Part 28 Flashcards
Macrocytic anemias are typically what type of anemias?
….B12 and folate deficiency anemias
B12 requires ___ to be maximally absorbed in the ____
intrinsic factor, terminal ileum
Pernicious anemia
An autoimmune form of megaloblastic anemia in which antibodies against intrinsic factor are developed preventing DNA production
3 new work arounds for B12 absorption independent of intrinsic factor and which is the best?
1) nasal spray
2) subcutaneous injection (preferred)
3) B12 high dosing can override the need for intrinsic factor and allow absorption
Swollen or sore tongue can be a sign of….
…B12 deficiency
B12 deficiency causes ___ symptoms, and the ___ is affected first affecting ___ and ____. If it takes too long to begin treatment, it can cause….
neurological, posterior column, proprioception and vibratory sensation
Irreversible damage
Methotrexate can cause ___ deficiency
Folic acid
Folate deficiency does not cause…
Neurological symptoms
Hemoconcentration vs hemodilution
Increase in proportion of RBC’s relative to the plasma vs decrease
Porphyria definition
Presence of an altered heme porphyrin ring on the hemoglobin molecule resulting in microcytic hypochromic anemia, very very very rare condition
Sideroblastic anemia definition, how does it appear on a peripheral smear?
Occurs when bone marrow produces ringed sideroblasts opposed to proper RBC’s
Appears to have central pallor in it like a donut hole
Plummer-Vinson syndrome triad of symptoms
- iron deficiency anemia
- dysphagia
- esophageal webs
Angular stomatitis is indicative of…
…iron deficiency anemia
Koilonychia definition and what is it indicative of?
abnormally thin spoon nails, indicative of iron deficiency anemia
Iron deficiency sees serum iron ___, total iron bindig capacity ___, and serum ferritin ____
- decrease
- increase
- decrease
Sideroblastic anemia is a __cytic, ___chromatic anemia with iron ____
micro, hypo, overload
Acquired sideroblastic anemia sources (4)
- alcohol
- lead
- B6 deficiency
- lupus
Sideroblastic anemia will have a ____chromatic peripheral smear with something called ____
hypo, basophilic stippling
Sideroblasic anemia treatment
Chelation therapy
Polycythemia vera defintion
A myeloproliferative blood cancer characterized by excessive proliferation of all blood elements in bonemarrow producting erythrocytosis, leukocytosis, and thrombocytosis
Polycythemia vera sequale (4)
- splenomegaly
- claudication
- hyperuricemia (kidney stone or gout development)
- Myelofibrosis (fibroses of bone marrow leading to aplastic anemia)
What causes polycythemia vera?
JAK 2 Mutation of hematoopoietic stem cells that causes proliferation independent of erythropoietin levels
Erythropoietin levels in polycythemia vera
Low
Signs and symptoms of polycythemia vera (7)
- headaches
- vertigo
- blurred vision
- fullness in head and left upper quadrant
- red discoloration esp. of face
- oozing from gums
- epistaxis
Classic sign of polycythemia vera
Pruritis often unbearable after bathing due to warm water facilitating excessive histamine release in overabundance of mast cells
Prognosis of polycythemia vera with and without treatment
Serious disease with survival of only 6-18 months with no treatment, can add 12 years of life with treatment
Treatment of polycythemia vera (5)
- Phlebotomy to decrease hematocrit btwn 40-50
- splenectomy
- prophylactic treatment against thrombosis with aspirin
- histamine blockers for pruritus
- hydroxyurea as myelosuppression
Hemochromatosis definition
Bronze diabetes, genetic disorder of iron metabolism causing body to store excess iron resulting in overload
Signs and symptoms of hemochromatosis (4)
- skin pigmentation
- arthalgia
- diabetes type I
- impotence
Classic triad of hemochromatosis
- cirrhosis
- diabetes mellitus
- skin pigmentation
Hemochromatosis prognosis
Patients with fully developed disease have 10 year survival rate of 6%, leading cause of death is liver complications, survival in treated patients detected pre-cirrhosis is identical to unaffected population
Fatigue vs malaise vs lassitude vs weakness
Inability to function due to prolonged exertion/uneasiness/weariness/physical strength lacking
Chronic fatigue syndrome/myalgic encephalomyelitis definition and what is it a diagnosis of?
Unexplained, persistent, or repapsing fatigue of 6 months duration that cannot be explained by other medical conditions, it is a diagnosis of exclusion
Classic Triad of epstein barr infection
- fever
- lymphadenopathy
- pharyngitis
Some examples of hypercoaguable states (4)
- post surgery
- thrombophilia
- dehydration
- estrogen therapy
What are some conditions that might encourage use of anticoagulant therapy prophylactically? (4)
- Immobilized patients
- atrial fib
- orthopedic surgery
- genetic coagulation anomalies
Some examples of vascular damages (4)
- thrombophlebitis
- venepuncture
- strain
- atheroschlerosis
Some examples of circulatory stasis (4)
- immobility
- venous obstruction
- varicose veins
- atrial fib
Prothrombin is also known as….
….factor II
Contraindications to warfarin (coumadin and jantoven) (4)
- history of hemorrhagic stroke
- uncontrolled hypertension
- active bleeding
- MI due to aortic dissection
Prolonged PT and PTT results indicate
Defective factor X, DIC
Dosing warfarin therapy
- Initiate therapy with estimated daily maintanance dose (2-5 mg daily) while maintaining current heparin management for 3-5 days or until therapeutic dosage reached
- check INR on days 3-5
- goal time is btwn 2-3, if less than 2 must increase dosage and if greater than 3 stop for that day and recheck next day (might take a few days to adjust)
- If 3-4.5 then decrease weekly dosage by 10% or 1mg/d for 3 days of next week and repeat PT in 1 week
- If 1.5-2 then increase weekly dose by 10% or 1mg/d for 3 days of next week and repeat PT in 1 week
Phases of clot formation and a brief explanation according to Pam (4)
1) vascular injury and spasm - constriction of injured vessel
2) platelet plug formation - von Willebrand factor needed to bridge platelets and collagen
3) Coagulation cascade - intrinsic or extrinsic fibrin formation
4) dissolution of clot
Tunica media compliance
Decreases as we age causing greater shear from blood flow such as with atherosclerosis
What 2 cells synthesize vonWillebrand factor?
Platelets
Endothelial cells
ASA causes ___ binding of a platelet acting for ___ to ___ days
irreversible, 7-10 or the life of the thrombocyte
4 major functions of platelets
1) adhesion/activation
2) aggregation
3) secretion
4) procoagulant activation
4 steps of platelet action mech of action
- platelet binds to subendothelial matrix von willebrand factor activating glycoprotein iib/iiia surface receptors
- Platelets cohere and aggregate and fibrinogen binds activated glycoprotein 2b/3a becoming fibrin
- Platelet granule proteins such as ADO, serotonin, factor V, and thromboxane are released
- Fibrin activates thrombin via the clotting cascade
Von Willebrand factor
An adherent glycoprotein on the sub endothelial matrix that allows for activation of glycoprotein IIb/IIIa surface receptors on thrombocytes to begin adhering to the surface
The most common herreditary bleeding disorder is….
…von wilibrand factor deficiency
Role of Ca2+ in clotting cascade
It acts as factor 4 in allowing fibrin to polymerize
Factor X
The convergent point between the extrinsic and intrinsic pathway that functions to convert prothrombin (factor II) to thrombin (factor IIa)
D dimer test function and why is it not sufficient?
Looks for breakdown of collagen chains indicating a clot has occurred in the body, but not specific as to where
The intrinsic clotting pathway is ___ than the extrinsic, the intrinsic involves ___ while extrinsic involves _____
Faster, factors in blood itself, tissue factor released from damaged vessels
Intrinsic clotting cascade pathway
Surface contact activates factor XII to XIIa, which activates factor XI to XIa, which activates IX to IXa, which activates VIII and Ca2+ (factor IV) to convert factor X to Xa
Extrinsic clotting cascade pathway
Tissue damage activates Tissue factor (VII), which activates factor X to Xa
List the vit K dependent procoagulants
Factor II, VII, IX, and X
Protein C and S action
Inactivate factor Va and VIIIa acting as a natural anticoagulant
Protein C and S deficiency results in…
Spontaneous thrombosis, suspected genetic inheritance in young with DVT or stroke
Factor V leidan definition
Mutation in factor V that allows it to resist protein C, resulting in increased venous thromboembolism
tPA function
Convert plasminogen to plasmin which will then degrade fibrin clots
Common forms of (4) endothelial injury
- atherosclerosis
- mechanical trauma
- hypoxia
- autimmune disorders
Name 3 thrombolytic agents
- streptokinase
- urokinase
- tPA activators
Disseminated intravascular coagulatoin (DIC) definition and some common causes (3)
Clotting cascade gone wild, with many small clots forming and affecting microcirculation leaving larger chance of bleeding excessively
- infection
- OB complication
- snake venom
Lab work for DIC will show ___ thrombocytes, ___ PT/INR, ___ PTT
low, prolonged, prolonged
Purpura definition
Large areas of skin discoloration due to blood leakage from a vessel in that spot
Petechiae definition
Small broken blood vessels on skin
How does ASA affect platelet function?
Binds COX irreversibly affecting thromboxane A2 preventing aggregation of platelets
The most common hypercoaguable disorder is…
…factor V leidan
Hemophilia A vs B vs C
Hemophilia A and B are the same presentation of deep tissue bleeding but B is due to christmas factor (IX), C is much less severe and just has prolonged bleeding
Protein S functions to activate….
….protein C
Hemolytic Uremic syndrome characteristics
Fever, purpura, severe CNS signs and involving kidneys
Belmont Report
Respect for persons that individuals are autonomous agents and make their own informed decisions and that those with diminished capacity (therefore diminished autonomy) should be protected (prisoners, children, handicapped), cornerstone document on ethical principles and HHS regulations for protection of research subjects
Material fact
What a reasonable patient would need/want to know to make a decision
Rule of double effect
The idea that one action could have 2 possible outcomes, one unethical and one ethical, but the guiding principle being intent
ex) if you alleviate pain with a narcotic but then the patient has a reaction and dies
Anti-kickback policy
Laws that prevent healthcare providers from referring to something that they profit off of
Who has a right to know the results of a test?
- Physician and other relevant healthcare providers
- the patient
- if the patient is a minor then the guardians
- any family the patient has approved to know
Gold standard test
The most accurate test possible under reasonable conditions, may not be able to perform due to complications
Can you tell a partner of a patient who has HIV and doesn’t want to share that info with them?(when is breach ethically justified?)
Yes because there is harm to a 3rd party and greater good would result from breaking confidentiality rather than maintaining it
Who created the PA profession? What day is National PA day/week?
Eugene A. Stead Jr, MD, October (6)-12
Beneficence
Act of kindness or charity, a duty to maximize benefits, prevent and remove harm, rescue those in danger
Autonomy
Respect for the patients right to remain in control of their lives
Non-maleficence
Do not kill, cause pain or suffering, incapacitate, cause offense, or deprive another of the goods of life
Utilitarianism
The doctrine that actions are right if they are useful for or benefit the majority (similar to consequentialism where if the outcome is good, it doesn’t matter the morality of the action - in this case if it benefits the majority)
Deontology/formalism
Theory that morality of an action should be based on whether that action itself is right or wrong under a set of rules rather than based on the consequences of that action (killing is wrong even in self defense)
Rules of discontinuing practice to a patient
- must supply 30 day of care after official notification
- must provide all medical records for their access
- must provide list of other providers that they can transfer to that are within their insurance plan
4 goals of medicine
- do no harm
- improve quality of life
- relieve pain and suffering
- extend life within construct
How long should a couple who is not conceiving go before undergoing a workup for complication?
12 months of unprotected sex under the age of 35, 6 months of unprotected sex over age 35
Coma definition
State of eyes closed, depressed consciousness from which a patient cannot be aroused by stimulus, distinguished from brain death by presence of brainstem responses, spontaneous breathing sometimes, or non-purposeful motor responses, either ends in progression to brain death, recovery of consciousness, or evolution to vegetative or minimally conscious state
Vegetative state definition
Severely impaired consciousness, although eyes may open spontaneously, but no awareness of environment, many patients do not acknowledge the examiner, they do not attend or track objects presented to them, movements are nonpurposeful, do not speak
Minimally conscious state definition
Severe alteration to consciousness, with intermittent but inconsistent, behaviors suggesting awareness, in contrary to patient in coma or vegetative state, may occasionally have purposeful movements and may track motions with eyes or speak slightly
Persistent vegetative state
Distinct from total brain death (le coma depasse), disorder where have severe brain damage and are in state of partial arousal rather than true awareness, has irregular but cyclic state of circadian sleeping and waking and may show primitive postural and reflex limb movements but no recognition of external stimuli or evidence of awareness, grasp or DTR’s may be intact, classified after 4 weeks of being in it defining it as persistent
Locked in state definition
When there is injury to brain where there is paralysis, may be able to track objects with eyes but can’t move but can’t speak but fully conscious
Kidney homeostatic functions (6)
- filters blood plasma eliminating waste, free radicals and drugs
- regulates blood volume and pressure
- regulates osmolarity of body fluids
- secretes renin
- secretes erythropoietin
- Activates vitamin D
Renin definition
Major component of the RAAS which allows the kidneys to control the body’s BP by regulating fluid volume
Erythropoietin definition
Hormone released in response to low plasma o2, acts on hemocytoblasts to convert them into erythrocytes to increase the number in circulation
Vitamin D3 activation by the kidney
Kidney functions to convert vit D3 to active form vit D2
Where is the kidney in relationship to the peritoneum?
Retroperitoneal - behind the peritoneum
Urine flow pathway from collecting duct to exit
- Collecting duct
- Renal papilla
- Minor calyx
- Major calyx
- Renal pelvis
- ureter
- bladder
- urethra (prostatic, membranous, spongy in men, just urethra in women)
Renal pyramids and renal columns definition
Renal pyramids are the triangles pointed toward the center of the kidney that are composed of the renal medulla
Renal columns are the projections that fill the space between the renal pyramids
2 types of nephrons and their definition
1) cortical - short nephron loops that have a shorter loop of henle that dips into the outer medulla
2) Juxtamedullary - long nephron loops with longer glomeruli that dip into the deeper medulla and are extremely important in maintaining a salt gradient as well as conserving water
How many nephrons are there in a kidney?
Approx 1 million
Components of a renal corpuscle (2)
- Glomerulus
- Bowman’s capsule
The afferent arteriole entering the glomerulus typically has ___ hydrostatic pressure relative to the efferent and is thus vaso____
higher, vasodilated
Portions of the nephron from glomerulus to collecting duct (6)
- Glomerulus
- proximal convoluted tubule
- Descending loop of henle
- ascending loop of henle
- distal convoluted tubule
- collecting duct
Glomerulus definition and function
A tuft of blood vessels from the afferent arteriole that allow for fluid filtration of the blood into the proximal convoluted tubule before the capillaries converge and exit as the efferent arteriole
Bowman’s capsule definition and function
Visceral and parietal epithelial cell layers surrounding and below a basement membrane of the glomerulus containing podocytes where fluid can pass onward into the proximal convoluted tubule from the glomerulus
Podocytes definition and function
Cytoplasmic extensions that wrap around capillaries of the glomerulus from bowman’s capsule, have openings called filtration slits that limit the substances that can be filtered through relaxation and contraction
Type of capillaries located in the glomerulus
Fenestrated
Filtration membrane of the glomerulus definition, and the 3 layers that make it up
Filtration membrane is the thickness between the endothelium of the capillary to the space of bowman’s capsule, the 3 layers are the 1)fenestrated endothelium, 2)basement membrane, and 3)filtration slits of the podocytes
Blood pathway through the kidney from renal artery to renal vein
- renal artery
- interlobar arteries traveling up columns of the kidney
- arcuate arteries that travel across pyramids of the kidney
- interlobular arteries that travel into the cortex
- afferent arterioles
- glomerulus
- efferent arterioles
- peritubular capillaries surround tubular portion of nephron capturing and reabsorbing substances
- interlobular vein
- arcuate veins
- interlobar veins
- renal vein
Juxtaglomerular apparatus definition and function
A specialized structure composed of macula densa, juxtaglomerular cells, and mesangial cells that functions to rregulate filtrate formation and systemic BP
Macula densa defnition and function
epithelial cells in the distal convoluted tubule adjacent to juxtaglomerular cells part of the juxtaglomerular aparatus. Senses changes in solute content of filtrate (decreased Na+) in lumen and secretes paracrine messenger to sitmulate JG cells
Juxtaglomerular cells definition and function
Modified smooth muscle cells that form a cuff around the afferent arteriole as it moves to the glomerulus part of the juxtaglomerular apparatus. Contains renin granules and are stimulated to release by acting as mechanoreceptors that directly sense BP in afferent arterioles
Mesangial cells definition and function
Cells between the afferent and efferent arterioles and among capillaries of the glomerulus part of the juxtaglomerular apparatus. Thought to mediate communication between juxtaglomerular cells and macula densa (i.e. macula densa at distal tubule sends paracrine signals thru messangial cells to reach JG cells to release renin)
Renal plexus definition and function
sympathetic division ANS nerves that follow the renal artery and function to regulate the rate of bloodflow thru the kidneys by regulating diameter of arterioles, can very quickly adjust blood flow
3 general processes in the formation of urine
1) glomerular filtration
2) tubular reabsorption into peritubular capillaries from nephron
3) tubular secretion from renal capillaries to nephron
Some drugs such as ___ and ____ are secreted via tubular secretion
NSAIDS, cephalosporins
How much renal filtrate is reabsorbed into the blood stream?
As much as 99%
Net filtration pressure is formed from these three components
- Blood hydrostatic pressure going into the proximal convoluted tubule (largest, variable)
- Colloid osmotic pressure pulling fluid into the efferent arteriole
- Capsular pressure pulling fluid into the efferent arteriole
Glomerular filtration rate definition (GFR)
Amount of filtrate formed by kidneys in 1 minute
How much urine is excreted per day
1 to 2 liters
Autoregulation of arterial pressure by kidneys definition
Refers to intrinsic ability of kidney to continually adjust to keep GFR constant over a wide range of arterial pressure (90-190mmHg)
When there is increased BP, the kidney will ___ afferent arteriole and ___ efferent arteriole
Constrict, dilate
When there is decreased BP, the kidney will ___ afferent arteriole and ___ efferent arteriole
Dilate, constrict
Constriction of any blood vessel causes ___ pressure upstream and ___ pressure downstream
Increased, decreased
3 mechanisms of renal autoregulation of GFR
1) myogenic mechanism
2) tubuloglomerular feedback
3) RAAS
Myogenic mechanism of renal autoregulation of GFR definition
Increased systemic BP causes afferent arteriole constriction due to vascular smooth muscle response to stretch, lowering glomerular BP and preventing it from rising too high and reducing GFR
Tubular feedback mechanism of renal autoregulation of GFR definition
JG cells sythesize, store, and release renin stimulated by hypovolemia or decreased renal perfusion
The macula densa detects flow or changes in filtrate at the distal convoluted tubule (decreased Na+) due to decreased GFR and stimulate paracrine messengers causing JG cells to relax dilating and increasing GFR to normal
How does angiotensin II cause increase in GFR
It acts as a potent vasoconstrictor of efferent arterioles at low concentrations
Nervous overriding of renal autoregulatory mechanisms
During extreme stress when blood must be shunted to heart, brain, and skeletal muscle at expense of kidneys and to conserve water (to maintain BP), the SANS releases epi and NE that strongly constrict afferent arterioles decreasing GFR greatly
The SANS can stimulate ___cells under extreme stress which activates the ___ system and causes increased vasoconstriction of both ___ and ____ arterioles. When this happens, there is…
JG, RAAS, afferent, efferent
…no blood coming in or going out of the kidney
3 hormones that cause vasoconstriction, decreasing renal blood flow and GFR
1) epi
2) norepi
3) angiotensin II
Explain how NSAIDS and ASA in high enough dosages can cause renal failure
-Prostaglandins that act as vasodilators are released by endothelium in arterioles, if formation and release inhibited blood flow may become too low due to excessive constriciton of the vasculature
Renin angiotensin aldosterone system mechanism of action
- JG cells release renin in response to reduced stretch caused by drop in BP or by macula densa stimulation due to decreased Na+ in filtrate or via sympathetic stimulation
- Liver constantly secretes angiotensinogen into blood stream
- Renin splits angiotensinogen to angiotensin I
- Angiotensin I is converted to Angiotensin II by ACE found primarily in lungs (activated when agiotensin I moves thru pulmonary circulation)
- Angiotensin II causes predominant constriction of efferent arteriole but in high conc can impact afferent as well
- Angiotensin II sitmulates release of aldosterone by adrenal cortex causing Na+ retention at the collecting duct, H2O follows
- BP returns to normal
Angiotensin II action on hypothalamus
Increase thirst
Atrial natriuretic peptide mech of action (ANP) (Note that it has action on vessels, sodium conc, and other hormonal systems)
- Polypeptide produced by atrial heart muscle
- stimulated for release due to atrial distension (hypervolemia)
- Increases vasoconstriction of efferent arteriole
- Dilation of afferent arteriole
- Increases Na+ loss
- Inhibits aldosterone and renin
Reabsorption in the proximal nephron mechanism of action
- In the tubular cells, the luminal side faces toward the nephron has several Na+ energy dependent cotransporters (glucose, AA, etc) to bring in and reabsorb nutrients (as well as water that follows
- This Na+ transport moves down its conc. gradient because of low Na+ conc. in the cell because on the basal side facing toward the interstitial space and thecapillary has many Na+/K+ pumps that actively pump out Na+
Aldosterone mech of action
-Increases reabsorption of Na+ ions and excretes K+ ions by increasing Na+ K+ ATPase activity in distal and collecting tubule cells
Solvent drag definition
Tendency for water absorbed by osmosis to carry other solutes with it
ADH/vasopressin mech of action (include where it is produced and stored)
- Produced in hypothalaus
- stored in posterior pituitary
- drop in pressure directed by baroreceptors in aorta and carotids or dehydration stimulate hypothalamus
- hypothalamus stimulates posterior pituitary
- ADH increases water absorption by binding the distal convoluted tuble and collecting duct and allowing aquaporin activation to decrease urine volume
Creatinine reabsorption and why is it useful?
Not reabsorbed so useful measurement of GFR and glomerular function
Substances that undergo tubular secretion from blood into renal tubules (3)
-ammonia
H+ ions
-K+ ions
Countercurrent multiplier of loop of henle mech of action
- As water moves down descending loop of henle, osmolarity continues to rise from 300 to 1200 mOsm in the interstitial space, drawing out more and more H2O
- The more water that leaves the descending limb, the saltier the remaining fluid in the tubule
- At the ascending limb, the ions are pumped into the interstitial fluid while it remains impermeable to water at this point
- The more salt that is pumped out of the ascending limb, the saltier the interstial space is for the water
- Vasa recta descending capillaries see water diffuse out of blood and NaCl diffuse into blood
- Vassa recta ascending capillaries see water diffusing into blood and NaCl out of blood, encouraging much greater water retention
Items absorbed in the proximal tubule, loop of henle, distal tubule, and colelcting duct
Proximal - Na+ maority, gluose, amino acids, K+, urea
Loop of henle descending - H2O reabsorption
Loop of henle ascending - Na+ reabsorption, impermeable to water
Distal - very little
Collecting duct - H2O mainly
Inhibitor of ADH release
alcohol
Aldosterone functionally decreases this ion and increases this ion both in blood levels.
It is what kind of hormone?
K+, Na+
Steroid
Caffeine mech of action as a diuretic
Dilates afferent arteriole, increases cardiac output driving blood flow to kidney resulting in increased GFR
Vit D2 function
Active form of vitamin D that causes increased absorption of Ca2+ and phosphorus in small intestine
Simple explanation of kidney acid base balance regulatory function
- Acidic blood causes more H+ secretion into filtrate and more HCO3- ions reabsorbed into blood
- Basic blood causes less H+ reabsortpion into blood and more HCO3- secretion into filtrate
Trigone definition, what can inflammation of it cause?
Little space between ureters and urethra on base of bladder that can become inflamed and cause interstitial cystitis
Internal urethral sphincter is __ muscle part of the ___ muscle and external is ____ muscle
Smooth, detrusor, skeletal
Micturition reflex
- stretch receptors upon 200mL of urine in bladder send signal to spinal cord (S2, S3)
- Parasympathetic reflex arc from spinal cord stimulates contraction of detrusor muscle
- relaxation of internal urethral sphincter
- sensory fibers also go up to brain in pons and allow it to analyze and keep external muscles tight preventing urination
