Block 10 week 1 Flashcards
- Normal body temperature is between 36.1 and 37 degrees.
- hyperthermia: above 38. Life threatening if over 40
- can lead to:
- confusion
-seizures - coma
- cardiovascular collapse
-hypothermia: below 35. Severe if below 28.
Clinical features:
- confusion
- coma
-cardiovascular collapse
-Thermoregulation is needed in response to internal and external temperature variations.
How do we detect internal temperature variations ?
-Internal temperature variations are sensed by nerve cells - thermoreceptors, located in the anterior hypothalamus.
- hypothalamus works as a thermostat.
The front part or the anterior hypothalamus responds to increased environmental temperatures and it also controls the core temperature of the body.
The back part or the posterior hypothalamus, on the other hand, responds to decreased environmental temperatures.
How are changes in the external temperature sensed ?
- skin thermoreceptors
- winter - skin receptors detect drop in temp and send info to anterior hypothalamus which will tell posterior hypothalamus that the body needs to generate heat.
-
Diurnal variation
Body Temperature: Body temperature tends to be lower during the early morning hours and higher in the late afternoon and evening. This temperature fluctuation is regulated by the body’s internal biological clock, known as the circadian rhythm.
Physiological mechanisms of heat production ?
- thyroid hormones are stimulated: T3 (triiodothyronine) and T4 (thyroxine)
- T3 is the active form
- one of their roles is heat production, they do that by stimulating the conversion of T4 to T3.
- T3 then increases the production of ATP in the body.
- ATP is basically the energy currency in the cell and the more we have, the more of it can be used to generate heat.
Hypothyroidism / hyperthyroidism
- when you have low levels of thyroid hormones - extremally sensitive to cold
- hyperthyroidism - heat intolerance
Sympathetic nervous system
- the posterior hypothalamus also sends signals that activate the sympathetic nervous system.
- The sympathetic nervous system is normally activated by fight-or-flight situations, and it leads to increased catecholamine production, like epinephrine or norepinephrine.
- Catecholamines bind to β receptors in brown fat. Brown fat burns calories to generate heat.
- SNS stimulates a1 receptors in vascular smooth muscle of skin blood vessels - vasoconstriction - less blood - reduces heat loss.
Shivering
- posterior hypothalamus signals the skeletal muscles, contractions - shivering
- muscles contract - ATP breaks down to ADP and phosphate molecule.
- 3 phosphate bonds attached to adenosine. The energy is stored in the phosphate bond in a high energy state.
- bond broken - hydrolysis - electrons go into a lower energy state.
- high energy released - exothermic reaction
ow, radiation occurs between any two objects when their temperature differs.
For example, on a sunny day the radiation from the sun warms the skin.
Conduction is the transfer of heat between objects that are in direct contact with each other.
For instance, when holding an ice pack on the forehead, the internally generated heat is transferred to the ice pack.
And convection refers to the transfer of heat by the movement of air or liquid moving past the body.
That explains why a breeze across the skin may cool one down.
Fever (pyrexia)
- during an infection microbes produce pyrogens
- pyrogens increase the production of interleukin 1 in phagocytic cells like neutrophils
- Interleukin-1 then signals the anterior hypothalamus to increase local prostaglandin production
- prostaglandins are lipid molecules that increase the set point temperature, basically, telling the anterior hypothalamus that the right body temperature is waaay above 37 degrees celsius.
- The result of this is that the new set point will make the normal core temperature appear too low and so the anterior hypothalamus activates heat generating mechanisms, such as shivering, to increase body temperature up to the value of the new set point.
Kidney Anatomy
- Renal capsule
- Renal cortex: outer layer, extending down between pyramids-
- Renal medulla: inner layer (middle) (renal pyramids
- Renal calyces (major and minor)
-Renal pyramids (w/ renal papilla)
- Renal columns
Poles of the kidney:
External features
Lateral border of the kidney
Inferior pole of the kidney
Medial border of the kidney
The medial border of each kidney has a concave area called the hilum. This is where the ureter exits the kidney and renal artery, renal vein, and lymph vessels enter and exit the kidney.
Anatomy
- Kidneys are located between T12 and L3 vertebrae
- Partially protected by the floating ribs - 11 and 12
- Retroperitoneal: they sit behind the peritoneal membrane alongside the vertebral column
- Right kidney is pushed down by the liver so it sits slightly lower than the left kidney.
- The kidney is surrounded by three layers of tissue. On the outside is the renal fascia which is a thin layer of dense connective tissue that anchors the kidney to its surroundings. The middle layer, or the adipose capsule, is a fatty layer that protects the kidney from trauma. And the deepest layer, called the renal capsule, is a smooth, transparent sheet of dense connective tissue that gives the kidney its distinctive shape.
Facts
- Adult’s kidneys filter about 150 liters of blood every day. If we assume that there are 5 liters of blood in the body. Entire blood volume is filtered 30 times. More than once an hour
- To reach the kidneys, blood flows from the aorta into the left and right renal arteries.
- As these renal arteries enter the kidney, they divide into segmental arteries and then into interlobar arteries which pass through the renal columns then to arcuate arteries that go over the bases of the renal pyramids and then into cortical radiate arteries which supply the cortex.
- The cortical radiate arteries continue to divide eventually forming afferent arterioles that split into a tiny bundle of capillaries called the glomerulus.
Function of kidneys
- Excretion and removal of metabolic waste and foreign substances through urine. They’re like a water purification plant that helps clean the drinking water for a city.
- The kidneys also activate vitamin D when needed, and help maintain the balance of fluid volume, pH, blood pressure, and electrolytes in the body.
- The kidneys also secrete important hormones, such as erythropoietin, which increases the production of red blood cells.
Nephrons
At the junction between the cortex and medulla are millions of functional units called nephrons. Each nephron can be divided into its major parts:
Glomerulus
- glomerulus is the site where blood filtration starts
- once the blood leaves these glomeruli it does not enter into venules. Instead the glomerulus funnels blood into efferent arterioles which divide into capillaries a second time
- After the nephron these peritubular capillaries then reunite to become the cortical radiate veins, then the arcuate veins, then interlobar veins and finally into the left and right renal veins which connect to the inferior vena cava. The flow of the veins are similar to the arteries but in reverse, the only difference is that there’s a segmental artery but no segmental vein.
Nephron
Within each kidney, there are about 1 million nephrons, and each nephron is made up of a renal corpuscle and a renal tubule. The renal corpuscle is where blood filtration starts and it includes the glomerulus, which is the tiny bed of capillaries, and the Bowman’s capsule which is made of renal cells that surround the glomerulus.
- As blood flows into the glomerulus, water and some solutes in the blood like sodium are able to pass through the endothelial lining of the capillary, move across its basement membrane, through the epithelial lining of the nephron and finally into the Bowman’s space of the nephron itself—at which point it is called filtrate.
- The epithelium of the nephron is made of specialized cells called podocytes which wrap around the basement membrane like the tentacles of an octopus. Between these tentacle-like projections are tiny gaps called filtration slits that act like a sieve allowing only small particles like water, glucose and ionic salts to pass through while blocking large proteins and red blood cells.
- As the filtrate leaves the Bowman’s capsule it flows into the renal tubule, which is surrounded by the peritubular capillaries.
Renal tubule parts
- PCT (proximal convoluted tubule)
- Loop of Henle ( descending and ascending limb)
- DCT ( distal convoluted tubule)
- Collection ducts
- After collection ducts send the urine to the minor calyces.
- the filtrate becomes fine tuned based on what the body wants to keep versus what it wants to discard, with water and solutes getting passed back and forth between the filtrate in the lumen of the renal tubule and the blood in the peritubular capillaries.
Juxtaglomerular complex
-Each nephron also has a really unique region called the juxtaglomerular complex which is involved in the regulation of blood pressure and the glomerular filtration rate—or the amount of blood that passes through the glomeruli each minute.
-The juxtaglomerular complex is located between the distal convoluted tubule and the afferent arteriole.
Juxtaglomerular complex 2
-There are three types of cells in the juxtaglomerular complex - macula densa cells, juxtaglomerular cells and extraglomerular mesangial cells.
- Macula densa cells are located in the distal convoluted tubule and they can sense when levels of sodium and chloride are low.
- So, in the case of hypovolemia and hypotension, the macula densa cells sense the low sodium and chloride levels and send a signal over to the juxtaglomerular cells which are located in the wall of the afferent arteriole.
- The extraglomerular mesangial cells help with the signaling between macula densa cells and juxtaglomerular cells.
- The juxtaglomerular cells then receive the signal and also independently sense the low pressure in the blood vessels and secrete an enzyme called renin which increases sodium reabsorption and this helps raise the blood volume. Renin also causes constriction of blood vessels which helps raise the blood pressure.
Where does the urine go once its made ?
- Once millions of nephrons have each made urine, it flows into the minor calyces, then major calyces, and finally into the renal pelvis. From there, it goes down the ureter which has a muscular lining which helps push the urine along.
- The ureters insert into the bladder at the ureterovesical junction at a sideways angle so that when the bladder becomes full, it compresses the openings to the ureters and prevents backflow of urine. It’s basically a one way valve that prevents urine from refluxing backwards from the bladder into the ureters.
URETHRA
-The urethra is a thin muscular tube that drains urine from the bladder, starting from the internal urethral orifice to the external opening. In people assigned male at birth, the urethra first passes through the prostate, where it is called the prostatic urethra, then it passes through deep muscles of the perineum, where it’s called the intermediate urethra and finally, it passes through the penis, where it’s called the spongy urethra. The male urethra is also used during ejaculation, except there - semen enters into the urethra via the ejaculatory ducts
-In people assigned female at birth, the urethra runs through the perineal floor of the pelvis and exits between the two labia minora, above the vaginal opening and below the clitoris in an area called the vulval vestibule.
- Around the internal urethral orifice, the detrusor muscle thickens to form the internal sphincter. This involuntary sphincter is controlled by the autonomic nervous system and keeps the urethra closed when the bladder isn’t full.
- Additionally, there’s an external sphincter, at the level of the urogenital diaphragm in the floor of the pelvis which is under voluntary control. By contracting the skeletal muscles around the external sphincter, urination can be stopped voluntarily. This is called a kegel exercise and it can be done to strengthen the pelvic floor.
-
Act of urination
The act of urination involves close coordination between the nervous system and the muscles of the bladder. Once the volume of the bladder is greater than about 300-400 milliliters, basically when it’s half full, pressure on the bladder walls increases and sends signals to the urination or micturition center in the spinal cord, located at S2 and S3. This sets off a reflex arc called the micturition reflex which causes contraction of the bladder and relaxation of the internal sphincter and external sphincter.
Now, the pontine storage center and the pontine micturition center are two areas in the pons part of your brain that help control urination. When you can’t find a toilet and you want to hold your urine in, then you activate the pontine storage center and that stops the micturition reflex. When you finally do find that toilet, and you’re ready to urinate, the pontine micturition center is active and it allows the micturition reflex to happen - and you can finally pee.
How does kidney disease often present ?
- Often Asymptomatic
When symptoms are present they are vague:
- Fatigue
- Anorexia and weight loss
- Shortness of breath
- Swelling in dependent areas
- Muscle cramps, palpitations, itchiness
- Oliguria: less urine (less than 400ml per day) (less than 20ml an hour)
- Anuria: refers to the lack of urine production. Sometimes called anuresis.
- Polyuria: urinating more than usual and passing abnormally large amounts of urine each time you urinate ( more than 3 liters a day).
- Normal daily urine output: 1-2 litres a day.
PMH
Medications that can cause Kidney disease symptoms
CKD and diabetes
The most common cause of CKD is diabetes, excess glucose in the blood starts sticking to proteins in the blood — a process called non-enzymatic glycation because no enzymes are involved.
This process of glycation particularly affects the efferent arteriole and causes it to get stiff and more narrow - a process called hyaline arteriosclerosis. This creates an obstruction that makes it difficult for blood to leave the glomerulus, and increases pressure within the glomerulus leading to hyperfiltration.
In response to this high-pressure state, the supportive mesangial cells secrete more and more structural matrix expanding the size of the glomerulus.
Over many years, this process of glomerulosclerosis, once again, diminishes the nephron’s ability to filter the blood and leads to chronic kidney disease.
CKD and Hypertension
One of the most common causes of chronic kidney disease is hypertension.
In hypertension, the walls of arteries supplying the kidney begin to thicken in order to withstand the pressure, and that results in a narrow lumen. A narrow lumen means less blood and oxygen gets delivered to the kidney, resulting in ischemic injury to the nephron’s glomerulus.
Immune cells like macrophages and fat-laden macrophages called foam cells slip into the damage glomerulus and start secreting growth factors like Transforming Growth Factor ß1 or TGF-ß1.
These growth factors cause the mesangial cells to regress back to their more immature stem cell state known as mesangioblasts and secrete extracellular structural matrix. This excessive extracellular matrix leads to glomerulosclerosis, hardening and scarr, and diminishes the nephron’s ability to filter the blood - over time leading to chronic kidney disease.
There are 3 categories of AKI
Prerenal AKI: things that occur before the kidney can lead to AKI
Intrarenal AKI : things that occur in the kidneys that lead to AKI
Postrenal AKI: Things that occur after the kidneys that lead to AKI. Things occurring in ureter, bladder or prostate.
- An acute kidney injury is typically reversible.
- Before AKI used to be called Acute renal failure. Its now called a separate thing because renal failure is much severe. AKI can eventually lead to Chronic renal failure.
- Chronic renal failure is irreversible
- Azotemia - increase in BUN and creatinine
What causes Pre-renal AKI
- HYPOTENSION due to heart failure or cirrhosis ( most common).
- Heart failure is when the heart is unable to pump blood effectively to meet the body’s demands. So blood pressure drops and the RAAS system in the kidneys detects this and thinks that there is less blood, which is not the case we have the right blood volume but the heart is not pumping that forwards
- Cirrhosis is scarring of the liver. In Cirrhosis you have a massive release of molecules that cause vasodilation. If we get vasodilation in the veins we can get blood pooling around the body. So less blood gets back to the heart and less is pumped to the kidneys.
- These things make it appear that their is a low volume state in the body
- Another cause is HYPOVOLEMIA. The patient has a true decrease in their volume status. So decrease in effective volume.
- Sweating, diarrhea, hemorrhage and vomiting all cause us to lose fluid so lower our blood volume.
- Also patients who have burns.
- These are all true low volume state in the bidy.
- Another reason is RENAL ARTERY STENOSIS. Narrowing of arteries means less blood flow to kidneys.
- Medications can cause Prerenal AKI. This includes Diuretics, NSAIDS and ACE inhibitors
NSAIDs and ACE Inhibitors and AKI
NSAIDS: cause afferent arteriole vasoconstriction. Less blood flow to the kidney. Reduced blood flow. Reduced GFR
ACE inhibitors: cause efferent vasodilation. The lumen in the efferent arteriole widens so more blood leaves via the efferent arteriole instead of being filtered by the glomerulus.
DIAGNOSING prerenal AKI
- Urine Osmolality (concentration) : over 500. In prerenal AKI we have lower blood volume so RAAS reabsorbs water from urine. So a high urine osmality indicates prerenal AKI
- Urinary sodium less than 20. Sodium has been reabsorbed back into the body less in urine.
Management
- Restore renal perfusion by giving IV fluids and Blood
- Discontinue medications - NSAID, ACE inhibitors, ARBS ( angiotensin receptor blockers)
-
Intrarenal AKI causes
- Intrarenal AKI which is due to damage to the tubules, the glomerulus, or the kidney interstitium, which is the space between tubules or vascular damage.
- The most common cause of intrarenal AKI is acute tubular necrosis, which is damage to the tubules due to ischemia.
- The other ways tubules can necrose is via nephrotoxins such as aminoglycoside antibiotics, methotrexate and heavy metals.
Intrarenal AKI cause: Acute Interstitial Nephritis
Acute interstitial nephritis, which is inflammation of the interstitium over the course of days to weeks. This is thought to be a type I or type IV hypersensitivity reaction, and is typically a response to a medication like NSAIDs, penicillin, and diuretics, such as thiazide diuretics, like chlorothiazide. Early symptoms include fever and rash.
