Kidney Embryology (Renal Emb)

Def: Kidney has specific developmental pattern

Pronephros
-wk 4, then degenerates

Mesonephros
-1st trimester kidney, then degenerates
=genital system in males

Metanephros (main kidney part)

-Ureteric bud= ureter, pelvises, calyses, collecting
duct
-Metanephric mesenchyme: interaction makes
the actual glomerulus to distal convuluted
tubules (most of nephron)

*ureteropelvic junction: most common site of

obstruction (hydronephrosis) in fetus
Potter's sequence (syndrome)
(Renal Emb)

Def: Atypical physical appearance of a fetus or

neonate due to oligohydramnios experienced in
the womb. Oligohydramnios is the decrease in
amniotic fluid volume sufficient to cause
deformations in morphogenesis of the fetus

Causes: ARPKD, bilateral renal agenesis

-results in no amniotic fluid flow

Sx:
-face and extremities compressed and distorted
-lungs compressed (pulmonary hypoplasia)
-renal failure (in utero)
Horseshoe kidney (Renal Emb)

Def: In this disorder, the patient's kidneys

inferior poles fuse together to form a
horseshoe-shape during development in the
womb. The fused part is the isthmus

-trapped under inferior mesenteric artery

Sx:
functions normally, hydronephrosis, increased
risk of ureteropelvic junction obstruction
Multicystic dysplastic kidney (Renal
Emb)

Def: Multicystic dysplastic kidney (MCDK) is a

condition that results from the malformation of
the kidney during fetal development

PPX:
-abnormal ureteric bud and metanephric
mesenchyme interaction
-often unilateral with contralateral hypertrophy

Dx: often prenatally Ultrasound

Kidney anatomy and glomerular
structure (Renal Anat)

Def: Kidney and glomerulus have specific

anatomy and structure

Renal vasculature
renal a.
segmental a.
interlobular a.
arcuate a.

Glomerulus
-macula densa connects with juxtaglomerular
cells
Ureters: course (Renal Anat)

Def: Ureters pass specific route to bladder

Ureters pass under:

vas deferens (male)
uterine artery (female)

Gynecology procedures need to be careful of

ureters
Fluid compartments (Renal Phys)

Def: Fluid in body is split into various

compartments

60-40-20 Rule
60% TBW = water
40% TBW = Intracellular (high [K])
20% TBW = Extracellular

albumin= measures plasma volume

inulin= measures extracellular volume
Glomerular filtration barrier (Renal
Phys)

Def: Glomerulus filters based off charge and size

capillary endothelium (filters by size)

Basement membrane (filters by charge)

-nephrotic syndrome this is damaged

epithelial layer (has podocyte foot processes)

Renal clearance (Renal Phys)

Def: The volume of plasma from which a

substance is completely removed by the kidney
in a given amount of time

C = UV/P
Glomerular filtration rate (GFR)
(Renal Phys)

Def: it estimates how much blood passes

through the tiny filters in the kidneys, called
glomeruli, each minute

GFR = Clearance of inulin

-since no reabsorption and no secretion
-normal ~ 100mL/min

*creatine is secreted so can overestimate GFR

*GFR decreases with chronic kidney disease
Effective renal plasma flow (ERPF)
(Renal Phys)

Def: GFR plus how much plasma is secreted

inside

-All PAH entering kidney is both filtered and

secreted (none leaves as renal vein)
*ERPF = Clearance of PAH

ERPF underestimates RPF by approx. 10%

Filtration (Renal Phys)

Def: How much of what passes through kidney is

because of glomerular filtration

Normal FF~ 20%

GFR (inulin clearance, creatine overestimates)

RPF (PAH)
Changes in glomerular dynamics
(Renal Phys)

Def: Different pressure changes can change how

much is filtered or secreted

afferent arteriole constriction:

-less GFR, Less RPF

efferent arteriole constriction:

-more GFR, less RPF

Plasma protein concentration

-pulls water back, affecting GFR only

Constriction of ureter
-increases Bowman space pressure
Calculation of reabsorption and
secretion rate (Renal Phys)

Def: Different things can be calculated for

kidney function
Glucose clearance (Renal Phys)

Def: Glucose is reabsorbed in the PCT

200 mg/dL (plasma) is threshold for glucosuria

~375 mg/dL (plasma) T.m (saturation of

transport)

*Pregnancy decreases PCT reabsorption

Amino acid clearance (Renal Phys)

Def: Sodium-dependent transporters reabsorb

amino acids in the PCT

Hartnup Disorder
-AR
-neutral AA transporter deficiency (eg.
tryptophan)
-neutral aminoaciduria, less gut absorption

Sx:
Pellegra-like (tryptophan)

Tx:
-high protein diet
-nicotinic acid (which tryptophan usually
becomes)
Nephron Physiology (Renal Phys)

Def: Nephron has 6 parts with unique functions

PCT
-brush border Reabsorbs a lot including gluc, AA
-secretes creatine, uric acid, diuretics

Thin Descending Loop of Henle

-only permeable to water
-makes urine more concentrated

Thick Ascending Loop of Henle

-mainly reabsorbs Na, K, Cl, Mg, Ca
-makes urine less concentrated

Proximal DCT
-PTH increases Ca reabsorption

Distal DCT
-Aldosterone regulates K, H secretion via Na
reabsorption

Collecting Duct
-ADH inserts aquaporins to reabsorb water
Renal tubular defects (Renal Phys)

Def: Various reabsorption problems in the

nephron can cause syndrome type problems

Fanconi (Wilsons = AR)

PCT

Bartter (AR)
ALH
*less K, Ca switching causes hypercalciuria

Gitelman (AR)
DCT
*K, Ca switching not relevant here

Liddle (AD)
CD
Relative concentrations along
proximal tubule (Renal Phys)

Def: Along PCT different things are reabsorbed

at different rates as a function of distance

Inulin increases in [Tubular Fluid] concentration

because of loss of water

Chloride relatively less reabsorbed in beginning

then rate increases distally to match Na rate
Renin-angiotensin-aldosterone
system (Renal Phys)
Def: A hormone system that regulates blood
pressure and water (fluid) balance

Low BP causes renin release eventually leads to

Angiotensin II

Angiotensin II has various important effects

-ADH (posterior pituitary) acts on CD
-Hypothalamus (more thirst)
-Artery smooth muscle (vasoconstriction)
-Aldosterone (from adrenal cortex) acts on DCT
Juxtaglomerular apparatus (Renal
Phys)

Def: Located on afferent arteriole to sense

lowered pressure

1. JG (arteriole) and MD (DCT) sense low BP

2. Renin secreted by JG converts to Angiotensin I
3. ACE converts to Angiotensin II
4. vasoconstriction, ADH + Aldosterone release
5. Aldosterone = Increased renal Na reabsorption
Kidney endocrine functions (Renal
Phys)

Def: Kidney has various endocrine functions

Eryhtropoietin:
-during hypoxia it is released and causes bone
marrow to release eryhtrocytes

1,25 (OH)2 Vit D

-PTH helps convert 25-OH vit D to this which then
goes to the gut

Renin
-helps regulate blood pressure

Prostoglandins
-paracrine secretion to increase RBF
*NSAIDS block renal-protective prostoglandin
synthesis
Hormones acting on kidney (Renal
Phys)

Def: Few important hormones have an effect on

the kidney

ANP
-More Na via more GFR
-Less Na reabsorption in DCT

AT II
-constricts efferent arteriole and compensatory
Na reabsorption later

PTH
-Either to increase Ca, Vit D or decrease plasma
PO43

Aldosterone
-More Na reabsorption
-More K, H secretion

ADH
-More water reabsorption due to either high
plasma osmolarity or low blood volume
Potassium shifts (Renal Phys)

Def: Potassium balance is important for

physiology
Electrolyte disturbances (Renal
Phys)
Def: Certain electrolytes need to be balanced in
physiological conditions
Acid-base Physiology (Renal Phys)

Def: Perturbations of bicarbonate or pressure of

gaseous carbon dioxide either from respiration
or kidneys can cause acid-base physiology
changes

Henderson-Hasselbalch eq
pH = 6.1 + log ( [HCO3-] / .03*PCO2 )

Winters Formula
PCO2 = 1.5*[HCO3-] + 8 +/- 2
-calculates predicted respiratory compensation
*if measured differs then think mixed acid-base
disorder
Acidosis/alkalosis (Renal Phys)

Def: Disturbances in PCO2 and/or bicarbonate

can indicate presence of acid-base type
disorders
Renal tubular acidosis (RTA) (Renal
Phys)
Def: a medical condition that involves an
accumulation of acid in the body due to a failure
of the kidneys to appropriately acidify the urine
Casts in urine (Renal Path)

Def: Urine casts help decipher what may be the

causative reason for kidney dysfunction
Nomenclature of glomerular
disorders (Renal Path)

Def: Different descriptives can help describe and

characterize glomerular diseases

membraneous = thickening of glomerular

basement membrane

prolferative = hypercellular glomeruli

Glomerular diseases (Renal Path)
Def: Distinguishing nephrotic or nephritic type
of glomerular disease can then help narrow
down differential diagnosis

nephrItic (I give U H2O)

Inflammation
Uremia
Hematuria
Hypertension
Oliguria

nephrOtic (paleo diet)

Protein urine
Albumin urine (podocyte gaps)
Lipid casts (hyperlipidemia)
Edema due to albumin loss
0
Nephrotic syndrome (Renal Path)
Def: Group of Kidney diseases which present
with Nephrotic type symptoms
Nephritic syndrome (Renal Path)

Def: Group of Kidney diseases which present

with Nephritic type symptoms
Kidney stones (Renal Path)
Def: a solid concretion or crystal aggregation
formed in the kidneys from dietary minerals in
the urine
Hydronephrosis (Renal Path)
Def: Refers to distension and dilation of the
renal pelvis and calyces, usually caused by
obstruction of the free flow of urine from the
kidney

Cause: urinary tract obstruction

* prostate hyperplasia (BPH)
* cervical cancer
* stones
* retroperitoneal fibrosis
* vesicouretral reflex

Short term effect: calyx and pelvis distension

Long term Effect: renal cortex and medulla

atrophy

*worst if both kidneys damaged

Renal cell carcinoma (Renal Path)

Def: A type of kidney cancer that starts in the

lining of very small tubes (PCT origin) in the
kidney

1) Start: Polygonal “clear cells” of PCT

*filled with lipids and carbs
2) Invades renal vein then invades IVC
3) Spreads then to lungs and bones

*Chromosome 3 tumor suppressor (von Hippel-

Lindau if inherited)

*Often metastatic so “silent” and resistant to

chemo and radiation therapy
Renal oncocytoma (Renal Path)

Def: Oncocytoma is an epithelial tumor

composed of oncocytes, large eosinophilic cells
having small, round, benign-appearing nuclei
with large nucleoli with excessive amounts of
mitochondria

Benign

Often originates from collecting duct cells

Eosinophilic cells, many mitochondria, no

perinuclear clearing (chromophobe if there is
clearing)
Wilms' tumor (nephroblastoma)
(Renal Path)

Def: Wilms' tumor is a rare kidney cancer that

primarily affects children

Ages 2-4

Embryonic glomerular structures linger

PPS: WT1/WT2 TS loss of function (Chrom 11)

*Beckwith-Wiedemann = Chrom 11 imprinting
*WAGR syndrome from deletion of Chrom 11
Transitional cell carcinoma (Renal
Path)

Def: Most common type of bladder cancer and

cancer of the ureter, urethra, and urachus

Sx: painless hematuria with no casts

Associations:
P- Phenacetin
S- Smoking
A- Aniline dyes
C- Cyclophosphamide
Squamous cell carcinoma of the
bladder (Renal Path)

Def: Squamous metaplasia leads to cancer in the

bladder

Sx: Painless hematuria

Risk factors:
-Schistosoma haematobium (Middle East)
-chronic cystitis
-smoking
-chronic nephrolithias
Acute infectious cystitis (Renal Path)

Def: Inflammation of the urinary bladder or

urinary tract

Sx:
suprapubic pain
dysuria

Risk factors:
-female shorter urethras
-”honeymoon cystitis”
-indwelling catheters

Causes:
-E Coli (most common)
-Staph saprophyticus (young sexualy active
woman)
-Klebsiella
-Proteus mirabilis
-Adenovirus (hemorragic)

Labs:
leukocyte esterase (+)
nitries (+) in gram neg. organisms
pyuria and (-) urine = chlamydia or gonorrhoeae
Pyelonephritis (Renal Path)

Def: An inflammation of the renal parenchyma,

calyces, and pelvis

Affects cortex and spares glomeruli

Sx: costovertebral tenderness

Cause: ascending UTI (often E Coli)

Lab: White cell casts

Risk factors: indwelling catheter, UTI, DM,

pregnancy

Complications: renal papillary necrosis,

perinephric abscess

Tx: antibiotics

*lots of acute can cause chronic pyelonephritis

= (scarring, eosinophilic casts resembling thyroid)
Drug-induced interstitial nephritis
(tubulointerstitial nephritis) (Renal
Path)
Def: Kidney diseases that involve structures in
the kidney outside the glomerulus. These
diseases generally involve tubules and/or the
interstitium of the kidney and spare the
glomeruli, as shown in the image below

Causes
-1-2 weeks after certain drugs (diuretics,
penicillin derivatives, sulfamides, rifampins)
-months after NSAID

Lab
Pyuria (eosinophils classically)
azotemia (hapten induced hypersensitivity)

Sx
fever, rash, hematuria
Diffuse cortical necrosis (Renal Path)

Def: Acute infarctaion of both kidneys

generalized to cortex

Causes:
-likely vasospasm/ DIC (disseminating
intravascular coagulation) combination

Associations:
-obstetric catastrophes and septic shock
Acute tubular necrosis (Renal Path)

Def: medical condition involving the death of

tubular epithelial cells that form the renal
tubules of the kidneys

Most common cause of renal failure

Casts: Muddy brown” granular

3 stages
1. inciting event
2. maintenance (oliguria, risk of hyperkalemia,
metabolic acidosis)
3. recovery (polyuria, risk hypokalemia)

Causes
1. ischemia
-due to less renal blood flow
2. toxicity
-toxic substances, injury,
*aminoglycosides, lead, cisplatin
Renal papillary necrosis (Renal Path)

Def: The renal papilla is the location where the

medullary pyramids empty urine into the minor
calyx in the kidney

Causes
recent infection or immune stimulus

Associations
-DM
-acute pyelonephritits
-chronic phenacetin use
-sickle cell anemia

Sx
gross hematuria and proteinuria
Acute renal injury (acute kidney
failure) (Renal Path)

Def: Abrupt decline in renal function with

increased creatine and BUN over a period of
several days

Prerenal
-Hypotension
-Converve water (conc urine)
-keep Na (low urine Na)
-keep urea (high BUN/Cr)

Intrinsic
-Less GFR, some epithelial/granular casts
-kidney/glom damage so more Na out (FENa)
-tubule damage, less BUN reabs (less BUN/Cr)

Postrenal
-some obstruction usually
- only severe when it backs into kidney (FENa)
Consequences of renal failure (Renal
Path)

Def: Inability to make urine and excrete

nitrogenous wastes

Acute (ATN)
Chronic (HT, DM, Congenital)

Metabolic Acidosis
Dyslipidemia
Hyperkalemia
Uremia
Na retention
Growth retardation
Erythropoietin failure
Renal osteodystrophy
Renal osteodystrophy (Renal Path)

Def: 1a-hydroxylase problem so less calcium and

phosphorus absorption

Kidney failure

1a-hydroxylase does convert 25vitD to 1,25vitD

Thus less Calcium and PO4 can be absorbed in

the intestine

Leads to bones having to release the Calcium and

PO4

Problem with SLC transporter leads to excess PO4

and less Calcium
*Hyperphosphatemia can promote tissue
calcification so even lower Calcium

=subperiosteal bone thinning

Renal cyst disorders (Renal Path)

Def: Cysts form around kidney and impair

normal function

Simple Cyst:
-usually in outer cortex
-majority and not that bad

Complex Cyst:
-often septated and have solid component
-removal (risk of renal cell carcinoma)
Diuretics: site of action (Renal Phrm)

Def: Various diuretics act in different locations

Mannitol (Renal Phrm)
Def: Osmotic Diuretic

Mechanism
-increases tubular fluid osmolarity
-increased urine flow

Clinical Use
-drug overdose
-to decrease intracranial/ocular pressure

Toxicity
-pulmonary edema
-dehydration
-anuria (contraindicated)
-CHF
Acetazolamide (Renal Phrm)

Def: Carbonic anhydrase inhibitor diuretic

Mechanism
-blocks HCO3 based diuresis

Clinical Use
-Glaucoma
-metabolic alkalosis
-altitude sickness
-pseudotumor cerebri

Toxicity
-Hyperchloremic metabolic acidosis
-paresthesias
-NH3 toxicity
-sulfa allergy
Loop diuretics (Renal Phrm)

Def: Diuretic that work in the loop of Henle

*Furosemide
Mechanism
-sulfa inhibits NaKCl cotransport
-stimulates PGE for afferent dilation
-NSAIDs inhibit
-increase Ca2+ excretion

Clinical Use
-edematous states, HT, hypercalcemia

Toxicity
Ototoxicity, Hypokalemia, Dehydration, Allergy
(sulfa), Nephritis (interstitial), Gout

*Ethacrynic acid
=same as furosemide but phenoxyacetic acid
instead of sulfa (for Sulfa allergies)
Hydrochlorothiazide (Renal Phrm)

Def: Distal convoluted tubule diuretic

Mechanism
-blocks NaCl reabsorption
-keeps Ca2+ in body (vs Loop = more exretion)

Clinical Use
-HT, CHF, hypercalciuria
-nephrogenic DI, osteoporosis

Toxicity
-HypoKalemic metabolic acidosis
-hyponatremia
-hyperGlycemia, hyperLipidemia, hyperUricemia,
and hyperCalcemia
-sulfa allergy
K+-sparing diuretics (Renal Phrm)

Def: Early part of collecting duct causes diuresis

while keeping K+ in the body

*Spironolactone, eplerenone; Triamterene, &

Amiloride

Mechanism
Either block aldosterone (S&E) or block Na
channels (T&A) thus leading to less K+ and H+
excreted in urine

Clinical Use
-Hyperaldosteronism, K+ depletion
-CHF

Toxicity
-Hyperkalemia (ever more K leads to
arrhythmias)
-Spironolactone can cause endocrine effects
(gynecomastia, antiandrogen effects)
Diuretics: electrolyte changes (Renal
Phrm)

Def: Diuresis can lead to changes in blood and

urine electrolyte levels

Urine NaCl
-all increase (except carbonic anhydrous inh)

Urine K+
-most increase (except K sparing)

Blood pH
-Acidic (carbonic anhydrous inh, K sparing)

-Basic (loop diuretics and thiazides)

1. more AT2 = more Na/H exchange = more
HCO3- reabsorption <contraction alkalosis>
2. K urinated = more H/K exchange in cells
3. Low K states = Na/H exchange instead of Na/K
in collecting tubule <paradoxical aciduria>

Urine Ca
* loop diuretics = more Ca also stays in nephron
* thiazides = more Ca can be reabsorbed in DCT
ACE inhibitors (Renal Phrm)

Def: Major drug for HT and CHF

Mechanism
1. less GFR (less vasoconstriction of efferent)
2. prevents inhibition of bradykinins (which
normally vasodilate)

*-sartans (angiotensin II receptor blockers) have

similar effect wihtout increased bradykinin = less
risk of cough and angioedema

Clinical Use
-HT, CHF
-proteinuria, diabetic nephropathy

Toxicity
-Cough
-angioedema (contraindicated: C1 esterase
inhibitor def)
-Teratogen (fetal renal formation)
-high creatinine (bc of less GFR)
-Hyperkalemia and Hypotension
-avoid in bilateral stenosis because even less GFR
results in renal failure
Respiratory tree (Resp Anat)

Def: Different types of cells exist along the

respiratory tract

Conducting Zone
-warms, humidifies, and filters air
-cartilage and goblet cells up to end of bronchi
-preudostratified ciliated columnar cell up to
terminal bronchiole => then becomes cuboidal
cells
-smooth muscles up to terminal bronchioles

Respiratory Zone
-lung parenchyma participating in gas exchange
-mostly cuboidal and simple squemous cells
*macrophages which clear debris
Pneumocytes (Resp Anat)
Def: Cells lining the alveoli important for various
functions

Type 1
-majority of surface and important for gas
diffusion

Type 2
-secrete surfactant and prevent atelectasis
-precursor cell also for both Type 1 and 2
*Collapsing pressure = 2(SurfTens) /Radius

**surfactant
-complex mix of lecithins (most important is
dipalmitoylphosphatidylcholine)
- lechtin/sphingoyemlin > 2 healthy fetal lung
-produced week 26-35 of gestation

Clara
-secretory granules important for surfactant and
degrading toxins
Lung relations (Resp Anat)

Def: Each lung has different number of lobes

and different relation to pulmonary arteries

Right has 3 lobes

Left less lobes and lingula (middle homologue)

*Upright things fall into lower right lobe

*Supine things fall into upper right lobe

Cross sections of hilus: “RALS” can show which

lung it is
Diaphragm structures (Resp Anat)

Def: Diaphragm is a dome-shaped, muscular

partition separating the thorax from the
abdomen in mammals important for breathing

I ate ten eggs at midnight(12)

T8: inferior vena cava
T10: esophagus
T12: aortic hiatus

Diaphragm innervated by phrenic nerve

*C3, 4, 5
-referred pain trapezius (C3, 4) shoulders (C5) if
pain from diaphragm irritation
Lung volumes (Resp Phys)

Def: Lungs can hold various amounts with

different breathes

IRV-inspire reserve volume

TV- normal tides of breath (~500mL)

ERV-expire reserve volume

Residual volume- air after maximal expiration

SUMS
1) inpiratory capacity (IC) = tidal + IRV
2) fxnal residual (FRC) = air after tidal expiration
3) vital capacity (VC) = total breath that can be
breathed in or out
4) total lung capacity (TLC) = maximum lung air
capacity
Determination of Physiologic dead
space (Resp Phys)

Def: Volume of air which is inhaled that does

not take part in the gas exchange, because (1)
remains in the conducting airways, or (2)
reaches alveoli that are poorly perfused

Dead space (VD)

= Tidal volume X (PaCO2 -PECO2)/PaCO2
*Pa = arterial CO2
*PE= expired air CO2

VA= alveolar ventilation

P= perfusion
Ventilation (Resp Phys)
Def: movement of air between two areas

Minute ventilation
-the total volume of gas entering the lungs per
minute

Alveolar ventilation
-the volume of gas per unit time that reaches the
alveoli
Lung and chest wall (Resp Phys)
Def: Lung compared to chest pressures dictate
how the system works

Lung- collapse with pressure

chest- expand with pressure

At Forced Residual capacity (after tidal expire)

-system at atmospheric pressure and balanced
*airway and alveolar pressure 0
*intrapleural pressure is negative (preventing
pneumothorax)
*Pulmonary vascular resistance is minimum

Compliance - how much volume changes for

changes in pressure
*decreases- fibrosis, pneumonia, edema
*increases- emphysema, aging
Hemoglobin (Resp Phys)
Def: Hemoglobin is a protein in red blood cells
that carries oxygen

Structure- has 2 alpha and 2 beta polypeptides

and heme groups that carry Oxygen

Relaxed gets oxygen from lungs

Taut form releases oxygen to tissues

*promoted by various substances and temp
*2,3-BPG less in HBFetal
Hemoglobin modifications (Resp
Phys)

Def: Hemoglobin can change structure with

certain groups and have less of oxygen delivery
to tissue

Methemoglobin
-oxidized Fe3+ form binds CN- more than O2
-nitrites can oxidize methylene blue can treat
*Cyanide poisoning can be treated with nitrites
and thio- binding to CN- group for excretion
-Sx: cyanosis and chocolate rain

Carboxyhemoglobin
-carbon monoxide affinity 200x of O2
-left shift in oxygen-hemoglobin curve
Oxygen-hemoglobin dissociation
curve (Resp Phys)

Def: Hemoglobin has different affinities for

oxygen depending on pressures and how much
bound

Sigmoidal shape - due to positive cooperativity

(not present in myoglobin which binds only 1 O2)

Right shift- less O2 affinity at a given pressure

-more oxygen to tissues
*2,3 BPG, Altitude, Temperature, Acid, CO2,
Exercise
*decrease in factors shifts it to the left
*HbF binds O2 stronger so shifted lift

Competitive inhibitors- decrease maximum

saturation of Hb (CO is example)
Oxygen content of blood (Resp Phys)
Def: Different situations can cause increase or
decrease in amount of oxygen in the blood. If
the level is below 90 percent, it is considered
low resulting in hypoxemia

O2 content = Hb + dissolved
= (binding cap *
% sat) + dissolve

O2 binding = 1.34 mL/g Hb

normal Hb = 15 g/dL
Thus binding capacity = 1.34*15
= 20.1 mL O2/dL

O2 delivery to tissues = CO * O2 content

*cyanosis = > 5 g/dL deoxygenated

*Polycythemia = more RBC % in blood
Pulmonary circulation (Resp Phys)

Def: Pulmonary circulation is the portion of the

cardiovascular system which carries
deoxygenated blood to lungs and returns
oxygenated blood back to the heart

Pulmonary vasculature
-typically low R, high compliance
-less alveolar O pressure = vasoconstriction
-Pulmonary HT = cor pulmonale = RV failure

Perfusion Limited
-depends on blood flow how much diffuses
*O2, CO2, N2O
*to increase diffusion must increase blood flow

Diffusion Limited
-diffusion properties (eg. membrane) determine
*Vgas = Area/Thickness * [Dk(P1-P2)]
*CO
*emphysema = less A
*pulmonary fibrosis = more thickness
Pulmonary vascular resistance (Resp
Phys)

Def: Resistance to flow that must be overcome

to push blood through vasculature in lungs

R = delta(P) / Q
= (Pin - Pout) / CO

*Pin = pulmonary artery

*Pout = Left atrium (aka. wedge pressure)

R = 8nL / pi*r^4
*n = blood viscosity
*L = Vessel length
*r = vessel radius
Alveolar gas equation (Resp Phys)

Def: Equation used to calculate the partial

pressure of oxygen in the alveoli

PAO2 = alveolar oxygen pressure

PIO2 = inspired oxygen pressure
PaCO2= artery CO2 pressure
R = respiratory quotient = CO2 produced/O2 in

Higher A-a gradient (can occur in hypoxemia)

*shunting
*V/Q mismatch
*fibrosis
Oxygen deprivation (Resp Phys)

Def: Various terms to describe less oxygen to

areas

Hypoxemia (less oxygen in blood)

-Normal A-a gradient (high alt, hypoventilation)
-increased A-a gradient
*V/Q mismatch
*Diffusion limited
*R-to-L shunt

Hypoxia (less oxygen to tissues)

-less CO
-Hypoxemia
-Anemia
-CO poisoning

Ischemia (loss of blood flow)

-less artery flow in or less venous drain out
V/Q mismatch (Resp Phys)

Def: Ratio of the amount of air reaching the

alveoli to the amount of blood reaching the
alveoli

Both ventilation and perfusion are greatest at

base of lung
*ventilation: because it can expand more
*perfusion: because of gravity

Apex- wasted ventilation

*Organisms that need O2 thrive in apex
base- wasted perfusion

Exercise (more CO) = vasodilation of apical brings

V/Q closer to 1

Phys Dead space (blood obstruct): V/Q higher

*100% O2 can improve PO2 here
Shunt (airway obstruct): V/Q lower
*100% O2 can does not improve PO2 here
CO2 transport (Resp Phys)

Def: Carbon dioxide has chemical reactions that

are important for shuttling from lungs to tissues
and vice versa

Forms of transport
1) HCO3- in plasma (90%)
2) Dissolved O2 (5%)
3) HbCO2 CarbaminoHb (5%)
* When CO2 binds to globin end of HB favors taut
Hb form that releases O2

Bohr Effect
H+ (acid) from metabolism shifts Hb curve to
right favoring O2 dissociation and release

Haldane Effect
O2 from lungs binding to Hb increases free H+
that then shifts equilibrium towards CO2
formation and release
Response to high altitude (Resp
Phys)
Def: Body physiology has some responses for
high altitude lowered PaO2

less PaO2 = more ventilation = less PaCO2

chronic hypoxia = more eryhtopoietin = more Hct

and Hb

more 2,3-BPG binding to Hb ( more O2 release)

More mitochondria

respiratory alkalosis leads to: more HCO3-

excretion (augment with acetazolamide)

Chronic vasoconstriction from hypoxia = Right

Ventricular Hypertrophy (RVH)
Response to exercise (Resp Phys)

Def: Exercise can cause a certain response in the

respiration

PaO2 & PaCO2 remain the same

veins: CO2 up and O2 down

increased ventilation for O2 demand

*more CO2 also produced

V/Q ratio becomes more uniform apex to base

increased CO= increased pulm blood flow

pH decreases (2’ lactic acidosis)

Rhinosinusitis (Resp Path)

Def: inflammation of the paranasal sinuses. It

can be due to infection, allergy, or autoimmune
problems

Causes:
-viral upper resp infection = most common

Sx:
-inflammation and pain over affected area
-superimposed bacterial infections
*S. pneumonia, H. influenzae, M. catarrhalis

*adults = most often maxillary sinus

Deep venous thrombosis (Resp Path)

Def: blood clot that forms in a vein deep inside a

part of the body. It mainly affects the large veins
in the lower leg and thigh and is leading cause of
pulmonary embolism

Virchow triad predisposes to DVT

*95% pulmonary emboli from DVT

Homan sign can suggest DVT

Pulmonary emboli (Resp Path)

Def: Pulmonary embolism is the sudden

blockage of a major blood vessel (artery) in the
lung, usually by a blood clot

V/Q mismatch = hypoxemia = respiratory

alkalosis

CT angiography = imaging of choice for PE

Sx:
-Sudden onset dyspnea, chest pain, tachypnea,
sometimes sudden death

Types:
1. Fat
*Associations: long bone fractures, liposuction
*Classic triad: hypoxemia, neurological abn, petechial rash
2. Air
*nitrogen bubbles can ppt in ascending divers
(Tx= hyperbaric oxygen)
3. Thrombus
4. Bacteria
5. Amniotic Fluid
*Can lead to DIC (clotting proteins overactive)
Obstructive lung diseases (Resp
Path)
Def: People with obstructive lung disease have
shortness of breath due to difficulty exhaling all
the air from the lungs

Airways close at high volumes during expiration

Spirometry test:
RV is increased (can’t exhale out everything)
FVC is less (can’t have as much air in lungs)
FEV1 much less (can’t expire strongly)

*Hallmark: FEV1/FVC decreased

Results in
V/Q mismatch

chronic hypoxic pulm vasoconstr = cor

pulmonade (failure of right side of heart)
Chronic bronchitis (Resp Path)
Def: chronic inflammatory condition in the lungs
that causes the respiratory passages to be
swollen and irritated, increases the mucus
production and damages the lungs

“blue bloater”
blue= hypoxemia
bloater= increased residual volume

A form of Chronic Obstructive Pulmonary Disease

-other one is emphysema

Reid Index > 50%

-due to hyperplasia of mucus glands in bronchial
wall

Dx:
-productive cough >3 months for > 2 years

Sx:
-wheezing, crackles, cyanosis
-early onset hypoxemia due to shunting
-late onset dyspnea
-CO2 retention in body
Emphysema (Resp Path)
Def: emphysema results when the delicate
linings of the air sacs in the lungs become
irreversibly damaged

-Air spaces are enlarged

-less recoil after inspiration
-more compliance (P needed to change V)
-less DLCO exchange of O2

Centroacinar = smoking
Panacinar = alpha1-antitrypsin deficiency
= less elastase activity
= increased lung compliance

Exhaling through pursed lips can increase airway

pressure = prevent airway collapse during
respiration
Asthma (Resp Path)
Def: chronic lung disorder that is marked by
recurring episodes of airway obstruction (as
from bronchospasm) manifested by labored
breathing

Sx:
-cough, weezing, tachypnea, dsypnea, -hypoxemia
-less I/E ratio
-pulsus paradoxus
-mucus plugging
-smooth muscle hypertrophy

Bronchial hyperresponsiveness =
bronchoconstriction

Triggers: viral URI, allergens, stress

Test: methacholine (bronchial) challenge test

Signs: Curschmann spirals and Charcot-Leyden

crystal

Treatment: “ASTHMA”
*A= Adrenergics (Beta2-agonist)
*S= Steroids
Bronchiectasis (Resp Path)
Def: irreversible dilation of part of the bronchial
tree caused by destruction of the muscle and
elastic tissue from a variety of infective and
acquired causes

chronic necrotizing infection (bronchi) = dilated

airways, purulent sputum, hemoptysis

Associations:
bronchial obstruction
smoking (bad cilia motility)
Kartagener syndrome (ciliary dyskinesia)
cystic fibrosis
allergic bronchopulmonary aspergillosis
Restrictive lung disease (Resp Path)

Def: Diseases that restrict lung expansion, resulting

in a decreased lung volume, an increased work of
breathing, and inadequate ventilation

Less Total Lung Cap and less forced vital cap

*FEV1/FVC ratio > 80% however

Poor breathing mechanics (normal A-a)

-muscle: polio, myasthenia gravis
-structural: scoliosis, morbid obesity

Interstitial Lung disease (inc. A-a gradient)

1) Inhaled
-Pneumoconiosis (inorganic, organic)
2) Drugs
-bleomycin, busulfan, amiodarone, methotrexate
3) Connective Tissue
-Sclerosis, Polymyositis, Dermatomyositis, SLE, R.Art
4) Infection
-pneumonia (PCP), TB, Chlamydia trachomatis, RSV
5) Idiopathic
- Sarcoidosis (more ACE and Ca2+), fibrosis
6) Malignancies
7) Respiratory Distress syndromes
&) Goodpasture’s and Wegener’s
Hypersensitivity pneumonitis (Resp
Path)

Def: Inflammation of the lungs due to breathing

in a foreign substance, usually certain types of
dust, fungi, or molds

Pathophysiology
-mixed type 3/ type 4 hypersensitivity to
environmental antigen

Sx
Dyspnea, cough, chest tightness, headache

Clinical
Often seen in farmers and those exposed to birds
Pneumoconiosis (Resp Path)

Def: Restrictive lung disease caused by the

inhalation of dust, often in mines

Asbestos
-Lower lobes
-Dumbbell shaped asbestos
-Calcified pleural plaques (non cancerous)
-Assoc: mesothelial and bronchial cancer

Coal workers’ pneumoconiosis (“Black Lung”)

-Upper lobes
-coal dust exposure = macrophages laden with
carbon= inflm and fibrosis
-”Anthracosis” - urban sooty air asymptomatic

Silicosis
-Upper lobes
-Metal shops (foundries), sandblasting, mines
-macrophages release fibrogenic factors = fibrosis
-increase risk of TB and bronchiole carcinoma
Neonatal respiratory distress
syndrome (Resp Path)

Def: Disease is mainly caused by a lack of

surfactant in the lungs and can cause alveolar
collapse and difficulty breathing

Pathophysiology
surfactant deficiency = alveolar collapse

Test
lecithin:sphingomyelin ratio < 1.5 in amniotic
fluid is predictive

Complications
Low O2 tension→ Patent Ductus arteriosus
*O2 therapy = retinopathy of prematurity (Terry
syndrome) and bronchopulmonary dysplasia

Risk factors
-premature, maternal diabetes (high fetal
insulin), C-section (less released glucocorticoids)

Tx
-maternal steroids before birth
-artificial surfactant for infant
Acute respiratory distress syndrome
(ARDS) (Resp Path)

Def: Sudden failure of the respiratory system

usually develops in people who are already very
ill with another disease or major injuries

Causes
-trauma, sepsis, shock, gastric aspiration, uremia,
acute pancreatitis, amniotic fluid embolism

Pathophysiology
-alveolar damage= leakage= protein leaks into
alveoli
*noncardiogenic pulm edema (so PCWP normal)

-damage due neutrophil, coagulation, free

radicals
*hyaline membrane forms in alveoli
Obstructive vs. restrictive lung
disease (Resp Path)

Def: Obstructive and restrictive lung diseases

can be differentiated based off FEV1 and FVC
changes in spirometry

Obstructive
-works at larger volumes (more TLC, RV)
-FEV1 more reduced than FVC is (ratio <80%)

Restrictive
-works at diminished volumes
FVC more reduced than FEV1 (ratio >80%)

*Can also have other depictions

Pulmonary hypertension (Resp
Path)

Def: Abnormally high blood pressure in the

arteries of the lungs. It makes the right side of
the heart work harder than normal

Normal pulm a. pressure = 10-14 mmHg

HT pulm. a. pressure = >25 mmHg

Pathology= arteriosclerosis, medial hypertrophy,

intimal fibrosis

Primary: BMPR2 gene (inhibits vascular SM

proliferation)

Secondary
-COPD (destroys lng parenchyma)
-mitral valve stenosis (more R =more P)
-thromboemboli (less cross-sect. area)
-autoimmune dz (intimal fibrosis = hypertrophy)
-L-to-R shunt (more shear stress)
-hypoxic vasoconstriction

Result: respiratory distress = cyanosis/RVH = cor

Sleep apnea (Resp Path)
Def: Common disorder in which you have one or
more pauses in breathing or shallow breaths while
you sleep

disrupted sleep = daytime somnolence

*normal PaO2 during day

Nocturnal hypoxia
-more EPO release
-hypertension
-arrhythmias (sometimes sudden death)

1) Central sleep apnea

-no respiratory effort

2) Obstructive sleep apnea

-respiratory effort needed
-Assoc: obesity, loud snoring

TX
weight loss, CPAP, surgery

Obesity hypoventilation syndrome

-hypoventilation leads to less PaO2 even during
Atelectasis (Resp Path)

Def: Atelectasis is the collapse of part or (much

less commonly) all of a lung

Causes
-common after surgery or hospital stay
-anesthesia
-object in lung (often children)

Sx
-chest pain, cough, breathing difficulty, fever

Complication
-pneumonia
Lung Consolidation (Resp Path)

Def: A condition in which lung tissue becomes

firm and solid rather than elastic and air-filled
because it has accumulated fluids and tissue
debris

pneumonia = can cause consolidation

Signs
-expansion reduced on affected side
-vocal fremitus increased on affected side
-percussion dull
-breath sounds = bronchial
-possible inspiratory crackles
-whispered pectoriloquy
-pleural rub may be present
Lung-physical findings (Resp Path)

Def: Different lung conditions can be narrowed

in differential by using physical exam findings

pleural effusion- buildup of fluid around lung

atelectasis- lung collapsed
spontaneous PT- air accum. in pleural space
tension PT- one way valve PT
consolidation- liquid inside of the lung

breath sounds- breathing mechanics

percussion- hollow air more percussion
fremitus- (99) vibration through liquid
tracheal deviation- trachea shifts to one side
Lung cancer (Resp Path)
Def: disease characterized by uncontrolled cell
growth in tissues of the lung and can spread
beyond the lung by process of metastasis

leading cause of cancer death (high smoking

association, except bronchial carcinoid)

Sx:
-cough, hemoptysis, breathing trouble
-Xray (coin lesion) CT (noncalcified nodule)

Complications (SPHERE):
Superior vena cava syndrome
Pancoast tumor
Horner syndrome
Endocrine (paraneoplastic)
Recurrent laryngeal (hoarseness)
Effusions (pleural and pericardial)

1)metastasis to (more than primary neoplasm)

-breast, colon, prostate, bladder
2)mestastis away
-adrenals, brain, bone, liver
Adenocarcinoma (Resp Path)
Def: Most common type of lung cancer that
comes from glandular epithelium and often
found in the periphery

peripheral locations

most occurring type of lung cancer (20%)

*large section of “never smokers”
*excellent prognosis

Mutations
k-ras, EGFR, ALK

Association
clubbing (hypertrophic osteoarthropathy)

Bronchoalveolar subtype grows within lungs

(causing thickened alveoli) instead of through
pleura like other types of lung cancer

CXR- can be similar to pneumonia

Squamous lung carcinoma (Resp
Path)
Def: Neoplasm of malignant squamous cells

Location: hilum of lung (central)

Associations
-Male cigarette smoking (high)
-Cavitation
-hyperCalcemia (PTHrP is produced, also in breast
cancer)

Histology
-keratin pearls
-intercellular bridges
Small cell (oat) carcinoma (Resp
Path)
Def: Neoplasm of lung involving small cells that
is very aggressive

Centrally located

-undifferentiated = very aggressive

-strong smoking association

Cause
-can be amplification of myc oncogene

Pathophysiology
-may produce ACTH, ADH
-may produce Ab against presynaptic Ca2+
channels (Lambert-Eaton myasthenic syndrome)

Tx
-small so must use chemo

Histology
Kultchitsky cells (neuroendocrine) neoplasm =
small blue cells
Large cell carcinoma (Resp Path)
Def: Least prevalent type of lung cancer from
large type of lung cells

peripherally located
Poor prognosis

Characteristics
-highly anaplastic
-undifferentiated

Tx
surgical (less responsive to chemo)

Histology
pleomorphic giant cells
Bronchial carcinoid (Resp Path)
Def: Malignant neoplasm arising from
epithelium of the bronchi

excellent prognosis (metastasis rare)

Sx
-due to mass effect
-occasionally carcinoid syndrome (5-HT secretion
= flushing, diarrhea, wheezing)

*tumors of colon, appendix, small intestine,

bronchi can cause carcinoid syndrome

Lab
-nests of neuroendocrine cells
-chromogranin A (+)
Mesothelioma (Resp Path)

Def: rare form of cancer that develops from cells

of the mesothelium, the protective lining that
covers many of the internal organs of the body

most commonly caused by exposure to asbestos

Visceral pleura- covers lungs

pleural space
Parietal pleural- outside lungs

Results in
-hemorrhagic pleural effusion
-pleural thickening

Histology
-psammoma bodies- round collection of calcium
Pancoast tumor (Resp Path)

Def: Tumor characterized by location of

pulmonary apex and most are non-small cell
cancers

Carcinoma of upper lung

Super vena cava (syndrome)

sympathetic plexus (ipsilateral Horner’s)
recurrent nerve (hoarseness)
sensorimotor deficits
Superior vena cava syndrome (Resp
Path)

Def: direct obstruction of the superior vena cava

by malignancies

Medical emergency

most common obstr: bronchogenic carcinoma

*indwelling catheters large risk factor

Sx
head (“facial plethora”)
*test with Pemberton’s
maneuver
neck (jugular venous distension)
upper extremities (edema)

If severe and untreated

-can raise Intracranial pressure (more risk of
cerebral aneurysm)
Pneumonia (Resp Path)
Def: inflammatory condition of the lung
affecting primarily the microscopic air sacs
known as alveoli usually caused by infection

-Dx based on CXR most often

Lobar (one lobe)

Broncho (infiltrates from bronchi)
Interstitial (areas between alveoli)
Lung abscess (Resp Path)
Def: necrosis of the pulmonary tissue and
formation of cavities containing necrotic debris
or fluid caused by microbial infection

Causes
-bronchial obstruction
-aspiration of oropharyngeal contents (alcoholics,
epileptics, anesthesia)

Sx
-pus in parenchyma (air-fluid on CXR)

Microbes
-S. aureus
-anaerobes (Bacteroides, Fusobacterium,
Peptostreptococcus)
Pleural effusions (Resp Path)

Def: Excess accumulation of fluid between the

two pleural layers which restricts lung
expansion during inspiration

Transudate
*Cause: CHF, nephrotic syndrome, hepatic
cirrhosis
-clear because less proteins

Exudate
*Cause: blocked vessel or inflammation
-cloudy because more proteins
-should be drained bc of infection risk

Lymphatic (“chylothorax)
*Cause: thoracic duct injury
-milky apprearance (high triglycerides)
Pneumothorax (Resp Path)

Def: abnormal collection of air or gas in the

pleural space that separates the lung from the
chest wall

On affected side: chest pain, dyspnea, chest

expansion, less (99) fremitus, hyperresonance
(percussion), less breath sounds

Spontaneous Pneumothorax
-often tall, thin, young males
-rupture of apical blebs

Tension Pneumothorax
-pneumothorax with a one way flap so air can
only come in one way
*trachea and mediastinum deviate away
-often from trauma or lung infection
H1 blockers (Resp Phrm)
Def: Reversible histamine antagonist of the H1
receptor that serves to reduce or eliminate
effects mediated by histamine (allergic
reactions)

1st Generation (-en, -ine, -ate)

Diphenhydramine, dimenhydrinate, chlorpheniramine
USE: allergy, sleep aid
TOX: sedation, anti-muscarinic, anti-a-adrenergic

2nd Generation (-adine)

Loratadine, fexofenadine, desloratadine, cetirizine
USE: allergy
TOX: less sedating (less entry into CNS)
Expectorants (Resp Phrm)

Def: class of drugs which aid in the clearance of

mucus from the airways

Guaifenesin
MECH: less viscous respiratory secretions
USE: less cough by bringing up mucus

N-acetylcystein
MECH: lysis of mucus
USE: CF mucus plugs, acetominophen OD
Dextromethorphan (Resp Phrm)

Def: antitussive (cough suppressant) drug

MECH
-NMDAR antagonist
-stops medulla cough reflex

USE
-cough

TOX
-Naloxone for OD
-Abuse potential
Pseudoephedrine, phenylephrine
(Resp Phrm)

Def: nasal/sinus decongestant, as a stimulant, or

as a wakefulness-promoting agent

MECHsympathomimetic a-agonist

USE-nasal decongestant
-hyperemia
-edema
-eustachian tube decongestion

TOX
-pseudophed used illicitly to make meth
-HT
-can cause CNS stimulation/anxiety
Asthma drugs PS Tone (Resp Phrm)

Def: Early response to asthma trigger is

modulate broncial tone with parasympathetic
system

B2- Agonist
-Albuterol: acute exercise
-Salme,formo-terol: long acting for prophylaxis
*adverse = tremor, arryhthmia

Methylxanthines (theophyline)
-blocks PDE to increase cAMP
-blocks adenosine
-narrow therapeutic index (toxicities)
-P-450 breaks down

Muscarinic antagonists
-ipratropium: blocks muscarinic
-tiotropium: long-acting block for COPD
Asthma drugs Inflammatory
Response (Resp Phrm)

Def: Late response to asthma trigger is

inflammation which can be inhibited in various
ways

Corticosteroids
-inhibit cytokine synthesis and infl agents
-inactivate NFK-B
-inactivate TNF-a’s TF
-1st line for chronic asthma

Antileukotrienes
- Montelukast, zafirlukast(block leukotriene
receptors)
*good for aspirin induced asthma

Zileuton: blocks 5-lipoxygenase (arachidonic acid

to leukotriene)

Omalizumab
-monoclonal anti-IgE antibody prevents IgE
binding to FcERI
-mainly used if steroid/B2-agonist resistance
Methacholine (Resp Phrm)

Def: Used in bronchial provocation challenge to

help diagnose asthma

methacholine (M3 muscarinic receptor agonist)

histamine (H1 receptor)

Both cause vasoconstriction

Asthmatic will respond at lower doses

(hyperreactivity)
*measured with spirometry
Bosentan (Resp Phrm)
Def: dual endothelin receptor antagonist used in
the treatment of pulmonary artery hypertension

MECH
Competitively antagonized endothelial-1
Receptors (constrict blood vessels)

USE
Pulmonary Hypertension (decreases Resistance)

TOX/OTHER
hepatotoxicity, teratogen