L-dopa, dopamine precursor
• complete invalidism may occur in 15-20 years
• new research suggests occupational exposure to organic roundwater contaminant and dry cleaning chemical increase risk

• rare hereditary disease involving the basal ganglia and cerebral cortex
• autosomal dominant trait with high penetrance
• defect on short arm of chromosome 4
• depletion of y-aminobutric acid (GABA; inhibitory neurotransmitter) -secreting neurons causes involuntary, fragmented movements
• onset around 24-45 years old

• degenrative disease in which CNS demyelination may result from immunogenic-viral causes
• viruses/antigens may attack myelin and cause hypersensitivity reaction
• steroids can shorten duration of acute exacerbations
• immunosuppresant therapy may slow progression
• new studies suggest low vitamin D levels may be linked to more severe disease symptoms, but no evidence proving that vitamin D prevents symptoms

Amyotrophic lateral sclerosis (ALS)

Lou Gehrig's Disease

• rare degenerative disorder involving lower and upper motor neurons
• flaccid paresis progressing to paralysis characterized the syndrome
• genetic factors now thought to be involved and may involve SOD
• glutamate toxicity may cause neuron degeneration
• new research suggests NFL players may be at higher risk of death from neurodegenerative disease like ALS or Alzheimer's

• A neuromuscular disorder of voluntary muscle characterized by weakness and fatigability
• autoimmune disease associated with other autoimmune disorders (SLE, rheumatoid arhtritis)
• deficit is in impulse transmission at neuromuscular junction
• postsynaptic Ach receptors on muscle cell not recognized as self - elicit antigenic response
• antibody binding blocks Ach binding
• receptors destroyed and impulse transmission diminished across neuromuscular junctions
• myasthenia crisis - severe muscle weakness causes quadriparesis or quadripelgia, respiratory insufficiency with reduced tidal volume and vital capacity, and extreme difficulty swallowing; in danger of respiratory arrest
• cholinergic crisis can arise from anitcholinesterase drug toxicity
• clinical picture of cholinergic crisis similar to myasthenia crisis, but associated with increased intestinal motility, diarrhea, intestinal cramps, bradycardia, pupillary constriction, increased salivation, and sweating
• cholinergic crisis is caused by too much Ach at neuromuscular junctions

• minimal damage and deficits almost unnoticed
• severe with hemiplegia, coma and/or death

• New gene variants linked to AD:
• provide new clues about causes of disease and potential targets for drug therapy
• new genes believed to afect 3 pathways: endocytosis, inflammatory immune responses, and lipid processing
• in 2010, a large collaberative genetic study know as the Internationsla Genomics of Alzheimer's Project was formed
• emerging evidence suggesting epigenetic (how and when genes are expessed) mechanisms may also contribute to disease

• hormore receptors
• plasma membrane receptors
• lipid-soluble receptors
• cell signaling

• increase number of receptors
• hormones will bind to receptors on a cell and after a lot of this for a long itme the cell will increase the amount of receptors it has

• decrese number of receptors
• hormone binds to a cell with receptors and after a lot of this after a long time the cell will decrease the amount of receptors

• plasma membrane (usually water soluble)
• nuclear/cytoplasmic (usually lipid soluble)

• G protein-linked
• enzyme-linked
• ion channel-linked

• first messenger - ex: hormone secreted into the blood
• second messenger - generated by first messenger-receptor binding; mediates signal of binding 

• hormone oversecretion and undersecretion
• decrease in receptor number

• syndrome of inappropriate ADH (SIADH)
• diabetes insipidus
• posterior pituitary secreates anti-diruetic hormone and oxytocin

• Hypopituitarism - hypofunction
• hyperpituitarism - hyperfunction

• located in neck
• produces hormones that regulate metabolic processes
• Thyrotoxicosis--TH from any source exerts greater than normal response; one form is hyperthyroidism, where excess TH secreted from thyroid gland
• Hyperthyroidism is caused by Graves disease, toxic multinodular goiter, thyroid cancer and increased TSH
• Other causes of thyrotoxicosis are subacutethyroiditis, ectopic thyroid tissue and ingestion of too much TH
• Graves disease is most common cause
• Thyrotoxic crisis or thyroid storm--dangerous worsening of thyrotoxic state; without treatment, death occurs in 48 hrs
• Hypothyroidism

• Form of hypothyroidism
• Myxedema results from altered composition of the dermis and other tissues
• Connective tissue separated by increased protein and mucopolysaccharides
• Mucopolysaccharides bind water and produce nonpitting, boggy edema
• Pronounced around eyes, feet, hands, and below clavicles
• Causes thickening of tongue, and pharyngeal and laryngeal membranes--leads to slurred speech and hoarseness 
• Different from edema 
• due to water drawn to proteoglycans, NOT Starling's forces like edema
• does not produce pitting edema
• in not gravity-dependent

• medical emergency due to severe hypothyroidism
• characterized by loss of consciousness
• symptoms: 
• hypothermia without shivering
• low BP
• low BS 
• lactic acidosis
• elderly are at risk

• Hyperparathyroidism
• Hypoparathyroidism

• hypersecretion of PTH causes excessive osteoclastic and osteocytic activities resulting in bone resorption
• pathological bone changes occur - fracture, kyphosis, and vertebral body compression fractures

• Abnormally low levels of PTH can be due to thyroid surgery or hereditary factors or damage to the glands
• serum calcium levels are depressed, serum phosphate is increased, and bone resorption becomes decreased
• some symptoms are similar to hypocalcaemia which will lower nerve and muscle threshold

• lymphadenophathy
• malignant lymphomas

• swollen lymph nodes
• when localized, usually means drainage from an inflammed lesion
• usually a redult of an infection
• when generalized, is it associates with diseases
• –neoplastic disease
• immunological or inflammatory disorders
• endocrine disorders
• lipid storage diseases

• very treatable nowadays
• type of malignant lymphoma
• there are distinctive abnormal chromosomes in many cells of the lymph nodes
• these abnormal cells are called Reed-Sternberg cells
• a virus may be involved in the mechanism
• familial clustering suggests an unknown genetic mechanism
• Hematology:
• initial sign is an enlarged, painless mass, usually in the neck
• local symptoms are due to pressure and obstruction from the lymphadenopathy
• treatment involves chemotherapy and radiation
• cures are possible in all stages of the disease
• relapses in less than 2 years have a poor prognosis

• cause unknown
• immune mechanisms may be involved, as there is a greater incidence in thsoe who are immunosuppressed
• often painless swelling and enlargement of the lymph nodes occurs over months or years
• survival with the disease is usually long

Remember:

Normal platelet count = 140,000-340,000/mm3

• platelet count over 4000,000/mm^3
• levels over 1 million/mm^3 are associated with intravascular clot formation (thrombosis)

• results from a stationary clot (thrombus) or a clot that has moved (embolus) to obstruct flow in a blood vessel 
• clots in the heart, lung and brain may cause death
• clots can form from insufficient anti-coagulation factors or conditions that promote venous stasis (like sitting with legs bent)
• triad of Virchow is a group of 3 factors involved in abnormal clot formation--loss of vessel wall integrity, abnormalities in blood flow and alterations in blood constituents

• Insulin-dependent diabetes mellitus (IDDM or Type I)
• Most common in children
  Non-insulin-dependent diabetes mellitus (NIDDM or type II)
  Malnutrition-related diabetes mellitus
  Others

• Type IA--cell-mediated destruction of the b-cells; leukocyte antigen HLA-DR4 associated with this type
• Type IB--uncommon primary autoimmune condition associated with other autoimmune problems (Hashimoto disease, Graves disease and myasthenia gravis); associated with HLA-DR3 in those between 30 to 50 years of age
• Affects CHO, fat and protein metabolism
• Glucose accumulates in blood and spills into urine as renal threshold exceeded
• Protein and fat breakdown occur from insulin lack
• Manifestations are usually acute with polydipsia, polyuria and polyphagia
• Weight loss and wide BS flucutations occur
• Ketoacidosis occurs--increased levels of ketones occur without insulin; ketones cause a drop in pH (metabolic acidosis); fruity breath occurs from blowing off acetone
• Little or no insulin secretion
• Occasionally, diabetic coma may be the initial symptom of the disease

• 90% of diabetes,common, and incidence rising
• Traditionally affected people after the age of 40, many of whom are obese
• Childhood Type II diabetes has recently been recognized as a problem
• MODY (maturity onset diabetes of the young)--subset who are normal to subnormal in weight; multiple genetic associations
• Obesity and subsequent insulin resistance is a factor in 60-80% of type II cases
• Decreased b-cell responsiveness to plasma glucose occurs with abnormal glucagon secretion
• Islet dysfunction may be due to decreased b-cell mass or abnormal function
• Has a strong inheritance pattern
• Relatives of type 2 diabetics have much higher risk of developing it as well
• Concordance among monozygotic twins is virtually 100%
• Many different genes associated, but no single gene found responsible 

• Hypoglycemia
• Diabetic ketoacidosis (DKA)
• Hyperosmolarnonacidotic diabetic coma
• Somogyi effect
• Dawn phenomenon

• Also called insulin shock or insulin reaction
• Plasma glucose below 45-60 mg/dl
• Occurs in 90% of those with type I disease and limits management of disease
• Symptoms due to neurogenic reaction and cell malnutrition; symptoms vary, but tend to be consistent in an individual
• Neurogenic (from low glucose sensed by hypothalamus)--increased HR, palpitations, diaphoresis, tremors, pallor, and anxiety
• Cell malnutrition--headache, dizziness, irritiability, fatigue, poor judgement, confusion, visual changes, hunger, seizures and coma
• Symptoms masked by b-blocking drugs

• Serious complication; responsible for many hospital admissions and deaths
• Occurs when there is a relative/absolute insulin deficiency and an increase in insulin counterregulatory hormones (catecholamines, cortisol, glucagon, and GH)
• Hepatic glucose production increases, peripheral glucose usage decreases, fat mobilization increases, and ketogenesis occurs
• Precipitated by--infection, trauma, surgery , MI, interruption of insulin, and emotional stress
• Symptoms--Kussmaul breathing (hyperventilation to compensate for metabolic acidosis), dizziness, CNS depression, ketonuria, abdominal pain, nausea, thirst and polyuria
•  

• Ketones normal, but glucose over 600 mg/dl
• Osmolarity over 310 mOsm/liter and BUN is 70-90 mg/dl
• Due to high BS, glycouria and polyuria cause severe volume depletion and intracellular dehydration
• Mortality 14-17%

• Hypoglycemia at night stimulates glucose counteregulation (epinephrine, GH, cortisol and glucagon release)
• Glucose increased by gluconeogenesis and glycogenolysis
• Fatty acids and proteins are mobilized, while peripheral glucose use is inhibited
• Blood glucose is high in the morning
• Common in type I diabetes and kids

• Early morning rise in glucose
• Due to waning of late insulin dose and elevated GH, which increase glucose metabolism by muscle and fat, during the night

• Include diabetic neuropathies, microvascular diseases (retinopathies and
  nephropathies), large blood vessel diseases (CAD, CVAs and peripheral
  vascular diseases), and infections
  - Some neuropathies progressive, others (foot and wrist drop) can be reversed
  •Microvascular problems due to thickening of basement membrane (diabetes is the most common cause of end stage renal disease)
  •CAD is the most common cause of death in those with type II diabetes
  •Infections due to sensory impairment (resulting in injury), hypoxia, increased pathogen growth in presence of high glucose, and reduced blood supply 
   
   

• Cushing syndrome and disease
• Hyperaldosteronism
• Hypocortisolism and Addison disease
• Pheochromocytoma
   
   

• Cushing syndrome (may or may not involve the pituitary) and Cushing disease (hypercortisolism with pituitary involvement) are due to adrenal cortical hyperfunction or hypercortisolism
• A Cushing-like syndrome may develop with administration of cortisone
• Syndrome may be due to excessive ACTH, pituitary adenoma, ectopic secretion or adrenal neoplasms
• Those with Cushing disease lose the ability to increase ACTH and cortisol with stress
• They gain weight, become glucose intolerant, and experience bone disease, muscle wasting, immunosuppression and hyperpigmentation
• Symptoms of Cushing syndrome include: moon face, supraclavicular fat pads, trunk obesity, thin extremities, pendulous abdomen, and increased facial/body hair with thin scalp hair
•  
   

• Increased aldosterone secretion
• Increased sodium reabsorption, hypervolemia and hypokalemia
   

• Due to inadequate adrenal stimulation by ACTH or primary cortisolhyposecretion (Addison disease)
• Addison disease--high ACTH and inadequate cortisol synthesis and release
• Addison disease may be due to autoimmune disease, TB of adrenal gland, familial adrenal insufficiency, or cancer or hemorrhage of the adrenals
• Secondary hypocortisolism is characterized by low ACTH leading to decreased cortisol production--caused by exogenous administration of steroids
• Symptoms of hypocortisolism are--weakness, low BS, poor response to stress, hypovolemia and hyperkalemia

• Catecholamine secreting tumor
• Usual cause of adrenal medulla hyperfunction
• Symptoms include--high BP, increased HR, excessive sweating, constipation and glucose intolerance

• maintain stable internal environment for cells and tissues by balancing solute and water transport, excreting metabolic wastes, conserving nutrients, and regulating acids and bases
• has endocrine functions
• erythropoietin
• calcitriol

• functional unit of kidney (urine forming unit)
• tubular structure with many subunits

filters blood through:

an inner capillary endothelium

a middle basement membrane

an outer epithelium

the membrane separates blood of golerular capillaries from fluid in Bowman's space

it passes through 3 layers of glomerular membrane and forms the primary urine

• Kidneys highly vascularized 
• Receive 20-25% C.O.--1000-1200 ml blood/min from renal plasma flow
• 20% (120-140 ml/min) is filtered at glomerulus and passes into Bowman’s capsule
• Glomerularcapillary blood flow is maintained at constant rate
• Blood vessels closely parallel the nephron structure
   
• Glomerular filtration rate (GFR)
  - Filtration of plasma per unit time
  –Directly related to perfusion pressure of glomerular capillaries
  –Approximately 120 ml/min
  –99% of the filtrate is reabsorbed--normally all but 1-2 ml of glomerular filtrate is reabsorbed and returned to circulation by peritubular capillaries
  –Creatinineis a commonly used measure of GFR
  - related directly to renal blood flow
   

• Intrinsic autoregulatory mechanisms
• Local mechanisms keep rate of renal blood flow and GFR constant at arterial pressures between 80-180 mm Hg
• Local mechanisms prevent wide fluctuations in systemic arterial pressure from being transmitted to glomerular capillaries
• Neural mechanisms
• Hormonal mechanisms
   

• Declining arteriolar pressure--
• Stretch on afferent arterial wall decreases
• Arteriole relaxes
• Renal blood flow increases
• Increasing arteriolar pressure--

  - Arteriole contracts

  – Renal blood flow decreases

   
   

• blood vessels of kidney innervated by ANS
• sympathetic fibers cause vasoconstriction
• factors influencing neural regulation:
• exercise
• hypoxia
• body position

• increased renal sympathetic activity (mediated through carotid sinus and baroreceptors of aortic arch)
• renal arteriolar vasoconstriction
• renal blood flow and GFR decreased
• decreased renal flow reduces excretion of Na+ and water
• Blood volume and systemic pressure increase

• induces intense sympathetic stimulation
• causes intense vasoconstriction
• reduces blood flow and GFR

• calcitriol (active Vitamin D)
• Erythropoietin
• renin is made in the kidney (enzyme in renin-angiotensin system)

• some renal functions can be measured by renal clearance
• renal clearance techniques determine howm uch of a substance in cleared from the body by the kidneys per unit time
• clearance permits indirect measures of GFR, tubular secretion, tubular reabsorption, and renal blood flow

• GFR provides the best estimate of functioning renal tissue
• loss/damage to nephrons leads to a corresponding decrease in GFR
• GFR measurement requires a special substance, such as inulin
• inulin is filtered at the glomerulus, and is not secreted, reabsorbed, or metabolized
• due to the inconvenience of measuring inulin clearance, creatinine is used

• made by muscle and released into blood at consistent rate
• filtered at golemrulus with a small amount secreted by renal tubules
• used clinically as a clearance indicator
• creatinine clearance overestimates GFR, but within tolerable limits
• good clinical indicator requiring a serum sample and a 34 hour urine collection

• Chronic decline in GFR is reflected in plasma creatinine (Pcr) concentration
• Normal Pcr is 0.6-1.5 mg/dl
• Pcr is stable when GFR is stable, because creatinine has a constant rate of production from muscle metabolism
• When Creatinine goes up, GFR goes down
• The amount of creatinine filtered is approximately equal to the amount excreted
• When GFR declines, Pcr increases proportionally (GFR and Pcr are inversely related)
• If GFR decreases 50%, Pcr rises twofold
• Elevated Pcr represent decreasing GFR
• Pcr elevated with trauma or muscle breakdown
• Not useful to evaluate GFR in these situations of muscle damage

• More recent marker for GFR
• Low molecular weight protein maintain at constant rate by all nucleated cells
• Reciprocal relationship with GFR more sensitive than creatinine
   

• BUN reflects glomerular filtration rate and urine-concentrating capacity
• Urea filtered at glomerulus, so BUN increases as glomerular filtration drops
• Urea reabsorbed through permeable tubules, so BUN increases with dehydration and acute and chronic renal failure when passage of fluid through tubules is slowed
• BUN changes with altered protein intake and protein catabolism
• Normal BUN is 8-25 mg/dl
   

Color: _________________Amber - yellow__Drugas and food may change color

Turbidity:______________Clear___________purulent matter will make cloudy

pH: ___________________4.6 - 8.0________bacteria creta alkaline urine

Specific gravity adults:___1.010-1.025_____concentration ability or density of urine

specific gravity infants:___1.010-1.018

blood:__________________Negative_______bleeding along urinary tract

bacteria:________________None__________infection

RBCs:__________________Negative_______bleeding along urinary tract

WBC:__________________Negative_______urinary tract infection

Crystals:_______________Negative_______may have potential for stones

Fat:____________________Negatvie_______can be associated with nephrosis

Casts:_________________Occasional______may represent renal disease

Bilirubin________________Negative________increase may cause dark orange 

ketones________________Negative____represents an increase in fat metabolism

glucose________________Negative_______usually signifies hyperglycemia

sodium_________________100-260 mEq/24 hrs__

                                                         ___can increase or decrease wiht renal disease

potassium______________25-100 mEq/24 hrs

protein_________________Negative - trace__dysfunction of glomerulus

• diminished urine
• less than 30mL/hr or 400 mL/day

increase production of highly dilute urine

• Obstructive
• Infectious
• Injurious
• Failure

• Interference with flow at any site along the tract
• Causes urine to accumulate behind obstruction
• Leads to infection of and injury to involved structures
• Critical determinants of obstruction:
• Location
• Unilateral or bilateral
• Partial or complete
• Acute or chronic
• Cause of obstruction

• Tumors
• Calculi (kidney stones)
• Pregnancy
• Trauma
• Prostatic hypertrophy
• Loss of ureteral peristalsis
• Loss of bladder muscle function
   

• Accumulation of urine behind obstruction with retrograde increase in hydrostatic pressure
• Increases in pressure are transmitted to proximal tubule resulting in decreased GFR--may go to 0
   

• Compression of kidney structures with ischemic atrophy of papilla and medulla
• Progressive atrophy of kidney with tubular damage resulting in decreased ability to conserve Na+ and water and to excrete H+ and K+

• Relief of obstruction:
• Usually alleviates pathophysiology
• Usually followed by massive diuresis due to return of normal GFR
• May result in excessive Na+ and water loss (>10 liters per day)
• Complications of obstruction. Can lead to:
• Infection
• Renal failure

• Renal disorder
• masses of crystals and protein including:
• Calcium oxylate and calcium phosphate
• Magnesium, ammonium phosphate (struvite)
• Uric acid
• Cystine stones
• Incidence of calculi is 10-20% in adults
• Calculi formation

  - Forms around a nidus

  –Becomes trapped

  –Accumulates other crystals

  •Location of calculi
  –Renal tubules, calyces and pelvis
  –Ureters
  –Bladder

• High urinary concentrations of stone-forming substances
• Urine pH that affects solubility
• Decreased nephrocalcin
• Diseases
• Diet
• Drugs
• Reduced fluid intake
   

• pain
• nausea and vomiting
• hematuria
• bacteriuria

• neurogenic bladder
• renal tumors
• bladder tumors

• Any infection of one or more structures in the urinary tract
• Usually caused by bacteria
• Bacterial contamination  of sterile urine by retrograde movement of bacteria into urethra and bladder, then to ureter and kidney
   
• Diagnosis:
• Culture of specific organisms of 100,000 bacteria per ml freshly voided urine
• Common organisms are gram negative--E. coli, Proteus, Pseudomonas
• Less common include Staphylococcus  and fungi

• Inflammation of bladder
• Most common type of UTI
• More common in women due to shorter urethra, urethra close to anus and contamination from vaginal secretions
• Altered bladder mucosa from cystitis:
• Hyperemia--mild inflammation
• Hemorrhage and pus formation--more advanced
• Sloughing and ulceration--more chronic
• Necrosis of bladder wall--most severe infections

• Frequency, urgency and dysuria
• Suprapubic, flank and/or low back pain
• Hematuriaand cloudy urine
• 10% have no symptoms; 30% with symptoms have no bacteria in urine

• Infection of renal pelvis and interstitium
• Can be unilateral or bilateral
• More frequent in women
• E. coli is the most common cause
• Proteus and Pseudomonas can also cause it
   

• Renal calculi
• Vesicourethral reflux
• The urine that is in the ureter goes back to the kidney
• Pregnancy
• Neurogenicbladder
• Instrumentation
• Sexual trauma in females
   

• Infection spread by organisms ascending the ureters or organisms in the blood
• Inflammatory process is focal and irregular
• Usually involves pelvis, calyces and medulla
• Medulla becomes infiltrated with WBCs
• Inflammation of the tubules (not glomeruli)
• Urine is purulent
• Localized abscess formation
• Necrosis of renal papillae
• Healing involves formation of scar tissue and atrophy of affected tubules
• Bacterial count decreases until urine is sterile
• Rarely causes renal failure
   

• Fever and chills
• Flank and/or groin pain
• Frequency and dysuria
• Costovertebraltenderness
• Children and the elderly show non-specific fever and malaise
   

• Persistent or recurrent autoimmune-infectious process of the kidney
• May be uni- or bilateral
• Causes may be hard to identify
• Chronic infections may be due to calculi or ureteral reflux
• Progression leads to renal failure
   

• Chronic urinary obstruction leads to progessive inflammation
• Inflammation alters renal pelvis and calyces
• Atrophy, dilation and diffuse scarring occur
• The tubules become destroyed
• Impaired ability to concentrate urine occurs
• Chronic renal failure occurs
   

• hypertension
• urinary frequency
• dysuria
• flank pain

• Inflammation of glomerulus
• Caused by immunologic abnormalities, drugs or toxins
• Consequence of vascular disorders and systemic diseases
• Most common cause of chronic and end-stage renal failure
• associated with:
• Throat and skin infections (b hemolytic streptococcus)
• Bacterial endocarditis (streptococcus and staphylococcus)
• Viral diseases (varicella, hepatitis B and C, HIV)

• Immune complexes deposit in glomerulus
• Complement activation and proliferation of macrophages
• T cell activation and ROS production
• Damage to glomerular epithelial cells
• Platelet aggregation and glomerular sclerosis
• Decreased glomerular blood flow
   

• Hematuriaand RBC casts
• Proteinuria
• Decreased GFR
• Oliguria
• Edema and 3rd spacing of fluid
• Hypertension
   

• Renal insufficiency is a decline in renal function to 25% of normal or a GFR to 25-30 ml/min
• Renal failure is significant loss of renal function between 10-25% of normal
• End-stage renal failure (ESRF) is when less than 10% of renal function remains
• Acute renal failure is an abrupt reduction in renal function
• Elevated BUN
• Elevated plasma creatinine
• Oliguria--urinary output less than 30 ml/hr
• Acute renal failure is reversible if treated early
•  

• Before the Kidney (blood flow)
• Caused by impaired renal blood flow leading to decreased filtration pressure, which causes decreased GFR
• Failure to restore blood flow leads to acute tubular necrosis or cortical necrosis
• Decreased renal blood flow and poor perfusion leading to prerenal acute renal failure can result from:
• Vasoconstriction of vessels going to kidney
• Hypotension
• Hypovolemia
• Hemorrhage
• Inadequate C.O.

• Within the kidney
• Usually results from acute tubular necrosis (ATN)
• ATN usually related to ischemia
• Ischemia generates toxic oxygen free radicals that cause cell swelling, injury and necrosis
• Associated with surgery (patchy involvement in any part of the nephron)
• Also associated with nephrotoxic drugs, X-ray media, and heavy metals (uniform involvement of proximal tubules)

• After the kidney
• Usually occurs with urinary tract obstruction
• Affects kidneys bilaterally
• Hours of anuria and flank pain followed by polyuria
• Usually due to edema of the tubular lumen
   

• Oliguria
• Diuresis
• Recovery

• Anorexia and weight loss
• Nausea, vomiting and diarrhea
• Itching
• Edema
• Neurological changes
   

• Diet--protein and K+ restriction, Na+ and water evaluation, and adequate caloric intake
• Erythropoietin as needed
• If related to DM, nephropathy can be improved with control of BS
• End-stage--dialysis or kidney transplant
   

• Mouth
• Esophagus
• Stomach
• Small intestine
• Large intestine
• Rectum
• Anus

• Hollow muscular tube
• Conducts substances from oropharynx to stomach
• Swallowed food is moved by peristalsis

• a hollow muscular organ that:
• Stores food during eating
• Secretes digestive juices
• Mixes food with digestive juices
• Propels partially digested food (chyme) into the duodenum of the small intestine

• lower esophageal sphincter
• pyloric sphincter

• Fundus (upper part)
• Body (middle part)
• Antrum (lower part)

• 5 meters long
• divided into duodenum, jejunum and ileum
• specialized for digestion and absorption
• absorption occurs through villi (functional units of the intestine)
• columnar epithelium with microvilli (brush border epitherlium) cover mucosa

• 1.5 meters long that consists of
• cecum - pouch that recieves chyme from ileum
• appendix - little/no physiological function
• colon
• rectum
• anal canal

• Parts include ascending colon, transverse colon, descending colon and sigmoid colon
• Absorbs water and some fatty acids
• By the time mass enters sigmoid colon, it consists entirely of waste and is called feces
• will absorb water and fatty acids

• liver
• gallbladder
• exocrine pancreas

• With GI disorders, one or more of the functions of the tract become disrupted
• Structural and neural problems can slow, obstruct or accelerate movement of chyme at any level
• Inflammatory and ulcerative conditions can alter secretion, motility and absorption
• Clinical manifestations of GI disorders include:
• Anorexia
• Vomiting
• Constipation
• Diarrhea
• Abdominal pain
• GI bleeding

• Lack of the desire to eat, though normal stimuli produce hunger
• Often associated with nausea, abdominal pain and diarrhea
• Can accompany other problems, e.g. CV disease and psychological stress

• Forceful emptying of stomach or intestinal contents through the mouth
• Stimuli initiating the vomiting reflex include severe pain; stomach or intestinal distention; trauma to kidneys, ovaries or testes; and activation of the chemoreceptor trigger zone in the medulla
• Nausea and retching usually procede vomiting
• Projectile vomiting is not preceded by nausea and retching, and is caused by direct stimulation of the vomiting center or GI obstruction

• Difficult or infrequent defecation
• Commonly caused by personal habits, drugs and various disorders
• Usually means a reduction in the number of stools, hard stools and difficult evacuation
• Definition of constipation is individually determined--normal bowel movements range from 2-3/day to 1/week
• Causes of and contributors to constipation
• Neurogenic disorders where pathways are absent or degenerated
• Low residue diets can contribute by decreasing volume and number of stools
• Sedentary life-style can contribute
• Hypothyroidism decreases GI motility, thus can lead to constipation
• Drugs--excessive antacids with calcium carbonate or aluminum hydroxide, or opiates, especially codiene
   

• The increase in frequency of evacuation, and fluidity and volume of feces
  Stool volume and consistency are determined by water content in the colon, and presence of unabsorbed food and intestinal secretions

• 9 liters of lumenal content/day is processed (2 liters are ingested and 7 liters are from intestinal secretions)
• 99% of the lumenal contents is reabsorbed
• Of the volume reabsorbed, 90% (7-8 liters) is reabsorbed in the small intestine and 9% (1-2 liters) in the colon
• 150 ml excreted in the stool

• osmotic
• secretory
• motility

• Nonabsorbable substance in the intestine draws to water
• Causes include intake of synthetic, nonabsorbable sugars or lactase deficiency
   

• Excessive mucosal secretion of fluid and electrolytes
• Causes include bacterial enterotoxins, tumors, and excessive motility of the intestine caused by diabetic neuropathy
• Small volume diarrhea is usually due to inflammatory disorders (ulcerative colitis or Crohn disease), but it can be due to fecal impaction
• E coli, cholera, tumor can stimulate secretions
  
   

• If food is not properly mixed, digestion is impaired and motility increases
• Causes include small bowel resection, surgical bypass of an intestinal area, and intestinal fistula

• mechanical factors 
• inflammation
• ischemia

• Stretching and distention activate nerve endings
• Pain accompanies rapid distention rather than gradual
• Traction on the peritoneum (serous membrane lining abdominal walls and covering viscera) from adhesions (union of surfaces not normally joined), common bile duct distention and forceful peristalsis 
• If organs swell, pain fibers in capsules surrounding the organ are stimulated due to stretching

• Parietal (somatic)
• visceral
• referred

• Comes from Parietal peritoneum
• More localized and intense than visceral pain
• Lateral because at any one point, the peritoneum is innervated by only 1 side of the nervous system

• Comes from stimuli acting on abdominal organs
• Usually felt midline in the epigastrum (upper mid abdomen), midabdomen or lower abdomen
• Diffuse and vague, as nerve endings in abdominal organs are sparse and multisegmented
   

• Visceral pain felt at a distance from affected organ
• Well-localized and felt in skin or deeper tissues sharing a central afferent pathway
• It generally develops as the intensity of the visceral pain increases

• Upper GI bleeding
• Lower GI bleeding
• Severe acute GI bleeding can be life-threatening depending on volume and rate of blood loss, associated disease processes, age and effectiveness of treatment

• From the esophagus, stomach, or duodenum
• Characterized by bright red blood or “coffee ground” material (due to the effects of acid on blood)
• Caused by bleeding varices (dilated veins) in the esophagus, peptic ulcers or tears in esophageal-gastric junction (Mallory-Weiss tear)
   

• from the jejumun, ileum, colon or rectum
• can be caused by polyps, inflammatory disease, cancer, or hemorrhoids

• Dysphagia
• Gastroesophageal reflux
• Hiatal hernia
• Pyloric obstruction
• Intestinal obstruction

• Difficulty swallowing
• Can result from mechanical obstruction of the esophagus or impaired esophageal motility
• Intrinsic obstructions can originate in the esophageal wall--tumors, strictures, outpouchings
• Extrinsic obstructions originate outside the esophagus--such as that caused by a tumor–Functional dysphagia is caused by neural and muscular disorders
• Problems with striated muscle of the upper esophagus interfere with voluntary swallowing--can occur with Parkinson’s disease and CVAs
• Some forms result from impairments of peristalsis in the mid and lower parts of the esophagus and lower esophageal sphincter--neural dysfunctions and psychosocial problems can be the cause
   

• Reflux of chyme from the stomach
• Lower esophageal sphincter may spontaneously and transiently relax 1-2 hrs after eating
• This causes gastric contents to regurgitate into the esophagus

• Protrusion of upper part of stomach through the diaphragm and into the thorax
• Two main types--sliding and paraesophageal
   

• Stomach slides through esophageal hiatus (opening in diaphragm for esophagus)
• Short esophagus, trauma and weakening of the diaphragmatic muscles at the gastroesophageal junction may contribute
• Coughing, bending, tight clothes, ascites and pregnancy accentuate the hernia
   

• Greater curvature of stomach herniates through a secondary opening in the diaphragm and lies along esophagus

• Gastroesophageal reflux
• Dysphagia
• Heartburn
• Epigastric pain
• Regurgitation and substernal discomfort during eating are common
   

• Narrowing or blocking of the opening between stomach and duodenum
• Can be congenital or acquired (e.g. peptic ulcer disease or cancer near pyloris)